Parasites and Biliary stones

Parasites and Biliary stones 

Essay 

Submitted in partial fulfillment 

for Master Degree 

In Endemic Medicine 

By 

Sameh Mahmoud Abdel Mone'em 

M.B.,B.Ch. 

Under supervision of: 

Prof. Dr. 

Hamid Mohammad Suliman 

Professor and Head of Tropical Medicine Department 

Faculty of Medicine 

Zagazig University 

Prof. Dr. 

Mohiedin Mohammad Abdul-Fattah 

Professor of Parasitology 



Dr. 

Tarik Ibrahim Zaher 

Lecturer of Tropical Medicine 





2007

ﻢﻴﺣﺮﻟا ﻦﻤﺣﺮﻟا ﷲا ﻢﺴﺑ 

"( 

٣٢) 

ﺔﻳﺁ ةﺮﻘﺒﻟا ةرﻮﺳ " 

ﻢﻴﻈﻌﻟا ﷲا قﺪﺻ

Dedication 

TO 

MY BELOVED DEAR MOTHER, 

TO MY GREAT FATHER, 

TO MY BROTHERS 

AND MY SISTERS 

WITH LOVE AND RESPECT

Acknowledgement 

First and foremost, my deep thanks to ALLAH. The most kind 

and the most merciful for giving me patience and strength to achieve 

this work. 

I would like to express my deepest and great gratitude and 

respect to my Prof. Dr. Hamid Mohammad Suliman, 

Professor of Tropical Medicine, Zagazig Univeristy, for his 

continuous instructive education, guidance, encouragement and 

supervision. 

My sincere thanks and deepest gratitude to my Prof. Dr. 

Mohiedin Mohammad Abdul-Fattah, Professor Of 

Parasitology, Zagazig Univeristy, for his valuable advices, 

appreciable encouragement, constant guidance, and helpful criticism 

throughout the whole work. 

Words fail to express my profound thanks and sincere gratitude 

to Dr. Tarik Ibrahim Zaher, Lecturer Of Tropical Medicine, 

Zagazig Univeristy, who devoted a lot of his time and efforts to help 

me, and for his valuable advice. Without his skills, this work would 

have never seen light . 

Finally, I would like to thank all the staff members in the 

Tropical Medicine Department, Zagazig Univeristy Hospitals who 

extended to me a helping hand during processing of this work. 

Sameh Mahmoud Abdel Mone'em

Abstract 

Gall stone disease remains one of the most common medical problems 

leading to surgical intervention. The risk factors predisposing to gallstone 

formation include obesity, diabetes mellitus, estrogen and pregnancy, 

hemolytic diseases, and cirrhosis . It is important to remember that 

gallstones can lead to a variety of other complications including 

choledocholithiasis. About 15% of patients with gallstones have 

choledocholithiasis. Stones in the common duct usually originate in the 

gallbladder but may also form de novo in the bile duct. Stones from gall 

bladder which migrate up to the intra-hepatic ducts leading to formation of 

Hepatolithiasis. 

Helminthic invasion of the human biliary tract is a prominent medical 

and surgical problem especially in tropical and subtropical areas where these 

parasites are endemic. Helminthic infestation may affect the liver and/or the 

biliary tract either during passage of worms through these structures or 

because these organs serve as their natural habitat. The parasitic infestations 

affecting the biliary tract including the nematode Ascaris lumbricoides, the 

trematodes Opisthorchis viverrini and felineus, Clonorchis sinensis, 

Dicrocoeliasis and Fasciola hepatica, and the cestodes Echinococcus 

granulosus and multilocularis, also some protozoa can cause biliary tract 

disease as Cryptosporidium, and Giardiasis.

ALP : 

CBD : 

CBDS : 

CMV : 

CT : 

EHL : 

EPBD : 

ERC : 

ERCP : 

ES : 

ESWL : 

EUS : 

FIG : 

GGT : 

IOC : 

IL : 

KG : 

LIST OF ABBREVIATIONS 

Alkaline phosphatase 

Common bile duct 

Common bile duct stones 

Cytomegalovirus 

Computed tomography 

Electro hydraulic lithotripsy 

Endoscopic papillary balloon dilatation 

Endoscopic retrograde Cholangiography 

Endoscopic retrograde cholangio-pancreatography 

Endoscopic sphincterotomy 

Extracorporeal shock wave lithotripsy 

Endoscopic ultrasonography 

Figure 

Gamma glutamyl transpeptidase 

Intra-operative cholangiography 

interleukin 

Kilogram

MTBE : 

ML : 

Methyl tertiary butyl ether 

Mechanical lithotripsy 

MRC : Magnetic resonance cholangiography 

MRCP : 

MRI : 

NO : number 

PO : 

PCR : 

PSC : 

PTC : 

SGOT : 

SGPT : 

SO : 

SOM : 

SOD : 

SPP : 

TUS : 

US : 

UDCA : 

Magnetic resonance cholangiopancreatography 

Magnetic resonance imaging 

Peroral 

Polymerase chain reaction 

Primary sclerosing cholangitis 

Percutaneous transhepatic cholangiography 

Serum glutamic oxalo-acetic transaminase 

Serum glutamic pyruvic transaminase 

Sphincter of oddi 

Sphincter of oddi manometry 

Sphincter of oddi dysfunction 

species 

Trans abdominal ultrasonography 

ultrasonography 

Ursodeoxy cholic acid

List of figures 

` 

Figure (1): 2 worms in the major papilla --------------------------- 6 

Figure (2): ERCP showing an ascarid worm in the common bile duct 

extending up to the proximal left hepatic duct ------------ 11 

Figure (3): The appearance of Fasciola hepatica fluke on ultrasonographic 

examination of the gallbladder ---------------------------- 16 

Figure (4): CT scan demonstrates :multiple subcapsular hypodense lesions in 

both lobes,dilatation of intra and extra hepatic bile ductes and 

ascites ---------------------------------------------------- 17 

Figure (5): ERCP of four additional patients showing a Fasciola worm 

in bile ducts ----------------------------------------------- 20 

Figure (6): ERCP showing a Fasciola worm in the bile duct and 

gallbladder ------------------------------------------------ 20 

Figure (7): ERCP showing a Fasciola worm in the bile duct and 

localized narrowing of the left hepatic duct --------------- 21 

Figure (8): Histopathological findings of clonorchiasis ------------- 24 

Figure (9): Hepatic ultrasonography in a 60-year-old woman and a 41-year 

old man with clonorchiasis ------------------------------- 27 

Figure (10): Transverse hepatic computed tomography in a 45-year-old 

woman and a 57-year-old man with clonorchiasis -------- 29 

Figure (11): Posteroanterior endoscopic retrograde cholangiography 

in a 54-year-old man with clonorchiasis ------------------ 29 

Figure (12): Metacercaria of Opisthorchiasis viverrini in cavity of caudal fin 

ray of cyprinoid fish, Cyclocheilichthys spp. ------------- 33 

Figure (13): The life cycle of Dicrocoeliasis ----------------------- 38

Figure (14): Cystic echinococcosis: Lung cyst on chest radiograph 47 

Figure (15): Sagittal US image ------------------------------------- 48 

Figure (16): Multiple stones in the common bile duct -------------- 78 

Figure (17): Stone during extraction from the common bile duct by basket 

forceps ---------------------------------------------------- 102 

Figure (18): Double-duct sign in ERCP ---------------------------- 107 

Figure (19): Cannulation of CBD ---------------------------------- 112 

Figure (20): Endoscopic sphincterotomy --------------------------- 116 

Figure (21): Single lumen Geenen cytology catheter with 3.5-cm 

Brush---------------------------------------------------------------------119 

Figure (22): Double lumen cytology catheter ---------------------- 119 

Figure (23): HBIN catheter with FNA needle ---------------------- 120 

Figure (24): Radiographic image of an open biopsy forceps within the 

common bile duct ----------------------------------------- 121 

Figure (25): Pre-cut of the major papilla --------------------------- 124

Contents 

Introduction ------------------------------------------------------- 1 

Billiary parasites ------------------------------------------------- 4 

Ascariasis ------------------------------------------------------ 8 

Fascioliasis ----------------------------------------------------- 13 

Clonorchiasis -------------------------------------------------- 22 

Opisthorchiasis ------------------------------------------------ 31 

Dicrocoeliasis -------------------------------------------------- 37 

Echinococcosis ------------------------------------------------ 42 

Cryptosporidiosis --------------------------------------------- 52 

Giardiasis ------------------------------------------------------- 57 

Billiary stones ----------------------------------------------------- 63 

Gallbladder stones -------------------------------------------- 63 

Choledocholithiasis ------------------------------------------- 69 

Hepatolithiasis ------------------------------------------------- 85 

Relationship between parasites and biliary stones -------- 93 

Relationship between Ascaris and biliary stones --------- 93 

Relationship between Clonorchis sinensis and biliary 

stones ---------------------------------------------------- 95 

Relationship between Opisthorchiasis and biliary stones 97 

Relationship between fascioliasis and biliary stones ----- 99 

Relationship between Echinococcosis and biliary stones 100 

Endoscopic retrograde cholangiopancreatography ------- 101 

Summary and conclusion --------------------------------------- 137 

Arabic summary --------------------------------------------------

List of tables 

Table (1): Diagnosis of biliary parasites ---------------------------- 5 

Table (2): Historical aspect of ERCP ------------------------------- 101 

Table (3): Reasons for failed duct clearance ------------------------ 122 

Table (4): Grading for the difficulty of ERCP procedures ---------- 125 

Table (5): Reasons for failed endoscopic retrograde 

cholangiopancreatography -------------------------------- 126 

Table (6): Consensus definitions for the major complications of 

ERCP ----------------------------------------------------- 127

Introduction ١ 

Introduction 

Gall stone disease remains one of the most common medical 

problems leading to surgical intervention. The risk factors predisposing to 

gallstone formation include obesity, diabetes mellitus, estrogen and 

pregnancy, hemolytic diseases, and cirrhosis. It is important to remember 

that gallstones can lead to a variety of other complications including 

choledocholithiasis (Schirmer et al., 2005). 

Choledocholithiasis occurs as a result of either the primary 

formation of stones in the common bile duct (CBD) or the passage of 

gallstones from the gallbladder through the cystic duct into the CBD. Bile 

stasis, bactibilia, chemical imbalances, pH imbalances, increased bilirubin 

excretion, and the formation of sludge are among the principal factors 

thought to lead to the formation of these stones (Dandan et al., 2005). 

Also, these factore are important in formation of intra hepatic stones 

(hepatolithiasis) which characterized by the finding of stones within the 

intra hepatic bile ducts proximal to the confluence of the right and the left 

hepatic ducts (Leung and Yu, 1997). 

In many parts of the world, biliary parasites are an important factor. 

Biliary parasites cause necrosis, inflammation, fibrosis, strictures, and 

cholangiectasis of the bile ducts by several mechanisms: As a direct result 

of the irritating chemical composition of the parasite, parasitic secretions, 

or eggs; physical obstruction of the bile ducts; induction of formation of 

biliary stones; and introduction of bacteria into the biliary system during 

migration from the duodenum. 

Common biliary parasites include the nematode Ascaris 

lumbricoides, the trematodes Opisthorchis viverrini and felineus,

Introduction ٢ 

Clonorchis sinensis, and Fasciola hepatica, and the cestodes 

Echinococcus granulosus and multilocularis (Carpenter, 1998). 

Hence, we can see that parasitosis especially fascioliasis should be 

considered in the diagnosis of cholestasis in Fasciola endemic areas 

(Elshazly et al., 2005). Generally speaking ,in cases of 

choledocholithiasis and extrahepatic jaundice, biliary tree parasitosis 

must be considered in the differential diagnosis (Machado et al., 1996). 

Management of biliary parasites begins with conservative measures, 

including analgesics and anti-helminthic therapy. In refractory cases or 

patients with acute cholangitis, endoscopic biliary drainage and the 

extraction of worms may be necessary. Improvement in sanitation plays a 

crucial role in the epidemiological control of these biliary diseases 

(Leung and Yu, 1997). 

ERCP was introduced in the early 1970s and has become the 

diagnostic and therapeutic tool of choice in patients with 

choledocholithiasis. The CBD is cannulated through the ampulla, contrast 

material is injected, and films are obtained. The experience of the 

endoscopist is the best predictor of success, which is 90-95% in expert 

hands. In most patients, ERCP is the modality of choice when 

choledocholithiasis is suggested (Dandan et al., 2005). ERCP 

management in biliary parasitosis include multiple procedures such as 

sphincterotomy , balloon dilatation of the sphincter of Oddi, forceps and 

dormia basket extraction of the parasite (Gavindamasy and Thomsom, 

2004).

Introduction ٣ 

Aim of the work: 

1. To discuss the relationship between biliary parasites and biliary stones. 

2. To discuss the differential diagnosis of biliary obstruction by stones 

and / or parasites.

Billiary parasites ٤ 

Billiary parasites 

Helminthic invasion of the human biliary tract is a prominent 

medical and surgical problem especially in tropical and subtropical areas 

where these parasites are endemic (Philips and Yung, 1960). Helminthic 

infestation may affect the liver and/or the biliary tract either during 

passage of worms through these structures or because these organs serve 

as their natural habitat. The parasitic infestations affecting the biliary tract 

including the nematode Ascaris lumbricoides, the trematodes 

Opisthorchis viverrini and felineus, Clonorchis sinensis, 

Dicrocoeliasis , and Fasciola hepatica, and the cestodes Echinococcus 

granulosus and multilocularis (Carpenter,1998), also some protozoa 

can cause biliary tract disease as Cryptosporidium (Mandell et al., 

2000), and Giardiasis (Tessier and Davies, 1999). 

Manifestations of biliary parasitic infestations: 

Parasites in the biliary tree can cause the syndrome commonly 

referred to as ‘Oriental cholangiohepatitis’. Features of this syndrome 

include helminthiasis, biliary stones formation, choledochal obstruction 

and recurrent cholangitis. A parasite may act as a nidus for stone 

formation (Yellin and Donovan, 1981). 

The stones associated with ‘Oriental cholangiohepatitis’ are darkly 

pigmented, soft and friable, different from gallstones seen in the Western 

part of the world. However, the relation between choledocholithiasis and 

parasites may be coincidental. Clinically, ‘Oriental cholangiohepatitis’ 

includes biliary colic, jaundice, cholecystitis and/or cholangitis 

(Shulman, 1987).

Billiary parasites ٥ 

Diagnosis of biliary parasitic infestations: 

The different diagnostic tools available for the diagnosis of biliary 

parasitic infestations are shown in table 1. None of the tests are specific 

except the demonstration of eggs in feces and/or duodenal contents. 

ERCP is extremely helpful in defining changes in the bile ducts as well as 

demonstrating the parasites directly (figure 1), their location and 

movements. Ultrasonography, CT, MRI can be used to demonstrate the 

parasites , dilatation of the biliary tree due to biliary obstruction caused 

by the parasites, the presence of stones, cholangiocarcinoma, hepatoma, 

liver abscesses or cysts.Also Eosinophilia is often present but 

insignificant (El Sheikh et al., 1991). Characteristic sonographic and CT 

features can be found for ascaris and clonorchis worms in the biliary tree 

(Choi et al., 1989 and Khuroo et al., 1989). 

History 

Clinical examination 

Clinical chemistry 

Parasitology 

Serology 

Radioisotopes 

Ultrasonography 

CT 

MRI 

ERCP 

+ 

+ 

+ 

++++ 

++ 

++ 

+++ 

++ 

++ 

++++ 

Table (1): Diagnosis of biliary parasites (Osman et al., 1998)

Billiary parasites ٦ 

Treatment: 

Figure (1): 2 worms in the major papilla (Courtesy of Dr. Tarik Zaher) 

The treatment of biliary parasites infection includes conservative 

treatment, endoscopy and/or surgery. Conservative treatment consists of 

antihelminthics. Previously, surgical treatment was necessary for the 

management of biliary parasites and related stones (Khuroo et al., 1987). 

Nowadays, endoscopic sphincterotomy and extraction of the biliary 

parasites is a good alternative to surgery, and carries less morbidity and 

mortality than the surgical approach. Surgery is still indicated in cases 

with acute or chronic cholecystitis due to parasitic infestation and related 

stones (Schulman et al., 1982). 

Biliary parasites causing recurrent pyogenic cholangitis due to 

biliary tree invasion and obstruction which is treated endoscopically by 

sphincterotomy, parasite extraction and nasobiliary drainage. The 

nasobiliary tube is also used for instillation of antihelminthics (Cremin, 

1982). ERCP is helpful during the active phase and sometimes worms 

may be seen moving actively into the biliary tree from the duodenum 

(Jessen et al., 1986).

Billiary parasites ٧ 

Prognosis: 

The prognosis is excellent in uncomplicated cases. It has been 

demonstrated that after treatment, continuous monitoring of the patient 

during follow-up shows disappearance of the symptoms; the biochemical 

tests return to normal, and control ultrasonography and ERCP show no 

worms left within the biliary tree (Khuroo and Zargar, 1985).

Ascariasis ٨ 

Ascariasis 

Ascariasis is caused by the parasite Ascaris lumbricoides, the largest 

intestinal nematode found in humans. Infection with this roundworm is 

most common in tropical and subtropical countries with the majority of 

infections in Southeast Asia (73%), Africa (12%), and South and Central 

America (8%) (Sarinas and Chitkara, 1997). 

Life cycle is characterized by an early pulmonary and later intestinal 

phase that follows the ingestion of infective eggs contained in 

contaminated food and soil. One of the most serious complications that 

may accompany heavy intestinal infestation is biliary ascariasis 

(Carpenter, 1998). 

The life cycle of Ascariasis lumbricoides is complex and begins with 

the ingestion of eggs. The larvae penetrate the intestinal wall and enter 

the surrounding capillaries where they migrate through the lungs 1–2 

weeks after the initial ingestion. In the lungs, the larvae again penetrate 

the capillary walls, entering the alveolar space where they ascend the 

tracheobronchial tree to the epiglottis, where they are eventually 

swallowed. The larvae reach the small intestines, most commonly the 

jejunum, where they mature into adult worms and they live from 10 to 24 

months (Valentine et al., 2001). 

Biliary involvement is the result of an erratic roundworm migration 

from the bowel, which may cause threatening complications such as 

cholecystitis, pancreatitis and hepatic abscesses (Sandouk et al., 1997). 

Intestinal ascariasis usually remains asymptomatic, but 

complications, such as appendicitis, intestinal obstruction, volvulus, or 

even bowel perforation may occur (Misra et al., 1999). Migration 

through the papilla of Vater can cause acute acalculous cholecystitis,

Ascariasis ٩ 

ascending cholangitis, obstructive jaundice, pancreatitis, and liver 

abscesses (Bahu et al., 2001). Invasion into the gallbladder is rare as the 

cystic duct is narrow and tortuous (Khuroo et al., 1992). 

Clinical presentations: 

All patients with biliary ascariasis have intestinal ascariasis. Many 

suffer from vomiting, intestinal colic and/or a palpable mass of intestinal 

worms. In advanced cases with massive biliary ascariasis the patients 

complain of severe intermittent right upper quadrant abdominal pain and 

vomiting. Fever accompanied by persistent pain is seen in many patients 

and suggests the presence of cholangitis and/or pyogenic liver abscess 

(Ong, 1979). 

On examination enlargement of the liver, tenderness and guarding of 

the right upper quadrant can found in up to 30% of the cases. Around 10– 

20% of the patients suffer from jaundice and about 20% of a palpable 

gallbladder (Lloyd, 1981). 

Biliary and pancreatic Ascariasis are complications that often mimic 

the presentation of more common illnesses of the hepatobiliary system. 

Biliary obstruction occurs when: The worms travel within the biliary or 

pancreatic ducts, causing a mechanical obstruction; the worms cause a 

spasm of the sphincter of Oddi; or the worms serve as a nidus for stone 

formation. 

Ascarids in the ampulla of Vater and multiple stones causing 

obstruction. Loeffler’s syndrome is another clinical manifestation of A. 

lumbricoides infection. It is most commonly seen in children and presents 

as cough; dyspnea; wheezing; sudden-onset fever; substernal chest 

discomfort; and less commonly, hemoptysis. This self-limiting 

pneumonia occurs during the pulmonary phase of A. lumbricoides

Ascariasis ١٠ 

migration. Symptoms develop 9–12 days after ingestion of the eggs and 

last from 2 to 3 weeks. The hallmark of Loeffler’s syndrome is fleeting 

pulmonary infiltrates on chest X-ray, often accompanied by peripheral 

eosinophilia. Also appendiceal Ascariasis is a relatively rare complication 

of A. lumbricoides infection. The phenomenon by which this occurs is 

due to the Ascarid entering the appendiceal lumen, advancing to the tip of 

the appendix and causing ischemic necrosis and gangrene of the epithelial 

layer (Schuster et al., 1977). 

Diagnosis: 

Laboratory studies: 

Stool examination may show ascaris ova or remnants of dead worm 

(Khuroo et al., 1990). In uncomplicated biliary ascarasis,the peripheral 

white blood cell counts usually normal,so leucocytosis is associated with 

suppurative biliary and hepatic complications (Lloyd, 1982). 

Imaging studies: 

Ultrasound is the diagnostic method of choice and the adult living 

worm can easily be identified by its characteristic slow, pendular, non- 

directional movements (the zig-zag sign) and its tube-like appearance 

consisting of three or four parallel echogenic lines in the longitudinal axis 

and the target sign or ‘‘bull’s eye’’ in the transverse axis. Its lumen can 

only be seen when distended with fluid using a high frequency ultrasound 

transducer (Koumanidou et al., 2004). Multiple Ascaris worms can fill 

up the whole duct causing a spaghetti-like appearance, can form a 

hyperechoic intrahepatic tumour-like mass, or when dead, can mimic 

medical devices (Schulman, 1998). 

ERCP is an excellent diagnostic tool and helpful during the active 

phase and sometimes worms may be seen moving actively into the biliary

Ascariasis ١١ 

tree from the duodenum (figure 2), also has a major therapeutic role, as it 

is possible to perform the endoscopic extraction of the worm across the 

papilla (Kamath et al., 1986). 

Figure (2): ERCP showing an ascarid worm in the common bile duct extending up to 

the proximal left hepatic duct (Quoted from Parente et al., 2004). 

Treatment: 

The treatment of ascariasis should start with conservative measures, 

including hydration, analgesics, antispasmodics and anti-helminthic 

therapy. For patients unresponsive to these, ERCP may be performed, and 

Ascaris worms can be easily removed by grasping forceps or tripod 

forceps (Jessen et al., 1986; Leung and Chung, 1988 and Tabbaa and 

Marshall, 1988). Frequently, the patulous papilla is easily cannulated 

without a sphincterotomy. Sphincterotomy should be avoided because it 

increases the risk of recurrent biliary ascariasis. Endoscopic worm 

extraction is successful in 90-100% of cases and results in rapid 

resolution of the clinical symptoms. The patient should be treated with 

anti-helminthic therapy to eradicate the gut infection, thus preventing 

reinfection of the biliary system.Mebendazole twice daily for 3 days is 

highly effective. Surgical intervention may be necessary in refractory 

cases. Preventive measures should include the improvement of sanitary

Ascariasis ١٢ 

conditions, including the avoidance of human faeces or night soil for 

fertilizing vegetables (Leung, 1997). 

More than 95% of patients with uncomplicated biliary ascariasis 

respond to conservative treatment. The indications for surgery are 

persistent severe right upper quadrant colic and signs of peritonitis or 

clinical evidence of other complications which cannot be treated 

endoscopically (Khuroo et al., 1990).

Fascioliasis ١٣ 

Fascioliasis 

Although fascioliasis is mainly a disease of herbivorous animals, it 

occurs incidentally in man. Human fascioliasis caused mainly by two 

species, Fasciola hepatica and Fasciola gigantica. Clinical cases of F. 

hepatica have been reported from more than 40 countries in Europe, 

America, Asia, Africa and the Western Pacific. Human disease due to F. 

gigantica infection has only been reported in comparatively limited 

geographical areas, mainly in Africa, the Western Pacific and Hawaii. 

The pathology and the clinical presentation of F. gigantica and F. hepatica 

infections in man are similar. F. hepatica is a large trematode, 30 x 13 

mm residing in the intrahepatic biliary tree. Fasciola infests the liver and 

biliary tree of cattle, sheep and goat, inflicting severe often fatal disease. 

In endemic countries almost 100% of sheep and 20% of cattle are 

infected. Man is accidentally infected by eating watercress contaminated 

with encysted metacercariae of the worm (Hadden and Pascarelli, 

1967). 

The adult worm lives in the bile ducts of the definitive host, the eggs 

are laid in the biliary duct and proceed with the bile to the intestine and 

are evacuated in the feces in immature state. The eggs hatch a free-living 

miracidium which escapes from the egg and penetrates the first 

intermediate host, the snail, where they mature. Once the metacercariae 

are ingested, they exist in the duodenum. The metacercariae migrate 

through the duodenal wall into the peritoneal cavity. From the peritoneal 

cavity, they penetrate the liver through the capsule of Glisson and 

transverse the parenchyma producing numerous tracts. The flukes become 

lodged in the bile ducts, where they become large (Hardman et al., 1970 

and Ashton et al., 1970). Aberrant migration of fasciola larvae can lead 

to ectopic fascioliasis with abscess formation involving almost any organ

Fascioliasis ١٤ 

(Acuna-Soto and Braun-Roth, 1987). This ectopic migration is not seen 

in other liver fluke diseases (Jones et al., 1977). 

Pathology: 

Fascioliasis can be characterized by three distinct phases: invasive 

(acute) phase; latent phase, and chronic phase. 

The invasive phase corresponds to the penetration and migration of 

the juvenile, immature parasites through the liver parenchyma with 

production of tissue necrosis, acute inflammation and hemorrhages 

leading to severe anemia (Kayabali et al., 1992). 

The chronic phase is established when the flukes gain access to 

biliary system. The fasciola produces biliary epithelial hyperplasia. 

Thickening and dilatation of the ducts and the gallbladder wall occur. 

Other complications of long-standing fascioliasis in humans have been 

reported, including portal and biliary fibrosis, cirrhosis and portal 

hypertension (Rivero and Marcial, 1989). 

Diagnosis: 

Clinical manifestations of F. hepatica have different presentations, 

according to the phase of infection (Kayabali et al., 1992). The acute 

phase may be severe but more commonly it passes without significant 

symptoms. In symptomatic patients, the invasive phase usually begins 

with a transitory period of dyspepsia, followed by high temperature (39– 

40°C), abdominal pain and tenderness. The clinical symptoms can also 

include urticaria and respiratory symptoms.Marked eosinophilia (40%) 

may be present (Balci, 1975). There may also be marked leukocytosis and 

hypergammaglobulinemia (Espina et al., 1987). No ova are present in 

the stool, making the diagnosis of acute fascioliasis difficult. The

Fascioliasis ١٥ 

diagnosis depends on clinical picture and various serological tests 

(Hadden and Pascarelli, 1967). 

On physical examination the following signs may appear: 

hepatomegaly and splenomegaly; ascites; chest signs and jaundice. In the 

latent phase patients may have gastrointestinal complaints or one or more 

relapses of the acute symptoms. The chronic phase is characterized by 

intermittent biliary obstruction and is due to the presence of the adult 

flukes in the main bile ducts (Munro, 1965). There are often fluctuating 

elevations of alkaline phosphatases, bilirubin and transaminases. The 

patients may suffer from upper abdominal pain (biliary colic), dyspepsia, 

fat intolerance, pruritus, nausea and episodes of jaundice and fever 

simulating acute cholangitis or cholecystitis with gallstones (Clay and 

Straight, 1961). 

Also on examination, the liver is usually enlarged with or without 

pain on palpation. Ascites may appear in advanced cases. The diagnosis 

in this phase is made by demonstrating the ova in the feces or duodenal 

contents. ERCP is useful in the diagnosis of fascioliasis in the chronic 

phase by visualizing the flukes directly (Rashed et al., 1995). 

Laparoscopy may reveal raised vermiform nodules at the surface of the 

liver (Cosme et al., 1990). 

Ultrasonography is important because it is often possible to show 

mobile vermiform structures, duct dilatation and irregular wall thickening 

(figure 3) (Han et al., 1993). Fasciola hepatica and F. gigantica appear as 

leaf shaped, not round in cross section, and have been described as 

hyperechogenic elements with or without acoustic shadowing (Kiladzeet 

al., 2000) or just causing a thickened gallbladder wall (Gupta, 1987).A 

characteristic pattern of Olympic ring type in u/s has been suggested to be 

diagnostic for bile duct fascioliasis (Eisenscher and Sauget, 1980). CT

Fascioliasis ١٦ 

can demonstrate peripheral tortuous lesions of the liver diagnostic of 

hepatic fascioliasis (Miguel et al., 1984). 

The image seen on ultrasound and CT is sometimes confused with 

malignancy or stones and appear in CT as subcapsular hypodense lesions 

(figure 4) (Dias et al., 1996). In the diagnosis of this disease, ultrasound 

may not provide certain information and CT is not superior. The most 

useful diagnostic test for viewing the bile ducts is cholangiography by 

ERCP, and more recently, by magnetic resonance 

cholangiopancreatograpy (MRCP) (Pantangco and Sahota, 2004). Some 

technical limitations make bile duct detail obtained by ultrasound, CT or 

MRCP imaging methods inferior to that obtained with ERCP. For this 

reason, ERCP is considered to be the gold standard for bile duct imaging 

(Suhocki, 2004). ERCP should also be considered the first choice in 

patients in the chronic phase, even if the diagnosis is established by 

ultrasound or CT (Dowidar et al., 1999). 

Figure (3): The appearance of Fasciola hepatica fluke on ultrasonographic 

examination of the gallbladder. During ultrasonography movements of the fluke can 

be demonstrated (quoted from Osman et al., 1998).

Fascioliasis ١٧ 

Figure (4): CT scan demonstrates :multiple subcapsular hypodense lesions in both 

lobes,dilatation of intra and extra hepatic bile ductes and ascites (quoted from 

Bafandeh et al., 2003). 

Fig 1: CT scan of the patient demonstrates: multiple 

Fascioliasis should be included in the list of the differential 

diagnosis for colicky abdominal pain, eosinophilia and bile duct 

dilatation. The condition could be concurrently diagnosed and treated by 

ERCP (Bafandeh et al., 2003). 

Treatment: 

Uncomplicated biliary fascioliasis may be managed by medical 

therapy (Racq et al., 1991). Triclabendazole, given in a single oral dose 

of 10 mg/kg, is the drug of choice for fascioliasis.Bithionol (30 to 50 

mg/kg on alternate days for 10 to 15 doses) and nitazoxamide (500 mg 

p.o., twise for 3 days) are alternatives. Praziquantel is not effective for 

fascioliasis (Wesley et al., 2006). 

Oral drug therapy remains the standard treatment for hepatic 

fascioliasis (Farag et al., 1998). However, there are few therapeutic 

options available for patients with fascioliasis resistant to oral therapy. 

When endoscopic therapy is unavailable, surgery in the form of 

cholecystectomy and bile duct exploration is the only option, even in 

young patients with uncomplicated fascioliasis. Endoscopic therapy,

Fascioliasis ١٨ 

which is more physiologic in its approach, appears to be the obvious 

alternative for this group of patients (Rashed et al., 1995). 

The use of ERCP in the treatment of patients with fascioliasis is not 

new (Hauser and Bynum, 1984). The worms appear on ERCP as filling 

defects with a characteristic peripheral radiolucency or as well-defined 

linear defects of various forms in close relation to the wall of the bile 

ducts (figures 5, 6 and 7). A third characteristic radiologic feature of 

fascioliasis that we observed is their inconsistent appearance during 

ERCP. This confuses the endoscopist with regard to whether a filling 

defect is present. We called this phenomenon the “disappearing stone.” 

Other radiologic signs, such as ductal dilation or narrowing, are not 

pathognomic of fascioliasis and their nature should be investigated even 

in the presence of a Fasciola worm. The shape of the filling defect 

produced by the worm as seen on the cholangiographic x-ray films 

depends on whether the worm is seen face on or from the side. When face 

on, it results in the characteristic leaf like filling defect. When viewed 

from the side, there are linear defects of various shapes (Boray, 1981). 

The peripheral enhancement of its radiolucency is the result of the 

edge of the worm folding on itself as it moves. The “disappearing stone” 

phenomenon is most probably the result of the temporary movement of 

the lower part of the worm’s body away from the bile duct wall while 

remaining attached to the wall by its ventral sucker. Most drugs used in 

the treatment of fascioliasis work by paralyzing the worm so that it 

detaches from the wall of the bile duct and is expelled into the duodenum 

with the bile (Bennet and Kohler, 1987). 

In the presence of a tight papilla, the worm might become trapped in 

the bile duct until the concentration and effect of the drug drops, after

Fascioliasis ١٩ 

which the worm recovers and reattaches itself to the wall of the bile duct, 

thereby resulting in the resistant state (El-Newihi et al., 1995). 

In such circumstances, papillotomy and extraction of the worm plug 

are mandatory. In contrast, the patients have a normal biliary tree with no 

obstruction or dilation and resistant to standard therapy. Mechanical 

extraction of the worm in such a situation, although feasible, does not 

have therapeutic success because other worms might be present in the 

gallbladder or in the small intrahepatic biliary radicles, where they are not 

amenable to mechanical extraction (Skar et al., 1986). In view of this, 

washing the biliary tree with a solution such as povidone iodine, which 

will kill all of the worms present in the biliary system regardless of their 

site, while preserving sphincter of Oddi function, is ideal. This is 

important because most patients with fascioliasis are young, and it is 

preferable to preserve sphincter function because the long-term 

consequences of its loss have yet to be defined (Sauerbruch et al., 

1983). 

Povidone iodine, an iodophor, acts through the liberation of free 

iodine, which has bactericidal, fungicidal, virucidal, and amebicidal 

effects. Its exact mechanism of action is unknown; however, its tissue 

toxicity is remarkably low, especially when compared with its germicidal 

potency (Gershenfeld, 1968). Povidone iodine has been used extensively 

in medicine with negligible side effects. Systemic absorption is minimal 

even in neonates (Aihara et al., 1993). The main potential complication 

of such treatment is the introduction of infectious agents into the biliary 

system, especially in the presence of a dead worm and an intact papilla 

(Merighi et al., 1996).

Fascioliasis ٢٠ 

Figure (5): ERCP of four additional patients showing a Fasciola worm (arrow)in bile 

ducts (quoted from Dowidar et al., 1999) 

Figure (6): ERCP showing a Fasciola worm in the bile duct (small arrow) and 

gallbladder (large arrow) (quoted from Dowidar et al., 1999)

Fascioliasis ٢١ 

Figure (7): ERCP showing a Fasciola worm in the bile duct (small arrow) and 

localized narrowing of the left hepatic duct (large arrow) (quoted from Dowidar 

et al., 1999)

Clonorchiasis ٢٢ 

Clonorchiasis 

Clonorchis sinensis is a small fluke measuring only 10–25 mm long 

and 3-5 mm wide. The fluke may live for up to 25 years the biliary tree of 

its host. Occasionally the flukes also live in the pancreatic duct and the 

gallbladder, where they lay eggs Operculated eggs are passed into the 

feces and when reaching fresh water the eggs are ingested by snails. From 

the snails cercariae are released and penetrate freshwater fish. Human 

infections originate from ingestion of the raw, dried, salted or pickled 

flesh or freshwater fish containing encysted metacercariae. The larva is 

released in the duodenum from where it enters the common bile duct and 

migrates to the second-order bile ducts. Besides humans, dogs, pigs, cats, 

and rats serve as disease reservoirs (Ona and Dytoc, 1991). 

Epidemiology: 

Clonorchis sinensis (the Chinese or Oriental liver fluke) is a small 

trematode commonly found in Southeast Asia. This organism can survive 

for up to 25 years inside the human biliary system. Hence infected 

patients may seek medical attention many years after moving from an 

endemic area. The prevalence of Clonorchis infection may reach 50-70% 

in some parts of the world where raw fresh water fish is considered, for 

example yue-shun in Southern China and sashima and sushi in Japan. The 

life cycle requires two intermediate hosts: the first various species of 

snails, the second a freshwater fish. This disease is not found in Egypt 

because of the lack of a proper snail host (Leung, 1997). 

Life cycle: 

The definitive hosts of C. sinensis are humans, dogs, hogs, cats, 

mink, and rats. The eggs, shed by adult worms, are deposited in the 

biliary tree of these mammalian hosts, enter the intestine, and are passed

Clonorchiasis ٢٣ 

with the feces. On reaching water, the eggs are ingested by snails. 

Although several species of snails serve as the first intermediate hosts, 

Parafossarulus and Bithynia are the most suitable. Within the snail, the 

eggs undergo metamorphosis and asexual reproduction for 4 to 5 weeks, 

after which cercariae are shed into the water. These free-swimming forms 

penetrate the skin between the scales of freshwater fish. Numerous 

species of freshwater fish, mostly belonging to the family Cyprinidae, 

serve as the second intermediate host (Monroe, 1995). 

After a few days in the fish muscle, the cercariae become encysted 

and form metacercariae. Humans and other fish-eating mammals then 

acquire the infection by ingesting raw or inadequately cooked fish. As a 

result of the digestive processes in the stomach and intestines, the 

metacercariae eventually excyst in the duodenum and migrate though the 

ampulla of Vater into the bile duct, where they mature into adult worms 

over a period of a month. In humans, the adult fluke inhabits the biliary 

tract, generally localizing within the intrahepatic bile ducts. The adult 

worm is a small trematode with an elliptical shape and an average length 

of 10 to 25 mm (Rim, 1986). 

The trematode is a true hermaphrodite and lays fully embryonated 

eggs. The adult fluke has a life span of 20 to 25 years, which explains the 

persistent infection for a long duration. The completion of this life cycle 

is restricted to areas of endemic infection, which reflect the geographic 

distribution of the essential snail species (Sun, 1982). 

Pathophysiology: 

Clonorchis sinensis causes inflammation around the biliary tree, 

severe hyperplasia of epithelial cells, metaplasia of mucin-producing cells 

in the mucosa, and progressive periductal fibrosis (Seo et al., 1981 and 

Hong et al., 1990). The severity of these pathological changes tends to

Clonorchiasis ٢٤ 

correlate with the duration of infection, and the susceptibility of the host 

(Harinasuta et al., 1984). 

The histopathological changes have been divided into several 

phases. The first phase is characterized by edema and desquamation of 

bile duct epithelium. This is followed by epithelial hyperplasia, 

pseudostratification of the biliary epithelium, and mucin-secreting cell 

metaplasia. Metaplastic squamous cells may appear in conjunction with 

glandular proliferation, giving an appearance suggestive of adenomatous 

hyperplasia. Heavy periductal infiltration of inflammatory cells, including 

eosinophils, is observed during the first 2 weeks of infection. After 12 

weeks, these infiltrates are composed of plasma cells, lymphocytes, and 

other mononuclear cell types (figure 8) (Lee et al., 1978 and Min, 1984). 

Figure (8): Histopathological findings of clonorchiasis (hematoxylin and eosin stain). 

Note the flukes (arrows) within the dilated bile ducts, biliary epithelial hyperplasia 

(arrowheads), and periductal fibrosis (quoted from Choi et al., 2004). 

Clinical manifestations: 

Clonorchiasis can present either acutely or chronically. Acute 

clonorchiasis produces a viral hepatitis-like illness characterized by fever, 

abdominal pain, diarrhoea, hepatomegaly, jaundice, leukocytosis and 

eosinophilia. Chronic clonorchiasis presents with upper quadrant 

abdominal pain, anorexia, nausea, low-grade fever and tender

Clonorchiasis ٢٥ 

hepatomegaly. With increasing parasite load, the signs and symptoms of 

chronic or intermittent biliary obstruction develop. Cholelithiasis, 

cholecystitis, hepatic abscesses and recurrent suppurative cholangitis may 

occur. Patients may develop secondary biliary cirrhosis and portal 

hypertension in very late stages of the illness. In endemic areas in 

Southeast Asia, a significant association has been found between 

cholangiocarcinoma and previous Clonorchis infection (Schwartz, 1986; 

Chan and Lam, 1987 and Bryan and Michelson, 1995). 

The complications of clonorchiasis are the results of biliary 

obstruction. Parasite-induced mucin-secreting cells create bile with a high 

mucin content, which, combined with adult flukes and eggs, serves as a 

nidus for bacterial superinfection and intrahepatic stone formation. 

Bacterial infections are of enteric origin, with Escherichia coli being 

identified most frequently as a pathogen. The ectasia of intrahepatic bile 

ducts may progress to pyogenic cholangitis, liver abscess, and hepatitis 

(Sun, 1984). 

Diagnosis: 

Laboratory studies: Clonorchiasis should be suspected in patients 

who develop manifestations of hepatic or biliary disease, if they have a 

history of ingesting raw freshwater fish in an area of endemic infection. 

The diagnosis of clonorchiasis is usually established by microscopic 

examination of the feces for eggs. The formalin-ether sedimentation 

technique is known to be more reliable than the direct-smear method for 

detecting eggs in feces. The cellophane thick-smear method has usually 

been used for mass screening (Rimetal, 1981). The eggs of clonorchis 

sinensis are oval and measure 27 to 35 μm. They have an operculum at 

the slender end, with prominent shoulders. The opposite (abopercular)

Clonorchiasis ٢٦ 

end is broad and has a small spine-like prominence (Dooley and Neafie, 

1976). 

A number of serological techniques have been developed as 

supplementary diagnostic methods. The intradermal test, which uses a 

diluted extract of adult C. sinensis antigens, was once used widely (Rim, 

1986). but is not recommended any more because of its very low 

specificity. Enzyme-linked immunosorbent assay for the detection of 

antibodies against C. sinensis has also been used as an alternative 

serological test (Chen et al., 1988). However, unfortunately, the 

serological methods currently available exhibit considerable cross- 

reactivity and therefore are not widely accepted as screening techniques 

(Ambroise-Thomas and Goullier, 1984). 

Imaging Findings: 

Cholangiography may also show a characteristic appearance of 

Clonorchis worms as filling defects within the ductal system. Depending 

on the projection, one of five patterns may appear on the cholangiogram: 

filamentous, wavy, curled-up, elliptical wavy and elliptical-shaped filling 

defects (Leung et al., 1989).Within the peripheral intrahepatic ducts; 

dilatation of the intrahepatic ducts, particularly in the periphery; and a 

hazy appearance of the intrahepatic ducts (Choi, 1984 and Okuda et al., 

1973). 

Filling defects are several millimeters in diameter which is 

compatible with the width of the fluke. The predominant dilatation of the 

peripheral ducts is related to the location of the worms. The haziness of 

the intrahepatic ducts is probably caused by the increased production of 

mucinous material and incomplete mixing of the contrast media (Choi 

and Han, 2001).

Clonorchiasis ٢٧ 

On ultrasonography, characteristic findings of clonorchiasis are 

summarized as diffuse, mild, uniform dilatation of the small intrahepatic 

bile ducts with no or minimal dilatation of larger bile ducts and without 

an obstructing lesion (Choi et al., 1989 and Lim, et al., 1989). The 

ductal wall is often thickened, and its echogenicity is increased. 

Occasionally, flukes or aggregates of eggs are shown as non-shadowing 

echogenic foci or casts within the bile duct (Figure 9A and B). These 

findings are regarded as pathognomonic for clonorchiasis in areas of 

endemic infection (Lim, 1990). 

Figure (9): Hepatic ultrasonography (right intercostal oblique plane) in a 60-year-old 

woman (a) and a 41-year-old man (b) with clonorchiasis. Note the diffuse, uniform 

dilatation of the intrahepatic bile ducts and the increased echogenicity of the ductal 

wall (arrowheads) (quoted from Choi et al., 2004). 

The sensitivity of ultrasonography was 52% and its specificity was 

51%. The low sensitivity was attributed to false- negative cases with mild 

infection, and the low specificity was attributed to false- positive cases 

with residual pathology after cure (Hong et al., 1998 and Lee et al.,

Clonorchiasis ٢٨ 

2003). Ultrasonography is less useful in the differentiation between cured 

clonorchiasis and active infection, since it reflects the pathological 

changes in the bile ducts, which may persist for years after cure (Lee et 

al., 1987 and Choi et al., 1999). 

Computed tomography findings of clonorchiasis are essentially the 

same as those observed by ultrasonography,which is mild, uniform 

dilatation of the peripheral intrahepatic bile ducts without a focal 

obstructing lesion. The extrahepatic duct has a normal diameter, and no 

definite obstructing lesion is seen, even by thin-section helical computed 

tomography (figure 10). These findings are considered pathognomonic 

for clonorchiasis (Choi et al., 1988). 

ERCP is useful in the diagnosis (Leung et al., 1988). Four ERCP 

patterns have been observed: Diffuse tapering of the intrahepatic ducts 

with dilatation of the intra- and extrahepatic ducts; a solitary cyst similar 

to a liver abscess cavity or retention cysts; multiple cystic dilatations of 

the intrahepatic ducts, mulberry-like appearance that is characteristic of 

liver fluke infestation, and a combination of these findings, with 

extensive cystic dilatation in some areas of the liver and biliary duct 

ectasia in others (figure 11) (Lim, 1990).

Clonorchiasis ٢٩ 

Figure (10): Transverse hepatic computed tomography in a 45-year-old woman (a) 

and a 57-year-old man (b) with clonorchiasis. Note the mild, uniform dilatation of the 

intrahepatic bile ducts (arrowheads) (Quoted from Choi et al., 2004). 

Figure (11): Posteroanterior endoscopic retrograde cholangiography in a 54-year-old 

man with clonorchiasis. Note the diffuse and uniform dilatation of the peripheral 

intrahepatic bile ducts with minimal dilatation of the extrahepatic bile duct and 

elliptical fillings (Quoted from Choi et al., 2004). 

Treatment: 

Praziquantel is effective and well-tolerated therapy for this disease. 

Praziquantel is administered at a dosage of 25 mg/kg orally three times a 

day for one day. An alternative investigative therapy is albendazole, 10 

mg/kg/day for 7 days. Initially, complications of Clonorchis sinensis 

infection, including calculi,cholangitis, and pancreatitis, are managed 

medically, although surgical drainage may be required (Wesley et al., 

2006).

Clonorchiasis ٣٠ 

The main indication for therapeutic ERCP in patients infected with 

Clonorchis is for biliary drainage in those with acute cholangitis. Bile 

duct dilatation, irregularities and ductal proliferation persisted despite 

eradication of the parasites (Leung et al., 1990).

Opisthorchiasis ٣١ 

Opisthorchiasis 

Clonorchis sinensis has three relatives: Opisthorchis felineus; 

Opisthorchis viverrini, and Dicrocoeliasis dendriticum. 

These are very much related to C. sinensis. The flukes have also 

been sporadically reported from nonendemic areas (Nodgaard and 

Kristensen, 1995). 

Opisthorchiasis caused by Opisthorchis viverrini remains a major 

public health problem in many parts of Southeast Asia particularly 

Thailand (Jongsuksuntigul and Imsomboon, 2003). The infection is 

associated with a number of hepatobiliary diseases, including cholangitis, 

obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis 

(Harinasuta et al., 1984). Pathological consequences of Opisthorchiasis 

infection occur mainly in the liver, extrahepatic bile ducts and gall 

bladder and have been described in both humans and experimental 

animals (Tansurat, 1971; Bhamarapravati et al., 1978; 

Koompirochana et al., 1978; Riganti et al., 1989 and Sripa and 

Kaewkes, 2002). Moreover, both experimental and epidemiological 

evidence strongly implicate the liver fluke infection in the etiology of bile 

duct cancer (cholangiocarcinoma) (Thamavit et al., 1978 and 

Vatanasapt et al., 1999). 

Clonorchis sinensis and Opisthorchiasis have similar lifecycles, 

location in the liver and pathogenicity and their morphologies, 

particularly in the egg and metacercariae forms, differ only slightly. 

These species have usually been diagnosed and distinguished from one 

another by detection of the eggs in feces or on examination of the 

reproductive organs of the adults if available (Bruckner, 1999 and Fried 

et al., 2004).

Opisthorchiasis ٣٢ 

Life cycle: 

The adult worms of Opisthorchiasis live in the intra- and extra- 

hepatic bile ducts, gall bladder, and rarely in the pancreatic duct. They 

attach to the wall of these ducts by the oral and ventral suckers under the 

regulatory function of the circular and radius muscles. Embryonated eggs 

containing ciliated miracidium laid from gravid worms are passed 

through the bile into the duodenum and excreted with faeces into the 

external environment. After reaching freshwater of natural reservoirs, 

these embryonated eggs do not hatch until they are ingested by Bithynia 

snails into the digestive tracts where hatching occurs and then miracidia 

transform to sporocysts. Rediae and cercariae are produced by the asexual 

reproduction of germinal cells in sporocysts and rediae, respectively. 

Free-living cercariae, after exit the snail will attach, penetrate and 

transform to metacercariae encysted mainly in the muscle of about 18 

susceptible species of fish in the family Cyprinidae (Harinasuta and 

Harinasuta, 1984 and Waikagul, 1998). Metacercariae are infective to 

final hosts including humans, dogs and cats when they ingest raw or 

inadequately cooked fish. After ingestion, the metacercaria is digested by 

gastric and intestinal juices, respectively (figure 12). Excysted juvenile 

flukes at the duodenum then migrate up through the ampulla of Vater and 

the common bile duct into the intra-hepatic bile ducts where they mature 

and fertilize. Some worms are formed in the common bile duct, cystic 

duct and gall bladder. The life span of Opisthorchiasis viverrini in human 

is not known, however, it may be over 25 years as recorded in C. sinensis 

(Attwood and Chou, 1978).

Opisthorchiasis ٣٣ 

Figure (12): Metacercaria of Opisthorchiasis viverrini in cavity of caudal fin ray of 

cyprinoid fish, Cyclocheilichthys spp. (MT = metacercaria) (Quoted from 

Kaewkes, 2003). 

Pathology of opisthorchiasis: 

Pathological features of opisthorchiasis infection have been reported 

both in man and experimental animal. The severity of the pathology 

appears to be associated with both intensity and duration of infection 

(Bhamarapravati et al., 1978 and Harinasuta et al., 1984). 

Liver: 

Grossly, the liver of heavily infected cases may be enlarged and the 

weight of the liver may be more than double the normal (3000–3500 g or 

more) (Tansurat, 1971). The subcapsular bile ducts of infected patients 

are usually dilated and show prominent fibrotic wall (Hitanant et al., 

1987 and Riganti et al., 1989). 

Microscopically, the intrahepatic lesions of opisthorchiasis are 

confined to the biliary tree, particularly to the large and medium-sized 

bile ducts where the flukes are harbored (Riganti et al., 1989). In the 

early stage or light infections, found no detectable change in the biliary 

epithelium and periductal areas of the liver (Tansurat, 1971). 

The predominant changes of infected liver are desquamation of the 

biliary epithelium, epithelial hyperplasia, bile duct hyperplasia, and

Opisthorchiasis ٣٤ 

periductal fibrosis. In addition, the cellular infiltrates consist of 

lymphocytes, monocytes, eosinophils and some plasma cells. 

Granulomatous inflammation in response to the parasite eggs that escape 

into the liver parenchyma, is occasionally seen in humans (Viranuvatti 

and Stitnimankarn, 1972). 

Gall bladder, extrahepatic bile ducts and pancreas: 

In heavy infections with Opisthorchis, adult flukes may be seen in 

the gall bladder, common bile duct, and pancreatic duct (Pungpak et al., 

1985). Wall irregularity, enlargement, bile sludge, and poor function were 

found among apparently healthy individuals with moderate and heavy O. 

viverrini infection (Haswell-Elkins et al., 1991; Mairiang et al., 1992 

and Elkins et al., 1996). Following anthelmintic treatment, many of the 

gall bladder abnormalities were eliminated, as indicated by the reduction 

of the length and regained contractility (Mairiang et al., 1993). 

The biliary sludge is often seen in the gall bladder in heavy O. 

viverrini infections (Elkins et al., 1990 and Mairiang et al., 1992). Eggs 

and worm fragments have been observed in the nidus of gallstones and in 

sludge supporting the role of the parasite in initiating cholelithiasis 

(Riganti et al., 1988). 

On microscopic examination, the changes seen in the gall bladder or 

extrahepatic bile ducts in opisthorchiasis are adenomatous formation, 

hyperplasia, desquamation, proliferation of epithelial lining cells and 

chronic inflammation (Tansurat, 1971 and Harinasuta et al., 1984). 

Kidney: 

Human renal diseases can occur in association with several 

infections with opisthorchiasis caused by Opisthorchiasis viverrini 

(Boonpucknavig and Soontornniyomkij, 2003). In Opisthorchiasis

Opisthorchiasis ٣٥ 

felineus infection, there was also associated nephropathy (Lapteva, 

1990). Acute renal failure in obstructive jaundice due to 

cholangiocarcinoma, which is associated with opisthorchiasis in 

Thailand, is observed (Mairiang et al., 1990). 

Pathogenesis of opisthorchiasis: 

As described above, the main histopathologic features of 

opisthorchiasis both in man are epithelial desquamation, epithelial and 

adenomatous hyperplasia, goblet cell metaplasia, inflammation, 

periductal fibrosis and granuloma formation. The pathogenesis of 

Opisthorchiasis viverrini-mediated hepatobiliary changes may be due to 

mechanical irritation caused by the liver fluke suckers and/or its 

metabolic products (Tansurat, 1971; Viranuvatti and Stitnimankarn, 

1972 and Harinasuta et al., 1984). 

Clinical presentation: 

The clinical picture of opisthorchiasis falls into three stages:(a) 

Asymptomatic mild infestations with proliferation of the biliary tract 

epithelium;(b)Progressive infestations with involvement of the liver 

parenchyma characterized by irregular appetite, diarrhea and edema, 

and;(c)Severe infestations with cirrhosis and portal hypertension (Wykoff 

et al., 1966) 

Diagnosis and treatment: 

Diagnosis depends on the demonstrations of eggs in stools. The eggs 

can only be demonstrated by an experienced technician . The patients are 

treated as if they were infected with C. sinensis. The indication for 

surgical or endoscopical treatment is the same as for other liver flukes

Opisthorchiasis ٣٦ 

(Sirisinha, 1986).Serological methods have been developed for diagnosis 

of Opisthorchiasis (Nagano et al., 2004). Antigens of Opisthorchis have 

been used for immunoblot methods (Choi et al., 2003). On 

ultrasonography; Opisthorchis viverrini infection can cause gall bladder 

sludge yet without sonographically visible parasites (Mairiang et al., 

1992).

Dicrocoeliasis ٣٧ 

Dicrocoeliasis 

Dicrocoeliasis is caused by several Dicrocoelium spp., which live in 

the bile ducts and gall bladder of domestic ruminants (sheep, goats, cattle, 

buffaloes, camels), and occasionally affects rabbits, pigs, dogs, horses 

and humans. Dicrocoelium cycles in two intermediate hosts (snails and 

ants)and is present throughout Europe, north Asia (China), Japan, North 

Africa, South America, and in some focal points in North America, 

Australia (Dicrocoelium dendriticum) and Africa (Dicrocoelium hospes) 

(Ducommun and Pfister, 1991). 

Life cycle: 

The life cycle requires a terrestrial snail and an ant as first and 

second intermediate hosts, respectively. The adults of Dicrocoelium 

dendriticum (a)are semi-transparent, 8–14 mm in length and, 2–3 mm in 

width. The dark brown eggs produced by the adults (b)are typically 

operculate, oval, but slightly flattened on one side, and contain a 

miracidium (MI)(c).When the eggs are ingested by a snail, they hatch and 

release the MI, which penetrate the glandular intestinal epithelium and 

migrates to the hepatopancreas. The mother sporocyst gives rise to 

daughter sporocysts(SP)(d),termed first (SP1) and second (SP2) 

generation sporocysts, in the first intermediate host by asexual 

multiplication. From SP2, numerous mature cercariae (CE).(e)migrate to 

the respiratory chambers of the snail and are extruded from the snails in 

clusters of 5000 CE which are enveloped in mucilaginous slime- 

balls(F).These slime balls are then ingested by ants (e.g. Formica fusca, 

F. pratensis and F. rufibarbis). In the second intermediate host, the CE 

transform to metacercariae (ME),which are formed in the abdominal 

cavity. One or two of these ME, localized in the ant’s subesophageal

Dicrocoeliasis ٣٨ 

ganglion (brain-worm), can cause a cataleptic cramp when the 

temperature is ,15–20 C or below (e.g. early in the morning). These 

cramps can ‘paralyse’ the ant on grass, where grazing ruminants can 

easily ingest it. In the gut of definitive hosts, the ME excyst and migrate 

to the small bile ducts, to the larger bile ducts and then to the gall bladder 

via the choledochus without any migration into the liver. ME develop into 

mature egg-producing flukes in the bile ducts. After reproduction by 

hermaphroditism or crossfertilization, adults of Dicrocoelium release 

eggs into the environment through their host faeces (figure 13)(Otranto 

and Traversa, 2003) 

Figure (13): The life cycle of Dicrocoeliasis (quoted from Otranto and 

Traversa, 2003)

Dicrocoeliasis ٣٩ 

Pathogenesis: 

It is difficult to identify the pathogenic effects of dicrocoeliasis 

because of concomitant gastrointestinal and lung infections caused by 

nematodes and distomatids. In addition, dicrocoeliasis is difficult to 

reproduce experimentally (Camara et al., 1996). The young flukes 

migrate directly up the biliary duct system of the liver without penetrating 

the gut wall, liver capsule, or liver parenchyma as in fasciolosis. Clinical 

symptoms are not usually manifested, even in heavy infections, and 

therefore, major lesions, due to liver impairment, are detectable only at 

necroptic examination of the liver (Theodoridis et al., 1991). 

Animals suffering from dicrocoeliasis may show anaemia, oedema, 

emaciation, and, in advanced cases, cirrhosis, scarring of the liver surface, 

and marked distension of bile ducts. Due to its buccal stilets, the small 

liver fluke irritates the bile duct surfaces, thus, causing proliferation and 

changes in the septal bile ducts of the lobular hepatic edges (Wolff et al., 

1984 and Camara et al., 1996). In heavy infections a large number of 

worms are detectable inside the bile ducts and gall bladder, the liver is 

swollen, with thickened ducts, cholangitis, whitish spots on the surface, 

marked scarring and cirrhosis which result in liver impairment 

(Jithendran and Bhat, 1996). 

An antibody response against D. dendriticum has been demonstrated 

in the bile products of naturally infected cattle. Immunoglobulin (Ig) A 

immunity plays a protective role in inhibiting parasite adherence to the 

gut mucosa and penetration (Wedrychowicz et al.,1995). 

Diagnosis of dicrocoeliasis: 

The disease is usually diagnosed during post-mortem examination of 

the liver, after the duodenal fluid has been examined or by coproscopical

Dicrocoeliasis ٤٠ 

assay for egg detection. Among the coproscopic techniques, flotation 

with high-density solutions with a specific gravity of 1.30–1.45 (which 

allows the parasites’ ova to rise to the surface because of their low 

specific gravity) is more efficient than sedimentation (Rehbein et al., 

1999). 

Coproscopy is the most commonly used technique for dicrocoeliasis 

diagnosis, although, sometimes, it has a low sensitivity. When the results 

of faecal examination were compared to those of liver necropsy of sheep 

and goats, faecal examination detected the presence of dicrocoeliasis in 

only one out of three cases (Jithendran and Bhat, 1996). 

Serological methods represent an important alternative for the 

detection of dicrocoeliasis. During the past 30 years, many 

immunodiagnostic techniques have been used to detect anti-D. 

dendriticum antibodies. Somatic (SO) and excretory–secretory (ES) 

products of D. dendriticum have been studied as antigens for ELISA with 

different results (Otranto, and Traversa, 2002). So, proteins and surface 

molecules appear to stimulate a antibody response, although problems of 

low specificity and sensitivity could occur when using entire worm 

extracts instead of ES products or purified antigens (Wedrychowicz et 

al., 1995). 

In the past few years, some studies have been carried out on the 

isoenzymatic characterization of D. dendriticum adults from naturally and 

experimentally infected sheep (Campo et al., 1998). 

Control of dicrocoeliasis: 

Methods against the intermediate hosts (e.g. using calcium 

cyanamide molluscicide and chemical fertilizers) are not feasible because 

of: High costs; and ecological reasons.

Dicrocoeliasis ٤١ 

As a form of sustainable control, but in small areas only, it would be 

possible to introduce turkeys, chickens and ducks to eat snails and ants, or 

to cover ant nests with branches of trees to reduce the infection (Badie 

and Rodelaud, 1988). 

Many benzimidazoles (albendazole, fenbendazole, mebendazole, 

cambendazole, thiabendazole, luxabendazole) and pro-benzimidazoles 

(thiophanate, netobimin) have been used against D. dendriticum at higher 

doses than those used against tapeworms, flukes, lung nematodes and 

gastrointestinal nematodes, with an efficacy rate ranging from 63 to 100% 

according to the drug, dosage and administration modalities used 

(Otranto, and Traversa, 2002). Other drugs against these small flukes 

such as netobimin, the nitrophenyl guanidine compound, have also been 

shown to reduce fluke burden in sheep (Rojo-Vazquez et al., 1989).

Echinococcosis ٤٢ 

Echinococcosis 

Introduction: 

The genus Echinococcus is of great importance because it contains a 

number of zoonotic species that can cause serious ill health in man. There 

are at least 4 species in the genus, but recent molecular evidence suggests 

that there should be a taxonomic revision to at least 5 species or even 

possibly 6 (Thompson and McManus, 2002). But nowadays with 

molecular studies, mainly with mitochondrial DNA (mtDNA) sequences, 

have identified 9 distinct genetic types (genotypes G1-9) within 

Echinococcus granulosus (McManus, 2002). 

Distribution: 

Cystic echinococcosis (CE) caused by the larval stage of 

Echinococcus granulosus is the most widespread of these parasites. In 

Europe, zoonotic strains of E. granulosus are present in every country 

with the exceptions of Ireland, Iceland and Denmark. It is most intensely 

endemic in the Mediterranean areas and parts of Eastern Europe such as 

Bulgaria. In Asia the parasite is intensely endemic in large parts of China 

and is an important re-emerging zoonosis in the former Soviet Republics 

in Central Asia (Torgerson, 2003). The parasite is also found throughout 

the Indian and the Middle East. In Africa, E. granulosus is widespread 

and is a particular problem in northern African countries including Egypt, 

In North and South America E. granulosus is also presnt (Jenkins and 

Morris, 1995 and Jenkins, 2002). 

Echinococcus multilocularis, commonly known as the fox 

tapeworm, can be found in areas of central and northern Europe, northern 

Asia, and parts of North America .It has also been proposed that E.

Echinococcosis ٤٣ 

multilocularis may be in parts of northern Africa, but currently there is 

not enough information to substantiate this claim (Schantz et al., 1995). 

Life cycle: 

Hydatid cysts of E granulosus develop in internal organs (mainly 

liver and lungs) of humans and other intermediate hosts as unilocular 

fluid-filled bladders. The definitive hosts of E granulosus are carnivores 

such as dogs and wolves, which are infected by ingestion of food 

containing hydatid cysts with viable protoscoleces. After ingestion, the 

protoscoleces evaginate, attach to the canine intestinal mucosa, and 

develop into adult stages. Sexual maturity (length of 3–6 mm) is reached 

4–5 weeks later. Eggs or gravid proglottids are shed in the faeces. 

Following ingestion by a human or intermediate host (sheep, goats, pigs, 

cattle, horses, and camels) an Oncosphere larva is released from the egg. 

The larvae then penetrate into the lamina propria and are transported 

passively through blood or lymph vessels to the liver, lungs, or other 

organs, where the oncosphere larvae develop into hydatid cysts 

(metacestode larvae). These consist of two parasite-derived layers: an 

inner nucleated germinal layer, and an outer acellular laminated layer 

surrounded by a host-derived fibrous capsule. Brood capsules and 

protoscoleces bud from the germinal membrane. The range of 

intermediate host species depends on the infecting strain of E. granulosus, 

regional or local differences in the availability of the various intermediate 

host species, and other factors (Eckert et al., 2001). 

Since the life cycle relies on carnivores eating infected herbivores, 

humans are usually a “dead-end” for the parasite. Dogs and wild 

carnivores are able to scavenge from the human remains; if the cadaver 

harbours cysts, then under these unique circumstances, human beings can 

act as intermediate hosts (Macpherson, 1983).

Echinococcosis ٤٤ 

Adult worm infections of E. multilocularis are perpetuated in a 

sylvatic cycle with wild carnivores mainly red (Vulpes vulpes) and arctic 

(Alopex lagopis) foxes regarded as the most important definitive hosts. 

Domestic dogs and cats can also harbour the tapeworm and may be 

involved in a synanthropic cycle. Small mammals (usually microtine and 

arvicolid rodents) act as intermediate hosts. The metacestode of E 

multilocularis is a tumour-like, infiltrating structure consisting of many 

small vesicle embedded in stroma of connective tissue. The metacestode 

mass usually contains a semisolid matrix rather than fluid. Larval growth 

in the liver remains indefinitely in the proliferative stage, resulting in 

invasion of the surrounding tissues. The sylvatic cycle accounts for most 

infections in man, although dogs may also play a role. It is unclear 

whether cats contribute to transmission to human beings (Thompson and 

McManus, 2001). 

Clinical features: 

Human echinococcosis results when man ingests eggs, which have 

been shed in the faeces of the definitive host (Pawlowski et al., 2001). 

The initial phase of primary infection is always asymptomatic. Small 

cysts not inducing major disease may remain asymptomatic for many 

years, if not permanently. The incubation period of cystic echinococcosis 

is unclear but probably lasts for many months to years. The infection may 

become symptomatic if the cysts either rupture or exert a mass effect. 

Recurrence may arise following surgery on primary cysts (Utrilla et al., 

1991). 

Up to 60% of all cystic echinococcosis cases may be asymptomatic, 

although an unknown proportion may become symptomatic. The 

mortality rate is estimated to be 0.2 per 100,000 population, with a case 

fatality rate of 22%. More than 90% of cysts occur in the liver, lungs, or

Echinococcosis ٤٥ 

both. Symptomatic cysts have been reported occasionally (2–3% each) in 

the kidney, spleen, peritoneal cavity, and the skin and muscles; and rarely 

in the heart, brain, vertebral column, and ovaries (1% or less each) 

(Menghebat et al., 1993). 

Presenting symptoms of cystic echinococcosis are highly variable 

(Al-Karawi et al., 1990). Presenting features depend not only on the 

organ involved, but also on the size of the cysts and their position within 

the organ, the mass effect within the organ and upon surrounding 

structures, and complications relating to cyst rupture and secondary 

infection. Manifestations of systemic immunological responses may be 

evident in response to cyst leakage or rupture. Common complications 

include rupture into the biliary tree with secondary cholangitis, biliary 

obstruction by daughter cysts or extrinsic compression, intracystic or 

subphrenic abscess formation, intraperitoneal rupture (with or without 

anaphylaxis), rupture into the bronchial tree, and development of a 

bronchobiliary fistula (Ammann and Eckert, 1996). 

Alveolar echinococcosis typically presents later than the cystic form. 

Cases of alveolar echinococcosis are characterised by an initial 

asymptomatic incubation period of 5–15 years, and a subsequent chronic 

course. Untreated or inadequately managed cases have high fatality rates. 

The peak age group for infection is from 50 to 70 years in Europe and 

Japan. The sex distribution is fairly equal. The metacestode develops 

almost exclusively in the liver (99% of cases). The right lobe is involved 

most frequently, with involvement of the porta hepatis or multiple lobes 

being less frequent. Parasitic lesions in the liver can vary from small foci 

a few millimetres in size to large (15–20 cm in diameter) areas of 

infiltration. Extrahepatic primary disease is very rare (1% of cases) (Sato 

et al., 1993). 13% of cases present as multiorgan disease where

Echinococcosis ٤٦ 

metacestodes involve the lungs, spleen, or brain in addition to the liver. 

One-third of cases present with cholestatic jaundice, one-third present 

with epigastric pain, and the remainder present with vague symptoms like 

weight loss or fatigue, or are noted to have incidental hepatomegaly 

(Ammann and Eckert, 1996). 

Diagnosis: 

Early diagnosis of cystic and alveolar echinococcosis can provide 

substantial improvements in the quality of the management and treatment 

of both diseases. The definitive diagnosis for most cases of cystic and 

alveolar echinococcosis in man is by physical imaging methods, such as 

radiology (figure 14), ultrasonography, computed axial tomography (CT 

scanning) (figure 15) and magnetic resonance imaging (Pawlowski et al., 

2001). Immunodiagnosis is useful not only in primary diagnosis but also 

for follow-up of patients after surgical or pharmacological treatment 

(Gottstein, 1992). 

Detection of circulating E. granulosus antigens in serum is less 

sensitive than antibody detection, which remains the method of choice. 

ELISA, indirect haemagglutination antibody assay, latex agglutination 

test, and immunoblot test are the most commonly used immunological 

methods. The immunofluorescence antibody test and arc-5 

immunoelectrophoresis are also used. Additionally, the lipoproteins 

antigen B and antigen 5, the major components of hydatid cyst fluid, are 

widely used in assays for immunodiagnosis of cystic echinococcosis. 

(Poretti et al., 1999). Hydatid cyst fluid antigens are the usual source of 

antigenic material for immunodiagnosis (Zhang and McManus, 2003). 

Some of the serologic tests (Casony intradermal test, Weinberg test, 

complement fixation and indirect hemagglutination tests) are not reliable 

(Morris and Richards, 1992). Cross-reactivity with antigens from other

Echinococcosis ٤٧ 

parasites, as cestodes, is a major problem. Overall, cystic echinococcosis 

serology may be improved by combining several defined antigens 

(including synthetic peptides), and the design of new E granulosus 

specific peptides that react with otherwise false-negative sera. Currently, 

however, there is no standard, highly sensitive, and specific test available 

for antibody detection in cases of the disease. Interleukin-4 detection may 

be useful in the follow up of patients with cystic echinococcosis (Rigano 

et al., 1999). 

The diagnosis of Echinococcus multilocularis in intermediate and 

aberrant hosts should be based on several criteria. These consist of the use 

of macroscopic and histological examinations, including the morphology 

and size of hooks on the protoscolices. In very small lesions additional 

techniques may be necessary such as immunohistology with monoclonal 

antibodies, DNA-hybridisation or PCR techniques (Eckert et al., 2001). 

The most reliable means of diagnosis of Echinococcus in the definitive 

host is by necropsy, as the worm burden can be estimated and parasites 

collected for identification (Eckert, 1997). 

Figure (14): Cystic echinococcosis: Lung cyst on chest radiograph (quoted from 

Craig et al., 2007)

Echinococcosis ٤٨ 

Figure (15) 

(a) Sagittal US image showing a small daughter cyst within a hydatid cyst. 

(b) Corresponding axial CT image showing similar appearances. 

(Doyle et al., 2006) 

Treatment of cystic echinococcosis: 

Asymptomatic hepatic cystic echinococcosis is common in endemic 

regions and up to 75% of infected people may remain symptom free for 

more than 10 years.Cysts may be seen to expand, become septate, or 

calcify when patients are monitored with serial ultrasound (Larrieu and 

Frider, 2001). 

Surgery: 

Surgical therapy is for large cysts, those that are superficial and 

likely to rupture, infected cysts, and those in vital anatomical locations or 

exerting a mass effect. Surgery may be impractical in patients with

Echinococcosis ٤٩ 

multiple cysts in several organs, or in places where technical expertise or 

facilities are inadequate. Surgical options include: pericystectomy, partial 

hepatectomy or lobectomy, open cystectomy (with or without 

omentoplasty), or (palliative) tube drainage of infected cysts. Cyst 

extrusion (Barrett’s technique) is also a surgical option for pulmonary 

disease. More radical surgery is associated with a higher complication 

rate but also a lower relapse rate. Recurrence is usually due to either 

inadequate cyst removal or previously undetected cysts. (Ammann and 

Eckert, 1996). 

The intraoperative use of protoscolicidal compounds is questionable. 

There is no ideal agent that is both effective and safe. Compounds that 

seem to be fairly safe and effective include 70–95% ethanol, 15–20% 

saline, and 0·5% cetrimide solution. Formalin should never be used. 

Chemical cholangitis (with frequently fatal secondary sclerosing 

cholangitis) can result if there is communication between the biliary tree 

and the cyst (Castellano et al., 1994). 

The puncture, aspiration, injection, reaspiration (PAIR) 

technique: 

PAIR technique was introduced in the mid-1980s (Filice and 

Brunetti, 1997). The cyst is punctured under ultrasound guidance, as 

much cyst fluid is aspirated as possible, a protoscolicide (eg. 95% 

ethanol) is injected, and cyst contents are reaspirated 15–20 min later. 

Cyst aspirates should be assessed for the presence of protoscolices and 

bilirubin. PAIR should only be used in patients with chemotherapeutic 

cover to minimise the risk of secondary cystic echinococcosis. There is 

no experience of this technique in children and pregnant women. PAIR is 

best used for liver cysts of 5 cm or greater diameter that are anechoic, 

multiseptate, or multiple. PAIR has been used in patients who have

Echinococcosis ٥٠ 

relapsed after surgery. It is contraindicated for superficial or inaccessible 

cysts, and for cysts that are calcified, solid, or have communication with 

bile ducts (Anonymous, 1996). 

Complication rates for PAIR range from 28% in the absence of 

albendazole to 5–10% with concomitant chemotherapy (Aygun et al., 

2001). PAIR with albendazole chemotherapy has been shown to be as 

effective as pericystectomy for hepatic cystic echinococcosis (Khuroo et 

al., 1997). 

Chemotherapy: 

The benzimidazole compounds (albendazole and mebendazole) 

have been the cornerstone of chemotherapy for cystic echinococcosis. 

Treatment with albendazole (10 mg/kg in divided doses usually 400 mg 

twice daily) results in the disappearance of up to 48% of cysts and 

reduction in size of a further 24%. Mebendazole (40–50 mg/kg per day in 

three divided doses) is less efficacious than albendazole (Horton, 1997). 

Praziquantel has been used (25 mg/kg per day) with albendazole for 

combined treatment of cystic echinococcosis, and an early trial in man 

shows improved efficacy over albendazole alone (Mohamed et al., 

1998). Praziquantel increases serum concentrations of albendazole 

sulfoxide fourfold. It remains to be seen if this treatment potentiates 

albendazole toxicity (Anonymous, 2000). 

Treatment of alveolar echinococcosis: 

Radical surgery as for hepatic malignancy has been the historical 

corner stone of treatment for alveolar echinococcosis (Bresson-Hadni et 

al., 2000). Early diagnosis is crucial, and results in a reduced rate of 

unresectable lesions and reduces the need for radical surgery (Sato et al., 

1997a).

Echinococcosis ٥١ 

Perioperative and long-term adjuvant chemotherapy with 

albendazole (doses up to 20 mg/kg per day) has been associated with 10- 

year survival of approximately 80%, compared with less than 25% in 

historical controls (Wilson et al., 1992). Albendazole is only 

parasitostatic against the E. multilocularis metacestode. Chemotherapy 

should be continued for 2 years after surgery. Liver transplantation has 

been under trials in some patients with alveolar echinococcosis The 

therapeutic immunosuppression may allow proliferation of metacestode 

remnants or proliferation of previously inapparent metastases elsewhere 

(eg, the brain) (Mboti et al., 1996). 

Prevention and control: 

Preventive measures that have been used to control Echinococcus 

infections include avoidance of contact with dog or fox faeces, 

handwashing and improved sanitation, reducing dog or fox populations, 

treatment of dogs with arecoline hydrobromide or praziquantel, 

incineration of infected organs, and health education (Conchedda et al., 

2002 and Gemmell et al., 2001). 

Control of E. multilocularis is especially problematic, since the 

primary cycle is almost always sylvatic. Some progress has been made in 

recent years, and praziquantel baits for control of E. multilocularis 

infections in foxes may prove of value (Tsukada et al., 2002).

Cryptosporidiosis ٥٢ 

Cryptosporidiosis 

Introduction: 

Cryptosporidium parvum first was noted in the human population in 

1976, however it did not draw much attention until the AIDS epidemic 

began in 1982. It is an important cause of chronic diarrhea in the 

immunosuppressed population (Guerrant, 1997). Its impact on public 

health has been so great that in 1992, it was recognized as an “emerging 

infectious disease”. ( Kirkpatrick and Sears, 2000). 

Host specificity: 

Most species of Cryptosporidium appear to have some host 

specificity but are not strictly host specific. For example, 

Cryptosporidium parvum, apparently the least host specific species, has 

been identified in mice, cattle, humans, horses, and many other 

mammalian hosts. Others, including C. baileyi, C. canis, C. felis, C. 

meleagridis, and C. muris, once thought to be host specific for chickens, 

dogs, cats, turkeys, and mice, respectively, have all been found to infect 

humans and therefore must also be considered zoonotic (Ditrich et al., 

1991 and Pedraza-Diaz et al., 2000). 

Life cycle: 

All species of Cryptosporidium are obligate intracellular parasites. 

The endogenous stages of C. parvum have been described in greater 

detail than those of other species (O’Donoghue, 1995 and Fayer et al., 

1997). The only stage found outside the host is the oocyst stage 

(Okhuysen et al., 1999). Some neonates taken at birth and immediately 

delivered to clean rooms began excreting oocysts 3 days later, suggesting 

susceptibility to an extremely low exposure dose or in utero transmission.

Cryptosporidiosis ٥٣ 

After the oocyst is ingested by a suitable host the contents excyst, 

releasing four motile sporozoites that invade and parasitize epithelial cells 

primarily in the gastrointestinal tract (and rarely in extra intestinal 

tissues). Subsequent developmental stages are intracellular but extra- 

cytoplasmic, usually found at the microvillar surface of epithelial host 

cells. Hijjawi et al. (2002) indicates that extra cellular stages were 

observed around 72 hours after experimental infection of mice, but their 

exact role in the life cycle is not clear. The prepatent period, the time 

from ingestion of infective oocysts to excretion of oocysts following 

completion of the life cycle, can be completed in as few as 3–5 days or 

can take as long as 2 weeks. In immunocompetent persons or animals, the 

patent period, the time over which oocysts are excreted, can last for 1 to 

several weeks with oocysts detected only intermittently during the later 

days. Immunocompromised individuals show chronic, long-term 

infection, often lasting several months. The number of oocysts excreted 

by an infected individual can vary greatly. 


Asymptomatic infections have been reported. The clinical course 

and severity of infection can vary considerably from person to person, 

depending on the immune status of the host. The main symptom in 

immunologically healthy persons is diarrhea, usually voluminous and 

watery. Mucous is sometimes present but blood and leukocytes are rare. 

Abdominal discomfort, anorexia, nausea, vomiting, weight loss, fever, 

fatigue and respiratory problems may accompany diarrhea (Jokipii and 

Jokipii, 1986). 

After cessation of symptoms, 19% of patients had positive stools for 

a mean period of 7 days. Parasites are generally restricted to the lower 

small intestine. In persons with immune deficiencies related to

Cryptosporidiosis ٥٤ 

malnutrition, viral infections such as measles and human 

immunodeficiency virus (HIV), and exogenous immunotherapy for 

cancer or other diseases, the duration and severity of illness depends on 

the extent of cellular immunity impairment. In general, as CD4 T cell 

numbers or function decreases, the severity of illness increases. Infections 

can become chronic and life threatening with frequent voluminous watery 

stools leading to dehydration. In severe cases life cycle stages have been 

seen in cells in the respiratory tree, liver, gall bladder, pancreas, and other 

extraintestinal sites.With the application of a cocktail of anti-viral drugs, 

the severity and number of cases of cryptosporidiosis in HIV infected 

persons decreased although there is no specific medication for treatment 

of cryptosporidiosis.Also animals exhibit the same prominent clinical 

sign of infection as humans, watery diarrhea. Clinical signs have been 

reported for cattle, sheep and goats (Angus, 1990). 

Loss of absorptive epithelium including apoptosis and villus atrophy 

results in malabsorption, and release of inflammatory cell mediators 

stimulating electrolyte secretion and diarrhea (Gookin et al., 2002). 

Argenzio et al. (1996) found that prostaglandins altered NaCl transport 

primarily by stimulating the enteric nervous system. Because of the 

profuse secretory diarrhea, it has been hypothesized that C. parvum 

produces an enterotoxin. 

Other findings may include cholecystitis, hepatitis, pancreatitis, 

reactive arthritis, and respiratory problems. These sites of infection are 

often under diagnosed because oocysts are more easily recognized in 

persons with diarrhea than in those without. Gallbladder disease affects 

less than 10% of AIDS patients with cryptosporidiosis. This condition 

usually presents with acalculous cholecystitis or sclerosing cholangitis 

with right upper quadrant pain and fever; diarrhea may or may not be

Cryptosporidiosis ٥٥ 

present. The respiratory tract also is a possible site of infection; however, 

the clinical presentation may be relatively nonspecific. In addition, most 

of the immunocompromised patients that were diagnosed with this form 

of cryptosporidiosis via bronchial lavage had a concurrent infection with 

cytomegalovirus (CMV) or Pneumocystis carinii (Mandell et al., 2000). 

Diagnosis: 

The “gold standard” for detecting Cryptosporidium oocysts in stool 

was a modified acid-fast stain of a fecal smear. However, the sensitivity 

for the detection of Cryptosporidium is better with enzyme-linked 

immunosorbent- based immunoassay formats or immunofluorescent 

assays that facilitate the visualization of fecal oocysts (Katanik et al., 

2001).Polymerase chain reaction (PCR) nucleic acid amplification for 

detection of Cryptosporidium oocysts also has been used as a research 

tool in both environmental and fecal samples. In addition to increased 

sensitivity, PCR can provide genotype and sequence information 

important for epidemiologic studies (Robinson et al., 2003). These tests 

hold agreat promise but are not standardized yet for routine clinical use. 

Other experimental methodologies include 2-color, flow cytometry and 

colorimetric detection systems. The 2-color flow cytometry provides 

better sensitivity than do any other assays for the quantitation of oocysts 

(Moss and Arrowood, 2001). 

As this is a non-inflammatory diarrhea that has both a malabsorptive 

and secretory component, levels of serum B12, stool fat, d-xylose 

adsorption, and electrolytes should be measured. In biliary disease, 

alkaline phosphate, gamma-glutamyl transferase, and bilirubin levels may 

be elevated. Imaging studies are not indicated as a first-line diagnostic 

approach. Abdominal radiographs and computed tomography (CT) scans 

are non-specific and may show distended loops of bowel or air fluid

Cryptosporidiosis ٥٦ 

levels. If there is a clinical or a laboratory suspicion that there is hepatic 

or biliary disease, then an ultrasound or CT scan may show a thickened 

gallbladder wall, dilated or irregular intrahepatic or extrahepatic bile 

ducts, or a stenotic common bile duct. Chest radiographs are also 

unremarkable when there is a respiratory involvement. There may be 

infiltrates or increased bronchial markings (Kourtis, 2001). 

Treatment: 

There is still no specific therapeutic or preventive modality approved 

for cryptosporidiosis. Non-specific supportive treatment, including 

rehydration and nutritional supplementation, remains the main of 

management of the clinical manifestations of cryptosporidiosis. In AIDS 

patients, reduction in viral load and concomitant rise in CD4 counts 

achieved by anti retroviral therapy results in rapid clinical improvement 

in symptoms as well as a reduction in oocyst excretion (Foudraine et 

al.,1998). 

The aminoglycoside paromomycin continues to be one of the few 

antimicrobial agents that remains consistently in clinical use (Hewitt et 

al., 2000). Nitazoxanide is a broad-spectrum, antiparasitic agent with 

activity against helminths and protozoan parasites, including 

Cryptosporidium (Rossignol et al., 2001). This drug is an inhibitor of 

pyruvate ferredoxin oxidoreductase. Nitazoxanide is well-tolerated and 

reduces the duration of diarrhea and the intensity of Cryptosporidium 

oocyst shedding, after a 3-days treatment regimen (Amadi et al., 2002 

and Diaz et al., 2003).

Giardiasis ٥٧ 

Giardiasis 

Epidemiology: 

The transmission of Giardia is essentially feco-oral (Meyer and 

Jarroll, 1980). Outbreaks of giardiasis have been linked to fecally 

contaminated water supply, infected animals, and situations involving 

person to person contact (as in nursing homes and day-care centers). The 

sexual transmission of Giardia is exclusively seen in male homosexuals. 

The incidence of Giardia is higher in developing countries where the 

parasite persists and flourishes as a result of poverty, inadequate 

sanitation, insufficient health care, and overcrowding (Hill, 1993). 

The incidence of giardiasis is significantly higher in homosexual 

males (4–18%) than in heterosexual controls. Sexual behaviors 

responsible for the transmission of this organism include, digital anal 

contact, and oral-genital contact after anal intercourse. There are many 

reports of Giardia vaginitis and proctitis, suggesting that this parasite may 

be transmitted by sexual activity (Levine, 1991). Other high-risk groups 

are individuals with Crohn’s disease, chronic pancreatitis, achlorhydria, 

cystic fibrosis, and the immunocompromised. A late summer and autumn 

peak in incidence has been noted (Flanagan, 1992). 

Life cycle: 

Giardia cysts have a hyaline wall that protects them from extremes 

of temperature and other environmental stressors. These cysts are not 

killed by chlorination of water, and they also may be resistant to boiling 

water at a high altitude. Cysts may survive in water for up to 3 months 

(Wolfe, 1992). After ingestion and passage through the stomach, 

excystation occurs in the proximal small intestine. This is thought to be 

triggered by exposure to gastric acid and/or the subsequent exposure to

Giardiasis ٥٨ 

the alkaline, protease-rich juice of the proximal duodenum (Adam, 

2001). 

Excystation yields the release of 2 motile trophozoites,which 

replicate by binary fission and principally inhabit the proximal small 

intestine. The trophozoites do not invade the epithelium; instead, they 

appear to adhere to the epithelial surface by suction with a ventral disk, 

although the precise molecular mechanism by which this occurs is 

unknown. Trophozoites encyst in the jejunum, in a process that is 

triggered by a particular composition of biliary secretions. In vitro studies 

have suggested that encystation is activated by deprivation of cholesterol 

from the environment (Lujan et al., 1996). 

Pathogenesis and pathology: 

Excystation of ingested cysts occurs in the stomach and duodenum. 

Released trophozoites reproduce by binary fission and in the small bowel 

attached to the mucosal surface. G. lamblia in feces encysts and is passed 

into the environment, continuing the cycle (Owen et al., 1979 and 

Bingham and Meyer, 1979). 

Acute and chronic diarrhea with weight loss and growth retardation 

are the clinical presentations of symptomatic giardiasis. The mechanisms 

through which G. lamblia causes disease are not known. Postulated 

mechanisms include mechanical obstruction and interference in 

absorption of fats and fat-soluble vitamins caused by trophozoite 

attachment to the mucosa ,direct irritation of the mucosa by the sucking 

disk (Owen et al., 1979 and Erlandsen and Chase, 1974), bacterial 

overgrowth and bile salt deconjugation (Tandon et al., 1977). Osmotic 

diarrhea from a parasite caused reduction in intestinal mucosal 

disaccharidase (Hoskins et al., 1967) and production of an enterotoxin 

(Meyer and Radulescu, 1979).

Giardiasis ٥٩ 

Villous atrophy, epithelial cell damage, and lymphocytic and plasma 

cell infiltrates of the mucosa have been described in symptomatic patients 

(Wright and Tomkins, 1977). Patchy location of parasites with blunting 

of the epithelial cell microvillus border has been seen in biopsy 

specimens (Erlandsen and Chase, 1974). Depletion of microvilli can be 

shown by using cultured epithelial cells, but this depletion occurs with 

Giardia isolates from symptomatic or asymptomatic patients (Chavez et 

al., 1995). 


Giardiasis may present with a wide variety of clinical 

manifestations. The majority (60–80%) of infected individuals have few 

or no symptoms.(Flanagan, 1992). Asymptomatic giardiasis may be 

epidemiologically more significant, as asymptomatic individuals are less 

likely to be detected or to seek treatment and therefore, are more likely to 

serve as carriers of the disease (Meyer and Jarroll, 1980). 

Symptomatic giardiasis is characterized by the acute onset of 

diarrhea, abdominal pain or cramps, and flatulence. Diarrhea is the 

predominant symptom, occurring in 90% of symptomatic individuals 

(Gorski, 1985). Patients pass approximately five loose or semiformed 

stools per day for 2–3 days. The episodes of diarrhea may be interposed 

with periods of normal bowel movements or constipation. The flatulence 

is characterized by a sulfur odor, which is frequently emitted from the 

breath, stool, or both. If untreated, these symptoms may persist for 

months and lead to malabsorption and weight loss. In infants and 

children, prolonged infection may lead to impaired growth and 

development (Farthing, 1992). 

Fever, chills, severe abdominal pain, and bloody stool are 

uncommon symptoms of Giardia infection, and, if present, other

Giardiasis ٦٠ 

diagnosis must be considered (Babb, 1995). Extraintestinal 

manifestations of giardiasis are rare but include maculopapular rash, 

urticaria, dermatitis, arthritis, and biliary tract disease. Acute giardiasis 

must be differentiated from other acute diarrheal illnesses, such as viral or 

bacterial gastroenteritis and food poisoning. Similarly, the differential 

diagnosis of chronic giardiasis includes inflammatory bowel disease, 

irritable bowel syndrome and celiac disease (Tessier and Davies, 1999). 

Diagnosis: 

Diagnosis of giardiasis should be considered in patients with a 

typical clinical history and epidemiological risk factors. In most cases, 

history, physical examination, and stool evaluation are sufficient to 

establish the diagnosis (Heresi and Cleary, 1997). 

Microscopic identification: 

Stool examination by light microscopy of stool for cysts, 

trophozoites, or both is the current standard procedure for diagnosis. Two 

problems for microscopic identification are that it requires a skilled 

technician and that G. lamblia cysts and trophozoites are excreted 

intermittently. At least 3 stool specimens collected on non consecutive 

days or during a 10-days period should be examined. A single stool 

examination will miss one-half of infected patients. If 3 stools are 

examined, the frequency of identification of the parasite increases to 97% 

(Wolfe, 1979). Stool culture for G. lamblia can be done (Meyer, 1976). 

Studies of duodenal fluids: A duodenal sample can be obtained by 

endoscopy or by absorption to a swallowed coiled nylon string 

(Enterotest); the latter procedure is safe and inexpensive. The sensitivity 

of this test may be higher than that of stool examination, (Kamath and 

Murugasu, 1974) but this observation has not been confirmed. Presently,

Giardiasis ٦١ 

duodenal sampling is recommended as complementary but not as a 

replacement for, stool examination (Wolfe, 1992). 

Immunodiagnosis: 

Immunofluorescence and ELISA assays: Directed to detection of 

Giardia antigens in the stools are available. They are based on the use of 

Giardia-specific polyclonal or monoclonal antibodies and have increased 

sensitivity compared with conventional staining methods (Zimmerman 

and Needham, 1995). 

Serodiagnosis: Measurements of serum antibodies have been helpful in 

epidemiological studies. However, IgG remains elevated for a long time 

after infection, rendering differentiation of recent from past infection 

difficult (Granot et al., 1998). 

Treatment: 

Although Giardia infections resolve spontaneously in 85% of 

patients within 6 weeks, all patients with symptomatic giardiasis should 

be treated (Flanagan, 1992). Metronidazole and quinacrine are the first- 

line treatment options and are more than 90% effective (Farthing, 1992). 

Quinacrine is no longer available. Alternative anti-giardial drugs include 

tinidazole, furazolidone, paromomycin, and mebendazole. Tinidazole, is 

90% effective in a single-dose regimen and, therefore,it is ideal. 

Furazolidone is well tolerated and available in a suspension form and is 

the treatment of choice in children (Walterspiel and Pickering, 1994). In 

pregnancy, there are no consistent recommendations for treating 

giardiasis (Hill, 1993). 

Relapses occur in up to 20% of patients and may be a result of 

patient non compliance, reinfection, or drug resistance (Shepherd and 

Boreham, 1989). If giardiasis persists or recurs, two agents should be

Giardiasis ٦٢ 

used for 14 days (Babb, 1995). The treatment of sexual contacts of 

confirmed cases is also recommended (Levine, 1991).

Gallbladder stones ٦٣ 

Gallbladder stones (cholelithiasis) 

Gallstones (cholelithiasis) are formed within the gallbladder, an 

organ that stores bile excreted from the liver. Bile is made up of bilirubin, 

water, salts, lecithin, cholesterol, and other substances. If the 

concentration of these components changes, gallstones may form. 

Gallstones may be as small as a grain of sand, or they may become as 

large as an inch in diameter, depending on how long they have been 

forming (Houchen, 2005). 

Gallstone disease remains one of the most common medical 

problems leading to surgical intervention. During the reproductive years, 

the female-to-male ratio is about 4:1, with the sex discrepancy narrowing 

in the older population to near equality. The risk factors predisposing to 


pregnancy, hemolytic diseases, and cirrhosis (Schirmer et al, 2005). 

Pathophysiology of gallstone formation: 

There are two types of gallstones: cholesterol and pigment stones. 

The pathogenesis is divided into three phases: supersaturation, nucleation 

and stone growth. Hypersecretion of biliary cholesterol, crystallization 

promoting and inhibiting factors, gallbladder hypomotility, arachidonyl 

lecithin, prostaglandins, mucin and calcium play an important role in the 

formation of gallstones. For the formation of pigment stones a decreased 

secretion of biliary acids, an increased secretion of unconjugated bilirubin 

into the bile and an infection of the biliary tract are the most important 

causative factors (Wermke and Borges, 1993). Crystallization results in 

suspension of cholesterol crystals or bilirubinate salts in gallbladder 

mucin gel and is known as "biliary sludge". It is believed today that this

Gallbladder stones ٦٤ 

stage is essential for evolution of both cholesterol and pigment stone 

(Carey, 1992). 

(A) Cholesterol stones: 

In the west, approximately 75% of gallstones are Cholesterol stones 

(Apstein and Cary, 1993). 

Risk factors for the development of cholesterol stones: 

• Sex: Before puberty, the disease is rare but of equal frequency in both 

sexes. Therefore,women are more commonly affected than men until 

after menopause when the discrepancy lessen (Doherty and Way, 

2003). 

• Heredity: About 25% of the predisposition to cholesterol gallstones 

appears to be hereditary. A rare syndrome of low phospholipid– 

associated cholelithiasis occurs in individuals with a hereditary 

deficiency of the biliary transport protein required for lecithin 

secretion (Heuman, 2006). 

• Race: The incidence is highest in American Indian, lower in 

Causcasian, and lowest in blacks, with a two folds gradient from one 

group to the next (Doherty and Way, 2003). 

• Obesity, high-fat diet and hypertriglyceridemia: They are strongly 

associated with the formation of gallstones, progesterone inhibits 

gallbladder motility leading to biliary stasis and stone formation. So 

Cholesterol gallstones are more common in women who have multiple 

pregnancies (Lee, 2006). 

• Gallbladder stasis: Due to high spinal cord injuries, prolonged 

fasting, total parenteral nutrition, rapid weight loss associated with low 

caloric diets (Migala, 2006).

Gallbladder stones ٦٥ 

• Drugs: Estrogens increase cholesterol formation, which supersaturate 

the bile, leading to precipitation of cholesterol stones (Lee, 2006). 

Clofibrate and other fibrate hypolipidemic drugs increase hepatic 

elimination of cholesterol via biliary secretion. Somatostatin analogs 

appear to predispose to gallstones by decreasing gallbladder emptying 

(Heuman, 2006). 

Composition of cholesterol stones: 

They have a protein matrix and although are composed 

predominantly of cholesterol, they contain also bile pigments and 

different amounts of calcium carbonate and palmitate. These calcium 

salts are deposited on the periphery of the stones and their amounts 

determines their radio density (Cuschieri et al., 2002). 

(B) Black pigment gallstones: 

Account for 20% of stones in the west although their prevalence is 

higher in Asian countries (Apstein and Carey, 1993). 

Risk factors: 

Disorders of hemolysis associated with pigment gallstones include 

sickle cell anemia, hereditary spherocytosis, and beta thalassemia. About 

half of all cirrhotic patients have pigment gallstones, due to red cell 

sequestration in enlarged spleen (Heuman, 2006). 

Composition and characters of black pigment stones: They are 

composed of bilirubin polymers without calcium palmitate, different 

amounts of cholesterol (3-25%) and a matrix of organic materials. These 

stones are usually multiple, small, irregular and dark green to black in 

color (Schwartz, 2005).

Gallbladder stones ٦٦ 

Complications of gall bladder stones: 

- Obstruction of the cystic duct or neck of the gall bladder. Mucocele if 

the contents are sterile. 

- acute cholecystitis with or without empyema, gangrene, or perforation 

of the gall bladder. 

- Chronic calcular cholecystitis: the gall bladder is usually thick wall 

and is commonly, contracted. 

- Carcinoma of the gall bladder due to squamous metaplasia in long 

standing cases. 

Diagnosis: 

(Schwartz, 2005) 

Symptoms (biliary colic): Symptoms usually start after a stone of 

sufficient size (larger than 8 mm) blocks the cystic duct.Characterized by: 

Fever, abdominal pain in the right upper abdomen or in the middle of the 

upper abdomen, which is recurrent, sharp, cramping, or dull, radiating to 

the back or below the right shoulder blade, worsen by fatty or greasy 

foods, and occurs within minutes of a meal. Additional symptoms that 

may be associated with this disease include, nausea, vomiting, heartburn 

and abdominal indigestion and fullness (Houchen, 2005). 

Physical examination (signs): 

During attacks of biliary colic, patients have tenderness to palpation 

over the gallbladder. This can be elicited by having the patient inhale 

while the examiner maintains steady pressure below the right costal 

margin (Murphy's sign). Localized rebound tenderness, guarding, or 

rigidity may occur. The Charcot's triad of severe right upper quadrant

Gallbladder stones ٦٧ 

tenderness with jaundice and fever is characteristic of ascending 

cholangitis (Heuman, 2006). 

Laboratory studies: 

They are normal in the asymptomatic patient and patients with 

uncomplicated biliary colic. An elevated white count should raise the 

suspicion for cholecystitis or other infectious process. However, up to one 

third of the patients with cholecystitis may not manifest leukocytosis. 

Elevated transaminases levels indicate a hepatic process. An elevated 

lipase is indicative of pancreatitis (Lee, 2006). 

Imaging studies: 

Plain radiography in these patients is of limited value because many 

stones are not visible. Ultrasonography (US) is the least expensive, safest, 

and most sensitive technique for visualizing the biliary system, 

particularly the gallbladder. Current accuracy is close to 95% (Bonheur, 

2006). 

Radionuclide scanning are used to assess gall bladder function, its 

ability to harbor and concentrate bile, and perhaps more importantly, its 

motility response to cholecystokinin or a fatty meal by quantifying the 

ejection fraction (Migala, 2006). 

Treatment: 

Medical care: Non-surgical management of gallstone disease is the use 

of ursodeoxycholic acid (natural bile acid). One study demonstrated a 

56% reduction in biliary pain after 3 months of therapy and a mean 

dissolution of gallstones in 59% of cases after 12 months of treatment 

with 10 mg/kg/day of ursodeoxycholic acid. The primary disadvantage 

with this approach is the incidence of recurrent gallstones, approximately

Gallbladder stones ٦٨ 

25% within 5 years. The non-surgical option is currently only indicated 

for patients either unfit or unwilling to undergo surgical intervention and 

has not been recommended in children (Migala, 2006). 

Surgical care: Removal of the gallbladder (cholecystectomy) is the 

treatment of choice for symptomatic cholelithiasis. In some cases of 

gallbladder empyema, temporary drainage of pus from the gallbladder 

(cholecystostomy) may be preferred to allow stabilization and to permit 

later cholecystectomy under elective circumstances. At the time of 

cholecystectomy, the surgeon can explore the common bile duct and 

remove common bile duct stones. Alternatively, the surgeon can create a 

fistula between the distal bile duct and the adjacent duodenum 

(choledochoduodenostomy), allowing stones to pass harmlessly into the 

intestine. Cholecystectomy is generally indicated in patients who have 

experienced symptoms or complications of gallstones, unless the patient's 

age and general health make the risk of surgery prohibitive (Heuman, 

2006). 

Cholecystectomy is not required for patients with asymptomatic 

gallstones. However, elective cholecystectomy for asymptomatic 

gallstones may be indicated in: Patients with large gallstones greater than 

2 cm in diameter, Cirrhosis, Portal hypertension, Sickle cell disease, 

transplant candidates and diabetic patient (Lee, 2006).

Choledocholithiasis ٦٩ 

Choledocholithiasis 

Pathophysiology: 

Choledocholithiasis occurs as a result of either the primary 

formation of stones in the common bile duct (CBD) or the passage of 

gallstones from the gallbladder through the cystic duct into the CBD 

(Schwartz, 1999). 

About 15% of patients with gallstones have choledocholithiasis. 

Stones in the common duct usually originate in the gallbladder but may 

also form de novo in the bile duct. Like gallbladder stones, common duct 

stones may remain asymptomatic for years and, if small, pass painlessly 

from the bile duct into the duodenum. More typically, they remain in the 

common duct and the patient presents with biliary pain, obstructive 

jaundice, ascending cholangitis (bacterial infection in the bile duct), or 

biliary pancreatitis (Sgourakis et al., 2005). 

Choledocholithiasis develops in about 10-20% of patients with gall 

bladder stones (Freitas et al., 2006), and occur in up to 3% -10% of all 

cholecystectomy patients (Schirmer et al., 2005). 

Classification: 

CBD stones are classified according to origin: Primary bile-duct 

stones, forming initially in the bile ducts; secondary to gallbladder stones, 

originating in the gallbladder and passing into the bile ducts; and 

secondary to or coexisting with intrahepatic bile-duct stones (Kaufman 

et al., 1989). 

Primary ductal calculi: 

Pathogenesis: Primary ductal calculi that originate in the CBD are brown 

pigment stones. In surgical practice, brown pigment stones are often

Choledocholithiasis ٧٠ 

encountered in the following conditions: Stasis in the biliary tract caused 

by strictures, tumours, aberrant sphincter of Oddi motility and sclerosing 

cholangitis (Cuschieri, 2002). Hydrolysis of bilirubin by bacterial b- 

glucuronidase leads to formation of unconjugated bilirubin which can 

precipitate as calcium bilirubinate (Swidsinski et al., 1995). 

In Asian populations, infestation with ascaris lumbricoides and 

clonorchis sinensis may promote stasis by either blocking the biliary 

ducts or by damaging the duct walls, resulting in stricture formation. 

Bactibilia is also common in these instances, probably secondary to 

episodic portal bacteremia. Some authors have suggested that the stones 

are formed because of the bactibilia alone and that the parasites' presence 

is just a coincidence (Dandan et al., 2005). 

Primary stones are often soft, smooth, yellowish in color, non- 

cholesterol in nature, and conform to the shape of the bile duct (Guirgiu 

and Roslyn, 1997). 

Secondary ductal calculi: 

Secondary stones are chemically similar to coexisting stones in the 

gallbladder. Predominantly, cholesterol in 80% and black pigment in 

20%. They have the typical spectrum of cholesterol and black pigment 

stones. Bacteria can be cultured from the surface of cholesterol and 

pigment stones but not from the core, suggesting that bacteria do not play 

a role in their formation (Dandan et al., 2005). 

Clinical manifestation of ductal calculi: 

A- Symptoms: 

If stones in the biliary tree are small enough, they may pass into the 

duodenum. However, the distal duct is only 2 to 3 mm in diameter, so 

stones exceeding this size can obstruct biliary outflow, which leads to

Choledocholithiasis ٧١ 

edema, spasm, and fibrosis of the ductal wall. The ducts concomitantly 

dilate and thicken, with migration and proliferation of inflammatory cells. 

Because the resultant clinical manifestations vary, CBD stones may 

remain asymptomatic for years (Halpin and Soper, 2001). 

A common presentation of common bile duct stones is biliary colic. 

The pain is often situated in the right hypochondrium or epigastrium 

lasting 30 minutes to several hours. Nausea and vomiting are common. 

Biliary colic typically is not eased by change in body position and is not 

specifically related to food intake. The pain is thought to be caused by 

distension of the common bile duct due to an increase in pressure caused 

by partial or complete obstruction by a CBDS. The presentation of CBDS 

may depend on the number of stones situated in the CBD (e.g. one to 

three stones more likely associated with cholangitis, biliary colic and 

higher bilirubin levels than patients presented with four or more stones 

who were more likely to present with painless jaundice) ( Shemesh et al., 

1989). In addition to the number of stones, the diameter of CBD is also 

important. The likelihood of stones passing spontaneously may be 

dependent on size (Esber and Sherman, 1996). Stones up to 8 mm may 

pass without problems (Chung et al., 1997 and Frossard et al., 2000). 

When a stone becomes impacted in the bile duct, obstructive jaundice 

will develop often the obstruction of the bile duct is incomplete but 

complete obstruction may occur. Frequently the obstructed bile becomes 

infected resulting in cholangitis. CBDS often contain bacteria embedded 

within their matrix. When obstruction of the bile duct occurs, the rise in 

biliary pressure results in the translocation of bacteria from the bile duct 

to the blood-stream. Approximately one-fifth of patients presenting with 

cholangitis from CBDS will have a bacteraemia, usually with gram 

negative organisms being cultured (Leung et al., 1994).

Choledocholithiasis ٧٢ 

The symptoms of cholangitis are described by Charcot’s triad of 

jaundice, fever and pain in up to 75% of patients. However, in a minority 

of patients (12%) pain alone may be the only presenting feature of 

cholangitis (Anciaux et al., 1986). Between 4% and 8% of patients with 

gallstones will develop gallstone pancreatitis secondary to migratory 

gallstones (Ayub et al., 2004). Developing gallstone pancreatitis is more 

likely with smaller stones than with larger stones. Patients presenting 

with gallstone pancreatitis had mean diameter bile duct stone size of 4 

mm compared to that of 9 mm for patients presenting with obstructive 

jaundice (Venneman et al., 2005). The majority of these patients will 

have a self limiting disease but mortality still remains around 10% (Toh 

et al., 2000). 

B- Signs: 

The patient may be icteric and toxic, with high fever and chills, or 

may appears to be healthy (Doherty and Way, 2003). In the jaundiced 

patient, it is useful to remember Courvoisier’s law in obstruction of CBD 

due to a stone, distension of the gallbladder seldom occurs. However, if 

there is no disease in the gallbladder and the obstruction is due to a cancer 

of the ampulla, pancreas or bile duct, then the gallbladder may will be 

distended (Russel et al., 2000). In cholangitis, the classic description of 

Charcot’s triad is often encountered. The less common Reynold’s pentad 

adds the elements of systemic shock and mental status changes 

(Schwartz, 1999 and Halpin and Soper, 2001). 

The cause of jaundice in an individual patient can be diagnosed or at 

least suspected from the clinical history, physical examination and routine 

laboratory tests (Canto et al., 1998). The mode of onset is extremely 

important factor in the diagnosis. The insidious appearance of deep 

jaundice over few weeks should suggest neoplastic obstruction. While

Choledocholithiasis ٧٣ 

jaundice that fluctuates in intensity, especially if accompanied by fever 

and abdominal pain, is characteristic of gallstone disease. Pyrexia with 

rigors suggests cholangitis associated with gallstones or biliary strictures 

(Bithartz and Horton, 1998). Anaemia and gross weight loss suggest 

cancer. The patient with prolonged biliary obstruction has deep greenish 

color. Sites to be examined for primary tumour include the breasts, 

thyroid, stomach, colon, rectum & lung. Lymphadenopathy also should 

be noted (Schwartz, 2005). 

Complication: 

Acute biliary obstruction is caused partly by the presence of stone 

itself, and partly by oedema of the duct wall that may be enhanced by the 

spasm of sphincter of Oddi. Chronic intermittent biliary obstruction 

occurs when a stone moves up and down in the ducts; it may produce 

repeated and transient episodes of jaundice. However, chronic obstruction 

results in progressive dilatation of the ducts which may become twice 

their normal caliber (Ellis, 1990). 

Although Hoemobilia is a rare complication, it presents with the 

triad of biliary colic, obstructive jaundice, and occult or gross intestinal 

bleeding (Lawrence and Way, 1994 and Doherty and Way, 2003). 

A fistulous track between the lower end of the CBD and the 

duodenum (a cholecocho-duodenal) fistula may occur secondary to ductal 

calculi (Cuschieri, 2002). 

A stone in the CBD may erode through the ampulla resulting in 

gallstone ileus, Hepatic failure or secondary biliary cirrhosis may develop 

in unrelieved obstruction of long duration (Doherty and Way, 2003). 

Acute cholangitis secondary to bile-duct stones develops when 

bacterial infection complicates obstruction within the biliary tract.

Choledocholithiasis ٧٤ 

Patients with partial obstruction are at increased risk compared to those 

with complete obstruction. Infection is generally thought to occur through 

direct extension of bacteria from the duodenum. Increased colonisation 

with coliforms (the most commonly isolated organisms in cholangitis) 

within the proximal small intestine may predispose to bactobilia (e.g. in 

the elderly with achlorhydria). Haematogenous spread through the portal 

venous system could be another route. Effectiveness of the reticulo- 

endothelial system may be compromised in the setting of increased bile 

(Van Erpecum, 2006). 

Small gallstones, excess cholesterol crystals (possibly related to high 

pro-nucleating biliary mucin levels) and good gallbladder emptying are 

associated with increased risk of pancreatitis (Venneman et al., 2005). 

Apparently, good gallbladder emptying promotes migration to the bile 

ducts, especially in the case of small gallstones and sludge. Large bile- 

duct stones lead to more proximal obstruction, with jaundice but no reflux 

into the pancreatic duct. In contrast, small stones could lead to more distal 

obstruction, with potential reflux of bile into the pancreatic duct. Bile 

reflux into the pancreatic duct (common channel hypothesis), pancreatic 

duct hypertension or functional obstruction at the sphincter of Oddi could 

then induce a common pathway of pancreatic duct injury with release of 

activated pancreatic enzymes into the glandular interstitium, thus 

triggering the release of cytokines and a bout of acute pancreatitis 

(Lightner and Kirkwood, 2001). 

Diagnosis of choledocholithiasis: 

Laboratory diagnosis: 

Patients presenting with common bile duct stones often have 

cholestatic liver function tests. Elevated serum gamma glutamyl

Choledocholithiasis ٧٥ 

transpeptidase (GGT) and alkaline phosphatase (ALP) were the most 

frequent biochemical abnormalities in patients with symptomatic 

choledocholithiasis (Anciaux et al., 1986). Serum bilirubin levels may be 

markedly elevated depending on whether the obstruction of the bile duct 

is complete or incomplete. (Sarli et al., 2000). Most of the studies have 

emphasised that laboratory investigations must be used in addition to 

other imaging modalities to predict the likelihood of common bile duct 

stones (Tham et al., 1998). 

Imaging Studies: 

Several diagnostic modalities are available, and these are best 

divided into preoperative, intraoperative, and postoperative studies. The 

latter are used for the diagnosis of retained common bile duct stones 

(Dandan et al., 2005). 

Preoperative studies: 

Plain abdominal radiography: A plain film of the upper abdomen may 

show radio-opaque calculi. It is uncommon to demonstrate a stone, in the 

duct by this technique, failure to demonstrate the presence of gallstones is 

no way invalidates the diagnosis since 10-15% only of gallstones are 

radio-opaque (Cuschieri, 2002). 

Transabdominal Ultrasonography (TUS): It remains the first line 

radiological investigation in patients with suspected CBDS. It has a high 

sensitivity of detecting both intrahepatic and extrahepatic biliary 

dilatation. The sensitivity of TUS compared to endoscopic retrograde 

cholangiopancreatography (ERCP) in detecting common bile duct 

dilatation was 96% (Stott et al., 1991). However, the sensitivity of TUS 

in detecting choledocholithiasis is much lower with sensitivities of 

between 25% and 63% when compared to endoscopic ultrasound (EUS)

Choledocholithiasis ٧٦ 

and ERCP (Sugiyama and Atomi, 1997 and Amouyal et al., 1994). 

Although with a specificity of approximately 95%, TUS remains an 

extremely useful test if CBDS are detected (Sugiyama and Atomi, 

1997). A negative TUS in a patient with suspected Choledocholithiasis 

does not rule out CBDS (Gross et al., 1983). 

Endoscopic ultrasonography (EUS): EUS is an accurate test for 

detection of CBDS, with a sensitivity range between 94% and 98% 

(Buscarini et al., 2003 and Canto et al., 1998). 

Computed tomography scan: Conventional computed tomography (CT) 

studies have found sensitivities between 70% and 90% in the detection of 

choledocholithiasis (Mitchell and Clark, 1984). The use of unenhanced 

helical CT for detection of choledocholithiasis has similar sensitivities of 

67%-88% (Jimenez et al., 2001). Oral enhanced CT cholangiography has 

an increased sensitivity of 92% (Soto et al., 2000). 

Magnetic resonance cholangiopancreatography (MRCP): Magnetic 

Resonance Cholangiography (MRCP) has become an accepted method of 

imaging the bile duct with a high sensitivity and specificity for 

choledocholithiasis.The accuracy rates of detection of choledocholithiasis 

comparable between EUS and MRCP (accuracy rate 93% and 91%, 

respectively) (Ainsworth et al., 2003). Laokpessi et al. (2001) found 

that both MRCP and ERCP comparable in detection of CBDS (sensitivity 

and specificity 93% and 100%; 94% and 100%, respectively). 

MRCP has emerged as an accurate, non-invasive diagnostic 

modality for investigating the biliary and pancreatic ducts (Hallal et al., 

2005), and has been recommended in some circles as the preoperative 

procedure of choice for the detection of CBD stones (Peng et al., 2005; 

Taylor et al., 2002 and Topal et al., 2003). MRCP provides excellent 

anatomic detail of the biliary tract and has a sensitivity of 81%-100% and

Choledocholithiasis ٧٧ 

a specificity of 92%-100% in detecting choledocholithiasis (Hallal et al., 

2005). MRCP is also very useful in differentiating common hepatic duct 

obstruction by Mirizzi syndrome from obstruction by gallbladder cancer 

or enlarged lymph nodes (Hintze et al., 1997). MRCP is very useful for 

ampullary tumours; it detects a dilated bile duct abutting on an irregular 

ampullary mass indenting the duodenum. Although it can detect proximal 

and body cancer of the pancreas, it offers no advantages over 

CT/ultrasound in this respect, except in cystic tumours in view of its 

ability to detect static fluid collections (Laubenberger et al., 1995 and 

Cuschieri, 2002). 

Cholangiography: This remains the criterion standard for the detection 

of CBD stones. In the past, intravenous cholangiography was the only 

available method for assessing the biliary tree, but the results had poor 

accuracy and sensitivity, not to mention major concerns with allergic 

reactions. Now intravenous cholangiography not used with the 

introduction of endoscopic retrograde cholangiopancreatography (ERCP) 

and percutaneous transhepatic cholangiography (PTC) (Dandan, 2005). 

Endoscopic retrograde cholangiopancreatograph confirms the diagnosis 

of choledocholithiasis as well as the location of the stone.(figure 16) This 

procedure was initially employed in diagnosis, but today is most often 

used as a therapeutic measure (Halpin et al., 2002).

Choledocholithiasis ٧٨ 

Figure (16): Multiple stones in the common bile duct (Courtesy of Dr. Tarik Zaher) 

Percutaneous transhepatic cholangiography (PTC) involves passing 

a guidewire through the liver parenchyma into the biliary tree to make a 

diagnosis. Although it permits interventions, PTC is usually inferior to 

ERCP in extracting stones, as it necessitates the pushing of stones into the 

duodenum as opposed to pulling them through the ampulla as with ERCP. 

The procedure is traumatic, with bleeding being the main complication 

(Liu et al., 2001 and Halpin et al., 2002). 

Intraoperative studies: Intraoperative cholangiography can be 

performed under fluoroscopy, and it has been proposed by some surgeons 

to be performed during every laparoscopic cholecystectomy. Intravenous 

glucagon may assist in visualizing the entire biliary tree (Halpin and 

Soper, 2001). 

Intraoperative ultrasonography: Special probes are used to visualize 

the biliary tree. It can be performed using either open or laparoscopic 

techniques, and results have a positive predictive value of approximately 

75%. With the recent introduction of a small high-frequency probe in a 

6F sheath, performing intraluminal ultrasonography is now possible.

Choledocholithiasis ٧٩ 

Operator dependency limits the usefulness of this modality. More 

recently intraoperative ultrasonography of the CBD during laparoscopic 

cholecystectomy has been shown to satisfactorily demonstrate stones and 

the biliarys tree. Use of intraoperative ultrasound requires a significant 

learning curves, but in experienced hands takes less operative time 

(Cathelin et al., 2002 and Halpin et al., 2002). 

Laparoscopic intracorporeal ultrasound is performed at the time of 

laparoscopic cholecystectomy, and it is faster and more sensitive than 

cholangiography. The benefits of this procedure include avoidance of 

both cystic duct cannulation and ionizing radiation exposure (Juttijudata 

et al., 1983 and Halpin, and Soper, 2001). 

Postoperative studies: T-tube cholangiography, retained CBD stones are 

identified in 2-10% of patients after CBD exploration. These are most 

commonly detected upon routine T-tube cholangiography performed 7-10 

days postoperatively. Also, ERCP and PTC are used as post operative 

studies (Dandan, 2005).

Treatment of calcular obstructive jaundice ٨٠ 

Treatment of calcular obstructive jaundice 

Role of medical therapy: 

Ursodeoxycholic acid (10 mg/kg) eliminated gallbladder 

microlithiasis and reduced the episodes of further pancreatitis. Continuing 

therapy with UDCA appeared to prevent recurrence of gallbladder 

microlithiasis (Ros et al., 1991). Its benefit in patient who cannot 

undergo surgery and may work best on solitary stones less than 2 cm in 

diameter. These treatment are now considered adjuncts to surgery rather 

than alternatives. Overall, results are poor compared with the 

interventions described below (Kelly et al., 2000). 

Patients with cholangitis or gallstone pancreatitis are acutely ill, and 

they often require aggressive rehydration. Antibiotics are indicated if 

infection is present, and complete bowel rest (nothing by mouth, 

nasogastric intubation) may be necessary. The patient may require 

correction of coagulopathy, especially when an intervention is planned 

(Halpin and Soper, 2001). 

ERCP (sphincterotomy or pneumatic dilatation): 

Endoscopic biliary sphincterotomy (ES) at ERCP was first described 

in 1974 and was initially advocated for elderly patients or patients with 

other co-morbid illness excluding them from surgical management. 

However, since this time, ES has become widespread in the practice for 

the removal of choledocholithiasis. The use of ES, particularly in younger 

patients, led to concern over the long term sequelae of a disrupted 

sphincter of Oddi caused by chronic enteric-biliary reflux (Tham et al., 

1997).

Treatment of calcular obstructive jaundice ٨١ 

Endoscopic balloon dilatation (EBD) of the sphincter had previously 

been performed in the 1980s but had subsequently lost favour in clinical 

practice due to increased complications (mainly that of pancreatitis). 

However the original risk of post-EBD pancreatitis was overestimated 

due to recruitment of patients with sphincter of Oddi (SOD) dysfunction 

(a group with a known increased risk of post-ERC pancreatitis) (Fujita et 

al., 2003). However, the rates of pancreatitis were significantly higher for 

the EBD group (7.4% versus 4.3%) but bleeding complications were 

reduced (0% versus 2%). Other complication rates of infection and 

perforation were similar between the two groups. Primary clearance of 

the bile duct was less successful using EBD compared to ES (70% versus 

80%), and the use of mechanical lithotripsy was more common (21% 

versus 15%). comparing the short term complications of EBD versus ES 

again confirmed an increase rate of pancreatitis with EBD versus ES 

(15.4% and 0.8%, respectively) (Disario et al., 2004). 

Mechanical lithotripsy (ML): 

Stone removal from the common bile duct may be technically 

difficult due to factors such as the size of the stone (>2 cm), impaction of 

the stone in a non-dilated bile duct, stones above a bile duct stricture or a 

narrowed retro-pancreatic portion of the distal CBD. In these 

circumstances, mechanical lithotripsy (ML) is commonly. Bile duct 

clearance rates using ML have been reported to be between 68% and 98% 

(Chang et al., 2005). 

Intraendoscopical lithotripsy: 

Pulsated laser lithotripsy: 

Laser lithotripsy uses an amplified light energy, at a particular 

wavelength, which is focused into a single beam and directed onto a stone

Treatment of calcular obstructive jaundice ٨٢ 

within the bile duct. This causes plasma formation on the surface of the 

stone, allowing more absorption of laser light, and results in an acoustic 

shockwave that can fragment the stone. Laser lithotripsy can be 

performed under direct vision using cholangioscopy using mini scopes or 

can be performed under fluoroscopic control using standard equipment. 

More recently the development of software coupled to the laser allows 

differentiation of light reflected back from bile duct epithelium compared 

to light reflected back from a stone. This causes a discontinuation of the 

laser pulse, and reduces any potential thermal injury to the epithelium 

(Behjou et al., 1997). 

Electrohydraulic lithotripsy (EHL) uses direct high voltage to 

generate a shockwave, through a liquid medium, to fragment the CBDS. 

The procedure has been performed successfully under cholangioscopic 

guidance (Arya et al., 2004), or under fluoroscopic control using a 

balloon catheter (Moon et al., 2004). The advantage of direct 

visualisation is to control the shockwave being applied to the stone rather 

than on the ductal wall and so reducing the complications. However, the 

disadvantage is the cost, and the expertise required in cholangioscopic 

techniques (Hixson et al., 1992). 

Stenting as definite treatment of bile duct stones: 

Insertion of an endoprothesis may be required on a temporary basis 

for difficult to retrieve choledocholithiasis. There is a potential advantage 

of pigtail stents over straight stents in that the duodenal portion of the 

stent comes out at an angle and may keep the biliary orifice open more 

effectively. If the stent becomes occluded after several months, it still has 

the potential to keep the common bile duct stones from impacting. Pigtail 

stents also have a lower rate of stent migration. The evidence for the use

Treatment of calcular obstructive jaundice ٨٣ 

of pigtail over straight stents for definitive treatment of CBDS is however 

limited (Hui et al., 2003). 

Extracorporeal shockwave lithotripsy: 

Extracorporeal shockwave lithotripsy (ESWL) was first used 

treating gallstones in 1980s following its successful use in fragmenting 

renal calculi (Sauerbruch et al., 1986). Shock waves are generated 

outside the body using electrohydraulic, electromagnetic shockwave 

systems. First generation lithotriptors required patients to be immersed in 

a water bath and often required general anaesthesia. Subsequent 

generation of lithotriptors do not require immersion in a water bath and 

can be performed under intravenous sedation. Complete duct clearance of 

common bile duct stones following ESWL range between 83% and 93%. 

The majority of patients will require endoscopic extraction of the bile 

stone fragments following ESWL, although approximately 10% of stones 

may subsequently pass spontaneously following treatment (Sackmann et 

al., 2001). 

Chemical dissolution therapy: 

Due to the side effects of the chemical used (diethyl ether), the 

procedure was not widely practiced. The discovery of mono-octanoin as a 

cholesterol stone dissolving agent, not also effective to remove CBDS 

(Palmer and Hofmann, 1986). The chemical is administered via a 

nasobiliary catheter, T-tube or percutaneous catheter and therapy is 

required for at least several weeks making therapy less practical. The use 

of methyl tertiary butyl ether (MTBE) has advantages over other 

chemical dissolution agents, mainly that of faster kinetics (Neoptolemos 

et al., 1990).

Treatment of calcular obstructive jaundice ٨٤ 

Operative management consists of choledocholithotomy(CBD 

exploration and stone retrieval) and biliary drainage procedures. The 

latter consists mainly of choledochoduodenostomy and Roux-en-Y 

choledochojejunostomy. These 1-stage operations as superior in outcome 

and cost efficiency as compared with other interventions as laparoscopic 

cholecystectomy and ERCP ( Schwartz, 1999). 

Laparoscopic cholecystectomy emerged as a minimally invasive 

alternative to open cholecystectomy. However, by the mid 1990s, 

laparoscopic surgeons had crossed the cystic duct to tackle common duct 

stones and since have challenged the role of therapeutic ERCP.Two 

approaches to CBD exploration are possible: the transcystic and direct 

choledochotomy. The transcystic approach is preferable because it avoids 

a direct incision of the CBD with the need for subsequent suture closure 

and T tube placement (Ido et al., 1996). 

Direct choledochotomy requires considerable skill and experience in 

laparoscopic biliary surgery. Compared with transcystic removal, the 

operative time and postoperative hospital stay are longer and the 

procedural complication rate is higher. Direct complications of 

choledochotomy include bile duct leakage and bile duct strictures 

(Strasberg et al., 1996).

Hepatolithiasis ٨٥ 

Hepatolithiasis 

Primary intrahepatic lithiasis is an entity defined by intrahepatic 

stones exclusively located in the intrahepatic ducts above the emergence 

of the common bile duct. The disease is classified in two types: Eastern 

type (stones formed primarily in intrahepatic ducts) and Western type 

(stones formed in the extrahepatic bile system, usually in gallbladder, 

which migrate up to the intra-hepatic ducts) (Pereira et al., 1994). 

Hepatolithiasis appears mostly as brown pigment stones (calcium 

bilirubinate stones) but contain more cholesterol in composition. The 

disease is characterized by its intractable nature and frequent recurrence. 

Moreover, the most unfavorable complication of the disease is an 

intrahepatic cholangiocarcinoma (Shoda et al., 2003). 

These stones are rough surfaced, ovoid or faceted in shape, brown- 

to-orange in colour, soft and friable in consistency, and easily crushed to 

form ‘biliary mud’. They usually number more than 10 in a single patient. 

Microscopically, they consist of calcium salts of bilirubin, fatty acid and 

cholesterol arranged in a glycoprotein matrix. Scanning electron 

microscopy often reveals microcolonies of bacteria mixed with the 

crystals (Strichartz et al, 1991). 

Hepatolithiasis is associated with bile stasis and bacterial infection. 

E coli were the most frequent isolate followed by Klebsiella, 

Streptococcus (D), and pseudomonas. Beta-glucuronidase from E coli has 

been thought to be responsible for the formation of calcium bilirubinate 

stones by effecting hydrolysis of bilirubin glucuronide to free bilirubin, 

which is insoluble in water. Bacteroides and Clostridium were the most 

frequent isolates from the biliary tract and were shown to have beta- 

glucuronidase activity. Anaerobes were often found together with

Hepatolithiasis ٨٦ 

aerobes, suggesting the possibility of a synergistic effect that may 

influence the occurrence and development of cholangitis, which is often 

associated with hepatolithiasis. when an infection of the biliary tract 

occurs the route by which bacteria reach the region is thought to be 

hematogenous, lymphatic, or direct intraluminal ascending infection 

(Tabata and Nakayama, 1984). 

Biliary infestation by Clonorchis sinensis and Ascaris lumbricoides 

leads to inflammation of the biliary epithelium, enhancing mucin 

secretion and providing a nidus for stone formation together with 

fragments of parasites and/or their eggs (Chen et al., 1984). 

Recent investigations indicate that intrahepatic stone formation is 

based upon the dual defects of up-regulation of cholesterol synthesis and 

down-regulation of bile-acid synthesis in the liver, possibly in association 

with defective secretion of phospholipid by its canalicular transporter, 

(Shoda et al., 2006). Also, the anatomical changes of the intrahepatic 

ducts, metabolic disorders, infections, idiopathic alteration. All these 

factors may facilitate biliary stasis leading to stone formation (Pereira et 

al., 1994). 

Congenital and acquired risk factors: 

Anatomical anomaly with branching of the right segmental bile 

ducts from the left hepatic duct with is possibly associated with left 

intrahepatic stone formation. Congenital choledochal dilatation, including 

choledochal cyst, has relationship to intrahepatic stones. In contrast, 

haemolytic diseases lead to bilirubin overproduction; this is associated 

with pigment stones regardless of stone location with intrahepatic, 

extrahepatic, common bile duct and/or gallbladder. Also less common 

causes of bile stasis include Caroli’s disease (Hamlyn et al., 1976 and 

Mercadier et al., 1984) which is a rare congenital condition

Hepatolithiasis ٨٧ 

characterized by non obstructive saccular or fusiform dilatation of large 

intra hepatic bile ducts. Cholangitis, liver cirrhosis, and 

cholangiocarcinoma are its potential complications. The diagnosis depend 

on demonstrating that cystic lesions are incontinuity with the biliary tree 

by US, CT, ERCP and MRCP (Yonem and Bayraktor, 2007). 

In contrast, acquired risk factors include postoperative biliary 

strictures caused after cholecystectomy, partial hepatectomy, and liver 

transplantation, and as well as benign and malignant bile-duct stenosis. 

Benign strictures can also occur after chemo-embolization of hepatic 

tumours and chronic pancreatitis. They are implicated in the cause of 

intrahepatic stones (Nakayama et al., 1986). 

Pathology: 

Intrahepatic stones are found mainly in the intrahepatic ducts and the 

segmental branch ducts. The stones and the corresponding strictures are 

found more commonly in the left hepatic ductal system (Leung and 

Cotton, 1991). The histological changes of the bile ducts are results of 

recurrent cholangitis. These include increased fibrous tissue in the portal 

tracts, proliferation of bile ducts, chronic granulomatous changes, 

glandular proliferation and round cell and neutrophil infiltration 

extending from the portal triads into the liver parenchyma. Tumors of the 

bile ducts can range from precancerous dysplasia to cholangiocarcinoma. 

Atypical epithetlial hyperplasia and mucosal dysplasia are considered to 

be precancerous lesions. The histology of cholangiocarcinoma varies 

from a periductal spreading type to a massive type. Cellular 

differentiation ranges from early papillary adenocarcinoma to poorly 

differentiated carcinoma (Leung, 1997).

Hepatolithiasis ٨٨ 

Clinical picture: 

Intrahepatic stones lead to the syndrome of recurrent pyogenic 

cholangitis (Miquel et al., 1998), presenting with abdominal pain, fever, 

and jaundice with the typical Charcot’s triad. Jaundice is due to persistent 

obstruction of the bile duct, but such an obstruction is usually incomplete. 

A typical attack can last for hours to days, with the biliary colic located in 

the upper right quadrant. In some cases, the pain is located in the 

epigastrium. The severe state of this attack, the Raynold’s pentad which 

defined as the onset of hypotension and mental confusion in addition to 

Charcot’s triad has a poor outcome. The recurrent pyogenic cholangitis 

leads to liver abscess and/or secondary liver cirrhosis (Chijiiwa et al., 

1993). 

The clinical course is characterized by recurrent attacks of pain and 

cholangitis, requiring multiple operative interventions. The incidence of 

residual stones after surgery is 77% and the incidence of recurrent stones 

is 15% (Cheung and Lai, 1996). 

Diagnosis: 

In patients with acute cholangitis, laboratory tests may reveal a 

leukocytosis with shift to the left, elevated liver biochemistry and 

hyperamylasaemia pattern that may resemble biliary sepsis resulting from 

choledocholithiasis. A combination of abdominal ultrasound, computed 

tomography (CT) and direct cholangiography complements the imaging 

investigation for hepatolithiasis. Abdominal ultrasonography (US) is a 

non-invasive imaging method useful for screening in hepatolithiasis. The 

stones are seen in the form of strong echoes with acoustic shadows. 

(Choi, 1989). CT demonstrates the extent of ductal dilatation and liver 

damage, such as abscess formation, relative atrophy and the hypertrophy

Hepatolithiasis ٨٩ 

of different liver lobes. Sometimes the pigment stones may be difficult to 

identify because of a CT density similar to that of the scarred or damaged 

liver. CT provides a good preoperative assessment of the disease and may 

help to localize obstructed segmental ducts not filled or visualized by 

direct cholangiography. Technetium-labelled HIDA scanning serves to 

evaluate the function of the underlying liver tissue associated with ductal 

stones. A delay in the excretion of the isotope occurs in the affected 

segments secondary to biliary obstruction and stasis, with subsequent 

pooling of the isotope in the affected bile ducts (Pavone et al., 1996). 

Endoscopic retrograde cholangiopancreatography (ERCP) and 

percutaneous transhepatic cholangiography (PTC) are the two major 

modalities for direct cholangiography. They serve to define the extent of 

ductal involvement, especially ductal stricture or obstruction. PTC is 

indicated to define ductal anatomy and the extent of disease, especially in 

patients who have undergone prior biliary-enteric anastomosis or when 

ERCP fails.Recent developments in non-invasive imaging include 

magnetic resonance cholangiopancreatography (MRCP). MRCP produces 

high-quality images without the injection of contrast agents, and the 

sensitivity in defining the stones and strictures is similar to that of 

conventional direct cholangiography (Liessi et al., 1996). MRCP is less 

operator dependent and is easily reproducible. It provides additional 

information on adjacent soft tissue not obtained from ERCP (Barish et 

al., 1996). The major limitation of MRCP for the evaluation of biliary 

disease is that it cannot offer therapeutic options (Outwater and 

Gordon, 1994 and McDermott and Nelson, 1995). 

Treatment: 

Stones in the intrahepatic biliary tree offer especially difficult 

treatment challenges, especially if the bile ducts are abnormal (stricture or

Hepatolithiasis ٩٠ 

dilatation). The primary goals of treatment are to eliminate attacks of 

cholangitis and to stop the progression of the disease (which leads to 

biliary cirrhosis) (Van Sonnenberg et al., 1986). Surgery has a primary 

role in hepatolithiasis because hepatolithiasis tends to recur, so that 

multiple sessions of the endoscopic approach (i.e. 2-3 times per year) are 

often required (Choi et al., 1982). There is no definitive treatment, 

reflecting the complicated nature of the disease and various patients’ 

conditions (Jeng et al., 1999). 

Endoscopic approach: 

Since obstruction and infection fasten the progression of recurrent 

pyogenic cholangitis, therapeutic goals include the complete clearance of 

biliary calculi and debris and adequate drainage of the affected segments 

of the biliary tree. Although ERCP is useful in the assessment of 

anatomy, its role in the treatment of hepatolithiasis is limited. The 

treatment of primary intrahepatic stones via the transpapillary route is 

difficult if not impossible in many circumstances because of strictures, 

peripheral stone impaction, or ductal angulation (Choi and Wong, 1986). 

Percutaneous approach: 

With technical development of percutaneous transhepatic drainage 

and dilation procedures, it is now possible to place catheters into the 

intrahepatic duct without laparotomy and to dilate the route up to 18 Fr in 

one stage. Moreover, when hepatolithiasis is not confined to one segment 

or lobe of the liver, the success rate of PTCS for complete stone removal 

and the rate of subsequent stone recurrence are comparable to those of 

surgical treatment of hepatolithiasis. However, the efficacy of PTCS for 

complete removal of stones is limited in patients with severe biliary 

strictures (Cheung et al., 2003).

Hepatolithiasis ٩١ 

Techniques of lithotripsy: 

Extracorporeal shock-wave lithotripsy used in conjunction with 

percutaneous radiological techniques was applied to the difficult stone 

problem associated with hepatolothiasis, with a success rate >90% 

(Adamek et al., 1999). 

Clinical management of cholangitis associated with 

hepatolithiasis: 

The conservative management of patients includes intravenous fluid, 

broad-spectrum antibiotics and correction of the underlying 

coagulopathy. Close monitoring is necessary to detect deterioration of the 

general condition. Potent analgesics may be required (Fan et al., 1991). 

Non-operative biliary drainage procedures play an important role in 

the management of acute cholangitis associated with hepatolithiasis, 

especially for those with concomitant common duct stones. Urgent ERCP 

and biliary drainage with a nasobiliary catheter or indwelling stent have 

reduced the overall mortality of acute cholangitis to 4.7%. A new 

rhodamine-6G dye laser, initially used for common duct stones, can be 

applied to the management of hepatolithiasis (Ell et al., 1993). With the 

laser system, intraductal stones can be fragmented by either the peroral or 

the percutaneous approach (Neuhaus et al., 1994). 

Management of biliary stricture: 

Biliary strictures predispose to recurrent stones or a failure of ductal 

clearance. Operative dilatation of strictures is needed (Lau et al., 1987). 

Successful treatment with non-operative balloon dilatation was performed 

in hepatolithiasis and intrahepatic biliary strictures (Jeng et al., 1990).

Hepatolithiasis ٩٢ 

Hepatic resection for localized disease: 

Hepatic resection is indicated for localized intrahepatic stones or 

biliary strictures when the affected liver segment is already atrophic or 

when an abscess is present in the surrounding parenchyma (Sato et al., 

1980 and Choi and Wong, 1986). With a localized intrahepatic 

cholangiocarcinoma, hepatic resection offers a chance for cure (Chen et 

al., 1989). When intrahepatic stones are restricted to the left side of the 

liver, lobar resection or left lateral segmentectomy ensures removal of the 

source of recurrent infection. Hepatic lobectomy, however, is rarely 

performed when stones are located in the right lobe, because of a high 

complication rate (Fan et al., 1993). 

Prevention of stone and stricture recurrence: 

Even in the absence of a significant biliary stricture, improvement of 

biliary drainage helps to minimize the chance of stone recurrence. 

Permanent biliary drainage ranges from sphincterotomy and surgical 

sphincteroplasty to surgical bilioenteric anastomosis at different levels of 

the biliary system, including choledochoduodenostomy, and 

hepaticojejunostomy constructed at the hepatic confluence, the left 

hepatic duct or the left lateral inferior duct. Creation of a 

hepaticocutaneous jejunostomy allows ready access to the bile ducts. The 

surgical anastomosis is made at the bifurcation, one end of the jejunal 

loop being brought to the skin surface via a straight and short route. The 

access enables repeated sessions of both stricture dilatation and stone 

extraction. After the completion of therapy, the stoma can be closed and 

buried subcutaneously (Gott et al., 1996). The stoma provides the option 

for accessing the conduit percutaneously or re-opening the stoma in case 

of stone recurrence (Fan et al., 1993).

Relationship between Ascaris and biliary stones ٩٣ 

Relationship between Ascaris and biliary stones 

Classical biliary symptoms occur if the large-sized Ascaris worm 

migrates into the bile duct. Patients may present with typical biliary colic, 

acute cholangitis, acalculous cholecystitis (Schulman, 1977 and Khuroo 

et al., 1990), hepatic abscess (Parodi-Hueck et al., 1972) or acute 

pancreatitis (Leung et al., 1987 and Khuroo et al., 1992). Clinical 

symptoms are related to the location of the worm. Biliary colic or 

pancreatitis are often related to a worm impacted at the ampulla. Worms 

inside the bile ducts may cause cholangitis or cholecystitis. In endemic 

areas, ascariasis may cause stones in the biliary tract (Goldman and 

Brandborg, 1996). 

Biliary and pancreatic Ascariasis are complications that often mimic 

the presentation of more common illnesses of the hepatobiliary system. 

Biliary obstruction occurs when: 1) the worms travel within the Biliary or 

pancreatic ducts, causing a mechanical obstruction; 2) the worms cause a 

spasm of the sphincter of Oddi; or 3) the worms serve as a nidus for stone 

formation (Schuster et al., 1977). 

History, physical examination and laboratory tests can not be used to 

distinguish between Ascaris and gallstone-induced biliary diseases. 

Serum eosinophilia may be significant in the larval migration phase but is 

rarely seen in established chronic infection. Possible exceptions are when 

a patient vomits an Ascaris worm during an attack of biliary colic or 

passes a large worm per rectum. Definite diagnosis is most easily 

established by characteristic eggs in stool specimens. Worms in the 

intestinal tract may be outlined by barium contrast studies. Abdominal 

ultrasound is a very sensitive method of diagnosing biliary ascariasis, 

with the typical appearance of a ‘four-line’ sign (Price and Leung, 

1988). Ultrasound can also be used to monitor the migration of the worm

Relationship between Ascaris and biliary stones ٩٤ 

(Kamath et al., 1986). Endoscopy or ERCP may reveal an adult worm 

ranging in length from a few centimeters to over 20cm (Chen et al., 1986 

and Manialawi et al., 1986). Cholangiography demonstrates a parallel, 

cylindrical filling defect in the bile ducts. Injection of contrast can 

occasionally prompt the worm to migrate out of the bile duct (Leung, 

1997).

Relationship between clonorchis sinensis and biliary stones ٩٥ 

Relationship between clonorchis sinensis and 

biliary stones 

When larvae of C. sinensis reach the biliary system and mature, the 

flukes provoke pathological changes, both as a result of local trauma and 

of toxic irritation. The appearances vary with duration and severity of the 

infestation, but they are sufficiently distinctive and characteristic to allow 

a classification into four phases as follows; 1st phase, desquamation of 

epithelial cells, 2nd phase, hyperplasia and desquamation of epithelial 

cells, 3rd phase, hyperplasia and desquamation of epithelial cells, and 

adenomatous tissue formation, and 4 th phase, marked proliferation of the 

periductal connective tissue with scattered abortive acini of epithelial 

cells and fibrosis of the wall of the bile duct (Min, 1984). Heavy 

infestation results in obstructive jaundice and has a close relationship 

with recurrent pyogenic cholangitis and cholangiocarcinoma (Lim, 1990). 

Biliary infestation by Clonorchis sinensis leads to inflammation of 

the biliary epithelium, enhancing mucin secretion and providing a nidus 

for stone formation together with fragments of parasites and/or their eggs 

(Chen et al., 1984). 

Clonorchiasis is a parasitic disease of the bile ducts that occurs in 

endemic areas after ingestion of the raw flesh of freshwater fish. The 

echogenic foci which present in US distinguished from stones because 

they were fusiform, weak in echogenicity, and floated with a change in 

position. Clonorchiasis should be considered when sonography discloses 

the characteristic pattern of bile duct dilatation with increased wall 

echogenicity and non shadowing, discrete, echogenic foci in the 

gallbladder lumen (Lim et al., 1989).

Relationship between clonorchis sinensis and biliary stones ٩٦ 

The diagnosis of clonorchiasis is confirmed by the presence of an 

adult worm in duodenal aspirate or bile or the presence of ova in the 

stool. Abdominal ultrasound and CT scanning demonstrate predominantly 

intrahepatic biliary disease with diffuse dilatation and clubbing. Bile duct 

fibrosis may be seen as increased echogenicity of ultrasound and 

thickening on CT. Individual Clonorchis worms may produce an 

echogenic focus without shadowing in the peripheral ducts, but in general 

they are too small to be seen by non-invasive imaging. ERCP is useful in 

the diagnosis of patients with jaundice. Four patterns have been observed: 

Diffuse tapering of the intrahepatic ducts with dilatation indistinguishable 

from that associated with extrahepatic obstruction; a solitary cyst similar 

to a liver abscess cavity or retention cyst; multiple cystic dilatations of the 

intrahepatic ducts, producing a mulberry-like appearance that is 

characteristic of liver fluke infestation; and a combination of these 

findings, with extensive cystic dilatation in some areas of the liver and 

biliary duct ectasia in others (Goldman and Brandborg, 1996). 

Cholangiography may also show a characteristic appearance of 

Clonorchis worms as filling defects within the ductal system. Depending 

on the projection, one of five patterns may appear on the cholangiogram: 

filamentous, wavy, curled-up, elliptical wavy and elliptical-shaped filling 

defects (Leung et al., 1989). Because of the location of the worms, the 

diagnosis should be suspected if there is significant peripheral ductal 

dilatation in the absence of extrahepatic ductal dilatation or stricture. 

(Leung, 1997).

Relationship between opisthorchiasis and biliary stones ٩٧ 

Relationship between opisthorchiasis and biliary 

stones 

Humans acquire opisthorchiasis by eating raw fish containing 

infective metacercariae. The flukes reside inside the small bile ducts and 

gallbladder and do not undergo systemic migration. The flukes are 

occasionally found in the pancreatic duct (Ming-gang et al., 1983). As in 

C. sinensis the pathological changes include: Dilated bile ducts with 

thickened walls; desquamation of bile duct epithelium followed by 

proliferative hyperplasia, fibrosis and goblet cell metaplasia, and 

development of cholangiocarcinoma (Upatham et al., 1985). 

The pathological changes are more or less related to the intensity 

and the duration of the infection, and are commonly seen in older patients 

with a large number of flukes. The pathogenesis is due to the mechanical 

irritation by the flukes and some toxic substances produced by them. 

(Harinasuta et al., 1984). 

There is a significant increase in the frequency of biliary sludge 

seen in the gall bladder in heavy O. viverrini infections (Elkins et al., 

1990 and Mairiang et al., 1992). Eggs and worm fragments have been 

observed in the nidus of gallstones and in sludge supporting the role of 

the parasite in initiating cholelithiasis (Riganti et al., 1988). Opisthorchis 

infection is associated with several hepatobiliary diseases including 

cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and 

cholelithiasis (Sripa, 2003). 

The histochemical findings on the calcium and bilirubin coatings on 

the opsithorchiasis eggs support this hypothesis. The presence of calcium 

coating on the outer surface of the parasite eggshell suggests that the eggs 

may act as a nucleus for stone formation. This may be similar to

Relationship between opisthorchiasis and biliary stones ٩٨ 

peripheral calcification of existing cholesterol stones (Moore, 1990). 

Since calcium is an active element, and can precipitate several bile 

constituents including bilirubin, carbonate and phosphate-major 

components of pigment stones (Rege, 2002). Mucin secreted by biliary 

epithelial cells has been recognized as an important local factor in 

gallstone pathogenesis. This process can produce mature pigment stones 

as generally described (Cahalane et al., 1998). 

Heavy Opisthorchis infection can induce poor emptying of the 

gallbladder (Mairiang et al., 1993). In addition, a recent report has 

shown that severe fibrosis of the gallbladder wall is the main 

histopathology of chronic opisthorchiasis (Sripa et al., 2003).

Relationship between Echinococcosis and biliary stones ٩٩ 

Relationship between fascioliasis and biliary 


Fascioliasis can be characterized by three distinct phases: Invasive 

(acute) phase; latent phase, and chronic phase. The invasive phase 

corresponds to the penetration and migration of the juvenile, immature 

parasites through the liver parenchyma with the production of tissue 

necrosis, acute inflammation and hemorrhage (Kayabali et al., 1992). 

The invasive phase occurs during the first 3 months after ingestion of the 

encysted metacercariae. After a period, healing takes place and evidence 

of tissue destruction disappears completely (Dawes, 1963). The chronic 

phase is established when the flukes gain access to the biliary system. 

The fasciola produces biliary epithelial hyperplasia. Thickening and 

dilatation of the ducts and the gallbladder wall occur. Other complications 

of long standing fascioliasis in humans including portal and biliary 

fibrosis, cirrhosis and portal hypertension (Rivero and Marcial, 1989). 

However, the etiological relationship between fasciola infection and 

cirrhosis is not clear (Jones et al., 1977). 

Associated lithiasis of the bile ducts or of the gallbladder is frequent 

(Chen and Mott 1990 and Wong et al., 1985). Eggs or fragments of 

dead parasites may constitute the nucleus for calculi. Acute pancreatitis as 

a complication of biliary fascioliasis has been reported (Maroy et al., 

1987). ERCP and sphincterotomy may be used to extract F. hepatica 

parasites from the biliary tree (Veerappan et al., 1991).

Relationship between Echinococcosis and biliary stones ١٠٠ 

Relationship between Echinococcosis and biliary 


Presenting features depend not only on the organ involved, but also 

on the size of the cysts and their position within the organ, the mass effect 

within the organ and upon surrounding structures, and complications 

related to cyst rupture and secondary infection. Common complications 

include rupture into the biliary tree with secondary cholangitis, biliary 

obstruction by daughter cysts or extrinsic compression (Ammann and 

Eckert, 1996).

Endoscopic retrograde cholangiopancreatography ١٠١ 

Endoscopic Retrograde 

Cholangiopancreatography (ERCP) 

Historical aspect: 

McCune et al 1968 First successful cannulation of bile 

and pancreatic duct using an 

endoscope. 

Demling et al 1974 First papillotomy 

Classen and Demling 1974 (Using a high frequency diathermy 

snare) and stone extraction from the 

common bile duct. 

Kawai et al 1973 First papillotomy in Japan (using a 

diathermy blade). 

Zimmon et al 1975 New therapeutic trial for patients 

with bile duct stones and removal 

after sphincterotomy. 

Table (2): Historical aspect of ERCP 

ERCP was first reported in 1968 and was soon accepted as a safe, 

direct technique for evaluating biliary and pancreatic disease (Kawai et 

al., 1974). ERCP is not indicated in the evaluation of abdominal pain of 

obscure origin in the absence of other objective findings, suggesting 

biliary-tract disease (Pasricha, 2002). It is valuable in diagnosis and 

treatment of pancreatic and biliary diseases with less morbidity than 

surgery (Cohen et al., 1996). 

Indications: 

Biliary tract disease: 

Cholangioscopy at ERCP is used infrequently but may be helpful in 

the management of bile-duct stones and in assessing suspected 

malignancies (Kozarek et al., 2003). Choledocholithiasis is the most

Endoscopic retrograde cholangiopancreatography ١٠٢ 

common source of biliary obstruction. The sensitivity and the specificity 

of ERCP for detecting common duct stones is over 95%; small stones 

occasionally are missed. Preoperative ERCP may be indicated when 

persistent jaundice, elevated liver enzymes, persistent or worsening 

pancreatitis, or cholangitis is present (NIH State-of-the-Science, 2002). 

Careful injection of contrast and early radiographs may help to 

detect stones, which avoids overfilling the ducts or pushing stones into 

the intrahepatic ducts. The accidental instillation of air bubbles into the 

duct by the injection catheter can lead to misdiagnosis of stones. ERCP 

and stone extraction can be performed after surgery (figure 17) (Eisen et 

al., 2001). 

Figure (17): Stone during extraction from the common bile duct by basket forceps 

(Courtesy of Dr. Tarik Zaher) 

Endoscopic sphincterotomy and stone extraction is successful in 

more than 90% of cases, with a complication rate of approximately 5% 

and a mortality rate of less than 1% in expert hands (Carr-Locke, 2002). 

In cases of failed primary biliary cannulation, pre-cut (e.g. needle knife) 

papillotomy or a combined percutaneous/endoscopic approach may be 

necessary. The complication rates associated with these techniques are

Endoscopic retrograde cholangiopancreatography ١٠٣ 

higher than for standard extraction techniques, reflecting greater technical 

difficulty (Freeman et al., 1996). 

An alternative to biliary sphincterotomy is balloon dilation of the 

biliary sphincter (balloon sphincteroplasty). This may be an alternative to 

biliary sphincterotomy in selected patients with common bile duct stones, 

e.g. underlying coagulopathy, patients with a higher risk of post-ERCP 

pancreatitis (Baron and Harewood, 2004). Stone removal is usually 

accomplished with soft Fogarty-type balloons or wire baskets. 

Occasionally, large or impacted stones may be difficult to remove. 

Fragmentation of large stones and the management of impacted baskets 

with entrapped stones can be facilitated by the use of mechanical 

lithotriptors (Leung and Tu, 2004). If stone removal is unsuccessful, 

biliary decompression should be accomplished with a stent or a 

nasobiliary drain (Pereira-Lima et al., 1998). 

Malignant and benign biliary strictures: 

ERCP is useful in the assessment and the treatment of malignant 

biliary obstruction. The presence of a ‘‘shelf ’’ instead of a smooth taper 

to the stricture can suggest a malignant etiology (although the ‘‘shelf ’’ 

can be present in patients with a normal sphincter of Oddi). Biopsies, 

brushings, and FNA are a definitive tissue diagnosis, but the combined 

sensitivity is no higher than 62% (Hawes, 2002). 

ERCP is indicated for the evaluation and the treatment of benign 

bile-duct strictures, congenital bile-duct abnormalities, and postoperative 

complications. This applies to patients with biliary obstruction after liver 

transplantation (Morelli et al., 2003 and Shah et al., 2004). Endoscopic 

sphincterotomy may successfully treat cholangitis or pancreatitis because 

of a choledochocele and choledochal cysts. Benign biliary strictures may 

be dilated with hydrostatic balloons or a graduated catheter passed over a

Endoscopic retrograde cholangiopancreatography ١٠٤ 

guidewire. Indications for endoscopic dilation of benign strictures include 

postoperative strictures, dominant strictures in sclerosing cholangitis, 

chronic pancreatitis, and stomal narrowing after choledochoenterostomy 

(Costamagna et al., 2003). Stent placement may be used to maintain 

patency after initial dilation (Draganov et al., 2002). 

Serial endoscopic dilations and stent placement can be used to 

achieve prolonged ductal patency in benign strictures secondary to 

chronic pancreatitis (Kahl et al., 2003). Although early results with this 

technique in patients with biliary strictures secondary to chronic 

pancreatitis are encouraging, long-term results tend to be poor, with 

mixed success rates but with some as low as 10% (Barthet et al., 1994). 

Strictures that develop in patients with primary sclerosing cholangitis 

(PSC) tend to respond well to endoscopic therapy, either with balloon 

dilation alone or in combination with the placement of endoscopic stents 

(Kaya et al., 2001). 

Pancreatic disease: 

Recurrent acute pancreatitis: 

ERCP should be reserved for treatment of abnormalities found by 

less invasive imaging techniques. EUS and MRCP allow pancreatic and 

biliary anatomy to be defined non-invasively, without risk of pancreatitis 

and radiation exposure, and may detect microlithiasis, 

choledocholithiasis, unsuspected chronic pancreatitis, and, in some cases, 

pancreas divisum (failure of fusion of the dorsal and ventral pancreatic 

ducts),and annular pancreas (Tandon et al., 2001). ERCP may still be 

required to obtain definitive imaging of the ductal anatomy. The need to 

perform manometry, minor papilla cannulation, pancreatic 

sphincterotomy, or pancreatic-duct stent placement should be anticipated 

(Kozarek, 2002).

Endoscopic retrograde cholangiopancreatography ١٠٥ 

In properly selected patients, minor papilla sphincterotomy may 

prevent further attacks of acute recurrent pancreatitis (Gerke et al., 

2004). In patients with acute recurrent pancreatitis when compared with 

patients with chronic pancreatitis or pancreatic-type pain only, stent 

placement of the minor papilla without sphincterotomy may produce 

results equivalent to minor papilla sphincterotomy (Heyries et al., 2002). 

Minor papilla manipulation may carry an increased risk of post-ERCP 

pancreatitis (Fennerty et al., 2001). 

Chronic pancreatitis: 

ERCP provides direct access to the pancreatic duct for evaluation 

and treatment of symptomatic stones, strictures and pseudocysts. 

Pancreatic-duct strictures often can be successfully treated with dilation 

and stent therapy. Pain relief during and after stent placement varies 

widely (Lehman, 2002). 

Obstructing pancreatic stones may contribute to abdominal pain or 

acute pancreatitis in patients with chronic pancreatitis. Pancreatic 

sphincterotomy and stone removal can be difficult because of underlying 

pancreatic duct strictures and may require extracorporeal shock wave 

lithotripsy (ESWL) to fragment the stones before endoscopic removal. In 

some patients, stones may be impossible to remove endoscopically 

(Brandabur et al., 2002). 

ESWL for pancreatic stones is a difficult procedure even in 

experienced hands, has significant risks, and patients may require therapy 

(>10 sessions) to obtain successful clearance of the duct (Brand et al., 

2000) While some investigators have reported high success rates with this 

technique (with or without pancreatic stents), others have had less 

impressive results, with improvement in pain seen in 35% of patients 

despite successful ESWL (Holm et al., 2003).

Endoscopic retrograde cholangiopancreatography ١٠٦ 

Pancreatic duct leaks: 

Pancreatic-duct disruptions or leaks occur as a result of acute 

pancreatitis, chronic pancreatitis, trauma, or surgical injury. Pancreatic 

leaks can result in pancreatic ascites, pseudocyst formation, or both. 

Pancreatic leaks can often be treated with transpapillary stents (Bracher 

et al., 1999). More severe duct disruptions sometimes can be treated by 

‘‘bridging’’ pancreatic stents to reconnect otherwise dislocated segments 

of pancreatic parenchyma (Telford et al., 2002). 

Pancreatic fluid collections: 

ERCP can be used to diagnose and treat pancreatic fluid collections, 

such as acute pseudocysts, chronic pseudocysts, and pancreatic necrosis. 

Fluid collections that communicate with the pancreatic duct are amenable 

to transpapillary therapy. Non communicating benign pancreatic fluid 

collections can be drained via a transgastric or a transduodenal approach. 

Pseudocysts that communicate with the pancreatic duct, including cysts in 

the tail of the pancreas, can be drained via a transpapillary approach. 

Pancreatic duct stent placement, pancreatic sphincterotomy, or a combi- 

nation of these techniques can allow successful non surgical resolution 

(Sharma et al., 2002). 

Pancreatic cancer and other pancreatic malignancies: 

Pancreatic malignancies usually produce both biliary and pancreatic- 

duct strictures (‘‘double-duct sign’’) (figure 18). High-resolution 

contrast-enhanced CT, MRCP, and EUS are now commonly performed in 

patients with suspected pancreatic cancer (Baron et al., 2003).

Endoscopic retrograde cholangiopancreatography ١٠٧ 

Figure (18): Double-duct sign in ERCP (quoted from Albert and Rilemann, 

Ampullary adenomas: 

2002). 

Adenomas in the region of the major duodenal papilla can be both 

diagnosed and treated via ERCP. Snare ampullectomy, combined with 

biliary and/or pancreatic sphincterotomy, allows complete removal of the 

adenoma in approximately 80% to 90% of patients without intraductal 

extension. Recurrences are more common in patients with familial 

adenomatous polyposis syndrome (Norton et al., 2002). 

Preparation and technique: 

(i) Preparation: 

Preparation for ERCP involves assembly of a skilled team that 

includes physician (S), nursing personnel, and a radiology technician. A 

quality flouroscopic unit is needed. A wide variety of catheters, guide 

wires, stone extraction balloons and baskets, sphincterotomes, stents, 

drainage catheters, lithotripters, and tissue sampling devices should be 

available (Whitehouse et al., 1996).

Endoscopic retrograde cholangiopancreatography ١٠٨ 

Patient preparation includes an updated history and physical 

examination, Recent laboratory studies in the form of complete blood 

count, liver function test, serum amylase and/or lipase and coagulation 

studies.), non invasive imaging of the upper abdomen with abdominal 

ultrasound or Computed Tomography (CT) scan, non steroidal anti- 

inflammatory drugs should be avoided for 7 days prior to the 

procedures,Informed consent for ERCP must be obtained and Patient 

should be fasting for 8-12 hours before procedures (Sherman and 

Lehman, 1999 and Ways, 2000). 

Coagulopathy should be corrected if sphincterotomy is 

anticipated.Antibiotic prophylaxis is indicated in the setting of suspected 

biliary obstruction, known pancreatic pseudocyst, or ductal leaks (Hirota 

et al., 2003). 

Patients with known or suspected allergy to iodinated contrast agents 

(e.g. given for computed tomography or urograms) should receive steroid 

prophylaxis prior to the procedure, and non iodinated contrast should be 

used for imaging (Draganov et al., 2000). 

(ii) ERCP technique: 

Position of the patient: 

The standard patient's position for ERCP is prone (chest and 

abdomen facing the table), with the left hand behind the patient's back. 

This position offers the best access for anterior-posterior fluoroscopy and 

X-ray imaging. This position can be modified for patients who cannot 

tolerate being prone (e.g. pregnant women, and those with painful limbs 

or recent surgical incisions): A semi-prone or lateral position may have to 

be accepted in these circumstances. Obese patients are vulnerable to sleep

Endoscopic retrograde cholangiopancreatography ١٠٩ 

apnea, and frequently develop hypoxia under conscious sedation (Jastak 

et al., 1991). 

Positioning "tricks'for Special Situations: When the intubatation of the 

pylorus with the duodenoscope is difficult, roiling the patient 90 degrees 

from the prone into the left lateral position is often helpful. Especially 

when the patient has a large stomach, or when much of the stomach has 

herniated into the chest. Changing the patient's position can also improve 

one's chances of intubating the afferent limb after Billroth-I1 gastrectomy 

(Wright et al., 2002). 

When the pancreatic duct proves difficult to fill completely during 

pancreatography, remove the catheter, withdraw the endoscope, and 

quickly roll the patient on to his or her back. Provided that some contrast 

remains in the duct, the tail will usually fill by gravity with this maneuver 

(Tham et al., 2003). 

In pregnant women, the fetus should be protected from irradiation by 

lead shielding; obviously, this is easiest in the first trimester and hardest 

in the last. It should be remembered that in most X-ray tables, the X-rays 

are generated from below and are detected above the patient. ERCP in 

pregnancy is safe and effective (for appropriate indications) (Jamidar et 

al., 1995). 

Sedation: 

Conscious Sedation versus General Anaesthesia (GA). Most 

endoscopic procedures can be accomplished using standard conscious 

sedation such as diazepam, but increasingly we are using GA for 

prolonged procedures, and when patients prove difficult to sedate 

(Raymondos et al., 2002). General anesthesia is normally required for 

ERCP in the following patient groups: infants and children under 16

Endoscopic retrograde cholangiopancreatography ١١٠ 

years of age, the developmentally delayed, uncooperative patients (eg, 

confused, demented, alcoholic), patients with a history of intolerance to 

conscious sedation and those at risk for ventilator or the morbidly obese 

(Koshy et al., 2000). 

Many patients with suspected type III sphincter of Oddi dysfunction 

(SOD) require GA, as they are typically chronic users of narcotic 

analgesia and benzodiazepine (Wehrmann et al., 1999). 

Introduction of the endoscope: 

The side viewing endoscope is introduced into the hypopharynx; the 

tip is advanced blindly to the cricopharyngeous, causing the patient to 

swallow. The duodenoscope is furtherly introduced into the esophagus, 

the stomach and the duodenum (Waye, 2000). 

Then a brief endoscopic examination of these segments was done. 

The finding of a large ulcer or neoplasm may cancel the need for ERCP. 

Other findings such as varices, a pseudocyst pressing on the gut wall, or 

oedema of the medial wall of the duodenum help to quantitate or localize 

disease processes (Sherman and Lehman, 1999). 

Carbon dioxide insufflation during ERCP significantly reduces 

postprocedural abdominal pain. No side effects were observed. Carbon 

dioxide should be the standard gas used for insufflation in ERCP 

(Bretthauer et al., 2007). 

Approaching the papilla: 

No cannulation of the papilla is attempted until the papilla is seen 

squarely and up close. Once it is found and the tip of the endoscope is 

perfectly aligned with the pyloric channel, the tip of the endoscope must 

be deflected up into the descending duodenum. Then straightening of the 

endoscope is done to get straight scope position which is done by 90-180

Endoscopic retrograde cholangiopancreatography ١١١ 

clockwise rotation of the shaft of the endoscope while its tip is deflected 

upwards, so that the descending duodenum is entered, and advancing the 

tip of the endoscope downward which is better achieved paraodoxically 

by withdrawing the endoscope (Mani et al., 1996). 

Sometime, it is difficult to achieve the “straight scope position” and 

in this condition the papilla is reached by advancing the shaft of the 

endoscope while the patient is in supine position using the “long loop 

technique”. However, it is unpleasant to the patient, and the fine 

movements of the tip are transmitted less effective as the control wire for 

tip deflection and catheter elevation are stretched. However, long loop 

route may sometimes be the only method of getting (face on) to the 

papilla, which is high up under the superior duodenal angle (Whitehouse, 

1996). 

Location and cannulation of the papilla: 

Biliary cannulation: 

The use of pancreatic techniques is a newer approach to improve 

safety and success at biliary access.Techniques include placement of a 

pancreatic guidewire, or a cannula, to aid cannulation, and/or placement 

of a pancreatic stent to reduce the risk of pancreatitis. Placement of a 

guidewire deep into the main pancreatic duct may facilitate cannulation 

of the bile duct (figure 19) with a second device beside the pancreatic 

wire. The pancreatic wire serves a number of functions, including to open 

a stenotic papillary orifice, to stabilize the papilla, to lift it toward the 

working channel, to straighten the pancreatic duct and the common 

channel, to drain the pancreatic duct, potentially to minimize repeated 

injections into the pancreatic duct, and to allow access for placement of a 

pancreatic stent if felt necessary (Dumoncea et al., 1998).

Endoscopic retrograde cholangiopancreatography ١١٢ 

Figure (19): Cannulation of CBD (Courtesy of Dr. Tarik Zaher) 

Major papilla pancreatic cannulation: 

Major papilla pancreatic cannulation techniques are similar to those used 

for biliary cannulation, with exceptions that the smaller size, the duct 

tortuousity, and the multiple side branches render deep wire passage more 

difficult in some cases. As biliary cannulation may be aided by placement 

of a pancreatic guidewire, placement of a biliary guidewire may serve to 

straighten the common channel and to improve pancreatic access. 

Pancreatic cannulation may either be facilitated or rendered more difficult 

by prior biliary sphincterotomy. Repeated access of the pancreatic duct 

immediately after biliary sphincterotomy for sphincter of Oddi 

dysfunction has 98% success rate (Tarnasky et al., 1998). 

Minor Papilla cannulation: 

The minor papillary orifice typically is located cephalad to the major 

papilla at approximately the 1 to 2 Oclock position to the major papilla as 

seen through a duodenoscope. The approach to minor papilla cannulation 

varies with anatomy (presence or absence of pancreas divisum) 

(Catalano et al., 2003).

Endoscopic retrograde cholangiopancreatography ١١٣ 

Initial cannulation often is optimal from the long or semi-long 

endoscope position. Although techniques are similar to those used for 

major papilla biliary and pancreatic cannulation, small-caliber guidewires 

and cannulas often are required. Common methods include primary 

cannulation with a 0.02-inch hydrophilic guidewire and use of a needle- 

tip catheter. Secretin can be used to facilitate pancreatic secretion and to 

enhance identification of the minor papilla and its orifice; in previously 

failed minor papilla cannulation, administration of synthetic porcine 

secretin improved cannulation from 7.7% in the placebo group to 81.3% 

in the secretin group (Devereaux et al., 2003). Methylene blue and 

indigo carmine have been sprayed onto the minor papilla after secretin 

administration to help identify the orifice (Park et al., 2003). Needle- 

knife papillotomy has been used to access minor papilla (Song et al., 

2004). EUS has been used to inject methylene blue into the dorsal 

pancreatic duct to aid in localization of an otherwise invisible minor 

papilla (Dewitt et al., 2004). 

Pharmacologic aids to cannulation: 

A number of drugs have been used to facilitate biliary and pancreatic 

duct cannulation. Glugacon and hysocyamine often are used to relax 

motility and have been found to be of similar efficacy (Lahoti et al., 

1997). Use of a cholecystokinin analogue helped in obtaining a 

cholangiogram after an initially failed ERCP, with visualization of the 

bile duct and deep cannulation in 50% of patients (Weston et al., 1997). 

Wehrmann et al. (2001) found that the uses of cholecystokinin and 

nitroglycerine spray are of no significant advantage. 

Injection of the contrast medium and filming: 

Standard contrast media (e.g. meglumine diatrizoate) at a 50% to 

60% concentration (full-strength) is used for pancreatography, while 25%

Endoscopic retrograde cholangiopancreatography ١١٤ 

to 30% (half-strength) concentration is recommended for 

cholangiography. Biliary stricture detail is better defined with full- 

strength contrast, however. Non-ionic and lower osmolality contrast 

media, which are more expensive, offer no safety advantage. Contrast 

media injection is done with continuous fluoroscopic monitoring. The 

extent of ductal filling should be correlated with the clinical need to know 

the ductal anatomy (Whithouse et al., 1996). 

Complete pancreatography involves filling of the main duct and side 

branches to the tail. High-resolution fluoroscopy is required to see such 

detail. In settings where there is excess overlying gas or obesity, under 

filling of the pancreatic duct is recommended to avoid acinarization 

(instillation of contrast media into the pancreatic parenchyma). For a very 

dilated duct, initial aspiration of fluid will allow better contrast 

visualization without over distention of the duct (Sherman and Lehman, 

1999). 

Contrast media mixes slowly with gallbladder bile and final films 

are best taken in the supine position after endoscope withdrawal (and 

additional time for mixing with gallbladder contents). Occasionally, 

delayed gallbladder films taken 4 to 12 hours after completion of the 

procedure allows for passage of intralumenal gas, giving better diagnostic 

film quality (Hawes and Sherman, 1995). 

In setting of tight biliary strictures, limited contrast filling upstream 

should be done until catheter access above the stricture is achieved. 

Similarly, limited pseudocyst filling should be done unless immediate 

drainage is certain. Several views of each ductal position are 

recommended both in the limited filling and more completely filled state 

(Varghese, 2000).

Endoscopic retrograde cholangiopancreatography ١١٥ 

Sphincter of Oddi manometry: The gold standard for diagnosing of 

sphincter of Oddi dysfunction (SOD) is by sphincter of Oddi manometry 

(SOM) performed during ERCP. Intravenous midazolam and meperidine 

do not alter sphincter pressure and both may be given for conscious 

sedation prior to ERCP with SOM. All drugs that relax (e.g. 

anticholinergics, nitrates, calcium channel blockers, glucagons) or 

stimulate (e.g. certain narcotics, cholinergic agents) should be avoided for 

at least 8 to 12 hours prior to SOM (Waye, 2000). Sphincter of Oddi 

manometry is associated with a markedly increased rate of pancreatitis 

and should be performed by experienced operators in well-selected 

patients (Kim et al., 2004). 

Endoscopic Sphincterotomy (ES): 

Sphincterotomy is done by the incision of the papilla and sphincter 

muscles to open the terminal portion of the CBD. The procedure is 

performed with a sphincterotome, which consists of a Teflon catheter 

with a cautery wire exposed for a length of 20 to 30 mm near the tip. The 

basic technique of sphincterotomy has changed little since its initial 

description in 1974 (Classen and Demling, 1974). After deep bile duct 

cannulation, the sphincterotome is retracted until one half to two thirds of 

the wire length is exposed outside of the papilla. (figure 20). 

The sphincterotome-cutting wire is “bowed” until it comes in 

contact with the roof of the papilla. Applying intermittent bursts of 

diathermic current makes the incision. The length of the incision may 

range from 0.5 to 1.5 cm, depending on the size of the stone to be 

extracted and the local anatomy. The length of the intraduodenal portion 

of the CBD will limit the maximum extent of the cut (Coppola et al., 

1997). Endoscopic sphincterotomy is contraindicated in the presence of

Endoscopic retrograde cholangiopancreatography ١١٦ 

stenosis of the bile duct proximal to the sphincter (Doherty and Way, 

2003). 

Figure (20):endoscopic sphincterotomy (Courtesy of Dr. Tarik Zaher) 

Endoscopic papillary balloon dilatation (EPBD): 

EPBD began by MacMathona et al. (1993), but it was discarded 

because of high frequency of acute pancreatitis. However, it has been 

revisited by Tanaka (2002) under the name “endoscopic 

sphincteroplasty” and it is still being evaluated. 

Technique: 

Endoscopic papillary balloon dilatation can be done using a special 

balloon catheter (8 mm diameter) that can be passed through the intact 

papilla. It is passed to the CBD then inflated twice to a maximum 

diameter of 8mm, each inflation for one minute. After the balloon is 

deflected, the stones are removed using a retrieval basket and a retrieval 

balloon. When the stone diameter is larger than 11 mm as shown by 

diagnostic ERCP, a mechanical lithotripter is used to break the stones into 

fragments (Yasuda et al., 2001).

Endoscopic retrograde cholangiopancreatography ١١٧ 

Advantages of EPBD: 

This procedure has the advantage that it preserves the sphincter. Its 

effect on the papillary function was studied using endoscopic manometry 

before and one week and one month after EPBD. 

• One week after EPBD: CBD pressure and sphincter of Oddi peak 

pressure and basal pressure were decreased significantly. 

• One month after: no serious complications occurred and there was at 

least partial recovery of papillary function. So EPBD seems to 

preserve the papillary function. 

ERCP tissue sampling techniques: 

(Sato et al., 1997b) 

Aspiration cytology: 

Pure bile and pancreatic juice can be sampled by deep cannulation of 

the appropriate duct at ERCP. This is obviously a quick and easy way to 

obtain specimens, but the results from most studies are relatively 

disappointing. In the case of the pancreatic duct, small samples (often less 

than 3 mL) are obtained, and it may take up to 20 minutes to collect even 

this amount (Lee et al., 1998). Intravenous injection of secretin is helpful 

in this regard. For collection of samples from the bile or pancreatic ducts, 

it is important to ensure that the specimen is free of iodinated contrast, as 

this can cause cellular degeneration and thus false-negatives (Goodale et 

al., 1981). For bile cytology, the sensitivity for diagnosis of cancer is low, 

ranging from 6% to 32% (Kerr et al., 1991). Aspiration cytology from 

the pancreatic duct seems to be more sensitive for cancer detection 

(ranging from 33% to 79%) (Del Favero et al., 1988).

Endoscopic retrograde cholangiopancreatography ١١٨ 

Tissue sampling from removed endoprostheses: 

Tissue or sludge found on biliary endoprostheses after their removal 

has been analyzed to make a cancer diagnosis (Leung et al., 1989) but 

this method delays diagnosis and its sensitivity is no better than other 

techniques such as brushing, biopsy and needle aspiration (Foutch, 

1996). 

Brush cytology: 

Samples can be obtained by using a single (fig.21)or double lumen 

brush cytology device.(fig.22 A,B) This is still probably the most 

commonly used ERCP sampling technique (Fogel et al., 1999) as it is 

easy to perform, but its sensitivity for malignant bile duct strictures for 

example ranges from 30% to 69%, far less than ideal, (Pugliese et al., 

1995). 

There are a variety of ways in which brush cytology can be 

performed during ERCP. Initially, bare cytology brushes were used 

primerly but they have been largely replaced by wire- guided brushes. 

Some still use single lumen brushes where the sheath is advanced into 

place over a wire and then exchanged for a brush. This is often useful in 

the pancreatic duct where double lumen catheters may be too large 

(Baron et al., 1994). 

The results of this technique vary widely between studies. It appears 

to be a safe technique with no procedure-related mortality, and little 

major morbidity. It is also a technique with a very high technical success 

rate, as high as 96% (Ponchon et al., 1995). However, the detection of 

cholangiocarcinoma may be increased by repeated brushings (Rabinovitz 

et al., 1990). It has also been shown that the sensitivity of brush cytology 

for pancreatic cancers is highest if the pancreatic duct is brushed rather

Endoscopic retrograde cholangiopancreatography ١١٩ 

than the bile duct. 85% of pancreatic cancers can be detected by this 

method.If there are strictures of both the bile duct and the pancreatic duct, 

brush cytology sampling from both ducts increases the diagnostic yield. 

Sawada et al. (1989) found an increase from 47% to 72% in the detection 

of pancreatic cancer if both ducts were sampled compared to the 

pancreatic duct alone. 

Figure (21): Single lumen Geenen cytology catheter with 3.5-cm brush (Byrne and 

Jowell, 2003) 

Figure (22) 

(A) Double lumen cytology catheter. 

(B) Magnified image of 3.5-cm brush and wire.(Quoted from Byrne and 

Jowell, 2003).

Endoscopic retrograde cholangiopancreatography ١٢٠ 

Fine needle aspiration: 

This technique allows aspiration of tissue from the site of interest by 

introduction of a needle through a catheter in the endoscope. There are 

limited data available on the use of this sampling technique. after 

performing a sphincterotomy, a 7-Fr precurved catheter with a retractable 

22-gauge needle is advanced through the duodenoscope up to the distal 

end of the stricture under fluoroscopy (figure 23A and B) (Howell et al., 

1992). 

Figure (23) 

(A) HBIN catheter (Wilson cook) with FNA needle 

(B) Cholangiogram showing FNA aspirate from bile duct stricture 

(Byrne and Jowell, 2003).

Endoscopic retrograde cholangiopancreatography ١٢١ 

Endoscopic biopsy: 

Biopsies can be taken in the standard endoscopic manner. However, 

biopsies can also be taken from both the biliary and pancreatic ducts at 

ERCP under fluoroscopic guidance or under direct vision using the 

"mother and baby" choledochoscope. Although forceps, particularly 

pediatric forceps, can be advanced directly through the papilla, a 

sphincterotomy is usually necessary before passing the biopsy forceps 

into the biliary or pancreatic duct (figure 24) (Lee and Leung, 1998). 

Any attempt to obtain deeper cytological specimens is desirable with 

ductal pathology, as tumors can be extrinsic, submucosal, or associated 

with a significant desmoplastic reaction. There is higher sensitivity for 

cancer detection for forceps biopsy than brush cytology (81% versus 

48%). Taking more biopsies may also increase the diagnostic yield, and 

probably three or four biopsies should be taken (Kubota et al., 1993). 

Figure (24): Radiographic image of an open biopsy forceps within the common bile 

duct (Byrne and Jowell, 2003)

Endoscopic retrograde cholangiopancreatography ١٢٢ 

Technical difficulties during endoscopic management of 

common bile duct stones: 

Failure to achieve bile duct clearance may occur for a variety of 

reasons (Cuschieri, 2002). These reasons are listed by Hawes and 

Sherman (1995) in table (3). 

No access to the papilla 

Roux-en-Y 

Gastrojejunostomy 

Choledochojejunostomy 

Strictures 

Upper gastrointestinal tract 

Anastomotic 

Unsuccessful cannulation 

Periampullary diverticulum 

Billroth II gastroenterostomy 

Ampullary neoplasm 

Papillary stenosis 

Papillary or duodenal inflammation 

Variant anatomy 

Inadequate sphincterotomy 

Complications 

Short intraduodenal segment 

Unsuccessful extraction 

“ Large” stone 

Narrow intrapancreatic segment 

Bile duct stricture 

Inadequate access to stone 

Intrahepatic 

Cystic duct. 

Table (3): Reasons for failed duct clearance (Hawes and Sherman, 

1995)

Endoscopic retrograde cholangiopancreatography ١٢٣ 

The most important causes are: 

No access to papilla: 

Inability to advance the endoscope to the papilla may occur as a 

result of esophageal or duodenal stricture. Reaching the papilla 

endoscopically is rare in patients with a roux-en-Y gastrojejunostomy. A 

transhepatically placed wire may be passed antegrade down the Roux 

limb in this circumstance and grasped by the endoscopist to “pull” the 

endoscope to the papilla (Tompkins, 1997). 

Unsuccessful cannulation: 

This can occasionally be difficult in cases of papillary stenosis or 

Billroth II gastroenterosotmy (where the normal landmarks are 180º 

opposite their usual position) or in the presence of a periampullary 

diverticulum. Difficult cannulation can often be overcome with the use of 

alternative techniques, such as wire-guided catheters or a papillotome 

(Cuschieri, 2002). Also unsuccessful cannulation include persistence of 

the same technique, trying a different technique, calling in a second staff, 

or stopping the procedure, especially if the indication is not clear, if a 

complication is apparent, or if the patient is not tolerating the procedure 

well (Freeman et al., 1996). 

Pre-cut (‘‘Access’’) papillotomy: 

Pre-cut papillotomy refers to a variety of endoscopic techniques 

used to gain access to the bile (or occasionally the pancreatic) duct. In 

most patients, pre-cut papillotomy is followed by conventional 

sphincterotomy, which permits completion of therapies, e.g., stone 

extraction. However, pre-cut sphincterotomy sometimes is used to gain 

access to the bile (or the pancreatic) duct for diagnostic cholangiography 

(or pancreatography) alone. Thus, the alternative term ‘‘access

Endoscopic retrograde cholangiopancreatography ١٢٤ 

papillotomy’’ probably is more accurate (Vandervoort and Carr-Locke, 

1996).(fig. 25) 

Figure (25): Pre-cut of the major papilla (Courtesy of Dr. Tarik Zaher) 

Pre-cut techniques most often are used after biliary cannulation have 

failed or, in performing biliary and pancreatic sphincterotomy over a 

pancreatic stent in patients with sphincter of Oddi dysfunction (Fogel et 

al., 2002). Use of pre-cut varies from none to as many as 38% of all 

biliary cannulation attempts (Akashi et al., 2004). 

There are several techniques to perform pre-cut papillotomy Most 

widely practiced is the free-hand needle knife, in which an incision is 

made starting at the orifice and extending cephalad for a variable distance 

Originally by described using an upward sweeping motion with the 

elevator, it has been suggested that improved control and safety can be 

achieved by ‘‘loading’’ the needle knife by upward traction on the 

endoscope (Desilets et al., 2004). A variation of the needle-knife 

technique involves making a puncture into the papilla above the orifice 

(often referred to as ‘‘fistulotomy’’).Any of the above techniques may be 

performed after placement of a pancreatic stent (Binmoeller et al., 1996).

Endoscopic retrograde cholangiopancreatography ١٢٥ 

Unsuccessful extraction: Failure to extract stones successfully after 

sphincterotomy most commonly occurs because the stones are too large. 

Stones greater than 15 mm in diameter are usually defined as large, and 

attempts to remove them with a standard basket can result in basket 

impaction (Tompkins, 1997). Alternatively, the stones may not be 

excessively large, but the intrapancreatic portion of the bile duct may not 

be dilated sufficiently to allow passage of the stone (Sherman and 

Lehman, 1999). 

Grading for the difficulty of ERCP procedures: 

Schutz and Abbott (2000) presented a grading system for the 

degree of difficulty of ERCP (table 4). 

Grade Biliary procedures Pancreatic procedure 

Grade 1 Standard cholangiogram Standard pancreatogram 

Grade 2 

Grade 3 

Grade 4 

Grade 5 

Biliary sphincterotomy 

Removal of 1-2 small stones 

Nasobiliary drain placement 

Cholangiogram in Billroth II 

Biliary cytology 

Pancreatic cytology 

Multiple or large stones 

Stricture dilation 

Common duct stenting 

Precut sphincterotomy 

Lithotripsy 

Intrahepatic therapy 

in Billroth II anatomy 

Cholangioscopy 

Pancreatogram in Billorth 

type II 

Minor papilla cannulation 

All pancreatic therapy 

Pancreatoscopy 

Table (4): Grading for the difficulty of ERCP procedures (Schutz and 

Abbott, 2000)

Endoscopic retrograde cholangiopancreatography ١٢٦ 

Reasons for failed ERCP 

Failure of cannulation 

Previous gastrectomy 

Periampullary diverticulum 

Previous whipple operation 

Previous roux-en-y choledochojejunostomy 

ERCP with oesophageal perforation 

Failure of extraction 

Impacted stone 

Incomplete stone clearance after multiple attempts 

Type II Mirrizi syndrome 

Relative common bile duct stricture 

Situs inversus 

Stent migration into common bile duct 

Repeated post-ERCP pancratitis 

Post-ES duodenal perforation 

Table (5): Reasons for failed endoscopic retrograde 

cholangiopancreatography (ERCP) (Tang et al., 2006) 

Complications of diagnostic and therapeutic ERCP: 

ERCP can cause a wide range of complications. In general, 

complications appear to be associated primarily with patients related 

factors and technical skill of the endoscopist (Freeman, 2002).

Endoscopic retrograde cholangiopancreatography ١٢٧ 

The complications of ERCP are listed by Freeman (2002) 

includes: 

Pancreatitis Cholecystitis 

Hemorrhage Stent-related 

Perforation Cardiopulmonary 

Cholangitis Miscellaneous 

In 1991, cotton and Consensus Panel of experts in the field 

introduced a standardized outcome-based set of definitions for 

complications of ERCP (table 6). 

Complication * Mild Moderate Severe + 

Pancreatitis 

Bleeding 

Perforation 

Infection 

(cholangitis) 

Clinical pancreatitis, 

amylase at least 3x 

normal > 25 hours after 

procedure, requiring 

admission or 

prolongation of 

planned admission to 

2-3 days 

Clinical (i.e. not just 

endoscopic) evidence 

of bleeding 

Hemoglobin drop 38ºC for 24-48 hours 

Pancreatitis requiring 

hospitalization of 4-10 

days 

Transfusion (≤ 4 units), 

no angiographic 

intervention or surgery 

Any definite 

perforation treated 

medically 4-10 days. 

Febrile or septic illness 

requiring > 3 days of 

hospital treatment or 

endoscopic 

percutaneous 

intervention 

Hospitalization > 10 

days,or hemorrhagic 

pancreatitis, phlegmon, 

pseudocyst, or 

(percutaneous drainage 

or surgery) 

Transfusion ≥ 5 units, 

or intervention 

(angiographic or 

surgical) 

Medical treatment > 10 

days, or intervention 

(percutaneous or 

surgical) 

Septic shock or surgery 

Table (6): Consensus definitions for the major complications of ERCP 

(Cotton et al., 1991) 

*Other rarer compilations can be graded by length of needed hospitalization. 

+ 

Any intensive care unit admission after a procedure grades the complication as 

severe. 

ERCP = Endoscopic Retrograde cholangiopancreatography.

Endoscopic retrograde cholangiopancreatography ١٢٨ 

Strategies of reduced complication of ERCP: 

The principal strategies to reduce complications of ERCP are listed 

by Freeman (2002) including the following: 

Improved training during fellowship,educating endoscopists 

regarding risk factors,avoiding marginally indicated ERCP, with 

preferential utilization of alternative imaging techniques and making 

referrals to advanced centers for complex or high-risk cases (Freeman, 

2002). 

1- Pancreatitis: 

Post-ERCP pancreatitis is abdominal pain for more than 24 hours 

after the procedure and levels of serum pancreatic enzymes three times 

above normal (Cohen et al., 1996). This definition excludes the 30%– 

75% of patients who are asymptomatic and have an elevated amylase 

level alone (Aliperti, 1996). Asymptomatic hyperamylasemia peaks 90 

minutes to 4 hours after ERCP and resolves within 48 hours. 

Measurement of a 4-hour serum amylase level has been suggested to 

identify outpatients at risk for developing pancreatitis before discharge 

(Testoni et al., 1999). 

Post-ERCP pancreatitis usually evolves over 2–6 hours and 

manifests as epigastric or back pain and nausea .The pancreatitis is mild 

or moderate in 90% of cases and resolves with intravenous hydration and 

analgesia (Baille, 1998). 

Risk factors for post-ERCP pancreatitis are sphincter of Oddi 

dysfunction and young age (Freeman, 1998). A higher rate of 

pancreatitis is caused by increased manipulation around the papilla and 

multiple injections of the pancreatic duct In addition to serum amylase 

and lipase levels, levels of trypsinogen 2 and trypsin 2– 1-antitrypsin

Endoscopic retrograde cholangiopancreatography ١٢٩ 

complex can be used to diagnose acute pancreatitis. The former is 

measured at 6 hours, and the latter is measured at 24 hours; the sensitivity 

of each is over 90% (Shimizu et al., 1999). Pancreatitis is also more 

likely to develop in patients with contrast material visualized in the renal 

collecting system on a plain radiograph obtained at the conclusion of the 

procedure (Roszler et al., 1985). 

Incidence: 

The rates of pancreatitis after ERCP and sphincterotomy have 

ranged from less than 1% to 40%. The wide variation between studies 

likely reflects varying definitions, methods of data collection, patient 

populations, indications for ERCP, types of procedures performed, and 

endoscopic expertise (Gottlieb and Sherman, 1998). 

Management of post-ERCP pancreatitis is: General guidelines for 

performing CT include(a)Cases in which the clinical diagnosis is not 

definite;(b)Patients with hyperamylasemia, severe clinical pancreatitis, 

abdominal distention, tenderness, fever, or leukocytosis;(c)Patients whose 

condition does not improve within 72 hours of commencing conservative 

treatment; and(d)Patients who develop an acute change after initial 

improvement in their condition (Simchuk et al., 2000) 

Patients may have focal edema or diffuse glandular swelling in post- 

ERCP inflammation (Kuhlman et al., 1989). Focal swelling of the 

pancreatic head has been referred to as pancreatic pseudotumor and can 

be seen after papillotomy (De Vries et al., 1997).

Endoscopic retrograde cholangiopancreatography ١٣٠ 

The pancreas can appear relatively normal in cases of mild 

inflammation .In more severe cases, the entire gland is enlarged and 

enhances heterogeneously (Balthazar, 1989). Pancreatic necrosis 

accounts for over 70% of deaths from acute pancreatitis because digestive 

enzymes leak with disruption of the pancreatic duct. The necrotic tissue 

can evolve into an intrapancreatic collection with a pseudocapsule. Foci 

of high attenuation are due to hemorrhage (Paulson et al., 1999). 

Patients with acute pancreatitis can develop pseudocysts after the 

initial attack has subsided.These are encapsulated collections that can 

have a barely perceptible wall or a thick, enhancing wall and 

communicate with the pancreatic duct .Other possible complications of 

acute pancreatitis are pseudoaneurysms, pleural effusions, and ascites 

(Balthazar, 1989). Involvement of the extraperitoneal portions of the 

colon can lead to perforation and stricture formation (Stanley et al., 

1998). 

Pharmacologic prophylaxis of pancreatitis: 

Several methods of pharmacologic prophylaxis have been proposed. 

Somatostatin and octreotide reduce pancreatic secretion and therefore 

may limit pancreatic duct hypertension (Binmoeller et al., 1992). Other 

agents have been used in an effort to reduce spasm of the sphincter of 

Oddi (Sand et al., 1993), inhibit proteolytic activity (gabexate), 

(Cavallini et al., 1996) block the production of free radicals (allopurinol) 

(Budzynska et al., 2001) or manipulate the cytokine cascade (IL-10) 

(Dumot et al., 2001). 

2- Hemorrhage: 

Hemorrhage is primarily a complication related to sphincterotomy 

rather than diagnostic ERCP. Clinically significant hemorrhage may be

Endoscopic retrograde cholangiopancreatography ١٣١ 

defined as the presence of melena, hematochezia, or hematemesis 

associated with a hemoglobin decrease of at least 2 g/dL or the need for 

blood transfusion (Freeman et al., 1996). The reported incidence of 

hemorrhage after sphincterotomy ranges from 0.76% to 2%. In roughly 

half of cases this bleeding is delayed (recognition 1 or more days after the 

examination) and can occur up to 1 to 2 weeks later. The risk of severe 

hemorrhage (i.e., requiring 2 or more units of blood, surgery, or 

angiography) is estimated to be 0.1% to 0.5% (Loperfido et al., 1998). 

Risk factors for hemorrhage include coagulopathy at the time of the 

examination, the use of anticoagulants within 72 hours of the 

sphincterotomy, the presence of acute cholangitis or papillary stenosis 

and the use of precut sphincterotomy, (Masci et al., 2001). 

Ways to prevent hemorrhage: 

Bleeding can mostly be avoided by correcting any coagulopathies, 

withholding anticoagulant medications for up to 3 days after a 

sphincterotomy and the use of alternating coagulating and cutting 

diathermy (Qaseem et al., 1996 and Tanaka, 2002). 

Catalano et al. (1995) suggested that prophylactic injection of the 

sphincterotomy site with epinephrine for endoscopically observed 

bleeding, or even a sclerosing agent in patients with coaglopathy, may 

reduce the risk of hemorrhage. 

ERCP-induced hemorrhage is monitored clinically and with 

laboratory tests (Baille, 1998), therefore, intraluminal bleeding is 

primarily recognized (Patel and Shaps, 1982). CT is not typically 

performed for diagnosis of hemorrhage; however, blood may be detected 

if CT is performed for another indication. CT findings of acute duodenal 

hemorrhage are duodenal wall thickening and a high-attenuation mass in

Endoscopic retrograde cholangiopancreatography ١٣٢ 

the duodenal wall. Over time, the attenuation of the fluid decreases and a 

pseudocapsule may form (Hahn et al., 1986). 

3- Perforation: 

Three distinct types of perforations have been described: guidewire- 

induced perforation, periampullary perforation during sphincterotomy, 

and perforation at a site remote from the papilla (Howard et al., 1999). 

Prompt recognition of periampullary perforation and treatment with 

aggressive biliary and duodenal drainage (by means of nasobiliary and 

nasogastric tubes) coupled with broad-spectrum antibiotics can result in 

clinical resolution without the need for operative intervention in up to 

86% of patients.Risk factors for perforation include the presence of a 

Billroth II partial gastrectomy, the performance of a sphincterotomy, the 

intramural injection of contrast, duration of procedure, biliary stricture 

dilation, and SOD (Enns et al., 2002). 

Free retroperitoneal air has been seen in 29% of asymptomatic 

patients on a CT scan obtained within 24 hours of the procedure. This 

finding may occur due to insufflation of air into the duodenum for 

endoscopy, which can lead to pneumatosis and extraluminal air 

(Genzlinger et al., 1999). Pneumatosis can also occur with misdirection 

of the catheter tip during duct cannulation and submucosal injection of 

contrast material and air (Kuhlman et al., 1989). 

The quantity of air seen is due to continued endoscopic insufflation 

of air after the injury has occurred (Zissin et al., 2000). Patients with only 

evidence of free air usually recover with conservative treatment, which 

consists of bowel rest and antibiotics (Stapfer et al., 2000). However, 

infection of bile and leakage of fluid through the perforation in cases of 

failed biliary drainage correlate with increased morbidity (Scarlett et al., 

1994).

Endoscopic retrograde cholangiopancreatography ١٣٣ 

4- Cholangitis and cholecystitis: 

Cholangitis (ascending bile duct infection) and cholecystitis 

(gallbladder infection if the gallbladder is still in sito) are potential 

complications or sequelae of ERCP and/or sphincterotomy that are 

sometimes difficult to distinguish from each other on clinical grounds 

(Cotton et al., 1991). 

Cholangitis: 

The rate of cholangitis is 1% or less. Risk factors include the use of 

combined percutaneous-endoscopic procedures, stent placement in 

malignant strictures, the presence of jaundice and incomplete or failed 

biliary drainage (Loperfido et al., 1998). 

Prevention: 

• The principal recommendation regarding prevention of cholangitis is 

obtaining successful and complete biliary drainage (Freeman, 2002). 

• Acute cholangitis can readily be prevented by routine stenting when 

immediate removal of CBD stones is not possible after ES (Tanaka, 

2002). 

• Whether or not prophylactic antibiotics should be given to patients for 

ERCP is unclear. Several studies have shown that prophylactic 

antibiotics can reduce the rate of bacteremia, but few studies have 

shown a reduction in clinical sepsis following ERCP (Harris et al., 

1999). 

Cholecystitis (if the gallbladder is still in situ): 

Cholecystitis may occur after sphincterotomy, but it is sometimes 

difficult to decide whether this is a complication of the ERCP or merely 

the natural history of gallbladder stones (Silvis, 1991).

Endoscopic retrograde cholangiopancreatography ١٣٤ 

Recent studies have shown that if the gallbladder is left intact after 

sphincterotomy, both early and late cholecystitis occur more frequently 

than previously thought. Both cholecystitis and recurrent bile duct stones 

are more common if the gallbladder that is left in-situ contains stones 

(Hill et al., 1991). 

Possible mechanisms of ERCP induced cholecystitis include 

contamination of the gallbladder by instillation of contrast media, or 

duodeno-biliary reflux and bacterobilia (Freeman, 2002). There are no 

clear means for preventing post-ERCP cholecystitis other than 

cholecystectomy (Boerma et al., 2002). 

5- Complications secondary to endoscopy: 

Other complications of ERCP are those related to endoscopy and 

include esophageal, liver, and splenic injury. Seventy-five percent of 

esophageal perforations in adults occur during endoscopy . The most 

common sites are the distal esophagus and adjacent to the 

cricopharyngeus. At CT, pneumomediastinum, mediastinitis, and 

extravasation of contrast material can be seen. Pleural effusion and 

pneumothorax can also develop within 12–24 hours (Stewart et al., 

1994). Surgery is usually needed for repair.Laceration of the liver or 

spleen can result from direct or indirect trauma as the endoscope is passed 

through the stomach and duodenum (Lewis et al., 1991 and Wu and 

Katon, 1993). 

6- Stent migration: 

Migration of a common bile duct or pancreatic duct stent occurs in 

up to 5.9% of cases. Migration can occur into the proximal duct or into 

the gut. Risk factors associated with proximal stent migration are 

malignant strictures, large stent diameter, and short stent length. Distally

Endoscopic retrograde cholangiopancreatography ١٣٥ 

migrating stents are usually expelled with stool, whereas proximally 

migrating stents are removed endoscopically. Stents can also be 

incorrectly placed at the time of the procedure. Imaging findings in stent 

migration are atypical location of the stent and bowel impaction in colonic 

diverticula (Aliperti, 1996). 

7- Long term complications and sequelae: 

There is increasing concern about the possible long term sequelae of 

endoscopic sphincterotomy. These include: Recurrent stone formation, 

Sphincterotomy stenosis, Bacterobilia resulting from duodenal biliary 

reflux, and cholangitis (Bergman et al., 1996). 

ERCP during pregnancy: 

The most common indication for ERCP during pregnancy is 

treatment of choledocholithiasis. Choledocholithiasis that causes 

cholangitis and pancreatitis during pregnancy increases the risk of 

morbidity and mortality for both the fetus and mother. ERCP, with 

modified techniques to reduce radiation exposure to the fetus, is safe 

during pregnancy (Kahaleh et al., 2004 and Simmons et al., 2004) 

ERCP in children: 

ERCP has been used in children for a variety of indications, usually 

related to recurrent acute pancreatitis, choledocholithiasis, or evaluation 

of suspected choledochal cysts. The success and the safety of ERCP in 

children in experienced hands is comparable with that in adults (Hsu et 

al., 2000 and Varadarajuluet al., 2004). 

ERCP in the pediatric age group is safe both as a diagnostic and 

therapeutic procedure. ERCP can provide valuable information which aid 

in the diagnosis of biliary and pancreatic diseases in children as well as

Endoscopic retrograde cholangiopancreatography ١٣٦ 

therapy with the technical feasibility of endoscopic sphincterotomy. This 

is specially so in the era of laparoscopic cholecystectomy, where ERCP 

should be the treatment of choice in children with CBD stones who are 

going or have previously undergone laparoscopic cholecystectomy (Issa 

et al., 2006).

Summary and conclusion ١٣٧ 

Summary and conclusion 

Gall stone disease remains one of the most common medical 

problems leading to surgical intervention. The risk factors predisposing to 


pregnancy, hemolytic diseases, and cirrhosis . It is important to remember 

that gallstones can lead to a variety of other complications including 

choledocholithiasis. About 15% of patients with gallstones have 

choledocholithiasis. Stones in the common duct usually originate in the 

gallbladder but may also form de novo in the bile duct. Stones from gall 

bladder which migrate up to the intra-hepatic ducts leading to formation 

of Hepatolithiasis. 

Helminthic invasion of the human biliary tract is a prominent 

medical and surgical problem especially in tropical and subtropical areas 

where these parasites are endemic. Helminthic infestation may affect the 

liver and/or the biliary tract either during passage of worms through these 

structures or because these organs serve as their natural habitat. The 

parasitic infestations affecting the biliary tract including the nematode 

Ascaris lumbricoides, the trematodes Opisthorchis viverrini and 

felineus, Clonorchis sinensis, Dicrocoeliasis and Fasciola hepatica, and 

the cestodes Echinococcus granulosus and multilocularis, also some 

protozoa can cause biliary tract disease as Cryptosporidium, and 

Giardiasis. 

Biliary parasites cause necrosis, inflammation, fibrosis, strictures, 

and cholangiectasis of the bile ducts by several mechanisms:As a direct 

result of the irritating chemical composition of the parasite, parasitic 

secretions, or eggs;Physical obstruction of the bile ducts;Induction of 

formation of biliary stones(act as a nidus for stone); and Introduction of 

bacteria into the biliary system during migration from the duodenum.

Summary and conclusion ١٣٨ 

Parasites in the biliary tree can cause the syndrome commonly 

referred to as ‘Oriental cholangiohepatitis’. Features of this syndrome 

include helminthiasis, biliary stones formation, choledochal obstruction 

and recurrent cholangitis. 

There are different diagnostic tools none specific for the diagnosis of 

biliary parasitic infestations except the demonstration of eggs in feces 

and/or duodenal contents. ERCP is extremely helpful in defining changes 

in the bile ducts as well as demonstrating the parasites directly, their 

location and movements. Ultrasonography, CT, MRI can be used to 

demonstrate the parasites, dilatation of the biliary tree due to biliary 

obstruction caused by the parasites, the presence of stones, 

cholangiocarcinoma, hepatoma, liver abscesses or cysts.Also 

Eosinophilia is often present but insignificant. 

The treatment of biliary parasites infection includes conservative 

treatment, endoscopy and/or surgery. Conservative treatment consists of 

antihelminthics. Previously, surgical treatment was necessary for the 

management of biliary parasites and related stones. Nowadays, 

endoscopic spincterotomy and extraction of the biliary parasites by ERCP 

is a good alternative to surgery, and carries less morbidity and mortality 

than the surgical approach. Surgery is still indicated in cases with acute or 

chronic cholecystitis due to parasitic infestation and related stones.

References ١٣٩ 

References 

A 

Acuna-Soto R and Braun-Roth G (1987): Bleeding ulcer in the common bile 

duct due to Fasciola hepatica. Am J Gastroenterol; 82: 560–562. 

Adam RD. (2001): Biology of Giardia lamblia. Clin Microbiol Rev ;14:447- 

75. 

Adamek HE, Schneider AR, Adamek MU et al. (1999): Treatment of 

difficult intrahepatic stones by using extracorporeal and intracorporeal 

lithotripsy techniques: 10 years’ experience in 55 patients. Scand J 

Gastroenterol ; 34: 1157-1161 

Aihara M, Sakai M, Iwasaki M, Shimakawa K, Kosaki S, Kubo M, et al. 

(1993):Prevention and control of nosocomial infection caused by 

methicillin-resistant Staphylococcus aureus in a premature infant ward: 

preventive effect of a povidone iodine wipe of neonatal skin. Postgrad 

Med J;69(Suppl):S117-21. 

Ainsworth AP, Rafaelsen SR, Wamberg PA et al. (2003): Is there a 

difference in diagnostic accuracy and clinical impact between endoscopic 

ultrasonography and magnetic resonance cholangiopancreatography? 

Endoscopy; 35(12): 1029-1032. 

Akashi R, Kiyozumi T, Jinnouchi K, Yoshida M, Adachi Y, Sagara 

K.(2004): Pancreatic sphincter precutting to gain selective access to the 

common bile duct: a series of 172 patients. Endoscopy;36: 405-10. 

Albert JG and Rilemann JF (2002): ERCP and MRCP when and why Best 

practice and research clinical gasteroenterology vol. 16 No 3 pp 399-419.

References ١٤٠ 

Aliperti G. (1996): Complications related to diagnostic and therapeutic 

endoscopic retrograde cholangiopancreatography. Gastrointest Endosc 

Clin N Am 1996; 6:379-407. 

Al-Karawi M, Mohamed AS, Yasawy M. (1990): Advances in diagnosis and 

management of hydatid disease. Hepatogastroenterology; 37: 327–31. 

Amadi B, Mwiya M, Musuku J, et al (2002): Effect of nitazoxanide on 

morbidity and mortality in Zambian children with cryptosporidiosis: a 

randomized controlled trial. Lancet 360:1375-1380. 

Ambroise-Thomas P, and Goullier A (1984): Parasitological examinations 

and immunodiagnostic advances in fluke infections. 

Arzneimittelforschung 34:1129-1132. 

Ammann R and Eckert J. Cestodes (1996): Echinococcus. Gastroenterol 

Clin N Am; 25: 655–89. 

Amouyal P, Amouyal G, Levy P et al (1994): Diagnosis of 

choledocholithiasis by endoscopic ultrasonography. Gastroenterology; 

106(4): 1062-1067. 

Anciaux ML, Pelletier G, Attali P et al. (1986): Prospective study of clinical 

and biochemical features of symptomatic choledocholithiasis. Dig Dis 

Sci; 31(5): 449-453. 

Angus KW (1990): Cryptosporidiosis in ruminants. In: Dubey, J.P., Speer, 

C.A., Fayer, R. (Eds.), Cryptosporidiosis in Man and Animals. CRC 

Press, Boca Raton, FL, pp. 83–103. 

Anonymous (1996): Guidelines for treatment of cystic and alveolar 

echinococcosis in humans. WHO Informal Working Group on 

Echinococcosis. Bull World Health Organ; 74: 231–42.

References ١٤١ 

Anonymous P. (2000):Appendix 7: Pregnancy and breastfeeding. In: Spicer J, 

Christiansen K, Currie B, et al, eds. Therapeutic Guidelines: Antibiotic. 

11 edn. North Melbourne: Therapeutic Guidelines,: 238–43. 

Apstein MD and Carey MC (1993): Biliary tract stones and associated 

diseases. In stein JH, Editor. Internal Medicine, 4 th ed .st.Louis:Mosby 

Yearbook. 

Argenzio RA, Armstrong M, Rhoads JM (1996): Role of the enteric 

nervous system in piglet cryptosporidiosis. J. Pharmacol. Exp. Ther. 279, 

1109–1115. 

Arya N, Nelles SE, Haber GB et al (2004): Electrohydraulic lithotripsy in 

111 patients: a safe and effective therapy for difficult bile duct stones. 

Am J Gastroenterol; 99(12): 2330-2334. 

Ashton WLG, Boardman PL, D’Sa CJ, Everall PH, Houghton AWJ 

(1970): Human fascioliasis in Shropshire. Br Med J;29:500. 

Attwood HD and Chou ST (1978): Longevity of Clonorchis 

sinensis.Pathology 10, 153–156. 

Aygun E, Sahin M, Odev K, et al. (2000): The management of liver hydatid 

cysts by percutaneous drainage. Can J Surg 2001; 44: 203–09. 

Ayub K, Imada R and Slavin J (2004): Endoscopic retrograde 

B 

cholangiopancreatography in gallstone-associated acute pancreatitis. 

Cochrane Database Syst Rev; 4. 

Babb RR (1995): Giardiasis: taming this pervasive parasitic infection. 

Postgrad Med;98:155–8.

References ١٤٢ 

Badie, A. and Rodelaud, D. (1988): Les fourmis parasite´es par 

Dicrocoelium lanceolatum Rudolphi en Limousin. Les relations avec le 

support ve´ge´tal. Rev. Me´d. Ve´t. 139, 629–633. 

Bafandeh Y, Daghestani D and Rad S (2003): Biliary Tract Obstruction Due 

to Fasciola hepatica Managed by ERCP. Iran J Med Sci; 28 (1):43-45. 

Bahu´ MdaGS, Baldisseroto M, Custodio CM, Gralha CZ, Mangili 

AR.(2001): Hepatobiliary and pancreatic complications of ascariasis in 

children: a study of seven cases. J Pediatr Gastroenerol Nutr;33:271-5. 

Baille J. (1998): Complications of ERCP. In: Jacobson IM, eds. ERCP and its 

applications. Philadelphia, Pa: Lippincott-Raven,; 37-54. 

Balci S (1975): Human fascioliasis: Gall bladder invasion by flukes in a five- 

year-old boy. Clin Pediatr;14:1068–1069. 

Balthazar EJ.(1989): CT diagnosis and staging of acute pancreatitis. Radiol 

Clin North Am; 27:19-37. 

Barish MA, Soto JA and Yucel EK (1996): Magnetic resonance cholangio- 

pancreatography of the biliary ducts: techniques, clinical applications, 

and limitations. Topics in Magnetic Resonance Imaging 8(5): 302-311. 

Baron TH and Harewood GC. (2004): Endoscopic balloon dilation of the 

biliary sphincter compared to endoscopic biliary sphincterotomy for 

removal of common bile duct stones during ERCP: a meta-analysis of 

randomized, controlled trials. Am J Gastroenterol; 99: 1455-60. 

Baron TH, Lee JG, Wax TD, et al. (1994): An in vitro, randomized, 

prospective study to maximize cellular yield during bile duct brush 

cytology. Gastrointest Endosc 40:146-149. 

Baron TH, Mallery JS, Hirota WK, Goldstein JL, Jacobson BC, Leighton 

JA, et al. (2003):The role of endoscopy in the evaluation and treatment

References ١٤٣ 

of patients with pancreaticobiliary malignancy. Gastrointest 

Endosc;58:643-9. 

Barthet M, Bernard JP, Duval JL, Affriat C, Sahel J ( 1994): Biliary 

stenting in benign biliary stenosis complicating chronic calcifying 

pancreatitis. Endoscopy;26:569-72. 

Behjou B, Prat F, Fritsch J et al (1997): Intra-corporeal shockwave 

lithotripsy in the treatment of complex lithiasis of the bile ducts. 

Comparison of endoscopic techniques and long-term results. 

Gastroenterol Clin Biol; 21(10): 648-654. 

Bennet JL and Kohler P (1987): Fasciola hepatica: action in vitro of 

triclabendazole on immature and adults stages. Exp Parasitol ;63:49-57. 

Bergman JJ, VanDerMey S and Rauws EAJ (1996): Long-term follow up 

after endoscopic sphincterotomy for bile duct stones in patients younger 

than 60 years of age. Gastrointest Endosc; 44: 643-9. 

Bhamarapravati N, Thammavit W, and Vajrasthira S, (1978): Liver 

changes in hamsters infected with a liver fluke of man, Opisthorchis 

viverrini. Am. J. Trop. Med. Hyg. 27, 787–794. 

Bilhartz and Horton (1998): Complications. In: Feldman M, Scharschmidt 

BF, gastrointestinal and liver disease: pathophysiology, diagnosis, 

management. 6th ed. Philadelphia: Saunders, 947-72. 

Bingham AK and Meyer EA: (1979):Giardia excystation can be induced in 

vitro in acidic solutions. Nature 277:301-302. 

Binmoeller KF, Harris AG, Dumas R, Grimaldi C, Delmont JP (1992): 

Does the somatostatin analogue octreotide protect against ERCP induced 

pancreatitis? Gut;33:1129-33.

References ١٤٤ 

Binmoeller KF, Seifert H, Gerke H, Seitz U, Portis M, Soehendra 

N.(1996): Papillary roof incision using the Erlangen-type pre-cut 

papillotome to achieve selective bile duct cannulation. Gastrointest 

Endosc;44:689-95. 

Boerma D, Rauws EAJ, Keulemans YCA, Janssen IMC, Bolwerk CJ, 

Timmer R, et al (2002): Wait-and-see policy or laparoscopic 

cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a 

randomised trial Lancet;360:761-5. 

Bonheur JL (2006): Biliary Obstruction, www.emedicine.com. 

Boonpucknavig V and Soontornniyomkij V (2003): Pathology of renal 

diseases in the tropics. Semin. Nephrol. 23, 88–106. 

Boray J. (1981): Fascioliasis and other trematodes of animals, I: recent 

Bracher GA, Manocha AP, DeBanto JR, Gates LK Jr, Slivka A, 

Whitcomb DC, et al.(1999): Endoscopic pancreatic duct stenting to treat 

pancreatic ascites. Gastrointest Endosc;49:710-5. 

Brand B, Kahl M, Sidhu S, Nam VC, Sriram PV, Jaeckle S, et al.(2002): 

Prospective evaluation of morphology, function, and quality of life after 

extracorporeal shockwave lithotripsy and endoscopic treatment of chronic 

calcific pancreatitis. Am J Gastroenterol ;95:3428-38. 

Brandabur JJ, Kozarek RA, , Ball TJ, Gluck M, Patterson DJ, Attia 

F.(2002):Clinical outcomes in patients who undergo extracorporeal shock 

wave lithotripsy for chronic calcific pancreatitis. Gastrointest Endosc; 

56:496-500. 

Bresson-Hadni S, Vuitton D, Bartholomot B, et al.(2000): A twenty-year 

history of alveolar echinococcosis: analysis of a series of 117 patients 

from eastern France. Eur J Gastroenterol Hepatol; 12: 327–36.

References ١٤٥ 

Bretthauer M, Seip B, Aasen S, Kordal M, Hoff G, Aabakken L (2007): 

Carbon dioxide insufflation for more comfortable endoscopic retrograde 

cholangiopancreatography: a randomized, controlled, double-blind 

trial.Endoscopy.;39(1):58-64. 

Bruckner DA (1999): Helminthic food-borne infections. Clinical Laboratory 

Medicine 19, 639–660. 

Bryan RT and Michelson MK (1995): Parasitic infections of the liver and 

biliary tree. In Surawicz C & Owen RL (eds) Gasfroinresrinal and 

Heparic Infections, pp 405454. Philadelphia: WB Saunders. 

Budzynska A, Marek T, Nowak A, Kaczor R, Nowakowska- Dulawa 

E.(2001): A prospective, randomized, placebocontrolled trial of 

prednisone and allopurinol in the prevention of ERCP induced 

pancreatitis. Endoscopy;33:766-72. 

Buscarini E, Tansini P, Vallisa D et al (2003): EUS for suspected 

choledocholithiasis: do benefits outweigh costs? A prospective, 

controlled study. Gastrointest Endosc; 57(4): 510-518. 

Byrne MF and Jowell PS (2003):ERCP Methods of Tissue Sampling 

C 

Techniques in Gastrointestinal Endoscopy, Vol 5, No 1,: pp 27-34. 

Cahalane MJ, Neubrand MW, Carey MC. (1988): Physical-chemical 

pathogenesis of pigment gallstones. Semin Liver Dis; 8: 317-328 

Camara L, Pfister K, Aeschlimann A, (1996): Analyse histopathologique de 

foie de bovin infestè par Dicrocoelium dendriticum. Vet. Res. 27, 87–92.

References ١٤٦ 

Campo R, Manga-Gonzàlez MY, Gonzàlez-Lanza C, Rollinson D, 

Sandoval H (1998): Characterization of adult Dicrocoelium dendriticum 

by isoelectric focusing. J. Helminthol. 72, 109–116. 

Canto MI, Chak A, Stellato T et al (1998): Endoscopic ultrasonography 

versus cholangiography for the diagnosis of choledocholithiasis. 

Gastrointest Endosc; 47(6): 439-448. 

Carey MC (1992): Pathogenesis of gallstones. Recenti Prog Med. Jul-Aug; 

83(7-8):379-91. 

Carpenter HA (1998).:Bacterial and parasitic cholangitis. Mayo Clin Proc; 

73:473–8. 

Carr-Locke DL (2002): Therapeutic role of ERCP in the management of 

suspected common bile duct stones. Gastrointest Endosc; 56(Suppl 6): 

S170-4. 

Castellano G, Moreno-Sanchez D, Gutierrez J, Moreno-Gonzalez E, 

Colina F, Solis-Herruzo J. (1994): Caustic sclerosing cholangitis. 

Report of four cases and a cumulative review of the literature. 

Hepatogastroenterology; 41: 458–70. 

Catalano Mf, Geenen JE and Johnson GK (1995): Endoscopic 

sphincterotomy in patients at high risk for Gastroinstestinal (GI) 

hemorrhage: A new technique. Gastrointest Endosc; 41: 392. 

Catalano MF, Linder JF, Bukeirat FA, Geenen JE.(2003): Difficult 

cannulation of the minor papilla in patients presenting with incomplete 

pancreas divisum: a new rendezvous technique . Gastrointest Endosc;57: 

AB207. 

Catheline JM, Turner R, PAries J(2002): Laparoscopic ultrasonogrphy is a 

complement to cholangiography for the detection of choledocholithiasis 

at laparoscopic cholecystectomy. Br J Surg; 89: 1235-9.

References ١٤٧ 

Cavallini G, Tittobello A, Frullioni L, Masci E, Mariana A, Di Francesco 

V.(1996): Gabexate for the prevention of pancreatic damage related to 

endoscopic retrograde cholangiopancreatography. N Engl J Med 

;335:919-23. 

Chan CW & Lam SK (1987): Diseases caused by liver flukes and 

cholangiocarcinoma. BailliereS Clinical Gastroenterology 1: 297-3 18 

Chang WH, Chu CH, Wang TE et al (2005): Outcome of simple use of 

mechanical lithotripsy of difficult common bile duct stones. World J 

Gastroenterol; 11(4): 593-596. 

Chavez B, Gonzalez-Mariscal L, Cedillo-Rivera R, et al (1995): Giardia 

lamblia: In vitro cytopathic effect of human isolates. Exp Parasitol 

80:133-138. 

Chen CY, Hsieh WC, Shih HH, and Chen SN (1988): Immunodiagnosis of 

clonorchiasis by enzyme-linked immunosorbent assay. Southeast Asian J. 

Trop. Med. Public Health 19:117-121. 

Chen HH, Zhang WH, Wang SS et al. (1984): Diagnosis and treatment of 

intrahepatic calculi. Surg Gynecol Obstet; 159: 519-524. 

Chen MF, Jan YY, Wang CS et al. (1989): Clinical experience in 20 hepatic 

resections for peripheral cholangiocarcinoma. Cancer 64: 2226-2232. 

Chen MG and Mott KE(1990): Progress in assessment of morbidity due to 

Fasciola hepatica infection: a review of recent literature. Tropical 

Diseases Bulletin;87:R1-38. 

Chen YS, Den BX, Huang BI et al. (1986): Endoscopic diagnosis and 

management of Ascaris-induced acute pancreatitis. Endoscopy 18: 127- 

128.

References ١٤٨ 

Cheung KL and Lai EC (1996): The management of intrahepatic stones. 

Advances in Surgery 29: 111-129. 

Cheung MT, Wai SH and Kwok PC (2003): Percutaneous transhepatic 

choledochoscopic removal of intrahepatic stones. Br J Surg; 90: 1409- 

1415. 

Chijiiwa K, Ichimiya H, Kuroki S et al. (1993): Late development of 

cholangiocarcinoma after the treatment of hepatolithiasis. Surgery, 

Gynecolog); and Obstetrics 177: 279-282. 

Choi BI, Han JK, Hong ST, and Lee KH, (2004): Clonorchiasis and 

Cholangiocarcinoma: Etiologic Relationship and Imaging Diagnosis Clin 

Microbiol Rev. July; 17(3): 540–552 

Choi BI, Kim HJ,Han MC, Do YS, Han MH, and Lee SH,. (1989): CT 

findings of clonorchiasis. Am. J. Roentgenol. 152:281-284. 

Choi BI, Park JH, Kim YI, Yu ES, Kim SH, Kim WH, Kim CY, and Han 

MC (1988): Peripheral cholangiocarcinoma and clonorchiasis: CT 

findings. Radiology 169:149-153. 

Choi D, Lim JH, Kim SK, Kim EY, Lee M, and Hong ST (1999): Long- 

lasting sonographic and histopathological findings in cured clonorchiasis 

of rabbits. Korean J. Parasitol. 37:77-83. 

Choi MH, Ryu JS, Lee M, Li S, Chung BS, Chai JY, Sithitharworn P, 

Tesana S, Hong ST (2003): Specific and common antigens of 

Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, 

Trematoda). Korean Journal of Parasitology 41, 35–39. 

Choi TK (1989): lntrahepatic stones. British Journul of Surgery 76: 213-214. 

Choi TK and Wong J (1986): Partial hepatectomy for intrahepatic stones. 

World Journal of Surgery 10: 281-286.

References ١٤٩ 

Choi TK,Wong J and Ong GB (1982): The surgical management of primary 

intrahepatic stones. Br J Surg; 69: 86-90. 

Choi, BI and, Han JK (2001): Other parasitic diseases, p. 579-581. In K. 

Okuda, D. G. Mitchell, Y. Itai, and J. Ariyama (ed.), Hepatobiliary 

disease pathophysiology and imaging. Blackwell Science, London, 

United Kingdom 

Chung RS, Chad V and Eisenstat M (1997): Choledocholithiasis treated 

with laparoscopic stenting of the papilla followed by stent guided 

sphincterotomy. Gastrointest Endosc; 45: A405. 

Classen M and Demling L (1974): Endoskopische sphinkterotomie der 

papilla vateri und steinextraktion aus dem ductus choledochus 

(German). Dtsch Med Wochenschr;99:496-7. 

Clay RC and Straight WM (1961): Surgical removal of liver flukes from the 

common bile duct. JAMA;177:786–788. 

Cohen SA, Siegel JH and Kasmin FE.(1996): Complications of diagnostic 

and therapeutic ERCP. Abdom Imaging; 21:385-394. 

Conchedda M, Ecca A, Gabrielle F, Bortoletti G, Palmas C. (2002): 

Options for control of echinococcosis: the Sardinian example. In: Craig P, 

Pawlowski Z, eds. Cestode zoonoses: echinococcosis and cysticercosis. 

Amsterdam: IOS Press,: 343–53. 

Coppola R, Riccioni ME, Ciletti S, et al. (1997): Analysis of complications 

of endoscopic sphincterotomy for biliary stones in a consecutive series of 

546 patients. Surg Endosc; 11:120–32. 

Cosme A, Alzate L, Orive V, Recasens M, Torrado J, Ruiz I, Arenas J 

(1990): Laparoscopic findings in liver fascioliasis: study of 13 cases. Rev 

Esp Enferm Dig;78:359–362.

References ١٥٠ 

Costamagna G, Shah SK and Tringali A (2003): Current management of 

post-operative complications and benign biliary strictures. Gastrointest 

Endosc Clin N Am;13:635-48, ix. 

Cotton PB, Lehman G and Vennes JA (1991): Endoscopic sphincterotomy 

compilations and their management: An attempt at consensus. 

Gastrointest Endosc; 37: 383-91. 

Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA,et al.,(2007): 

Prevention and control of cystic echinococcosis 

http://infection.thelancet.com Vol 7. 

Cremin BJ (1982): Ultrasonic diagnosis of biliary ascariasis. (A bull’s eye in 

thee triple O). Br J Radiol;55:683. 

Cuschieri A, LezocheE, Morino M et al. (1999): multicenter prospective 

randomized trial comparing two-stage vs one-stage management of 

patients with gall stones disease and ductal calculi. surg. Enodsc, 

13(10):952-7. 

Cuschieri A. (2002): Disorders of the biliary tract. In Essential surgical 

D 

practice (Higher surgical training in general surgery) edited by Sir Al 

Fred Cuschieri et al., forth edition published by Arnold Module 10 pp 

375-453. 

Dandan, Soweid AM, Abiad F (2005) :Choledocholithiasis, e. medicine 

from Gastroenterology magazine.www. e. medicine.com. 

Dawes B (1963): Fasciola hepatica: A tissue feeder. Nature;198:1011–1012. 

De Vries JH, Duijm LEM, Dekker W, Guit GL, Ferwerda J, Scholten ET. 

(1997): CT before and after ERCP: detection of pancreatic pseudotumor,

References ١٥١ 

asymptomatic retroperitoneal perforation, and duodenal diverticulum. 

Gastrointest Endosc; 45:231-235. 

Del Favero G, Fabris C, Angonese C, et al. (1988): Cytology in the 

diagnosis of pancreatic cancer. Int J Pancreatol 3: 137-141. 

Demling L, Koch H, Classen M. (1974): endoscopic papillotomy and 

removal of gall stones animal expermint and first clinical results; 

99:2255-2257. 

Desilets DJ and Howell DA (2004): Precut sphincterotomy: another 

perspective on efficacy and complications. Available at: 

www.uptodateonline. com. Accessed 11-1 

Devereaux BM, Fein S, Purich E, Trout JR, Lehman GA, Fogel EL, et al. 

(2003): A new synthetic porcine secretin for facilitation of cannulation of 

the dorsal pancreatic duct at ERCP in patients with pancreas divisum: a 

multicenter, randomized, double-blind comparative study. Gastrointest 

Endosc;57:643-647. 

Dewitt J, McHenry L, Fogel EL, Leblanc J, McGreevy K, Sherman S 

(2004): EUS-guided methylene blue pancreatography for minor papilla 

localization after unsuccessful ERCP. Gastrointest Endosc;59: 133-6. 

Dias LM, Silva R, Viana HL, Palhinhas M, Viana RL (1996): Biliary 

fascioliasis: diagnosis, treatment and follow-up by ERCP. Gastrointest 

Endosc;43:616-9. 

Diaz E, Mondragon J, Ramirez E, et al. (2003):Epidemiology and control of 

intestinal parasites with nitazoxanide in children in Mexico. Am J Trop 

Med Hyg 68:384-385. 

Disario JA, Freeman ML, Bjorkman DJ et al. (2004): Endoscopic balloon 

dilation compared with sphincterotomy for extraction of bile duct stones. 

Gastroenterology; 127(5): 1291-1299.

References ١٥٢ 

Ditrich O, Palkovic L, Sterba J, Prokopic J, Loudova J, Giboda M, 

(1991): The first finding of Cryptosporidium baileyi in man. Parasitol. 

Res. 77, 44–47. 

Doherty GM and Way LW (2003): Biliary tract. In: Current Surgical 

Diagnosis and Treatment. Lange Medical Books/McGraw-Hill; 595-625. 

Dooley JR and Neafie RC (1976): Clonorchis and opisthorchiasis, p. 509- 

516. In C. H. Binford, and D. H. Connor (ed.), Pathology of tropical and 

extraordinary diseases, vol. 1. Armed Forces Institute of Pathology, 

Washington, D.C. 

Dowidar N, Sayad ME, Osman M and Salem A (1999): Endoscopic therapy 

of fascioliasis resistant to oral therapy. Gastrointest Endosc 50:345-51. 

Doyle DJ, Hanbidge AE, O’Malley ME (2006): Imaging of hepatic 

infections Clinical Radiology 61, 737-748. 

Draganov P and Cotton PB. (2000): Iodinated contrast sensitivity in ERCP. 

Am J Gastroenterol 95:1398-1401. 

Draganov P, Hoffman B, Marsh W, Cotton P, Cunningham J.(2002): 

Long-term outcome in patients with benign biliary strictures treated 

endoscopically with multiple stents. Gastrointest Endosc;55:680-6. 

Ducommun, D. and Pfister, K. (1991): Prevalence and distribution of 

Dicrocoelium dendriticum and Fasciola hepatica infections in cattle in 

Switzerland. Parasitol. Res. 77, 364–366 

Dumonceau JM, Deviere J and Cremer M.(1998): A new method of 

achieving deep cannulation of the common bile duct during endoscopic 

retrograde cholangiopancreatography. Endoscopy;30:S80. 

Dumot JA, Conwell DL, Zuccaro G, Vargo JJ, Shay SS, Easley KA, et 

al.(2001): A randomized double blind study of interleukin 10 for

References ١٥٣ 

prevention of ERCP-induced pancreatitis. Am J Gastroenterol;96:2098- 

102. 

E 

Eckert J, Deplazes P, Craig PS, Gemmell MA, Gottstein B,Heath D, 

Jenkins DJ, Kamiya M, Lightowlers M (2001): Echinococcosis in 

animals: clinical aspects, diagnosis and treatment. In: Eckert J, Gemmell 

MA, Meslin FX, Pawlowski ZS (Eds.), WHO/OIE Manual on 

Echinococcosis in Humans and Animals: a Public Health Problem of 

Global Concern. World Organisation for Animal Health, Paris, pp. 72–99. 

Eckert J., (1997): Epidemiologyof Echinococcus multilocularis and E. 

granulosus in central Europe. Parassitologia 39, 337–344. 

Eisen GM, Dominitz JA, Faigel DO, Goldstein JL, Kalloo AN, Petersen 

BT, et al.(2001): An annotated algorithm for the evaluation of 

choledocholithiasis. Gastrointest Endosc;53:864-6. 

Eisenscher A. and Sauget Y.(1980): Ultrasonic patterns of Ascariasis and 

Fascioliasis in the biliary ducts. Journal de Radiologie 61(5) 319-322. 

El Sheikh ARM, Al-Karawi MA, Yasawy MI (1991): Modern techniques in 

the diagnosis and treatment of gastrointestinal and biliary tree parasites. 

Hepatogastroenterology;38:180– 188. 

Elkins DB, Haswell-Elkins MR, Mairiang E, Mairiang P, Sithithaworn P, 

Kaewkes S, Bhudhisawasdi V, Uttaravichien T (1990): A high 

frequency of hepatobiliary disease and suspected cholangiocarcinoma 

associated with heavy Opisthorchis viverrini infection in a small 

community in north-east Thailand. Trans. R. Soc. Trop. Med. Hyg. 84, 

715–719.

References ١٥٤ 

Elkins DB, Mairiang E, Sithithaworn P, Mairiang P, Chaiyakum J, 

Chamadol N, Loapaiboon V, Haswell-Elkins MR (1996): Cross- 

sectional patterns of hepatobiliary abnormalities and possible precursor 

conditions of cholangiocarcinoma associated with Opisthorchis viverrini 

infection in humans. Am. J. Trop. Med. Hyg. 55, 295–301. 

Ell C, Hochberger J, May A et al. (1993): Laser lithotripsy of difficult bile 

duct stones by means of a rhodamine-laser and an integrated automatic 

stone-tissue detection system. Gastrointestinal Endoscopy 39(6): 755- 

762. 

Ellis H (1990): Choledocholithiasis in Maingot's abdominal operations, 

Seymour. I. Schwartz, Harold Ellis, and Wendyowles Husser (Eds.) (9th 

edn.) Appleton and Lange PP. 1431-50. 

El-Newihi HM, Waked IA, Mihas AA. (1995): Biliary complications of 

Fasciola hepatica: the role of endoscopic retrograde Cholangiography in 

management. J Clin Gastroenterol;21:309-11. 

El-Shazly AM, El-Nahas HA, Soliman ME,et al. (2005): Cholestasis in 

human fascioliasis in Dakahlia Governorate, Egypt. J Egypt Soc Parasitol. 

Apr;35(1):83-94. 

Enns R, Eloubeidi MA, Mergener K, Jowell PS, Branch MS, Pappas TM, 

et al. (2002): ERCP-related perforations: risk factors andmanagement. 

Endoscopy;34:293-8. 

Erlandsen SL and Chase DG: (1974): Morphological alterations in the 

microvillous border of villous epithelial cells produced by intestinal 

microorganisms. Am J Clin Nutr 27:1277-1286. 

Esber EJ and Sherman S (1996): The interface of endoscopic retrograde 

cholangiopancreatography and laparoscopic cholecystectomy. 

Gastrointest Endosc Clin N Am; 6(1): 57-80.

References ١٥٥ 

Espina AM, Dumenigo BE, Fernandez R, Finley CM (1987): 

F 

Immunodiagnosis of human fascioliasis by enzyme-linked 

immunosorbent assay using excretory-secretory products. Am J Trop. 

Fan ST, Lai EC and Wong J (1993): Hepatic resection for hepatolithiasis. 

Archives of Surgery 128: 1070-1074. 

Fan ST, Lai EC, Mok FP et al (1991): Acute cholangitis secondary to 

hepatolithiasis. Archives of Surgery 126: 1027-1031. 

Fan ST, Mok F, Zheng SS et al. (1993): Appraisal of hepaticocutaneous 

jejunostomy in the management of hepatolithiasis. American Journal of 

Surgery 165: 332-335. 

Farag HF, El-Khoby TA, Salem AI, Abou-Elhoda M, Amin GA. (1998): 

Triclabendazole in treatment of established human fascioliasis. East 

Mediterr Health J;4:244-51. 

Farthing MJ.(1992): Giardiasis comes of age: progress in epidemiology, 

immunology, and chemotherapy. J Antimicrob Chemother;30:563–6. 

Fayer R, Speer CA, Dubey JP, (1997): The general biology of 

Cryptosporidium. In: Fayer R (Ed.), Cryptosporidium and 

Cryptosporidiosis. CRC Press, Boca Raton, FL, pp. 1–41. 

Fennerty MB, Freeman ML, DiSario JA, Nelson DB, Lee JG, Bjorkman 

DJ, et al.(2001): Risk factors for post-ERCP pancreatitis: a prospective, 

multicenter study. Gastrointest Endosc;54:425-34. 

Filice C, and Brunetti E (1997): Use of PAIR in human cystic 

echinococcosis. Acta Trop; 64: 95–107.

References ١٥٦ 

Flanagan PA. (1992):Giardia: diagnosis, clinical course, and epidemiology a 

review. Epidemiol Infect;109: 1–22. 

Fogel EL and Sherman S (1999): How to improve the accuracy of diagnosis 

of malignant biliary strictures. Endoscopy 31:758-760. 

Fogel EL, Eversman D, Jamidar P, Sherman S, Lehman GA.(2002): 

Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with 

pancreatic stent placement has a lower rate of pancreatitis than biliary 

sphincterotomy alone. Endoscopy;34:280-5. 

Foudraine NA,Weverling GJ, van Gool T,Roos MT,DeWolf F, Koopmans 

PP, Van den Broek PJ,Meenhorst, PL, Van Leeuwen R,Lange JM, 

Reiss P, (1998): Improvement of chronic diarrhoea in patients with 

advanced HIV-1 infection during potent antiretroviral therapy, AIDS 12 

35–41. 

Foutch PG (1996): Endobiliary cytotechniques for cancer diagnosis. 

Endoscopy 28:712-717. 

Freeman ML (1998): Complications of endoscopic sphincterotomy. 

Endoscopy; 30:A216-A220. 

Freeman ML (2002): Adverse outcomes of endoscopic retrograde 

chalngiopancreatography. Reviews in Gastroenterological disorders; 2(4): 

147-68. 

Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher 

PT, et al. (1996): Complications of endoscopic biliary sphincterotomy. N 

Engl J Med;335:909-18. 

Freitas ML, Bell RL and Duffy AJ (2006): Choledocholithiasis: evolving 

standards for diagnosis and management. World J Gastroenterol; 12 (20): 

3162-7.

References ١٥٧ 

Fried B, Graczyk TK and Tamang L (2004): Food-borne intestinal 

trematodiases in humans. Parasitology Research 93, 159–170. 

Frossard JL, Hadengue A, Amouyal G et al. (2000):Choledocholithiasis: a 

prospective study of spontaneous common bile duct stone migration. 

Gastrointest Endosc; 51(2): 175-179. 

Fujita N, Maguchi H, Komatsu Y et al. (2003): Endoscopic sphincterotomy 

G 

and endoscopic papillary balloon dilatation for bile duct stones: A 

prospective randomized controlled multicenter trial. Gastrointest Endosc; 

57(2): 151-155. 

Gavindamasy V and Thomson SR (2004): A worm wanted dead or alive. 

SamJ ,July vol (9). 

Gemmell M, Roberts M, Beard T, Campano-Diaz S, Lawson J, 

Nonnemaker J.(2001): Control of echinococcosis. In: Eckert J, Gemmell 

M, Meslin F-X, Pawlowski Z, eds. WHOI/OIE manual on echinococcosis 

Genzlinger JL, McPhee MS, Fisher JK, Jacob KM, Helzberg JH.(1999): 

Significance of retroperitoneal air after endoscopic retrograde 

cholangiopancreatography with sphincterotomy. Am J Gastroenterol; 

94:1267-1270. 

Gerke H, Byrne MF, Stiffler HL, Obando JV, Mitchell RM, Jowell PS, et 

al.(2004): Outcome of endoscopic minor papillotomy in patients with 

symptomatic pancreas divisum. JOP;5:122-31. 

Gershenfeld L (1968): Iodine. In: Disinfection, sterilization, and preservation. 

Lawrence CA, Block SS, editors. Philadelphia: Lea & Febiger;. p. 329- 

47.

References ١٥٨ 

Giurgiu DIN and Roslyn JJ (1997): Calculous biliary disease. In:Essentials 

of Surgery. Chapter 41; 305-12. 

Goldman IS and Brandborg LL (1996): Parasite diseases of the liver. In 

Zakim D and Boyer TD (eds) Hepatology: A Textbook of Liver Disease, 

pp 1206-1231. Philadelphia: WB Saunders. 

Goodale RL, GajI-Peczalska K, Dressel T, et al (1981): Cytologic studies 

for the diagnosis of pancreatic cancer. Cancer 47:1652-1655. 

Gookin JL, Nordone SK, Argenzio RA (2002): Host responses to 

Cryptosporidium infection. J. Vet. Int. Med.16, 12–21. 

Gorski ED.(1985): Management of giardiasis. Am Fam Physician;32:157–64. 

Gott PE, Tieva MH, Barcia PJ et al (1996): Biliary access procedure in the 

management of oriental cholangiohepatitis. American Surgeon 62(11): 

930-934. 

Gottlieb K and Sherman S (1998): ERCP and endoscopic biliary 

sphincterotomy-induced pancreatitis. Gastrointest Endosc; Clin N Am; 8: 

87-114. 

Gottstein B (1992): Molecular and immunological diagnosis of 

echinococcosis. Clin Microbiol Rev; 5: 248–61. 

Granot E, Spira DT, Fraser D, et al. (1998): Immunologic response to 

infection with Giardia lamblia in children: Effect of different clinical 

settings. J Trop Pediatr 44:241-246. 

Gross BH, Harter LP, Gore RM et al (1983): Ultrasonic evaluation of 

common bile duct stones: prospective comparison with endoscopic 

retrograde cholangiopancreatography. Radiology; 146(2): 471-474. 

Guerrant RL (1997): Cryptospridiosis: an emerging, highly infectious threat. 

Emerg Infect Dis;3:51–7.

References ١٥٩ 

Gupta NM (1987): Fasciola gigantica in gall bladder. Indian J Gastroenterol; 

6:113. 

H 

Hadden JW and Pascarelli EF (1967): Diagnosis and treatment of human 

fascioliasis. JAMA; 202:149–151. 

Hahn PF, Stark DD, Vici LG and Ferrucci JT.(1986): Duodenal hematoma: 

the ring sign in MR imaging. Radiology; 159:379-382. 

Halla AH, Amortegui JD, Jeroukhimov IM, Casilla J, et al (2005): 

Magnetic resonance cholangiopancreatography accurately detects 

common bile duct stones in resolving gallstone pancreatitis. Am J Surg; 

200: 869-75. 

Halpin VJ and Soper NJ (2001). The management of common bile duct 

stones. Current Surgical Therapy. 7th ed.:435-440. 

Halpin VJ, Dunnegan D, Soper NJ (2002): Laparoscopic intracorporeal 

ultrasound versus fluoroscopic intraoperative cholangiography: after the 

learning curve. Surg Endosc. 2002; 16:336-341. 

Hamlyn AN, James OF, Douglas AP et al. (1976): Caroli’s disease with 

intrahepatic gallstones and Salmonella infection. Posrgraduare Medical 

Journal 52: 656-659. 

Han JK, Choi BI, Cho JM, Chung KB, Han MC, Kim CW (1993): 

Radiological findings of human fascioliasis. Abdom Imaging;18:261– 

264. 

Hardman EW, Jones RLH, Davies AH (1970): Fascioliasis: A large 

outbreak. Br Med J;29: 502–505.

References ١٦٠ 

Harinasuta C and Harinasuta T (1984): Opisthorchis viverrini: life cycle, 

intermediate hosts, transmission to man and geographical distribution in 

Thailand. Arzneimittelforschung 34, 1164–1167. 

Harinasuta T, Riganti M and Bunnag D (1984): Opisthorchis viverrini 

infection: pathogenesis and clinical features.Arzneimittelforschung. 34, 

(9B):1167–1169. 

Harris A, Chan AC and Torres-Viera C (1999): Meta analysis of antibiotic 

prophylaxis in Endoscopic Retrograde Cholangiopancreatography 

(ERCP). Endoscopy; 31: 718-24. 

Haswell-Elkins MR, Sithithaworn P, Mairiang E, Elkins DB, 

Wongratanacheewin S, Kaewkes S, Mairiang, P, (1991): Immune 

responsiveness and parasite-specific antibody levels in human 

hepatobiliary disease associated with Opisthorchis viverrini infection. 

Clin. Exp. Immunol. 84, 213–218. 

Hauser SC and Bynum TE (1984):Abnormalities on ERCP in a case of 

Hawes RH (2002): Diagnostic and therapeutic uses of ERCP in pancreatic and 

biliary tract malignancies. Gastrointest Endosc;56(Suppl 6): S201-5. 

Hawes RH and Sherman S (1995): Choledocholithiasis. In: 

Gastroenterology. 5th edition, Chapter. 142; 2745. 

Heresi G and Cleary TG (1997): Giardia. Pediatr Rev 18:243-247. 

Heuman DM (2006):Cholelithiasis,e.medicine from,Gastroenterology 

magazine. WWW. emedicine. Com 

Hewitt RG,Yiannoutsos CT, Higgs ES, Carey JT, Geiseler PJ, Soave R, 

Rosenberg R, Vazquez GJ, Wheat LJ, Fass RJ, Antoninievic Z, 

Walawander AL, Flanigan TP, Bender JF, (2000): AIDS Clinical Trial 

Group, Paromomycin: no more effective than placebo for treatment of

References ١٦١ 

cryptosporidiosis in patients with advanced human immunodeficiency 

virus infection, Clin. Infect. Dis. 31 1084–1092. 

Heyries L, Barthet M, Delvasto C, Zamora C, Bernard JP, Sahel J.(2002): 

Longterm results of endoscopic management of pancreas divisum with 

recurrent acute pancreatitis. Gastrointest Endosc;55:376-81. 

Hijjawi NS, Meloni BP, Ryan UM, Olsen ME, Thompson RCA (2002): 

Successful in vitro cultivation of Cryptosporidium andersoni: evidence 

for the existence of novel extracellular stages in the life cycle and 

implications for the classification of Cryptosporidium. Int. J. Parasitol. 

32, 1719–1726. 

Hill DR (1993): Giardiasis: issues in diagnosis and management. Infect Dis 

Clin North Am;7:503–25. 

Hill J, Martin DF and Tweedle DE (1991): Risk of leaving the gallbladder in 

situ after endoscopic sphincterotomy for bile duct stones. Br J Durg; 78: 

554-7. 

Hintze RE, Alder A and Velzke W (1997): Clinical significance of magnetic 

resonance cholangiopancreatography (MRCP) Compared to Endoscope 

Retrograde Cholangiopancreatography; 29: 182-7. 

Hirota WK, Petersen K, Baron TH, Goldstein JL, Jacobson BC, Leighton 

JA, et al.(2003): Guidelines for antibiotic prophylaxis for GI endoscopy. 

Gastrointest Endosc;58:475-82. 

Hitanant S, Tan-Ngarm Trong D, Damrongsak C, Chinapak O, 

Boonyapisit S, Plengvanit U, Viranuvatti V, (1987): Peritoneoscopic 

findings in 203 patients with Opisthorchis viverrini infection. 

Gastrointest. Endosc. 33, 18–20.

References ١٦٢ 

Hixson LJ, Fennerty MB, Jaffee PE et al. (1992): Peroral cholangioscopy 

with intracorporeal electrohydraulic lithotripsy for choledocholithiasis. 

Am J Gastroenterol; 87(3): 296-299. 

Hokkaido University School of Medicine,: 63–68. 

Holm M and Matzen P (2003): Stenting and extracorporeal shock wave 

lithotripsy in chronic pancreatitis. Scand J Gastroenterol;38:328-31. 

Hong ST, Huh S, Kho WG, Ryu J R, Chai JY, Lee SH and Kim EJ (1990): 

Changes of histopathological and serological findings of the liver after 

treatment in rabbit clonorchiasis. Seoul J. Med. 31:117-127. 

Hong ST, Yoon KS, Lee MJ, Seo M, Choi MH, Sim JS, Choi BI, Yun CK, 

and Lee SH (1998): Control of clonorchiasis by repeated praziquantel 

treatment and low diagnostic efficacy of sonography. Korean J. Parasitol. 

36:249-254. 

Horton R (1997): Albendazole in treatment of human cystic echinococcosis: 

12 years of experience. Acta Trop; 64: 79–93. 

Hoskins LC, Winawer SJ, Broitman SA, et al. (1967): Clinical giardiasis 

and intestinal malabsorption. Gastroenterology 53:265-279. 

Houchen CW (2005): Division of Gastroenterology, Washington University 

School of Medicine, St. Louis, MO. ; ADAM Health Illustrated 

Encyclopedia. WWW. Healthline. Com 

Howard TJ, Tan T, Lehman GA, Sherman S, Madura JA, Fogel E, et al. 

(1999): Classification and management of perforations complicating 

endoscopic sphincterotomy. Surgery;126:658-65. 

Howell DA, Beveridge RP, Bosco J, et al. (1992): Endoscopic needle 

aspiration biopsy at ERCP in the diagnosis of biliary strictures. 

Gastrointest Endosc 38:531-535.

References ١٦٣ 

Hsu RK, Draganov P, Leung JW, Tarnasky PR, Yu AS, Hawes RH, et 

al.(2000): Therapeutic ERCP in the management of pancreatitis in 

children. Gastrointest Endosc ;51:396-400. 

Hui CK, Lai KC, Ng M et al. (2003): Retained common bile duct stones: a 

I 

comparison between biliary stenting and complete clearance of stones by 

electrohydraulic lithotripsy. Aliment Pharmacol Ther; 17(2):289-296. 

Ido K, Isoda N, Taniguchi Y, et al (1996): Laparoscopic transcystic 

cholangioscopic lithotripsy for common bile duct stones during 

laparoscopic cholecystectomy. Endoscopy; 28:431–5 

Issa H, Al-Haddad A and Al-Salem AH, (2006): Diagnostic and therapeutic 

ERCP in the pediatric age group. Pediatr Surg Int. 

J 

Jamidar PA, Beck G J, Hoffman B J, et al. (1995): Endoscopic retrograde 

cholangiopancreatography in pregnancy. Am J Gastroenterol; 90: 1263- 

1267.

References ١٦٤ 

Jastak JT and Peskin RM (1991): Major morbidity or mortality from office 

anesthetic procedures: a closed-claim analysis of 13 cases. Anesth Prog 

38:39-44. 

Jeng KS, Sheen IS and Yang FS (1999): Are expandable metallic stents 

better than conventional methods for treating difficult intrahepatic biliary 

strictures with recurrent hepatolithiasis? Arch Surg; 134: 267-273. 

Jeng KS, Yang FS, Ohta I et al. (1990): Dilatation of intrahepatic biliary 

strictures in patients with hepatolithiasis. World Journal of Surgery 14(5): 

587-592. 

Jenkins DJ (2002): Echinococcus in Australia: the role of wildlife in 

transmission, with particular reference to South Eastern 

Australia.In:Craig P, Pawlowski Z (Eds.), Cestode Zoonoses: 

Echinococcosis and Cysticercosis an Emergent and Global problem. IOS 

Press, Amsterdam, pp. 327–332. 

Jenkins DJ and Morris B (1995): Unusuallyheavy infection of Echinococcus 

granulosus in wild dogs in south eastern Australia. Australian 

VeterinaryJournal 66, 36–37. 

Jessen K, Al-Mofleh I and Al-Mofarreh M (1986): Endoscopic treatment of 

ascariasis causing acute obstructive cholangitis. Hepatogastroenterology 

;33:275–277. 

Jimenez CI, del Olmo ML and Perez HM (2001): Helical CT without 

contrast in choledocholithiasis diagnosis. Eur Radiol; 11(2): 197-201. 

Jithendran KP and Bhat TK (1996): Prevalence of dicrocoeliosis in sheep 

and goats in Himachal Pradesh. India.Vet. Parasitol. 61, 265–271. 

Jokipii L and Jokipii AM (1986): Timing of symptoms and oocyst excretion 

in human cryptosporidiosis. N. Engl. J.Med. 315, 1643–1647.

References ١٦٥ 

Jones EA, Kay JM, Milligan HP, Owens D (1977): Massive infection with 

Fasciola hepatica in man. Am J Med;63:836. 

Juttijudata P, Palavatana C, Chiemchaisri C, Churnratanakul S (1983): 

K 

Percutaneous transhepatic cholangiography with the Chiba needle in 

patients with biliary calculi Radiology.;146:643-645. 

Kaewkes S (2003):Taxonomy and biology of liver flukes Acta Tropica (88) 

177–186 

Kahaleh M, Hartwell GD, Arseneau KO, Pajewski TN, Mullick T, Isin G, 

et al. (2004): Safety and efficacy of ERCP in pregnancy. Gastrointest 

Endosc;60:287-92. 

Kahl S, Zimmermann S, Genz I, Glasbrenner B, Pross M, Schulz HU, et 

al.(2003): Malfertheiner risk factors for failure of endoscopic stenting of 

biliary strictures in chronic pancreatitis: a prospective follow-up study. 

Am J Gastroenterol;98:2448-53. 

Kamath KR and Murugasu R: (1974): A comparative study of four methods 

for detecting Giardia lamblia in children with diarrheal disease and 

malabsorption. Gastroenterology 66:16-21. 

Kamath PSDC, Joseph R, Chandran SR, Rao ML, Prakash AJ D’Cruz 

(1986):Biliary ascariasis: Ultrasonography, endoscopic retrograde 

cholangiography and biliary drainage. Gastroenterology;91:730–732. 

Katanik MT, Schneider SK, Rosenblatt JE, et al. (2001): Evaluation of 

ColorPAC Giardia/Cryptosporidium rapid assay and ProSpecT 

Giardia/Crypto-sporidium microplate assay for detection of Giardia and 

Cryptosporidium in fecal specimens. J Clin Microbiol 39:4523-4525,

References ١٦٦ 

Kaufman HS, Magnuson TH, Lillemoe KD et al. (1989): The role of 

bacteria in gallbladder and common duct stone formation. Ann Surg; 209: 

584-592. 

Kawai K, Akasaka Y and Nakajima M,(1973): a preliminary report on 

Endoscopical papillotomy j Kyoto pref univ med;82:353-355. 

Kawai K, Akasaka Y, Murakami K, Tada M, Koli Y.(1974): Endoscopic 

sphincterotomy of the ampulla of Vater. Gastrointest Endosc;20:148-51. 

Kaya M, Petersen BT, Angulo P, Baron TH, Andrews JC, Gostout CJ, et 

al.(2001): Balloon dilation compared to stenting of dominant strictures in 

primary sclerosing cholangitis. Am J Gastroenterol;96:1059-66. 

Kayabali I, Gokcora IH, Yerdel MA, Ormeci N (1992): Hepatic fascioliasis 

and biliary surgery. Int Surg;77:154–157. 

Kelly E, Williams JD and Organ CH (2000): A history of the dissolution of 

retained choledocholithiasis. Am J Surg.; 180:86-98. 

Kerr DM, Foutch PG, Harlan JR, et al. (1991): A prospective, controlled 

analysis of endoscopic cytotechniques for diagnosis of malignant biliary 

strictures. Am J Gastroenterol 86:577-580. 

Khuroo M, Wani N, Javid G, et al. (1997) Percutaneous drainage 

compared with surgery for hepatic hydatid cysts. N Engl J Med; 337: 

881–87. 

Khuroo MS and Zargar SA (1985): Biliary Ascariasis: A common cause of 

biliary and pancreatic disease in an endemic area. Gastroenterology 

;88:418–423. 

Khuroo MS, Mahajan R, Zargar SA, Javid G, Sapru S (1989): Prevalence 

of biliary tract disease in India: A sonographic study in adult population 

in Kashmir. Gut;30:201–205.

References ١٦٧ 

Khuroo MS, Zargar SA, Mahajan R, Bhat LR, Javid G (1987): 

Sonographic appearances in biliary ascariasis. Gastroenterology;93:267– 

272. 

Khuroo MS, Zargar SA, Mahajan R. (1990)Hepatobiliary and pancreatic 

ascariasis in India. Lancet;335:1503-1506. 

Khuroo MS, Zargar SA, Yattoo GN et al (1992) Ascaris-induced acute 

pancreatitis. Brirish Journal of Surgery 79(12): 1335-1338. 

Khuroo MS, Zargar SA, Yattoo GN, Dar MY, Javid G, Khan BA, et al. 

(1992): Sonographic findings in gallbladder ascariasis. J Clin 

Ultrasound;20:587-91. 

Kiladze M, Chipashvili L, Abuladze D, Jatchvliani D (2000): Obstruction 

of common bile duct caused by liver fluke-Fasciola hepatica.Sb 

Lek;101:255-9. 

Kim KP, Kim MH, Song MH, Lee SS, Seo DW, Lee SK.(2004): 

Autoimmune chronic pancreatitis. Am J Gastroenterol;99:1605-16. 

Kirkpatrick BD and Sears CL (2000):Cryptosporidiosis. In: Goldman L, 

Bennett CJ,eds. Cecil textbook of medicine. 21 st ed. Philadelphia: W.B. 

Saunders, :1967–9. 

Koompirochana V, Sonakul S, Chinda K, Stitnimankarn T (1978): 

Opisthorchiasis: a clinicopathologic study of 154 autopsy cases. 

Southeast Asian J. Trop. Med. Public Health 9, 60–64. 

Koshy G, Nair S, Norkus EP, et al. (2000): Propofol versus midazolam and 

meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol 

95:1476-1479.

References ١٦٨ 

Koumanidou C, Manoli E, Anagnostara A, Polyviou P, Vakaki M. (2004): 

Sonographic features of intestinal and biliary ascariasis inchildhood: case 

report and review of the literature. Ann TropPaediatr;24:329-35. 

Kourtis AP (2001).Cryptosporidiosis. eMed J;2:1–11. 

Kozarek R (2002): Role of ERCP in acute pancreatitis. Gastrointest 

Endosc;56(Suppl 6):S231-6. 

Kozarek R, Kodama T and Tatsumi Y (2003): Direct cholangioscopy and 

pancreatoscopy. Gastrointest Endosc Clin N Am;13:593-607. 

Kubota Y, Takaoka M, Tani K, et al. (1993): Endoscopic transpapillary 

biopsy for diagnosis of patients with pancreaticobiliary ductal strictures. 

Am J Gastroenterol 88:1700-1704. 

Kuhlman JE, Fishman EK, Milligan FD, Siegelman SS (1989): 

Complications of endoscopic retrograde sphincterotomy: computed 

tomographic evaluation. Gastrointest Radiol; 14:127-132. 

L 

Lahoti S, Catalano MF, Geenen JE, Hogan WJ (1997): A prospective, 

double-blind trial of L-hyoscyamine versus glucagon for the inhibition of 

small intestinal motility during ERCP. Gastrointest Endosc;46:139-42. 

Laokpessi A, Bouillet P, Sautereau D et al. (2001):Value of magnetic 

resonance cholangiography in the preoperative diagnosis of common bile 

duct stones. Am J Gastroenterol; 96(8): 2354-2359.

References ١٦٩ 

Lapteva GF (1990):Opisthorchiasis-related nephropathy. Vrach.Delo. 2, 67– 

69. 

Larrieu E and Frider B (2001) Human cystic echinococcosis: contributions 

to the natural history of the disease. Ann Trop Med Parasitol; 95: 679–87. 

Lau WY, Fan ST, YIP WC et al (1987): Surgical management of strictures 

of the major bile ducts in recurrent pyogenic cholangitis. British Journal 

of Surgery 74(12): 1100-1102. 

Laubenberger J, Buchert M and Schneider B (1995): Breath-hold 

projection Magnetic Resonance Cholangiopancreatography (MRCP): A 

new method for the examination of the bile and pancreatic ducts. Magn 

Reson Med; 33: 18-23. 

Lee FM (2006): Cholelithiasis. www.emedicine.com. 

Lee JG and Leung J (1998): Tissue sampling at ERCP in suspected 

pancreatic cancer. Gastrointest Endosc Clin N Am 8:221-235. 

Lee KH, Hong ST, Han JK, Yoon CJ, Lee S, Kim SH and Choi BI (2003): 

Experimental clonorchiasis in dogs: CT findings before and after 

treatment. Radiology. 228:131-138. 

Lee SH, Hong ST and Kim JS (1987): Histopathological changes of the liver 

after praziquantel treatment in Clonorchis sinensis infected rabbits. 

Korean J. Parasitol. 25:110-122. 

Lee SH, Shim TS, Lee SM, and Chi JG (1978): Studies on pathological 

changes of the liver in albino rats infected with Clonorchis sinensis. 

Korean J. Parasitol. 16:148-155. 

Lehman GA (2002): Role of ERCP and other endoscopic modalities in 

chronic pancreatitis. Gastrointest Endosc;56(Suppl 6):S237-40.

References ١٧٠ 

Leung J, Sung JY, Ling T, Chung S, Metreweli C (1988): Filamentous 

filling defects on ERCP is pathognomonic of hepatic clonorchiasis. 

Gastrointest Endosc;34:189–190. 

Leung JW (1997): Hepatolithiasis and biliary parasites. Baillieres Clin 

Gastroenterol ;11(4):681-706. 

Leung JW and Chung SC (1988): Endoscopic management of biliary 

ascariasis. Gastrointestinal Endoscopy 34(4): 3 18-320. 

Leung JW and Cotton PB (1991): Endoscopic nasobiliary catheter drainage 

in biliary and pancreatic disease. American Journal of Gastroenterology 

86: 389-394. 

Leung JW and Tu R.(2004): Mechanical lithotripsy for large bile duct stones. 


Leung JW, Ling TK, Chan RC et al. (1994). Antibiotics, biliary sepsis, 

and bile duct stones. Gastrointest Endosc; 40(6): 716-721. 

Leung JW, Mok SD and Metreweli C (1987): Ascaris-induced pancreatitis. 

American Journal of Roentgenology 149(3): 511-512. 

Leung JW, Sung JY, Banez VP et al. (1990): Endoscopic 

cholangiopancreatography in hepatic clonorchiasis-a follow-up study. 

Gasfrointesrinal Endoscopy 36(4): 360-363. 

Leung JW, Sung JY, Chung SC et al. (1989): Hepatic clonorchiasis-a study 

by endoscopic retrograde cholangiopancreatography. Gastrointestinal 

Endoscopy 35(3): 226-23 1. 

Leung JW, Sung JY, Chung SC, et al. (1989): Endoscopic scraping biopsy 

of malignant biliary strictures. Gastrointest Endosc 35:65-66. 

Levine GI. (1991): Sexually transmitted parasitic diseases. Prim Care;

References ١٧١ 

Lewis FW, Moloo N, Stiegmann GV, Goff JS (1991): Splenic injury 

complicating therapeutic upper gastrointestinal endoscopy and ERCP. 

Gastrointest Endosc; 37:632-633. 

Liessi G, Cesari S, Dell’Antonio C et al. (1996): Cholangiopancreatography 

with magnetic resonance. Clinical use of a new ‘inversion-recovery’ 

sequence. Radiologia Medica 92(3): 252-256. 

Lightner AM and Kirkwood KS (2001): Pathophysiology of gallstone 

pancreatitis. Front Biosci; 6: E66-E76. 

Lim JH,Ko YT, Lee DH, Kim SY.(1989): Clonorchiasis: sonographic 

findings in 59 proved cases. AJR Am J Roentgenol.Apr;152(4):761-764.. 

Lim JH. (1990): Radiologic findings of clonorchiasis.AJR Am J Roentgenol. 

;155(5):1001-1008. 

Liu CL, Lo CM, Chan JK, et al. (2001): Detection of Choledocholithiasis by 

EUS in acute pancreatitis: a prospective evaluation in 100 consecutive 

patients. Gastrointest Endosc.;54:325-330. 

Lloyd DA (1981): Massive hepatobiliary ascariasis in childhood. Br J 

Surg;68:468–473. 

Lloyd DA (1982): hepatobiliary ascariasis in children.surg A nnu 14:277-297. 

Loperfido S, Angelini G, Benedetti G, Chilovi F, Costan F, De Berardinis 

F, et al.(1998): Major early complications from diagnostic and 

therapeutic ERCP: a prospective multicenter study. Gastrointest 

Endosc;48:1-10. 

Lowrence W and Way MD (1994): Calculous Biliary Disease. In Biliary 

Tract Current Surgery, 537.

References ١٧٢ 

Lujan HD, Mowatt MR, Byrd LG, Nash TE (1996): Cholesterol starvation 

M 

induces differentiation of the intestinal parasite Giardia lamblia. Proc Natl 

Acad Sci U S A;93:7628-33. 

Machado A, Lozano A, Astete M, et al (1996): Endoscopic retrograde 

cholangiopancreatography and sphincterotomy in parasitic diseases. Rev 

Gastroenterol Peru. Sep-Dec;16(3):258-63,. 

MacMathuna P, Lennon J and Crowe J (1993): Endoscopic balloon 

sphincteroplasty for benign papillary stenosis-an alternative to surgical or 

endoscopic papillotomy? Itish J Med Sci; 162: 355-7. 

Macpherson CNL (1983):An active intermediate host role for man in 

Mairiang E, Elkins DB, Mairiang P, Chaiyakum J, Chamadol N, 

Loapaiboon V, Posri S, Sithithaworn P, Haswell-Elkins MR (1992): 

Relationship between intensity of Opisthorchis viverrini infection and 

hepatobiliary disease detected by ultrasonography. J. Gastroenterol. 

Hepatol. 7, 17–21. 

Mairiang E, Haswell-Elkins MR, Mairiang P, Sithithaworn P, Elkins DB, 

(1993): Reversal of biliary tract abnormalities associated with 

Opisthorchis viverrini infection following praziquantel treatment. Trans. 

R. Soc. Trop. Med. Hyg. 87:194–197. 

Mairiang P, Bhudhisawasdi V, Borirakchanyavat V, Sitprija V (1990): 

Acute renal failure in obstructive jaundice in cholangiocarcinoma. Arch. 

Intern. Med. 150, 2357–2360

References ١٧٣ 

Mandell GL, Bennett JE, Dolin R (2000).Cryptosporidium. In: Principles 

and practice of infectious diseases. 5 th ed. Philadelphia: Churchill- 

Livingston;:2903–14. 

Mani S, Ravi R and Parikh S (1996): Sonographic evaluation of CBD 

stones. Bombay Hospital Journal. 

Manialawi MS, Khattar NY, Helmy MM et al (1986) Endoscopic 

diagnosis and extraction of biliary Ascaris. Endoscopy 18: 203-204. 

Maroy R, Moullot P, Daloubeix H, Mathey JC (1987): Pancreatiteaigue 

compliquant une distomatose biliare a Fasciola hepatica chez un patient 

porteur d'un diverticule choledocien . Ann Gastroenterol Hepatol 

(Paris);23:67-70. 

Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, et al. 

(2001):Complications of diagnostic and therapeutic ERCP: a prospective 

multicenter study. Am J Gastroenterol;96: 417-23. 

Mboti B, Stadt JVd, Carlier Y, et al. (1996): Long-term disease-free 

survival after liver transplantation for alveolar echinococcosis. Acta Chir 

Belg ; 96: 229–32. 

Mc cune WS, Shorb PE,Moscovitz H (1968): endoscopic cannulation of the 

ampulla of vater apreliminary report. Annuals of surgery;167:752-756. 

McDermott VG and Nelson RC (1995): Re: MR cholangiopancreatography: 

efficacy of threedimensional turbo spin-echo technique. American 

Journal of Roentgenology 165: 301-302. 

McManus DP (2002): The molecular epidemiologyof Echinococcus 

granulosus and cystic hydatid disease. Transactions of the Royal 

Societyof Tropical Medicine and Hygiene 96, s1/151–s1/157. 

Med Hyg;37:605–608.

References ١٧٤ 

Menghebat L, Jiang L, Chai J (1993): A retrospective survey for surgical 

cases of cystic echinococcosis in the Xinjiang Uygur Autonomous 

Region, PRC (1951–90). In: Andersen F, Chai J, Liu F, eds. 

Compendium on cystic echinococcosis with special reference to the 

Xinjiang Uygur Autonomous Region, People’s Republic of China . 

Provo: Brigham Young University Print Services,: 135–45. 

Mercadier M, Chigot JP, Clot JP et al. (1984): Caroli’s disease. World 

Journal of Surgery 8: 22-29. 

Merighi A, Contato E, Scagliarini R, Miroio G, Tampieri ML, Pazzi P, et 

al. (1996): Quality improvement in gastrointestinal endoscopy: 

microbiologic surveillance of disinfection. Gastrointest Endosc;43:457- 

62. 

Meyer EA (1976): Giardia lamblia: Isolation and axenic cultivation. Exp 

Meyer EA and Jarroll EL (1980): Giardiasis. Am J Epidemiol;111:1–12. 

Meyer EA and Radulescu S (1979): Giardia and giardiasis. Adv Parasitol 

Migala AF (2006): Cholelithiasis, www.emedicine.com. 

Miguel F, Garrasca J, Garcia N, Bustamanta V, Beltran J (1984): CT 

findings in human fascioliasis. Gastrointest Radiol;9:157–159. 

Min HK (1984); Clonorchis sinensis: pathogenesis and clinical features of 

infection. Arzneimittelforschung. ;34(9B):1151-1153. 

Ming-gang C, Yiang-Jiu H, Zhan-ru W, Yue-qui W, Chen MG, Hua XJ, 

Wan ZR, Weng YO, Wang MJ, Zhu PJ, He BZ, Yu MY (1983): 

Praziquantel in 237 cases of clonorchis sinensis. Chin Med J;96:935-940. 

Miquel JF, Covarrubias C, Villaroel L et al. (1998): Genetic epidemiology 

of cholesterol cholelithiasis. Gastroenterology; 0115: 937-946.

References ١٧٥ 

Misra SP, Dwivedi M, Misra V, Singh PA, Agarwal VK (1999): 

Preoperative sonographic diagnosis of acute appendicitis caused by 

Ascaris lumbricoides. J Clin Ultrasound;27:96-7. 

Mitchell SE and Clark RA (1984): A comparison of computed tomography 

and sonography in Choledocholithiasis. Am J Roentgenol; 142(4): 729- 

733. 

Mohamed A, Yasawy M, Karawi MA (1998): Combined albendazole and 

praziquantel versus albendazole alone in the treatment of hydatid 

Monroe LS (1995): Gastrointestinal parasites, p. 3181-3183. In Haubrich WS, 

Schaffner F, and Berk JE (ed.), Bockus gastroenterology, 5th ed. The W. 

B. Saunders Co., Philadelphia, Pa. 

Moon JH, Cha SW, Ryu CB et al (2004): Endoscopic treatment of retained 

bile-duct stones by using a balloon catheter for electrohydraulic 

lithotripsy without cholangioscopy. Gastrointest Endosc; 60(4): 562-566. 

Moore EW (1990): Biliary calcium and gallstone formation. Hepatology 

12(3 Pt 2): 206S-214S. 

Morelli J, Mulcahy HE, Willner IR, Cunningham JT, Draganov P (2003): 

Longterm outcomes for patients with post-liver transplant anastomotic 

biliary strictures treated by endoscopic stent placement. Gastrointest 

Endosc;58:374-9. 

Morris DL and Richards KS (1992): Hydatid Disease: Current Medical and 

Surgical Management. London: Butterworth-Heinemann. 

Moss DM and Arrowood MJ (2001): Quantification of Cryptosporidium 

parvum oocysts in mouse fecal specimens using immunomagnetic 

particles and two-color flow cytometry. J Parasitol 87:406-412. 

Munro AI (1965): Liver fluke in the common bile duct. Br J Surg;52:76–77.

References ١٧٦ 

Nagano I, Pei F, Wu Z, Wu J, Cui H, Boonmars T, Takahashi Y (2004): 

Molecular expression of a cysteine proteinase of Clonorchis sinensis and 

its application to an enzyme-linked immunosorbent assay for 

immunodiagnosis of clonorchiasis. Clinical and Diagnostic Laboratory 

Immunology 11, 411–416. 

Nakayama F, Soloway RD, Nakama T et al. (1986): Hepatolithiasis in East 

Asia. Retrospective study. Dig Dis Sci; 31: 21-26. 

Neoptolemos JP, Hall C, O’Connor HJ et al. (1990): Methyl-tert-butyl-ether 

for treating bile duct stones: the British experience. Br J Surg; 77(1): 32- 

35. 

Neuhaus H, Hoffman W, Gottlieb K et al. (1994): Endoscopic lithotripsy of 

bile duct stones using a new laser with automatic stone recognition. 

Gastrointestinal Endoscopy 40(6): 708-715. 

NIH state-of-the-science statement (2002):on endoscopic retrograde 

cholangiopancreatography (ERCP) for diagnosis and therapy. NIH 

Consens State Sci Statements;19:1-26. 

Nodgaard H, and Kristensen B (1995): Dicrocoelium dendriticum eggs in 

faeces of 2 Somali boys in Denmark: Transitory elimination after arrival 

toDenmark. Ugeskr Laeger;157:4140 

Norton ID, Gostout CJ, Baron TH, Geller A, Petersen BT, Wiersema MJ 

O 

N 

(2002): Safety and outcome of endoscopic snare excision of the major 

duodenal papilla. Gastrointest Endosc;56:239-43.

References ١٧٧ 

O’Donoghue P (1995): Cryptosporidium and cryptosporidiosis in man and 

animals. Int. J. Parasitol. 25, 139–195. 

Okhuysen PC, Chappell CL, Crabb JH, Sterling CR, DuPont HL,(1999): 

Virulence of three distinct Cryptosporidium parvum isolates for healthy 

adults. J. Infect. Dis. 180, 1275–1281. 

Okuda K, Emura T, Morokuma K, Kojima S, and Yokagawa M (1973): 

Clonorchiasis studied by percutaneous cholangiography, and a 

therapeutic trial of toluene-2,4-diisothiocyanate. A case report. 

Gastroenterology 65:457-461. 

Ona FV and Dytoc JNT (1991): Clonorchis-associated cholangiocarcinoma: 

A report of two cases with unusual manifestations. 

Gastroenterology;101:831–839. 78. 

Ong GB (1979):Helminthic diseases of the liver and biliary tract; in Wright R, 

Alberti KGMM, Karran S, Millward-Sadler GH (eds): Liver and Biliary 

Disease. Philadelphia, Saunders, , pp 1267–1303. 

Osman M, Lausten SB, El-Sefi T, Boghdadi I, Rashed MY, Jensen SL 

(1998): Biliary Parasites: Dig Surg;15:287–296. 

Otranto D and Traversa D (2002): A review of dicrocoeliosis of ruminants 

including recent advances in the diagnosis and treatment. Vet. Parasitol. 

107, 317–335. 

Otranto D and Traversa D (2003): Dicrocoeliosis of ruminants: a little 

known fluke disease TRENDS in Parasitology Vol.19 No.1. 

Outwater EK and Gordon SJ (1994): Imaging the pancreatic and biliary 

ducts with MR. Radiology 192:19-21. 

Owen RL, Nemanic PC, Stevens DP (1979): Ultrastructural observations on 

giardiasis in a murine model. I. Intestinal distribution, attachment, and

References ١٧٨ 

relationship to the immune system of Giardia muris. Gastroenterology 

P 

76:757-769. 

Palmer KR and Hofmann AF (1986): Intraductal mono-octanoin for the 

direct dissolution of bile duct stones: experience in 343 patients. Gut; 

27(2): 196-202. 

Pantangco EU and Sahota A (2004): Biliary Stricture. In: Johnson LR 

(editor). Encyclopedia of Gastroenterology. San Diego, California: 

Elsevier,:200-2. 

Parentea F, Bargiggiaa S, Anderlonia A, Bianchi Porrob G (2004): An 

unusual cause of recurrent biliary colics Digestive and Liver Disease 36 

763–765. 

Park SH, de Bellis M, McHenry L, Fogel EL, Lazzell L, Bucksot L, et al. 

(2003): Use of methylene blue to identify the minor papilla or its orifice 

in patients with pancreas divisum. Gastrointest Endosc;57:358-63. 

Parodi-Hueck LE, Wenger F and Montiel-Villasmil D (1972): Ascaris 

hepatic abscess in children. Journal of Pediatric Surgery 7: 69. 

Pasricha PJ (2002): There is no role for ERCP in unexplained abdominal pain 

of pancreatic or biliary origin. Gastrointest Endosc;56(Suppl 6):S267-72. 

Patel R and Shaps J (1982): Intramural duodenal hematoma: a complication 

of ERCP (letter). Gastrointest Endosc; 28:218-219. 

Paulson EK, Vitellas KM, Keogan MT, Low VHS, Nelson RC (1999): 

Acute pancreatitis complicated by gland necrosis: spectrum of findings 

on contrast-enhanced CT. AJR Am J Roentgenol; 172:609-613.

References ١٧٩ 

Pavone P, Laghi A, Catalano C et al. (1996): Biliary-enteric anastomosis: 

role of cholangiography with magnetic resonance. Radiologia Medica 

92(3): 247-25 1. 

Pawlowski ZS, Eckert J, Vuitton DA, Ammann RW, Kern P, Craig PS, 

Dar KF, De Rosa F, Filace C, Gottstein B, Grimm F, Macpherson 

CNL, Sato N, Todorov T, Uchino J, Von Sinner W, Wen H, (2001): 

Echinococcosis in humans: clinical aspects, diagnosis and treatment. In: 

Eckert J, Gemmell MA, Meslin FX, Pawlowski ZS (Eds.), WHO/OIE 

Manual on Echinococcosis in Humans and Animals: a Public Health 

Problem of Global Concern. World Organization for Animal Health, 

Paris, pp. 20–71. 

Pedraza-Diaz S, Amar C and McLauchlin J (2000): The identification and 

characterisation of an unusual genotype of Cryptosporidium from human 

faeces as Cryptosporidium meleagridis. FEMS Microbiol. Lett. 189, 189– 

194. 

Peng WK, Sheikh A, Paterson-Brown S and Nixon SJ (2005): Role of liver 

function tests in predicting common bile duct stones in acute calculous 

cholecytitis. Br J Surg; 92: 1241-7. 

Pereira E, Kannebley J, Carvalho M, et al. (1994): Primary intrahepatic 

lithiasis. Arq Gastroenterol. Apr-Jun; 31(2):63-8. 

Pereira-Lima JC, Jakobs R, Winter UH, Benz C, Martin WR, Adamek 

HE, et al. (1998): Long-term results (7 to 10 years) of endoscopic 

papillotomy for choledocholithiasis. Multivariate analysis of prognostic 

factors for the recurrence of biliary symptoms. Gastrointest 

Endosc;48:457-64. 

Philips RD and Yung YH (1960): Surgical helminthiasis of the biliary tract. 

Ann Surg;152:905–910.

References ١٨٠ 

Ponchon T, Gagnon P, Berger F, et al (1995): Value of endobiliary brush 

cytology and biopsies for the diagnosis of malignant bile duct stenosis: 

results of a prospective study. Gastrointest Endosc 42:565- 572. 

Poretti D, Felleisen E, Grimm F, et al. (1999): Differential immunodiagnosis 

between cystic hydatid disease and other cross-reactive pathologies. Am J 

Trop Med Hyg; 60: 193–98. 

Price J and Leung JW (1988): Ultrasound diagnosis of ascaris lumbricoides 

in the pancreatic duct: the ‘four-lines’ sign. Brifish Journal ofRadiology 

61(725): 411-413. 

Pugliese V, Conio M, Nicolo G, et al. (1995): Endoscopic retrograde forceps 

biopsy and brush cytology of biliary strictures: A prospective study. 

Gastrointest Endosc 42:520-526. 

Pungpak S, Riganti M, Bunnag D and Harinasuta T (1985): Clinical 

Q 

features in severe Opisthorchis viverrini. Southeast Asian J. Trop. Med. 

Public Health 16, 405–409. 

Qaseem T, Howell DA and Elton E (1996): Prevention of post-Endoscopic 

R 

sphincterotomy (ES) bleeding: Is epinephrine usages safe? Am J 

Gastroenterol; 91: 1940. 

Rabinovitz M, Zajko AB, Hassanein T, et al. (1990): Diagnostic value of 

brush cytology in the diagnosis of bile duct carcinoma: A study in 65 

patients with bile duct strictures. Hepatology 12:747-752.

References ١٨١ 

Racq Y, Besnier JM, Duong TH, Pavie G, Metman EH, Choutet P (1991): 

Successful treatment of acute fascioliasis with Bithionol. Hepatology 

;14:1066–1069. 

Rashed MYT, El-Sefi T, Boughdadi I (1995): Endoscopic retrograde 

cholangiographic patterns of biliary fascioliasis. Proc Eur IHPBA Congr 

Raymondos K, Panning B, Bachem I, et al. (2002): Evaluation of 

endoscopic retrograde cholangiopancreatography under conscious 

sedation and general anesthesia. Endoscopy 34:721-726. 

Rege RV (2002): The role of biliary calcium in gallstone pathogenesis. Front 

Biosci 7: E315-325. 

Rehbein S, Kokott S and Lindner T (1999): Evaluation of techniques for the 

enumeration of Dicrocoelium eggs in sheep faeces. Zentralbl. 

Veterinarmed A. 46, 133–139. 

Rigano R, Profumo E, Buttari B, Teggi A, Siracusano A (1999): Cytokine 

gene expression in peripheral blood mononuclear cells (PBMC)from 

patients with pharmacologically treated cystic echinococcosis. Clin Exp 

Immunol; 118: 95–101. 

Riganti M, Pungpak S, Punpoowong B, Bunnag D, Harinasuta T (1989): 

Human pathology of Opisthorchis viverrini infection: a comparison of 

adults and children. Southeast Asian J. Trop. Med. Public Health 20, 95– 

100. 

Riganti M, Pungpak S, Sachakul V, Bunnag D, Harinasuta T (1988): 

Opisthorchis viverrini eggs and adult flukes as nidus and composition of 

gallstones. Southeast Asian J. Trop. Med. Public Health 19, 633–636. 

Rim HJ (1986): The current pathobiology and chemotherapy of clonorchiasis. 

Korean J. Parasitol. 24:(Suppl.):5-141. 108.

References ١٨٢ 

Rim HJ, Lyu KS, Lee JS and Joo KH (1981): Clinical evaluation of the 

therapeutic efficacy of praziquantel (Embay 8440) against Clonorchis 

sinensis infection in man. Ann. Trop. Med. Parasitol. 75:27-33. 

Rivera IN, Lipp EK, Gil A, Choopun N, Huq A, Colwell RR (2003): 

Method of DNA extraction and application of multiplex polymerase 

chain reaction to detect toxigenic Vibrio cholerae O1 and O139 from 

aquatic ecosystems. Environmental Microbiology 5, 599–606. 

Rivero MA and Marcial MA (1989): Biliary tract disease due to Fasciola 

hepatica: Report of a case Bol Asoc Med P R;81:272–274. 

Robinson P, Okhuysen P, Chappell CL, et al. (2003): Substance P 

expression correlates with severity of diarrhea in cryptosporidiosis. J 

Infect Dis 188:290-296. 

Rojo-Vazquez FA, Meana A, Tarazona JM, Duncan JL (1989): The 

efficacy of netobimin, 15 mg/kg, against Dicrocoelium dendriticum in 

sheep. Vet. Rec. 124, 512–513. 

Ros E, Navarro S, Bru C et al. (1991): Occult microlithiasis in ‘idiopathic’ 

acute pancreatitis: prevention of relapses by cholecystectomy or 

ursodeoxycholic acid therapy. Gastroenterology; 101(6): 701-1709. 

Rossignol JF, Ayoub A and Ayers MS (2001): Treatment of diarrhea caused 

by Cryptosporidium parvum: a prospective randomized, double-blind, 

placebocontrolled study of Nitazoxanide. J Infect Dis 184:103-106. 

Roszler MH and Campbell WL (1985): Post-ERCP pancreatitis: association 

with urographic visualization during ERCP. Radiology; 157:595-598. 

Russell RCG, Williams NS and Bulstrode CJK (2000): The Gallbladder and 

S 

Bile Ducts. In: Baily and Love’s Short Practice of Surgery. Oxford 

University Press Inc; 965-84.

References ١٨٣ 

Sackmann M, Holl J, Sauter GH et al (2001): Extracorporeal shock wave 

lithotripsy for clearance of bile duct stones resistant to endoscopic 

extraction. Gastrointest Endosc; 53(1): 27-32. 

Sand J and Norback I. (1993):Prospective randomized trial of nifedipine on 

pancreatic irritation after endoscopic retrograde 

cholangiopancreatography. Digestion;54:105-11. 

Sandouk F, Haffar S, Zada MM, Graham DY, Anand BS. (1997): 

Pancreaticbiliary ascariasis: experience of 300 cases. Am J Gastroenterol 

;92:2264–7. 

Sarinas PS and Chitkara RK (1997): Ascariasis and hookworm. Semin 

Respir Infect;12:130 –7. 

Sarli L, Costi R, Gobbi S et al (2000): Asymptomatic bile duct stones: 

selection criteria for intravenous cholangiography and/or endoscopic 

retrograde cholangiography prior to laparoscopic cholecystectomy. Eur J 

Gastroenterol Hepatol; 12(11): 1175-1180. 

Sato H, Kodama T and Takaaki J (1997b): Endoscopic papillary balloon 

dilatation may preserve sphincter of Oddi function after common bile 

duct stone management: Evaluation from the viewpoint of endoscopic 

manometry. Gut; 41 (4): 541-4. 

Sato N, Akoi S, Matsushita M, Uchino J. (1993): Clinical features. In: 

Sato N, Namieno T, Furuya K, et al. (1997a): Contribution of mass 

screening system to resectability of hepatic lesions involving 

Echinococcus multilocularis. J Gastroenterol; 32: 351–54.

References ١٨٤ 

Sato T, Suzuki N, Takahashi W et al (1980): Surgical management of 

intrahepatic gallstones. Annals of Surgery 192: 28-32. 

Sauerbruch T, Delius M, Paumgartner G et al (1986): Fragmentation of 

gallstones by extracorporeal shock waves. N Engl J Med; 314: 818-822. 

Sauerbruch T, Stellaard F, Paumgartner G. (1983): Effect of endoscopic 

sphincterotomy on bile acid pool size and lipid composition in man. 

Digestion;27:87-92. 

Sawada Y, Gonda H, Hayashida Y (1989): Combined use of brushing 

cytology and endoscopic retrograde pancreatography for the early 

detection of pancreatic cancer. Acta Cytol 33:870-874. 

Scarlett PY and Falk GL. (1994): The management of perforation of the 

duodenum following endoscopic sphincterotomy: a proposal for selective 

therapy. Aust N Z J Surg; 64:843-846. 

Schantz P, Chai J, Craig PS, Eckert J, Jenkins DJ, Macpherson CNL, 

Thakur A (1995): Epidemiologyand control of hydatid disease. In: 

Thompson, R.C.A., Lymbery, A.J. (Eds.), Echinococcus and hydatid 

disease. CAB International, Wallingford, Oxon, pp. 232–331. 

Schirmer BD,Winters KL,and Edlich RF (2005): Cholelithiasis and 

chlecystitis. J Long Term Eff Med Implants. 15(3):329-38 

Schulman A (1977) Biliary ascariasis presenting in the United States. 

American Journal of Gastroenferology 6: 167-170. 

Schulman A, Loston AJ, Heyenrych JJ, Abdurahman KE (1982): 

Sonographic diagnosis of biliary ascariasis. AJR;139:485–489. 

Schulman A. (1998): Ultrasound appearances of intra- and extrahepatic 

biliary ascariasis. Abdom Imaging;23:60-6.

References ١٨٥ 

Schuster DI, Belin RP, Parker JC.(1977): Ascariasis—its complications, 

unusual presentations and surgical approaches. South Med J; 70:176–8. 

Schutz SM and Abbott RM (2000): Grading ERCPs by degree of difficulty: 

a new concept to produce more meaningful outcome data. Gastrointest 

Endosc; 51: 535-9. 

Schwartz D (1986) Cholangiocarcinoma associated with liver fluke 

infection: a preventable source of morbidity in Asian immigrants. 

American Journal of Gasrroenterology 81: 76-79. 

Schwartz SI (2005): Gall bladder and extrahepatic biliary system. In 

principles of Surgery. Edited by Schwartz SS 7 th ed. MacGrow-Hill, 

1437-67. 

Schwartz SI. (1999): Gallbladder and extrahepatic biliary system. Principles 

of Surgery. 7th ed. 1437-1466. 

Seo BS, Lee SH, Cho SY, Chai JY, Hong ST, Han IS, Sohn JS,. Cho BW, 

Ahn SR, Lee SK, Chung SC, Kang KS, Shim HS, and Hwang IS 

(1981): An epidemiologic study on clonorchiasis and metagonimiasis in 

riverside areas in Korea. Korean J. Parasitol. 19:137-150 

Sgourakis G, Dedemadi G, Stamatelooulos A, Leandros E et al. (2005): 

Predictors of common bile duct. Lithiasis in laparoscopic era. World J 

Gastroenterol; 11: 3267-72. 

Shah JN, Ahmad NA, Shetty K, Kochman ML, Long WB, Brensinger 

CM, et al.(2004): Endoscopic management of biliary complications after 

adult living donor liver transplantation. Am J Gastroenterol;99: 1291-5. 

Sharma SS, Bhargawa N, Govil A.(2002): Endoscopic management of 

pancreatic pseudocyst: a long-term follow-up. Endoscopy;34: 203-7.

References ١٨٦ 

Shemesh E, Czerniak A, Bar-El J et al. (1989): Choledocholithiasis: a 

comparison between the clinical presentations of multiple and solitary 

stones in the common bile duct. Am J Gastroenterol; 84(9): 1055-1059. 

Shepherd RW and Boreham PF.(1989).Recent advances in the diagnosis 

and management of giardiasis. Scand J Gastroenterol Suppl;169:60– 

4. 

Sherman S and Lehman GA (1999): Endoscopic retrograde 

cholangiopancreatography, enoscopic sphincterotomy and stone removal 

and endoscopic biliary and pancreatic drainage. In: Textbook of 

Gastroenterology. Chapter 123; 2718. 

Shimizu S, Kutsumi H, Fujimoto S,and Kawai K.(1999): Diagnostic 

endoscopic retrograde cholangiopancreatography. Endoscopy; 31:74-79. 

Shoda J, Inada Y and Osuga T. (2006): Molecular pathogenesis of 

hepatolithiasis. Front Biosci; 11: 669-675. 

Shoda J, Tanaka N and Osuga T (2003): Hepatolithiasis-epidemiology and 

pathogenesis update. Front Biosci. May 1; 8: 398-409. 

Shulman A. (1987): Non-Western patterns of biliary stones and the role of 

ascariasis. Radiology;161:425–430. 

Silvis SE (1991): Endoscopic sphincterotomy with an intact gallbladder. 

Gastrointest Endosc Clin N Am; 1: 65-77. 

Simchuk EJ, Traverso LW, Nukui Y, Kozarek RA.(2000): Computed 

tomography severity index is a predictor of outcomes for severe 

pancreatitis. Am J Surg; 179:352-355. 

Simmons DC, Tarnasky PR, Rivera-Alsina ME, Lopez JF, Edman 

CD.(2004): Endoscopic retrograde cholangiopancreatography (ERCP) in

References ١٨٧ 

pregnancy without the use of radiation. Am J Obstet Gynecol;190: 1467- 

9. 

Sirisinha S (1986): Immunodiagnosis of human liver fluke infestation. Asian 

Pac J Allergy Immunol;4:81. 

Skar V, Skar AG, Midtvedi T, Osnes M. (1986): Bacterial growth in the 

duodenum and in the bile of patients with gallstone disease treated with 

endoscopic papillotomy (EPT). Endoscopy;18:10-3. 

Song MH, Kim MH, Lee SK, Lee SS, Han J, Seo DW, et al.(2004): 

Endoscopic minor papilla interventions in patients without pancreas 

divisum. Gastrointest Endosc;59:901-5. 

Soto JA, Alvarez O, Munera F et al.(2000): Diagnosing bile duct stones: 

comparison of unenhanced helical CT, oral contrast-enhanced CT 

cholangiography, and MR cholangiography. Am J Roentgenol; 

175(4):1127-1134. 

Sripa B, Hawell-Elkins MR, Sinawat P. (2003): Histological analysis of 

cholecystitis in relation to opisthorchiasis in endemic areas of Thailand. 

Acta Trop; 88: 239-246 

Sripa, B., Kaewkes, S., (2000): Localisation of parasite antigens and 

inflammatory responses in experimental opisthorchiasis. Int. J. Parasitol. 

30, 735–740. 

Sripa, B.,and Kaewkes, S., (2002): Gall bladder and extrahepatic bile duct 

changes in Opisthorchis viverrini-infected hamsters. Acta Trop. 83, 29– 

36. 

Stanley RJ, Semelka RC. Pancreas. In: Lee JKT, Sagel SS, Stanley RJ, 

Heiken JP,(1998): eds. Computed body tomography with MRI 

correlation. Philadelphia, Pa: Lippincott-Raven,; 873-960.

References ١٨٨ 

Stapfer M, Selby RR, Stain SC, et al. (2000): Management of duodenal 

perforation after endoscopic retrograde cholangiopancreatography and 

sphincterotomy. Ann Surg; 232:191-198. 

Stewart ET, Dodds WJ. Radiology of the esophagus. In: Freeny PC, 

Stevenson GW,(1994): eds. Margulis and Burhenne’s alimentary tract 

radiology. St Louis, Mo: Mosby–Year Book,; 192-263. 

Stott MA, Farrands PA, Guyer PB et al (1991). Ultrasound of the common 

bile duct in patients undergoing cholecystectomy. J Clin Ultrasound; 

19(2): 73-76. 

Strasberg SM, Callery MPand Soper NJ (1996): Laparoscopic surgery of 

the bile ducts. Gastrointest Endosc Clin North Am; 6:81–105. 

Strichartz SD, Abedin MZ, lppoliti AF et al (1991) Intrahepatic 

cholesterol stones: a rationale for dissolution therapy. Gasrroenterology 

100: 228-232. 

Sugiyama M and Atomi Y (1997): Endoscopic ultrasonography for 

diagnosing choledocholithiasis: a prospective comparative study with 

ultrasonography and computed tomography. Gastrointest Endosc ; 45(2): 

143-146. 

Suhocki PV.(2004) Percutaneous Transhepatic cholangiography (PTC). 

In: Johnson LR (editor). Encyclopedia of Gastroenterology. San 

Diego,California: Elsevier,:154-9. 

Sun, T. (1982): Clonorchiasis and opisthorchiasis, p. 243-252. In T. Sun (ed.), 

Pathology and clinical features or parasitic diseases. Masson, New York, 

N.Y. 

Sun, T. (1984): Pathology and immunology of Clonorchis sinensis infection in 

the liver. Ann. Clin. Lab. Sci. 14:208-215.

References ١٨٩ 

Swidsinski A, Ludwig W, Pahlig H et al (1995): Molecular genetic evidence 

T 

of bacterial colonization of cholesterol gallstones. Gastroenterology; 108: 

860-864. 

Tabata M and Nakayama F (1984): Bacteriology of hepatolithiasis. Prog 

Clin Biol Res.;152:163-74. 

Tabbaa MI and Marshall JB (1988): Endoscopic balloon catheter extraction 

of Ascaris lumbricoides from the biliary tree. Gastrointestinal Endoscopy 

34: 272-274. 

Tanaka M (2002): Bile duct clearance, endoscopic or laparoscopic? J 

Hepatobiliary Pancreat Surg; 9: 729-32. 

Tandon BN, Tandon RK, Satpathy BK, et al: (1977): Mechanism of 

malabsorption in giardiasis: A study of bacterial flora and bile salt 

deconjugation in upper jejunum. Gut 18:176-181. 

Tandon M and Topazian M. (2001): Endoscopic ultrasound in idiopathic 

acute pancreatitis. Am J Gastroenterol;96:705-9. 

Tang, CN, Tsui KK, Ha JPY, Siu WT and Li MKW (2006): Laparoscopic 

exploration of the common bile ducts: 10-years experience of 174 

patients from a sirngle center. Hong Kong Med J Vol 12, No 3. 

Tansurat,P.(1971): Opisthorchiasis. In: Marcial-Rojas, R.A. (Ed.). Pathology 

of Protozoal and Helminthic Diseases. Williams and Wilkins, Baltimore, 

pp. 536–545. 

Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PD, Cotton PB, 

Hawes RH.(1998): Pancreatic stenting prevents pancreatitis after biliary

References ١٩٠ 

sphincterotomy in patients with sphincter of Oddi dysfunction. 

Gastroenterology;115:1518-24. 

Taylor AC, Little AF, Hennessy OF, Banting SW et al (2002): Prospective 

assessment of magnetic resonance cholangiopancreatography for 

noninvasive imaging of the biliary tree. Gastrointest Endosc; 55: 17-22. 

Telford JJ, Farrell JJ, Saltzman JR, Shields SJ, Banks PA, Lichtenstein 

DR.(2002): Pancreatic stent placement for duct disruption. Gastrointest 

Endosc;56:18-24. 

Tessier JL and Davies GA (1999): Infectious diseases update, Giardiasis 

(Prim Care Update Ob/Gyns; 6:8–11. 

Testoni PA, Bagnolo F, Caporuscio S, Lella F.(1999): Serum amylase 

measured four hours after endoscopic sphincterotomy is a reliable 

predictor of postprocedure pancreatitis. Am J Gastroenterol; 94:1235- 

1241. 

Tham TC, Carr-Locke DL and Collins JS (1997): Endoscopic 

sphincterotomy in the young patient: is there cause for concern? Gut; 

40(6): 697-700. 

Tham TC, Lichtenstein DR, Vandervoort J et al (1998): Role of endoscopic 

retrograde cholangiopancreatography for suspected choledocholithiasis in 

patients undergoing laparoscopic cholecystectomy. Gastrointest Endosc; 

47(1): 50-56. 

Tham TC, Vandervoort J, Wong RC, et al (2003): Safety of ERCP during 

pregnancy. Am J Gastroenterol 98:308-311. 

Thamavit, W., Bhamarapravati, N., Sahaphong, S., Vajrasthira, S., 

Angsubhakorn, S., (1978): Effects of dimethylnitrosamine on induction 

of cholangiocarcinoma in Opisthorchis viverrini infected Syrian golden 

hamsters. Cancer Res. 38, 4634–4639.

References ١٩١ 

Theodoridis, Y., Duncan, J.L., MacLeanl, J.M., Himonas, C.A., (1991): 

Pathophysiological studies on Dicrocoelium dendriticum infection in 

sheep. Vet. Parasitol. 39, 61–66. 

Thompson RCA and McManus DP.( 2001): Aetiology: parasites and life- 

cycles. In: Eckert J, Gemmell M, Meslin F-X, Pawlowski Z, eds. 

WHOI/OIE manual on echinococcosis in humans and animals: a public 

health problem of global concern. Paris: World Organisation for Animal 

Health,: 1–19. 

Thompson, R.C.A. and McManus, D.P.,(2002): Towards a taxonomic 

Toh SK, Phillips S and Johnson CD (2000): A prospective audit against 

national standards of the presentation and management of acute 

pancreatitis in the South of England. Gut; 46(2): 239-243. Symptoms, 

diagnosis and endoscopic management of common bile duct stones 1097. 

Tompkins RK (1997): Choledocholithiasis and cholangitis. In: Maingot’s 

Abdominal Operations. 10th edition, 2: 1739-54. 

Topal B, Van de Moortel M, Fieuw S et al. (2003): The value of magnetic 

resonance cholangiopancreatography in predicting common bile duct 

stones in patients with gallstone disease. Br J Surg; 90: 42-7. 

Torgerson, P.R., (2003): The use of mathematical models to simulate control 

options for echinococcosis. Acta Tropica 85, 211–221. 

Tsukada H, Hamazaki K, Ganzorig S, et al.(2002): Potential remedy against 

U 

Echinococcus multilocularis in wild red foxes using baits with 

antihelminthic distributed around fox breeding dens in Hokkaido, Japan. 

Parasitology; 125: 119–29.

References ١٩٢ 

Upatham ES, Brokleman WY, Viyanant V, et al (1985): Indidence of 

endemic Opisthorchis viverrini infection in a village in Northeast 

Thailand. Am J Trop Med Hyg;34:903-906 

Utrilla J, Eyre F, Muguerza R, Alami H, Bueno J. (1991): Hidatidosis en la 

V 

infancia. Arch Hidatid; 30: 721–31. 

Valentine CC, Hoffner RJ and Henderson SO (2001): The Journal of 

Emergency Medicine, Vol. 20, No. 2, pp. 135–139. 

Van Erpecum KJ (2006): Complications of bile-duct stones: acute 

cholangitis and pancreatitis, Best Practice & Research Clinical 

Gastroenterology ,Vol. 20, No. 6, pp. 1139-1152. available online at 

http://www.sciencedirect.com 

Van Sonnenberg E, Casola G, Cubberley DA et al (1986): Oriental 

cholangiohepatitis: diagnostic imaging and interventional management. 

AJR Am J Roentgenol; 146(2): 327-331. 

Vandervoort J and Carr-Locke DL (1996): Needle-knife access 

papillotomy: an unfairly maligned technique? Endoscopy;28:365-6. 

Varadarajulu S, Mel Wilcox C, Hawes RH, Cotton PB.(2004): Technical 

outcomes and complications of ERCP in children. Gastrointest 

Endosc;60:367-71. 

Varghese I, Farrel MA and Liddell RP (2000): Diagnostic accuracy of 

MRCP and US compared with direct cholangiography in the detection of 

choledocholithiasis. Clinical Radiology; 55: 52-5. 

Vatanasapt, V., Sripa, B., Sithithaworn, P., Mairiang, P., (1999): Liver 

flukes and liver cancer. Cancer Surv. 33, 313–343.

References ١٩٣ 

Veerappan A, Siegel JH, Podany J, Prudente R, Gelb A. (1991) Fasciola 

hepatica pancreatitis: endoscopic extraction of live parasites. 


Venneman NG, Buskens E, Besselink MG et al (2005): Small gallstones are 

associated with increased risk of acute pancreatitis: potential benefits of 

prophylactic cholecystectomy? Am J Gastroenterol; 100(11): 2540-2550. 

Viranuvatti, V., and Stitnimankarn, T., (1972): Liver fluke infection and 

infestation in Southeast Asia. In: Popper, H., Schaffner, F. (Eds.), 

Progress in Liver Disease. Grune and Stratton, New York, pp. 537–547. 

W 

Waikagul J., (1998): Opisthorchis viverrini metacercaria in Thai freshwater 

fish. Southeast Asian J. Trop. Med. Public Health 29, 324–326. 

Walterspiel JN and Pickering LK. (1994): Giardia and giardiasis. Prog Clin 

Parasitol ;4:1–26. 

Waye JD (2000): Basic techniques of ERCP. Gastrointestinal Endoscopy, 

American Society for Gastrointestinal Endoscopy, volume 51. 

Wedrychowicz, H., Ducommun, D., Gòrski, P., Pfister, K., (1995): Somatic 

antigens of adult Dicrocoelium dendriticum recognised by bile antibodies 

of naturally infected cattle. Vet. Parasitol. 56, 47–56. 

Wehrmann T, Kokabpick S, Lembcke B, et al (1999): Efficacy and safety 

of intravenous propofol sedation during routine ERCP: A prospective، 

controlled study. Gastrointest Endosc 49:677-683. 

Wehrmann T, Schmitt T, Stergiou N, Caspary WF, Seifert H. (2001): 

Topical application of nitrates onto the papilla of Vater: manometric and 

clinical results. Endoscopy;33:323-8.

References ١٩٤ 

Wermke W and Borges AC (1993): Pathophysiology of gallstone formation 

Ther Umsch. Aug; 50(8):541-6. 

Wesley C. Van Voorhis, Peter F. Weller (2006): Infectious Disease 

Helminthic Infections: Trematode Infections, From ACP Medicine 

Online. 

Weston AP. (1997): Sincalide: a cholecystokinin agonist as an aid in 

endoscopic retrograde cholangiopancreatography: a prospective 

assessment. J Clin Gastroenterol;24:227-30. 

Whitehouse Graham H and Worthington Brian S (1996): Techniques in 

Diagnostic Imaging. 3rd (Eds), Blackwell Scientifics Ltd; 74. 

WHO Technical Research Series 849 (1995): Control of foodborne 

trematode infections. WHO, Geneva, pp. 69–70. 

Wilson J, Rausch R, McMahon B, Schantz P. (1992): Parasiticidal effect of 

chemotherapy in alveolar hydatid disease: review of experience with 

mebendazole and albendazole in Alaskan Eskimos. Clin Infect Dis 15: 

234–49. 

Wolfe MS (1979): Giardiasis. Pediatr Clin North Am 26:295-303. 

Wolfe MS. (1992):Giardiasis. Clin Microbiol Rev;5:93-100. 

Wolff, K., Hauser, B., Wild, P., (1984): Dicrocoeliose des schafes: 

untersuschungen zur pathogenese und zur regeneration der laber nach 

therapie. Berl. Münch Tierärztl. Wschr. 97, 378–387. 

Wong RKH, Peura DA, Mutter ML, Heit HA, Birns MT,Johnson LF. 

(1985): Hemobilia and liver flukes in a patient from Thailand. 

Gastroenterology;88:1958-63.

References ١٩٥ 

Wright BE, Cass OW and Freeman ML.(2002): ERCP in patients with 

long-limb Roux-en-Y gastrojejunostomy and intact papilla. Gastrointest 

Endosc 56:225-232. 

Wright SG and Tomkins AM (1977): Quantification of the lymphocytic 

infiltrate in jejunal epithelium in giardiasis. Clin Exp Immunol 29:408- 

412. 

Wu WC and Katon RM.(1993): Injury to the liver and spleen after diagnostic 

ERCP. Gastrointest Endosc; 39:824-827. 

Wykoff DE, Chittayasothorn K, Winn M (1966): Clinical manifestation of 

O. viverrini infection in Thailand. Am J Trop Med Hyg;15:914–918. 

Y 

Yasuda K, Nakajima M and Kawai K (2001): Technical aspects of 

endosocpic ultrasonography of the biliary system. Scand J Gastroenterol; 

21:143-50. 

Yellin AE and Donovan AJ (1981): Biliary lithiasis and helminthiasis. Am J 

Surg;142:128–136. 

Yonem O. and Bayraktor Y.(2007): clinical characteristic of Caroli’s disease 

Z 

world J gastroenterol. 7;13(13):1930-3. 

Zhang W, Li J, McManus DP. (2003): Concepts in immunology and 

diagnosis of hydatid disease. Clin Microbiol Rev; 16: 18–36. 

Zimmerman SK and Needham CA (1995): Comparison of conventional 

stool concentration and preserved-smear methods with Merifluor 

Cryptosporidium/ Giardia Direct Immunofluorescence Assay and

References ١٩٦ 

ProspecT Giardia EZ Microplate Assay for detection of Giardia lamblia. J 

Clin Microbiol 33:1942-1943. 

Zimmon DS, Falkenstien DB and Kessler RE,(1975): endoscopic 

papillotomy for choledocholithiasis new England journal of 

medicine;293:1181-1182. 

Zissin R, Shapiro-Feinberg M, Oscadchy A, Pomeranz I, Leichtmann G, 

Novis B. (2000): Retroperitoneal perforation during endoscopic 

sphincterotomy: imaging findings. Abdom Imaging; 25:279-282.

ﻰﺘﻟاو ًﺎﻋﻮﻴﺷ ﺔﻴﺒﻄﻟا ﻞآﺎﺸﻤﻟا ﺮﺜآأ 

أ 

ﻰﺑﺮﻌﻟا ﺺﺨﻠﻤﻟا 

ﻦﻣ ﺔﻳراﺮﻤﻟا ﺔﻠﺼﻳﻮﺤﻟا ﻲﻓ تاﻮﺼﺤﻟا ﻞﻈﺘﺳ 

ﺔﻨﻤﺴﻟا تاﻮﺼﺤﻟا ﻚﻠﺗ ﻦﻳﻮﻜﺗ ﻰﻟإ 

يدﺆﺗ ﻰﺘﻟا ﻞﻣاﻮﻌﻟا ﻦﻣو .ﻰﺣاﺮﺠﻟا ﻞﺧﺪﺘﻟا ﻰﻟإ 


يدﺆﺗ 

ﺮﻴﺴﻜﺗ ضاﺮﻣأو 

رﺮﻜﺘﻤﻟا ﻞﻤﺤﻟاو ﻦﻴﺟوﺮﺘﺳﻹا 

ﺔﺒﺴﻧ عﺎﻔﺗرإو 

يﺮﻜﺴﻟا لﻮﺒﻟا ضﺮﻣو 

ﻰﻟإ 

ىدﺆﺗ ﺪﻗ ةراﺮﻤﻟا ﻲﻓ تاﻮﺼﺤﻟا نأ 

ﺮآﺬﺘﻧ نأ 

ﻢﻬﻤﻟا ﻦﻣ ﻪﻧإو 

.ﺪﺒﻜﻟا ﻒﻴﻠﺗو مﺪﻟا 

ﻦﻣ % ١٥ ﻰﻟاﻮﺣ . ﺔﻳراﺮﻤﻟا ﻩﺎﻨﻘﻟا ﻲﻓ تاﻮﺼﺣ ﻦﻳﻮﻜﺗ 

ﻞﻤﺸﺗ ةﺪﻳﺪﻋ تﺎﻔﻋﺎﻀﻣ 

ﺔﻳراﺮﻤﻟا ﻩﺎﻨﻘﻟﺎﺑ تاﻮﺼﺣ نﻮﻜﻠﺘﻤﻳ ةراﺮﻤﻟﺎﺑ تاﻮﺼﺣ ﻦﻣ نﻮﻧﺎﻌﻳ ﻦﻳﺬﻟا ﻰﺿﺮﻤﻟا 

ﺎﻬﻨﻜﻟو ﺔﻠﺼﻳﻮﺤﻟا ﻲﻓ نﻮﻜﺘﺗ 

ﺎﻣ ةدﺎﻋ ﺔآﺮﺘﺸﻤﻟا ﺔﻳراﺮﻤﻟا ةﺎﻨﻘﻟا ﻲﻓ تاﻮﺼﺤﻟا نإ 

ﺪﻌﺼﺗ ﻢﺛ ﺔﻳراﺮﻤﻟا ﺔﻠﺼﻳﻮﺤﻟا ﻲﻓ نﻮﻜﺘﺗ وأ . ﺎﻬﺴﻔﻧ ﺔﻳراﺮﻤﻟا ﻩﺎﻨﻘﻟا ﻲﻓ ًﺎﻧﺎﻴﺣأ 

.ﺔآﺮﺘﺸﻤﻟا 

نﻮﻜﺘﺗ ﺪﻗ 

. ﺪﺒﻜﻟا ﻞﺧاد تاﻮﺼﺣ ﻪﻧﻮﻜﻣ ﻰﻠﻋأ 

ﻰﻟإ 

ﺔﻴﺒﻄﻟا 

ﺔﻴﺣﺎﻨﻟا ﻦﻣ ﺔﻴﺴﻴﺋر ﺔﻠﻜﺸﻣ ﺪﻌﺗ تﺎﻴﻠﻴﻔﻄﻟﺎﺑ ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟا ﺔﺑﺎﺻإ نإ 

تﺎﻴﻠﻴﻔﻄﻟا ﻩﺬه نإ 

ﻦﻋ ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟا وأ ، و 

ﺚﻴﺣ ﺎﻬﻨﻣ ﺔﺒﻳﺮﻘﻟا ﻖﻃﺎﻨﻤﻟاو ةرﺎﺤﻟا ﻖﻃﺎﻨﻤﻟا ﻲﻓ ﺔﺻﺎﺧ ﺔﻴﺣاﺮﺠﻟاو 

ﺪﺒﻜﻟا ﺐﻴﺼﺗ ﺪﻗ تﺎﻴﻠﻴﻔﻄﻟا ﻩﺬهو .ﻖﻃﺎﻨﻤﻟا ﻚﻠﺗ ﻲﻓ ﺔﻨﻃﻮﺘﻣ 

.تﺎﻴﻠﻴﻔﻄﻟا ﻚﻠﺘﻟ ﻲﻌﻴﺒﻄﻟا ﻦﻜﺴﻤﻟا ﺪﻌﺗ ءﺎﻀﻋﻷا 

ﻩﺬه نﻷ 

وأ 

ﺎﻬﻟﻼﺧ ﻦﻣ روﺮﻤﻟا ﻖﻳﺮﻃ 

سﺪﻳﻮﻜﻳﺮﺒﻣﻮﻟ سرﺎﻜﺳا :ﻞﻤﺸﺗ ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟا ﺐﻴﺼﺗ ﻲﺘﻟا تﺎﻴﻠﻴﻔﻄﻟاو 

ﺎﻜﻴﺘﺒﻴه ﻻﻮﻴﺷﺎﻓو ﻢﻴﻠﻴآوﺮﻜﻳد و ﺲﺴﻨﻨﻴﺳ ﺲآﺮﻧﻮﻠآو ﺲﻨﻴﻠﻴﻓو 

ﻲﻨﻳﺮﻔﻴﻓ ﺲآرﻮﺜﺑاو 

.ﺎﻳدرﺎﻴﺠﻟا و مﻮﻳﺪﻳرﻮﺒﺳﻮﺘﺒﻳﺮﻜﻟا و 

زرﻻﻮﻴآﻮﻟ ﻲﺘﻟﺎﻣو سزﻮﻟﻮﻴﻧاﺮﺟ سﺎآﻮآﻮﻨﻴآاو

تﺎﻗﺎﻨﺘﺧﻹا 

ﻦﻳﻮﻜﺗو ﻒﻴﻠﺘﻟاو بﺎﻬﺘﻟﻹاو 

زﺮﻜﻨﺘﻟا ﻰﻟإ 

.ﻪﺗﺎﻀﻳﻮﺑو ﻪﺗازاﺮﻓإو 

ﻞﻴﻔﻄﻠﻟ ﺞﻴﻬﻤﻟا ﻲﺋﺎﻴﻤﻴﻜﻟا 

ب 

ﺔﻳراﺮﻤﻟا تﺎﻴﻠﻴﻔﻄﻟا ىدﺆﺗو 


: ةﺪﻳﺪﻋ تﺎﻴﻟﺂﺑ ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟا عﺎﺴﺗإو 

ﺐﻴآﺮﺘﻠﻟ ةﺮﺷﺎﺒﻣ ﺔﺠﻴﺘﻨآ 

ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻠﻟ ﻲﺋﺎﻳﺰﻴﻔﻟا داﺪﺴﻧﻹا 

ﺔﻳراﺮﻤﻟا تاﻮﺼﺤﻟا ﻦﻳﻮﻜﺗ ﺰﻴﻔﺤﺗ 

.ﺮﺸﻋ ﻰﻨﺛﻹا 

ﻦﻣ ةﺮﺠﻬﻟا ءﺎﻨﺛأ 

ىراﺮﻤﻟا زﺎﻬﺠﻟا ﻰﻟإ 

ﺎﻳﺮﺘﻜﺑ لﺎﺧدإ 

يﺪﺒﻜﻟا بﺎﻬﺘﻟﻹا" 

ﻢﺳﺈﺑ 

فﺮﻌﺗ ﺔﻴﺿﺮﻣ ﺔﻟﺎﺣ ﺔﻳراﺮﻤﻟا تﺎﻴﻠﻴﻔﻄﻟا ﺐﺒﺴﺗ ﺪﻗو 

تاﻮﻨﻘﻟﺎﺑ داﺪﺴﻧإو 

ﺔﻳراﺮﻣ تاﻮﺼﺣ ﻦﻳﻮﻜﺗو تﺎﻴﻠﻴﻔﻃ دﻮﺟﻮﺑ ﺰﻴﻤﺘﺗو "ﻪﺟﻮﻤﻟا يراﺮﻤﻟا 

. ١ 

. ٢ 

. ٣ 

. ٤ 

.ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟﺎﺑ رﺮﻜﺘﻣ بﺎﻬﺘﻟإو 

ﺔﻳراﺮﻤﻟا 

مﺪﺨﺘﺴﺗ ﺎﻬﻠآو ﺔﻳراﺮﻤﻟا تﺎﻴﻠﻴﻔﻄﻟﺎﺑ ﺔﺑﺎﺻﻹا 

ﺺﻴﺨﺸﺘﻟ ةﺪﻳﺪﻋ قﺮﻃ كﺎﻨهو 

و زاﺮﺒﻟا ﻦﻣ ﺔﻨﻴﻋ ﻲﻓ تﺎﻀﻳﻮﺒﻠﻟ ﺔﻴﺑﻮﻜﺳوﺮﻜﻴﻤﻟا ﺔﻳؤﺮﻟا ﻞﺜﻣ ىﺮﺧأ 

ضاﺮﻣأ 

ﺔﻴﺼﻴﺨﺸﺘﻟا تاودﻷا 

ﻦﻣ يراﺮﻤﻟا رﺎﻈﻨﻤﻟا 

ﺺﻴﺨﺸﺘﻟ 

ﺪﻌﻳو . ﺮﺸﻋ ﻰﻨﺛﻻا ﻦﻣ ةذﻮﺧﺄﻣ ﺔﻨﻴﻋ وأ ، 

ﺔﻳؤر ﻰﻟإ ﺔﻓﺎﺿﻹﺎﺑ 

ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟا ﻲﻓ ثﺪﺤﺗ ﻰﺘﻟا تاﺮﻴﻴﻐﺘﻟا ﺢﺿﻮﻳ ﻪﻧأ 

ﺚﻴﺣ 

.تﺎﻴﻠﻴﻔﻄﻠﻟ ةﺮﺷﺎﺒﻣ 

ﺎﻬﻠآ مﺪﺨﺘﺴﺗ ﻲﺴﻴﻃﺎﻨﻐﻤﻟا ﻦﻴﻧﺮﻟا ﺔﻌﺷأو ﺔﻴﻌﻄﻘﻤﻟا ﺔﻌﺷﻷاو 

ﺔﻴﻧﻮﻳﺰﻔﻴﻠﺘﻟا ﺔﻌﺷﻷا نإ 

تﺎﻴﻠﻴﻔﻄﻟﺎﺑ تاﻮﻨﻘﻟا ﻩﺬه داﺪﺴﻧﻹ 

ﺔﺠﻴﺘﻧ ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟا عﺎﺴﺗإو 

تﺎﻴﻠﻴﻔﻄﻟا 

ﺔﻳؤﺮﻟ 

تﻼﺼﻳﻮﺣ وأ 

ﺞﻳراﺮﺧو ﺪﺒﻜﻟا نﺎﻃﺮﺳو ﺔﻳراﺮﻤﻟا تاﻮﻨﻘﻟﺎﺑ نﺎﻃﺮﺳو تاﻮﺼﺣ دﻮﺟوو 

. (ﻞﻴﻓﻮﻨﻳﺰﻳإ)نﻮﻠﻟا 

ﺔﻳدرو ﺔﻐﺒﺼﻟا تاذ ﺎﻳﻼﺨﻟا ﺔﺒﺴﻧ عﺎﻔﺗرإ 

ًﺎﻀﻳ أو 

.ﺔﻳﺪﺒآ 

. ﺔﺣاﺮﺠﻟا وأ ، و رﺎﻈﻨﻤﻟاو 

ﻰﻈﻔﺤﺘﻟا جﻼﻌﻟا ﻞﻤﺸﻳ ﺔﻳراﺮﻤﻟا تﺎﻴﻠﻴﻔﻄﻟا جﻼﻋو 

ﻞﺧﺪﺘﻟا نﺎآ 

ًﺎﻤﻳﺪﻗو .تﺎﻴﻠﻴﻔﻄﻠﻟ ةدﺎﻀﻤﻟا ﺮﻴﻗﺎﻘﻌﻟا لوﺎﻨﺗ ﻦﻣ ﻰﻈﻔﺤﺘﻟا جﻼﻌﻟا نﻮﻜﺘﻳو

ج 


ًﺎﺜﻳﺪﺣ ﺎﻣأ 

. ﺎﻬﺗاﻮﺼﺣو ﺔﻳراﺮﻤﻟا تﺎﻴﻠﻴﻔﻄﻟﺎﺑ ﺔﺑﺎﺻﻹا 

تﻻﺎﺣ جﻼﻌﻟ ًﺎﻳروﺮﺿ ﻰﺣاﺮﺠﻟا 

رﺎﻈﻨﻤﻟا ﺔﻄﺳاﻮﺑ ﺔﻳراﺮﻤﻟا تﺎﻴﻠﻴﻔﻄﻟا جاﺮﺨﺘﺳإو 

مﺎﻤﺼﻟا ﻖﺷ ﺮﺒﺘﻌﻳ مﺎﻳﻷا 

ﻩﺬه ﻲﻓ 

ﻞآﺎﺸﻣو تﺎﻔﻋﺎﻀﻣ ﻰﻟإ 

ىدﺆﻳ ﻪﻧأ 

ﺚﻴﺣ ﻰﺣاﺮﺠﻟا ﻞﺧﺪﺘﻟا ﻦﻣ ﻞﻀﻓأ 

ًﻼﻳﺪﺑ يراﺮﻤﻟا 

ﻲﻓ ًﺎﻣﺎه لازﺎﻣ ﻰﺣاﺮﺠﻟا ﻞﺧﺪﺘﻟا ﻦﻜﻟو . ﻰﺣاﺮﺠﻟا ﻞﺧﺪﺘﻟا ﺎﻬﺒﺒﺴﻳ ﺎﻤﻣ ﻞﻗأ 

ﺔﻴﺿﺮﻣ 

.تاﻮﺼﺤﻟاو تﺎﻴﻠﻴﻔﻄﻟﺎﺑ ﺔﻳراﺮﻤﻟا 

ﺔﻠﺼﻳﻮﺤﻠﻟ 

ﺔﻨﻣﺰﻤﻟاو ةدﺎﺤﻟا ﺔﺑﺎﺻﻹا 

تﻻﺎﺣ

ﺔﻳراﺮﻤﻟا تاﻮﺼﺤﻟاو تﺎﻴﻠﻴﻔﻄﻟا 

ﺚﺤﺑ 

ﻦﻣ مﺪﻘﻣ 

ﻢﻌﻨﻤﻟا ﺪﺒﻋ دﻮﻤﺤﻣ ﺢﻣﺎﺳ 

/ ﺐﻴﺒﻄﻟا 

ﺔﻨﻃﻮﺘﻤﻟا ضاﺮﻣﻷا ﻲﻓ ﺮﻴﺘﺴﺟﺎﻤﻟا ﺔﺟرد ﻲﻠﻋ لﻮﺼﺤﻠﻟ ﺔﺌﻃﻮﺗ 

فاﺮﺷإ 

ﺖﺤﺗ 

نﺎﻤﻴﻠﺳ ﺪﻤﺤﻣ ﺪﻣﺎﺣ 

· د· 

أ 

ﺔﻨﻃﻮﺘﻤﻟا ضاﺮﻣﻷا ﻢﺴﻗ ﺲﻴﺋرو ذﺎﺘﺳأ 

ﻖﻳزﺎﻗﺰﻟا ﻪﻌﻣﺎﺟ -ﺐﻄﻟا 

ﺔﻴﻠآ 

حﺎﺘﻔﻟا ﺪﺒﻋ ﺪﻤﺤﻣ ﻦﻳﺪﻟا ﻲﺤﻣ 

تﺎﻴﻠﻴﻔﻄﻟا ذﺎﺘﺳأ 

ﻖﻳزﺎﻗﺰﻟا ﺔﻌﻣﺎﺟ -ﺐﻄﻟا 

ﺔﻴﻠآ 

ﺮهاز ﻢﻴهاﺮﺑإ قرﺎﻃ 

· د 

ﺔﻨﻃﻮﺘﻤﻟا ضاﺮﻣﻷا سرﺪﻣ 

ﻖﻳزﺎﻗﺰﻟا ﺔﻌﻣﺎﺟ -ﺐﻄﻟا 

ﺔﻴﻠآ 

ﺐﻄﻟا ﺔﻴﻠآ 

ﻖﻳزﺎﻗﺰﻟا ﺔﻌﻣﺎﺟ 

٢٠٠٧ 

· د· 

أ

Parasites and Biliary stones

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?