Gastroenterology Today Spring 2022

Gastroenterology Today Spring 2022

Gastroenterology Today Spring 2022


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Volume 32 No. 1

Spring 2022

The Perfect Pair...

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6 FEATURE Gastric polyps: a 10-year analysis of 18,496

upper endoscopies

14 FEATURE Endoscopic retrograde appendicitis therapy

versus laparoscopic appendectomy versus open

appendectomy for acute appendicitis: a pilot study

22 FEATURE An extremely dangerous case of acute massive

upper gastrointestinal bleeding: a case report



This issue edited by:

Hesam Ahmadi Nooredinvand

c/o Media Publishing Company



Upper Sapey, Worcester, WR6 6XR


Media Publishing Company

Greenoaks, Lockhill

Upper Sapey, Worcester, WR6 6XR

Tel: 01886 853715

E: info@mediapublishingcompany.com



March, June, September and December.


Media Publishing Company



Upper Sapey, Worcester, WR6 6XR


At Diagmed Healthcare our mission is to provide our Customers with innovative products

to better diagnose, prevent, and treat disease of the gastrointestinal tract. From advanced

polypectomy and GI emergency devices, to procedural infection prevention solutions we

are continuously developing new innovations and technologies.

The perfect pair…

The Exacto ® Cold Snare and eTrap ® Polyp Trap support resection and retrieval of

diminutive polyps.

Clinically proven to achieve a signifi cantly high rate of complete resection, the Exacto cold

snare offers control and placement for a precise, clean cut 1,2 . The Exacto snare supports

the cold snare polypectomy technique and can be used to resect a variety of different

types of polyps in multiple sizes (including diminutive and large) and features the following:

• Features a shield shape design that maximises its width for control and placement

during cold snare polypectomy

• 33% thinner wire diameter than traditional braided wires allowing for stiffness and

fl exibility due to its thin, seven braided wire confi guration

• Reduces polyp “fl y away” from the resection site making it possible tocollect specimen

for pathology 2

Designed by GI nurses, the eTrap polyp trap supports retrieval of multiple specimens,

while safeguarding clinicians and nurses from unnecessary exposure to biomaterials.

• Two removable polyp specimen collector strainer trays allowing for retrieval of multiple

polyps with uninterrupted suction

• A clear magnifying window allows direct visualization of the collected specimen

• A measurement guide designed to aid in specimen sizing

For more information on our complete offering of polypectomy solutions, visit

diagmed.healthcare today.

1) Horiuchi A, Hosoi K. “Prospective, Randomized Comparison of 2 Methods of Cold Snare Polypectomy for Small

Colorectal Polyps.” Gastrointestinal Endoscopy (2015): 1-7.

2) Din S, Ball A. “Cold Snare Polypectomy: Does Snare Type Infl uence Outcomes?” Digestive Endoscopy (2015): 1-6.


The views and opinions expressed in

this issue are not necessarily those of

the Publisher, the Editors or Media

Publishing Company.

Next Issue Summer 2022

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appears to

be shifting

towards an



with most





to normal,

the positive

impact of

which will


be felt by


Disruption to the health service during the last couple of years as a result of the

pandemic has undoubtedly had a detrimental impact on certain aspects of patient care.

A recent healthcare survey by Crohn’s and Colitis UK highlights how a delay in diagnosis,

difficulty in accessing specialist advice and disruption to surgery and endoscopy services

have had a negative impact on both physical and mental wellbeing of many patients with

Inflammatory Bowel Disease (IBD).

There is however light at the end of the tunnel. COVID-19 pandemic appears to be shifting

towards an endemic disease with most healthcare services gradually returning to normal,

the positive impact of which will certainly be felt by patients.

We have a number of fascinating articles included in this Spring edition of Gastroenterology

Today including,

• Role of Endoscopic Retrograde Appendicitis Therapy (ERAT) as an alternative to surgical

appendectomy in acute uncomplicated appendicitis

• Scientists in Munich explore the mechanism that triggers problematic interaction between

intestinal bacteria and cells in intestinal mucus layer in patients with IBD which could offer

targets for development of new drug therapy

• Coeliac UK highlights the role of the Rare Disease Collaborative Network in supporting

with diagnosis and management of patients with refractory coeliac disease

• Retrospective study looking at the frequency of gastric polyps and their association with

certain factors

• An interesting case report of massive gastrointestinal bleeding secondary to a fish bone!

Hesam Ahmadi Nooredinvand,

St George’s Hospital


Prescribe Entocort ® CR by brand

instead of prednisolone

• Rapid induction of remission from 2 weeks with

Entocort ® CR* 1

• ~50% fewer corticosteroid-associated side effects

than prednisolone 2,3

• Unlike Entocort ® CR, prednisolone increases

susceptibility to, and severity of, infections †2,4

• Entocort ® CR is the only controlled-release

oral budesonide indicated for Crohn’s disease 2

Help keep your Crohn’s patients out of hospital...

...and where they want to be

*Remission was defined as a score of ≤150 on the Crohn’s disease activity index.

†Entocort ® CR should be used with caution in patients with infections where the use of glucocorticosteroids may have unwanted effects. 2

ENTOCORT CR 3mg Capsules (budesonide) - Prescribing


Please consult the Summary of Product Characteristics (SmPC) for full

prescribing Information

Presentation: Hard gelatin capsules for oral administration with an

opaque, light grey body and an opaque, pink cap marked CIR 3mg in black

radial print. Contains 3mg budesonide. Indications: Induction of remission

in patients with mild to moderate Crohn’s disease affecting the ileum and/or

the ascending colon. Induction of remission in patients with active

microscopic colitis. Maintenance of remission in patients with microscopic

colitis. Dosage and administration: Active Crohn’s disease (Adults): 9mg

once daily in the morning for up to eight weeks. Full effect achieved in 2-4

weeks. When treatment is to be discontinued, dose should normally be

reduced in final 2-4 weeks. Active microscopic colitis (Adults): 9mg once

daily in the morning. Maintenance of microscopic colitis (Adults): 6mg once

daily in the morning, or the lowest effective dose. Paediatric population: Not

recommended. Older people: No special dose adjustment recommended.

Swallow whole with water. Do not chew. Contraindications:

Hypersensitivity to the active substance or any of the excipients. Warnings

and Precautions: Side effects typical of corticosteroids may occur. Visual

disturbances may occur. If a patient presents with symptoms such as

blurred vision or other visual disturbances they should be considered for

referral to an ophthalmologist for evaluation of the possible causes.

Systemic effects may include glaucoma and when prescribed at high doses

for prolonged periods, Cushing’s syndrome, adrenal suppression, growth

retardation, decreased bone mineral density and cataract. Caution in

patients with infection, hypertension, diabetes mellitus, osteoporosis,

peptic ulcer, glaucoma or cataracts or with a family history of diabetes or

glaucoma. Particular care in patients with existing or previous history of

severe affective disorders in them or their first degree relatives. Caution

when transferring from glucocorticoid of high systemic effect to Entocort

CR. Chicken pox and measles may have a more serious course in patients

on oral steroids. They may also suppress the HPA axis and reduce the stress

response. Reduced liver function may increase systemic exposure. When

treatment is discontinued, reduce dose over last 2-4 weeks. Concomitant

use of CYP3A inhibitors, such as ketoconazole and cobicistat-containing

products, is expected to increase the risk of systemic side effects and

should be avoided unless the benefits outweigh the risks. Excessive

grapefruit juice may increase systemic exposure and should be avoided.

Patients with fructose intolerance, glucose-galactose malabsorption or

sucrose-isomaltase insufficiency should not take Entocort CR. Monitor

height of children who use prolonged glucocorticoid therapy for risk of

growth suppression. Interactions: Concomitant colestyramine may

reduce Entocort CR uptake. Concomitant oestrogen and contraceptive

steroids may increase effects. CYP3A4 inhibitors may increase systemic

exposure. CYP3A4 inducers may reduce systemic exposure. May cause low

values in ACTH stimulation test. Fertility, pregnancy and lactation: Only

to be used during pregnancy when the potential benefits to the mother

outweigh the risks for the foetus. May be used during breast feeding.

Adverse reactions: Common: Cushingoid features, hypokalaemia,

behavioural changes such as nervousness, insomnia, mood swings and

depression, palpitations, dyspepsia, skin reactions (urticaria, exanthema),

muscle cramps, menstrual disorders. Uncommon: anxiety, tremor,

psychomotor hyperactivity. Rare: aggression, glaucoma, cataract, blurred

vision, ecchymosis. Very rare: Anaphylactic reaction, growth retardation.

Prescribers should consult the summary of product characteristics in

relation to other adverse reactions. Marketing Authorisation Numbers,

Package Quantities and basic NHS price: PL 36633/0006. Packs of 50

capsules: £37.53. Packs of 100 capsules: £75.05. Legal category: POM.

Marketing Authorisation Holder: Tillotts Pharma UK Ltd, The Stables,

Wellingore Hall, Wellingore, Lincoln, LN5 0HX. Date of preparation of PI:

February 2020

Adverse events should be reported.

Reporting forms and information can be

found at https://yellowcard.mhra.gov.uk.

Adverse events should also be reported to

Tillotts Pharma UK Ltd. Tel: 01522 813500.

References: 1. Campieri M et al. Gut 1997; 41: 209–214. 2. Entocort ®

CR 3 mg capsules – Summary of Product Characteristics. 3. Rutgeerts

P et al. N Engl J Med 1994; 331: 842–845. 4. Prednisolone 5 mg tablets

– Summary of Product Characteristics.

Date of preparation: August 2021. PU-00572.





Haythem Yacoub 1,2* , Norsaf Bibani 1,2 , Mériam Sabbah 1,2 , Nawel Bellil 1,2 , Asma Ouakaa 1,2 , Dorra Trad 1,2 and Dalila Gargouri 1,2

Yacoub et al. BMC Gastroenterology (2022) 22:70 https://doi.org/10.1186/s12876-022-02154-8



Gastric polyps (GPs) are usually asymptomatic lesions of the upper

gastrointestinal tract observed in 1–3% of esophagogastroduodenoscopies

(EGD). Most GPs are benign. The aim of this study was to precise the

frequency of different types of gastric polyps in our population, and to

analyze their possible association with other factors.

Materials and methods

A total of 18,496 consecutive patients undergoing EGD over a

10-year period (between 2007 and 2018) in a tertiary hospital were

retrospectively reviewed. Eighty-six patients diagnosed with gastric

polyps were analysed. Demographics, medical history of the patients,

and indication for gastroscopy were collected. Morphological,

histological characteristics of polyps, and therapeutic management data

were also collected.

fundic gland are the most common in our country. The high frequency of

Helicobacter pylori infection in our patients and in our area may explain

the high frequency of HP.


Stomach, Polyp, Polypectomy, Endoscopic mucosal resection


Gastric polyps (GPs) are defined as luminal projections above

the plane of the adjacent mucosa regardless of its histological

type [1]. Gastric polyps are usually discovered incidentally during

esophagogastroduodenoscopies (EGD) and their prevalence is

estimated from 0.5 to 23% of all upper gastrointestinal endoscopies [2].

Some polyps can occasionally present with bleeding, anemia, or gastric

outlet obstruction [3].



GPs were found in 86 out of 18,496 (0.46%) reviewed EGD,

corresponding to a total of 141 polyps. There were 64 female (74.4%)

and 22 male patients (25.6%) with a sex ratio (M/F) of 0.34. The

average age was 58.1 years. One hundred and forty one polyps were

included, and histopathology was obtained on 127 GPs. The most

common location was the fundus (59.6%) and 48.9% were smaller than

5 mm. The polyp was unique in 75.6% of cases. According to Paris

classification, 80% of the polyps were sessile (Is). Hyperplastic polyps

were the most common (55.9%), followed by sporadic fundic gland

polyps observed in 23 patients (18.1%), 7 (5.5%) were adenomas and

4 (3.1%) were neuroendocrine tumors type 1. The following factors

were associated with hyperplastic polyps: anemia (p =0.022), single

polyp (p=0.025) and size≥5 mm (p=0.048). Comparing hyperplastic

polyps’ biopsies to resected polyps, no difference was found in the

evolutionary profile of the 2 groups. A size less than 10 mm (p =0.013)

was associated with fundic gland polyps. Sixty polyps (47.2%) were

treated by cold forceps, 19 (15%) treated by a mucosal resection and

15 (11.8%) with diathermic snare. Five procedural bleeding incidents

were observed (3.9%). Only the use of anticoagulant treatment was

associated with a high bleeding risk (p=0.005). The comparative

histological study between specimens of biopsied GPs and endoscopic

polypectomy led to an overall agreement of 95.3%.


In our study, the GPs frequency was 0.36%. Hyperplastic polyps and

The majority of polyps are benign (> 85% of cases). The risk of

malignancy or malignant transformation of gastric polyps depends on

their histological nature. GPs have been associated with multiple factors,

such as H. pylori infection for hyperplastic polyps and adenomas,

proton-pump inhibitor (PPI) use for fundic gland polyps [4, 5].

The aim of this study was to precise the frequency of different types of

gastric polyps in our population and to analyze their possible association

with other factors to evaluate the results of curative endoscopic

resection of gastric polyps and to study the evolutionary status of

unresected gastric polyps.


Study design

A retrospective study in which all consecutive patients with GPs were

enrolled was performed at a tertiary-level hospital (Habib Thameur

Hospital of Tunis) from 2008 to 2017. A total of 18,496 consecutive

EGD over a 10-year period were retrospectively reviewed. Eightysix

patients diagnosed with gastric polyps were analysed. Follow-up

gastroscopies performed on the same patient were not excluded. This

study was performed according to the Declaration of Helsinki, following

the guidelines for good clinical practice. Habib Thameur Hospital ethics

committee approved the study protocol.


*Correspondence: yacoubhaythem@hotmail.com


Gastroenterology and Hepatology Department, Habib Thameur Hospital, Tunis, Tunisia

©The Author(s) 2022


All cases of gastric polyps were identified from endoscopy reports.

All data regarding patients were obtained from the electronic medical

record. Demographic data (sex, age), relevant pathological history

(colorectal cancer or hereditary polyposis syndrome, colon polyp,

cirrhosis), routine hemograms, as well as data related to the EGD

indication of gastroscopy, number and size of GPs, location, histological

type, and the presence of chronic gastritis or H. pylori infection using

the Hematoxylin eosin staining) were collected. The polyp size was

estimated by comparing it with the opening size of the used biopsy

forceps. In patients with multiple polyps, we collected the endoscopic

characteristics of the four largest polyps. GP recurrence following

resection were also collected (number, location, size, histological type

and, recurrence interval after polypectomy) Patients whose hemoglobin

levels were less than 13 g/dl in males and 12 g/dl in females were

considered with anemia.

was based on endoscopic findings; the most common localization

for gastric polyps was the fundus, followed by the antrum and the

corpus (Table 2).

Histopathologic diagnosis of polyps was obtained for 127 polyps.

The histological study showed hyperplastic polyps in 71 of the polyps

(55.9%), followed by fundic gland polyps (n=23, 18.1%) (Table 3). The

“other” category included pancreatic heterotopias, lipoma and polypoid

foveolar hyperplasia.

H. pylori infection identification was carried out with the hematoxylin

eosin staining in 64 patients (patients with gastric mucosa

abnormalities). H. pylori infection was detected in 45 patients

(62.3%). H. pylori was positive in 30 of the 49 (61.2%) of patients with

hyperplastic polyps.

Ethics approval and consent to participate

This study was performed according to the Declaration of Helsinki,

following the guidelines for good clinical practice. “Habib Thameur

Hospital ethics committee” approved the study protocol. All methods

were carried out in accordance with relevant guidelines and regulations.

Informed consent to participate in the study was obtained from


Statistical analysis

The data were analyzed on the Statistical Package for the Social

Sciences (SPSS) version 23, IBM SPSS Inc.; Chicago, IL, USA). Results

for the continuous variables that followed a normal distribution were

expressed as mean±standard deviation and range while variables that

did not follow a normal distribution were presented in median and the

interquartile range.

For comparisons, Student’s t-test was used for quantitative variables.

A univariate analysis was conducted to identify the possible associated

factors with the different histological types of GPs. A multivariate analysis

was carried out with variables that achieved statistical significance. The

level of statistical significance was established with a p value ≤ 0.05.

The factors independently associated with hyperplastic polyps were

the presence of anemia, being a single polyp, and sized≥5 mm. The

associated variable for fundic gland polyps, was only size 70 years. Age distribution of the patients with

GPs was summarized in Fig. 1.

More than the three-quarters of the patients had single polyps.

The average polyp diameter was 6 mm (range: 2–30 mm). The

diameters of the polyps were < 5 mm in 69 of cases (48.9%), 5–9

mm in 53 (37.6%) patients, 10–19 mm in 15 (10.7%) patients,

and ≥ 20 mm in 4 (2.8%) patients (Table 2). The location of GPs

Age (median years),(range, years) 58.1 ± 15.4, (18–84)


Male 22 (25.6)

Female 64 (74.4)

Personal history

GERD 26 (30.2)

Anemia 36 (44.2)

Colon polyps 2 (2.3)

Cirrhosis 11 (12.8)

Gastrectomy 3 (3.5)

Hereditary polyposis syndrome 0 (0)


Epigastric pain 30 (34.9)

Dyspepsia 16 (18.6)

Anemia 21 (24.4)

UGIB 2 (2.3)

Monitoring of PHT 13 (15.1)

Other 4 (4.7)

GP gastric polyps, GERD gastro-esophageal reflux disease, PHT portal

hypertension, UGIB upper gastrointestinal bleeding




Anticoagulant or anti-aggregating medication was significantly correlated

with the onset of bleeding (p=0.002).

Twenty-one polyps were biopsied and then resected. A comparison of

the histological results between biopsy specimen and polypectomy was


Adenomas analysis showed a 100% agreement between primary and

final results. The agreement rate was 93% for hyperplastic polyps

(13 polyps out of 14). The comparative histological study between

specimens of biopsied GPs and endoscopic polypectomy led to an

overall agreement of 95.3% (Table 7).


One hundred and twenty-seven specimens, corresponding to eightysix

patients, of the total of 18,496 upper gastrointestinal endoscopic

procedures, taken from gastric polypoid lesions (0.46%) were reported.

In the literature, a great variability was observed in the prevalence of

GPs, ranging from 0.5 to 6.35% [2, 6, 7]. In our study, the prevalence

of GPs is lesser than reported in literature. This can be explained by

the fact that follow-up EGD performed on the same patient was not


This is the first study that evaluates the GPs frequency in Tunisia. In our

study, we found that the most common symptoms in patients with GPs

were epgastric pain and anemia. We also found that GPs were localized

mostly in the fundus, and mostly Is according to Paris classification and

the hyperplastic type was the most common.

Table 2 Morphological and histological characteristics of the

141 polyps

Parameter n (%)

Table 2 Morphological and histological characteristics of the

Patient with GPs 86 (100)

141 polyps

Single 65 (75.6)

Parameter Multiple n (%) 21 (24.4)


Patient with GPs 86 (100)

Fundus 51 (59.3)

Single 65 (75.6)

Body 5 (5.8)

Multiple 21 (24.4)

Antrum 28 (32.6)


Multiple location 2 (2.3)

Fundus 51 (59.3)

Size in mm

Body 5 (5.8)

1–4 mm 69 (48.9)

Antrum 28 (32.6)

5–9 mm 53 (33.6)

Multiple location 2 (2.3)

10–14 mm 8 (5.7)

Size in mm

15–19 mm 7 (5)

1–4 mm 69 (48.9)

> 20 mm 4 (2.8)

5–9 mm 53 (33.6)

Paris classification

10–14 mm 8 (5.7)

Ip 17 (12)

15–19 mm 7 (5)

Is 112 (80)

> 20 mm 4 (2.8)

IIa 11 (8)

Paris classification

IIb, IIc 0 (0)

Ip 17 (12)

Is GP gastric polyps

112 (80)

IIa 11 (8)

IIb, IIc 0 (0)

Hyperplastic polyps and fundic gland polyps together make up to 90%

GP gastric polyps

[6,7,8] followed by adenomas and other histological type, which are

much less common. These rates are similar to those observed in our

population with a predominance of hypeplastic type.


Fig. 1 The age distribution of patients with gastric polyps

Fig. 1 The age distribution of patients with gastric polyps



Table Table 3 3 Histological analysis analysis of the of the 127 127 GP GP

Table Table 5 5 Univariate analysis analysis of of associated factors factors with with fundic fundic

Table 3 Histological analysis of the 127 GP

gland Tablepolyps 5 Univariate analysis of associated factors with fundic

Histological Table 3 type Histological type analysis of the 127 GP


n (%) n (%) Tablepolyps 5 Univariate (n=127) analysis of associated factors with fundic

gland polyps (n=127)

Histological type n (%)

Parameter gland polyps (n=127)

Histological type n (%)

Fundic Fundic gland gland polyps polyps Non-fundic p value p value

Hyperplastic 71 (55.9) 71 (55.9)

Parameter Fundic gland polyps gland Non-fundic gland polyps polyps

Parameter Fundic gland polyps Non-fundic p value p value

Fundic Hyperplastic Fundic Hyperplastic gland gland polyps polyps 23 71 (18.1) (55.9) 23 71 (18.1) (55.9)

n (%) n (%) gland n (%) gland n (%) polyps polyps

Adenoma Fundic Adenoma Fundic gland gland polyps polyps 237 (5.5) (18.1) 237 (5.5) (18.1)

n (%) n (%) n (%) n (%)

Age Age (years) (years) 53.3 53.3 ± 21.3 ± 21.3 58.8±14.1 0.303 0.303

Adenoma Neuroendocrine Adenoma neoplasia neoplasia 47 (3.1) (5.5) 47 (3.1) (5.5)

Age Gender (years) 53.3 ± 21.3 58.8±14.1 0.303 0.289

Xanthelasmaneoplasia 14 (0.8) (3.1) 1 (0.8) Age Gender (years) 53.3 ± 21.3 58.8±14.1 0.289 0.303

Neuroendocrine neoplasia 4 (3.1)

Male Gender Male 1 (11.1) 19 (27.5) 0.289

Xanthelasma Inflammatory fibroid fibroid polyp polyp 91 (7.2) (0.8) 9 (7.2) Gender 1 (11.1) 19 (27.5) 0.289

Xanthelasma 1 (0.8)

Male Female 18 (11.1) (88.9) 19 50 (27.5) (72.5)

No Inflammatory true No true polyp polyp fibroid polyp 79 (5.5) (7.2) 7 (5.5) Male Female 18 (11.1) (88.9) 19 50 (27.5) (72.5)

Inflammatory fibroid polyp 9 (7.2)

Female 8 (88.9) 50 (72.5) 0.170

Other No true Other polyp 57 (3.9) (5.5) 5 (3.9) Female Single/multiple 8 (88.9) 50 (72.5) 0.170

No true polyp 7 (5.5)

Single/multiple 5 (55.6) 53 (76.8)

GP Other gastric polyps

5 (3.9)

Single/multiple 5 (55.6) 53 (76.8) 0.170 0.170

GP Other gastric polyps

5 (3.9)

Single Multiple Single Multiple 54 (55.6) (44.4) 54 (55.6) (44.4) 53 16 (76.8) (23.2) 53 16 (76.8) (23.2)

GP gastric GP gastric polyps polyps

GERDMultiple 4 (44.4) 4 (44.4) 16 (23.2) 16 (23.2) 0.7 0.7

Table Table 4 4 Univariate analysis analysis of of associated factors factors with with

GERDYes GERD 5 (55.6) 5 (55.6) 20 (29) 20 (29) 0.7 0.7

Table hyperplastic Table 4 Univariate 4 polyps Univariate polyps (n analysis = (n 127) analysis = 127) of of associated associated factors factors with with Yes No Yes No 54 (55.6) (44.4) 54 (55.6) (44.4) 20 49 (29) (71) 20 49 (29) (71)

hyperplastic polyps (n = 127)

Parameter hyperplastic polyps Hyperplastic (n = 127) polyps polyps Non-


p value p value No Anemia No Anemia 4 (44.4) 4 (44.4) 49 (71) 49 (71) 0.115 0.115

p value Yes Anemia 8 (88.9) 43 (62.3) 0.115

Parameter Hyperplastic polyps Nonhyperplastic


Parameter Hyperplastic polyps Nonhyperplastic

Yes No Yes No 81 (88.9) (11.1) 81 (88.9) (11.1) 43 26 (62.3) (37.7) 43 26 (62.3) (37.7)

p value

Yes Anemia 8 (88.9) 43 (62.3) 0.115


n (%) n (%) n polyps (%) polyps n (%)

No Location No Location 1 (11.1) 1 (11.1) 26 (37.7) 26 (37.7)

n (%) n (%) n (%) n (%)

Age Age (years) (years) 57.7 57.7 ± 13.4 ± 13.4 58.8 58.8 ± 17.4 ± 17.4 0.7 0.7 Fundus Location Fundus Location 23 (100) 23 (100) 56 (53.9) 56 (53.9)

Age Gender Age Gender (years) (years) 57.7 57.7 ± 13.4 ± 13.4 58.8 58.8 ± 17.4 ± 17.4 0.7


Fundus Non Fundus Non fundus fundus 23 0 (0) (100) 23 0 (0) (100) 56 48 (53.9) (46.1) 56 48 (53.9) (46.1)

Male Gender Male Gender 12 (24.5) 12 (24.5) 8 (27.6) 8 (27.6) 0.7 0.7

Non Size Non Size in fundus mm in fundus mm 0 (0) 0 (0) 48 (46.1) 48 (46.1) 0.013 0.013

MaleFemale 37 12 (75.5) (24.5) 37 12 (75.5) (24.5) 21 8 (27.6) (72.4) 21 8 (27.6) (72.4)

< Size 5 mm < Size in 5 mm in mm 14 (60.9) 14 (60.9) 55 (53) 55 (53) 0.013 0.013

Female Single/multiple Female 37 (75.5) 37 (75.5) 21 (72.4) 21 (72.4) 0.05 0.05 < ≥5 mm < ≥5 mm 14 9 (39.1) (60.9) 14 9 (39.1) (60.9) 55 49 (53) (47) 55 49 (53) (47)

Single/multiple Single/multiple 40 (81.6) 40 (81.6) 11 (38) 11 (38) 0.05 0.05

≥Paris 5 mm ≥Paris 5 mm classification 9 (39.1) 9 (39.1) 49 (47) 49 (47)

Multiple Single Multiple Single 940 (18.4) (81.6) 940 (18.4) (81.6) 18 11 (62) (38) 18 11 (62) (38)

Ip Paris Ip Paris classification classification 3 (13) 3 (13) 12 (11.5) 12 (11.5) 0.524 0.524

GERD Multiple GERD Multiple 9 (18.4) 9 (18.4) 18 (62) 18 (62) 0.7 0.7 Ip Is Ip Is 316 (13) (69.5) 316 (13) (69.5) 12 85 (11.5) (81.7) 12 85 (11.5) (81.7) 0.524 0.273 0.524 0.273

GERDYes GERD 15 (30.6) 15 (30.6) 10 (34.5) 10 (34.5) 0.7 0.7

Is IIa Is IIa 16 4 (17.5) (69.5) 16 4 (17.5) (69.5) 85 7 (6.8) (81.7) 85 7 (6.8) (81.7) 0.273 0.105 0.273 0.105

No Yes No Yes 34 15 (69.4) (30.6) 34 15 (69.4) (30.6) 19 10 (65.5) (34.5) 19 10 (65.5) (34.5)

IIa IIb, IIc IIa IIb, IIc 40 (17.5) (0) 40 (17.5) (0) 70 (6.8) (0) 70 (6.8) (0) 0.105 – 0.105 –

Anemia No Anemia No 34 (69.4) 34 (69.4) 19 (65.5) 19 (65.5) < 10 < –3 10 –3 GP: IIb, IIc gastric GP: IIb, IIc gastric polyps, polyps, GERD: GERD: 0 (0) 0 gastro-esophageal (0) reflux reflux disease 0 (0) disease 0 (0) – –

Yes Anemia Yes Anemia 28 (57.2) 28 (57.2) 3 (10.3) 3 (10.3) < 10 < –3

10 –3 Significant GP: gastric Significant GP: gastric polyps, p value polyps, p value GERD: < 0.05 GERD: < 0.05 are in gastro-esophageal are bold in bold reflux reflux disease disease

No Yes Yes No 21 28 (42.8) (57.2) 21 28 (42.8) (57.2) 26 3 (10.3) (89.7) 26 3 (10.3) (89.7)

Significant Significant p value p value < 0.05 < 0.05 are in are bold in bold

Location No Location No 21 (42.8) 21 (42.8) 26 (89.7) 26 (89.7) 0.009 0.009

Table Table 6 Risk 6 Risk value value for the for the significant variables variables in the in the multivariate

Antrum Location Antrum Location 34 (47.9) 34 (47.9) 43 (76.8) 43 (76.8) 0.009 0.009

analysis Table analysis Table 6 Risk 6 Risk value value for the for the significant significant variables variables in the in the multivariate multivariate

Non Antrum Non Antrum antrum antrum 37 34 (52.1) (47.9) 37 34 (52.1) (47.9) 13 43 (23.2) (76.8) 13 43 (23.2) (76.8)


Size Non Size in antrum mm in mm 37 (52.1) 13 (23.2) 0.002 0.002 Variable Variable analysis

Non antrum 37 (52.1) 13 (23.2)

Odds Odds ratio ratio 95% 95% CI CI p value p value

< Size 5 mm < Size in 5 mm in mm 30 (42.3) 30 (42.3) 39 (69.6) 39 (69.6) 0.002 0.002

Variable Variable Hyperplastic polyps polyps

Odds Odds ratio ratio 95% 95% CI CI p value p value

≥< 5 mm ≥< 5 mm 41 30 (47.7) (42.3) 41 30 (47.7) (42.3) 17 39 (30.4) (69.6) 17 39 (30.4) (69.6)

Anemia Hyperplastic Anemia Hyperplastic polyps polyps 4.28 4.28 (1.39–13.17) 0.022 0.022

Paris ≥ 5 mm Paris ≥ 5 mm classification 41 (47.7) 41 (47.7) 17 (30.4) 17 (30.4)

Single Anemia Anemia Single 2.85 4.282.85 (1.39–13.17) (0.95–8.59) (1.39–13.17) 0.025 0.022 0.025 0.022

Ip Paris Ip Paris classification classification 10 (14) 10 (14) 5 (8.9) 5 (8.9) 0.371 0.371

Size≥5 Single Size≥5 Single mm mm 2.851.85 (0.95–8.59) (1.29–2.67) (0.95–8.59) 0.048 0.025 0.048 0.025

Is Ip Is Ip 58 10 (81.7) (14) 58 10 (81.7) (14) 43 5 (8.9) (76.8) 43 5 (8.9) (76.8) 0.496 0.371 0.496 0.371 Fundic Size≥5 Fundic Size≥5 mmgland polyps polyps 1.85 1.85 (1.29–2.67) (1.29–2.67) 0.048 0.048

IIa Is IIa Is 358 (4.3) (81.7) 358 (4.3) (81.7) 843 (14.3) (76.8) 843 (14.3) (76.8) 0.055 0.496 0.055 0.496 Size Fundic Size Fundic < 5gland mm < 5gland mm polyps polyps 2.31 2.31 (1.37–4.11) < 0.001 < 0.001

IIb, IIa IIc IIb, IIa IIc 03 (0) (4.3) 03 (0) (4.3) 08 (0) (14.3) 08 (0) (14.3) – 0.055 – 0.055 Size GP gastric GP Size < 5gastric mm < polyps, 5 mm polyps, GERD GERD gastro-esophageal 2.31 2.31 (1.37–4.11) reflux (1.37–4.11) reflux disease disease < 0.001 < 0.001

GP IIb, gastric IIc GP IIb, gastric IIcpolyps, polyps, GERD GERD 0 (0) 0 gastro-esophageal (0) reflux reflux disease 0 disease (0) 0 (0) – –

GP gastric GP gastric polyps, polyps, GERD GERD gastro-esophageal reflux reflux disease disease

Significant GP gastric Significant GP gastric polyps, p value polyps, p value GERD < 0.05 GERD < 0.05 are gastro-esophageal in are bold in bold reflux reflux disease disease

Significant Significant p value p value < 0.05 < 0.05 are in are bold in bold

are the most common [9,10,11,12,13]. It has been suggested that

the prevalence of hyperplastic polyps could be related to the high

Argüello et al. reported the frequency of GP as 42.8% for

hyperplastic polyps, and 37.7% for fundic gland polyps. The

mean age of the patients was 65.6 years and 38% were males

[9]. Carmack et al. found the incidence of GP as 6.3% in 121.564

EGD. Fundic gland polyps were the most frequent polyp type,

which accounted for 77% of all polyps of all polyps [6]. Fundic

gland polyps were the second most common type (18.1%) of GPs

lesions in our study. In the majority of series, hyperplastic polyps

prevalence of H. pylori infection in our population (62.3%). Freeman

et al. reported tendency of fundic gland polyps to arise in H. pylori

-free stomachs [14] (OR 0.007, 95% CI 0.003–0.015). The same

findings were also reported in Carmack et al. study (OR 0.007,

95% CI 0.003–0.016) [6]. Fundic gland polyps tend also to arise

in patients who receive long-course PPI treatment [14, 15]. The

widespread of PPIs use and the low H. Pylori infection rate may be

the most important reasons behind the large frequency of fundic




gland polyps reported in American studies [6, 14]. Although in three

Spanish series, hyperplastic polyps were the most common which

is comparable to our study [8, 9, 16].

Hyperplastic polyps are associated with chronic gastritis such

as H. pylori gastritis, and particularly autoimmune gastritis.

Patients with hyperplastic polyp have an increased risk of gastric

adenocarcinoma [1, 17, 18].

In our study, adenomas were detected in seven patients (5.5%).

The majority of cases we reported were low-grade intestinal-type.

These polyps constitute less than 10% and have a malignant

potential. They are more common in communities where gastric

cancer is frequent [19]. Malignant potential of adenomas is variable

(6.8% − 55.3%) [20]. Risk factors for malignancy transformation are:

high-grade dysplasia, and size of the lesion [19].

It has been reported that between 16 and 37.5% of cases, and

despite the endoscopic appearance of a polyp, the final histological

study shows normal mucosa [6, 16]. In our study the percentage of

biopsies with normal mucosa was 5.5%.

Although the majority of GP do not cause symptoms, they can be

the cause of bleeding and gastric obstruction. Frequently, GP are

detected during EGD performed to study gastrointestinal symptoms

not attributable to polyps or asymptomatic patients examined for

other reasons [6, 21].

In our study, an association between hyperplastic polyps and

anemia, single polyps and size > 5 mm. It has been described in

the literature between anaemia and hyperplastic polyps, while the

gastrointestinal reflux was associated with fundic gland polyps [22].

A total of 94 polyps were resected with snare. Five patients had

hemorrhage requiring endoscopic treatment and bleeding was



Table 7 Agreement between polypectomy and biopsy

specimen in different histological types

Histological type



Table 7 Agreement between

specimen (n)



and biopsy

specimen Adenomas in different histological types

Histological With low grade typedysplasia Biopsy 4 Polypectomy


With high grade dysplasia specimen 1 (n) (n) 1

Fundic gland polyps


1 1

Hyperplastic polyps

With low grade dysplasia





Type I neuroendoscrine tumor

With high grade dysplasia





Inflammatory mucosa

Fundic gland polyps





Hyperplastic polyps 13 14

Type I neuroendoscrine tumor 1 1

controlled Inflammatory by mucosa endoscopic procedures. 1 Perforation did 0not occur in

any of our patients. In the literature, bleeding as a complication of

gastric polypectomy was reported in 3.5% [23].

Relationship between long-term PPIs use and fundic gland polyps’

occurring has not yet been fully established. Jalving et al. [4] found

in their study a significant association only in the subgroup of

patients treated with PPI for over 1 year. Our data do not support a

relationship between PPI and fundic gland polyps.

In patients with GP, evaluating H. pylori infection state by obtaining

biopsies of the surrounding gastric mucosa is recommended and

treatment is required if present [24, 25].

Hyperplastic polyps should be biopsied according to the British

society of gastroenterology and an examination of the whole

stomach should be made. H pylori infection should be detected and

eradicated when present [24]. GP of the non-adenomatous type

are at a low risk of malignant transformation, therefore endoscopic

resection is not necessary.









14 14












Cold snare Hot snare



Monoblock Piece-meal


Fig. 2 The distribution of polypectomy. EMR endoscopic mucosal resection

Cold snare Hot snare EMR

Monoblock Piece-meal

Fig. 2 The distribution of polypectomy. EMR endoscopic mucosal resection





Guidelines on management of hyperplastic polyps, recommend

resection of polyps greater than 5 mm [26, 27].

Complete removal of the adenoma should be performed when safe to

do according to the British recommendations [24].

Polypectomy is not required for sporadic fundic gland polyps. Biopsy of

probable fundic gland polyps is recommended to exclude dysplasia. In

patients with multiple fundic gland polyps who are under 40 years-old,

or where biopsies specimens show dysplasia, colonoscopy should be

performed to exclude familial adenomatous polyposis [24].

Szaloki et al. reported that there were important disagreements in 12

cases of examined forceps biopsy specimens. In 14 neoplastic, and

1 hyperplastic polyps, the degree of dysplasia seen on histological

examination of the forceps biopsy specimens differed from that

observed for the resected specimens. Complete agreement between

the histological results on ectomized polyp, and the forceps biopsy

was observed in only 55.3% of the cases [28]. In our study, Adenomas

analysis showed a 100% agreement between primary and final results.

The agreement rate was 93% for hyperplastic polyps (13 polyps out of

14). The overall agreement was of 95.3%.

Ethics approval and consent to participate

This study was performed according to the Declaration of Helsinki,

following the guidelines for good clinical practice. “Habib Thameur

Hospital ethics committee” approved the study protocol. All methods

were carried out in accordance with relevant guidelines and regulations.

Informed consent to participate in the study was obtained from


Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Author details


Gastroenterology and Hepatology Department, Habib Thameur

Hospital, Tunis, Tunisia. 2 Faculty of Medicine of Tunis, El Manar

University, Tunis, Tunisia.

Received: 8 July 2021 Accepted: 7 February 2022

Published online: 19 February 2022

Our study included the greatest number of EGD with patients diagnosed

with GP in our country.


Gastric polyps’ frequency in our study was low (0.46%). Hyperplastic

polyps are the most common gastric polyps in our country. In case of

single polyps, biopsies are recommended to rule out a diagnosis of

adenoma or hyperplastic polyps with dysplasia. Good knowledge of

practical guidelines is important for the management of GP.


Not applicable.

Authors’ contributions

H.Y.: concept, design, definition of intellectual content, literature

search, manuscript preparation, manuscript editing, manuscript review.

N.B.: concept, design, definition of intellectual content, manuscript

preparation, manuscript review. M.S.: definition of intellectual content,

manuscript preparation. N.B.: design. A.O.: design, manuscript

review. D.T.: manuscript review. D.G.: definition of intellectual content,

manuscript review. All authors read and approved the final manuscript.


Not applicable.

Availability of data and materials

The data that support the findings of this study are available on

request from the corresponding author, [HY]. The data are not publicly

available due to [restrictions e.g. their containing information that could

compromise the privacy of research participants].



1. Lesur G. Gastric polyps: how to recognize? Which to resect?

Gastroenterol Clin Biol. 2009;33(4):233–9.

2. Voutilainen M, Mantynen T, Kunnamo I, Juhola M, Mecklin JP,

Farkkila M. Impact of clinical symptoms and referral volume on

endoscopy for detecting peptic ulcer and gastric neoplasms. Scand

J Gastroenterol. 2003;38(1):109–13.

3. Barbosa SHB, Lazaro GCF, Franco LM, Valenca JTJ, Nobre

SMA, Souza M. Agreement between different pathologists in

histopathologic diagnosis of 128 gastric polyps. Arq Gastroenterol.


4. Jalving M, Koornstra JJ, Wesseling J, Boezen HM, Jong DE,

Kleibeuker SJH. Increased risk of fundic gland polyps during

long-term proton pump inhibitor therapy. Aliment Pharmacol Ther.


5. Elhanafi S, Saadi M, Lou W, Mallawaarachchi I, Zuckerman AM,

Othman MO. Gastric polyps: a association with Heli-cobacter

pylori status and the pathology of the surrounding mucosa, a cross

sectional study. World J Gastrointest Endosc. 2015;7:995–1002.

6. Carmack SW, Genta RM, Schuler CM, Saboorian MH. The current

spectrum of gastric polyps: a 1-year national study of over 120,000

patients. Am J Gastroenterol. 2009;104(6):1524–32.

7. Morais DJ, Yamanaka A, Zeitune JM, Andreollo NA. Gastric polyps:

a retrospective analysis of 26,000 digestive endoscopies. Arq

Gastroenterol. 2007;44(1):14–7.

8. Garcia Alonso FJ, Marti Mateos RM, Gonzalez Martin JA, Foruny

JR, Vazquez Sequeiros E, Boixeda de Miquel D. Gastric polyps:

analysis of endoscopic and histological features in our center. Rev

Esp Enferm Dig. 2011;103(8):416–20.

9. Argüello Viúdez L, Córdova H, Uchima H, Sánchez Montes C, Ginès

À, Araujo I, et al. Gastric polyps: retrospective analysis of 41,253

upper endoscopies. Gastroenterol Hepatol. 2017;40(8):507–14.




10. Bassene ML, Diallo S, Thioubou MA, Diallo A, Gueye MN, Diouf ML.

Gastric polyps in a digestive endoscopy center in Dakar. Open J

Gastroenterol. 2017;7(10):279–86.

11. Olmez S, Sayar S, Saritas B, Savas AY, Avcioglu U, Tenlik I, et

al. Evaluation of patients with gastric polyps. North Clin Istanb.


12. Ljubicic N, Kujundzic M, Roic G, Banic M, Cupic H, Doko M, et al.

Benign epithelial gastric polyps-frequency, location, and age and sex

distribution. Coll Antropol. 2002;26(1):55–60.

13. Sivelli R, Del Rio P, Bonati L, Sianesi M. Gastric polyps: a clinical

contribution. Chir Ital. 2002;54(1):37–40.

14. Freeman HJ. Proton pump inhibitors and an emerging epidemic

of gastric fundic gland polyposis. World J Gastroenterol.


15. Raghunath AS, O’Morain C, McLoughlin RC. Review article: the

long-term use of proton-pump inhibitors. Aliment Pharmacol Ther.


16. Macenlle García R, Bassante Flores LA, Fernández Seara J. Pólipos

gástricos epiteliales. Estudio retrospectivo 1995–2000. Rev Clin

Esp. 2003;203(8):368–72.

17. Abraham SC, Singh VK, Yardley JH, Wu TT. Hyperplastic polyps of

the stomach: associations with histologic patterns of gastritis and

gastric atrophy. Am J Surg Pathol. 2001;25(4):500–7.

18. Scoazec JY. Les polypes gastriques: pathologie et génétique. Ann

Pathol. 2006;26(3):173–99.

19. Hattori T. Morphological range of hyperplastic polyps and

carcinomas arising in hyperplastic polyps of the stomach. J Clin

Pathol. 1985;38(6):622–30.

20. Stolte M. Clinical consequences of the endoscopic diagnosis of

gastric polyps. Endoscopy. 1995;27:32–7.

21. Gencosmanoglu R, Sen Oran E, Kurtkaya Yapicier O, Avsar E, Sav

A, Tozun N. Gastric polypoid lesions: analysis of 150 endoscopic

polypectomy specimens from 91 patients. World J Gastroenterol.


22. Sonnenberg A, Genta RM. Prevalence of benign gastric polyps in a

large pathology database. Digest Liver Dis. 2015;47:164–9.

23. Russo A, Sanfi lippo G, Magnano A, La Malfa M, Belluardo N.

Complications de la polypectomie endoscopique gastrique et

duodénale expérience italienne. Acta Endosc. 1986;16(5):251.

24. Goddard AF, Badreldin R, Pritchsard DM, Walker MM, War-ren B. on

behalf of the British Society of Gastroenterology. The management

of gastric polyps. Gut. 2010;59:1270–6.

25. Sharaf RN, Shergill AK, Odze RD, Krinsky ML, Fukami N, Jain R, et

al. ASGE Standards of Practice Committee. Endoscopic mucosal

tissue sampling. Gastrointest Endosc. 2013;78:216–24.

26. Evans JA, Chandrasekhara V, Chathadi KV, Decker GA, Early DS,

Fisher DA, et al. ASGE guideline: the role of endoscopy in the

management of premalignant and malignant conditions of the

stomach. Gastrointest Endosc. 2015;82:1–8.

27. Han AR, Sung CO, Kim KM, Park C, Min B, Lee JH, et al.

Theclinicopathological features of gastric hyperplastic polyps with

neoplastic transformations: a suggestion of indication for endoscopic

polypectomy. Gut Liver. 2009;3:271–5.

28. Szaloki T, Toth V, Tiszlavicz L, Czako L. Flat gastric polyps: results

of forceps biopsy, endoscopic mucosal resection, and long-term

follow-up. Scand J Gastroenterol. 2006;41(9):1105–9.

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Gastric cancer is typically diagnosed at a very late stage,

leading to a poor prognosis for the patient, and the strain

on healthcare services through the COVID-19 pandemic

has only made things worse. However, detection of precancerous

conditions – such as atrophic gastritis (AG) and

gastric intestinal metaplasia (GIM) – before endoscopy could

potentially support diagnostic pathways, allowing doctors

in primary care to identify and prioritise patients for whom

endoscopy would be useful, streamlining NHS resources and

improving patient outcomes.

What are AG and GIM?

AG is a chronic inflammatory condition of the gastric mucosa.

It can be an autoimmune disorder, but most commonly arises

following prolonged inflammation caused by Helicobacter


infection. This disrupts the mucus barrier that helps

to protect the cells of the stomach lining from digestive

juices, causing them to be slowly destroyed. AG significantly

increases the risk of stomach cancer, with 18 % of cases

progressing to cancer within 10 years. However, studies

suggest that in some cases the progression of AG can be

halted, and even improved, reinforcing the importance of early

diagnosis and monitoring. 1

GIM is common in cases of AG and occurs when the cells

of the stomach lining are replaced with cells similar to the

lining of the intestines. Again, H. pylori is often implicated in

this process, which predisposes individuals to intestinal-type

gastric adenocarcinoma and neuroendocrine tumours (NETs).

Patients with GIM are often over 50 years of age, and the risk

is further increased by factors such as smoking or having a

first-degree relative with gastric cancer.

Challenges of diagnosis

The current gold standard for diagnosing AG and GIM is

gastroscopy with targeted biopsies, which relies on referral

of patients from primary care. However, AG and GIM are often

asymptomatic – or present with very general symptoms such as

stomach pain, loss of appetite, nausea or vomiting, anaemia and

stomach ulcers – making them hard to detect. Tests for

H. pylori infection, along with blood tests for levels of

pepsinogens and gastrin-17, may help to identify some patients

for whom a referral would be beneficial. However, current

practice is not to actively look for AG and GIM cases before

endoscopy, and so patients may remain undiagnosed in primary

care for prolonged periods if they do not qualify for referral.

Rapid detection of AG and GIM

GastroPanel from BIOHIT is a simple, non-invasive blood test

that can be used in primary care settings for effective diagnosis

of AG and GIM. It gives detailed information on the structure

and function of the stomach mucosa, by quantifying pepsinogen

I, pepsinogen II and gastrin-17, and can also differentiate the

cause of AG by identifying IgG antibodies to H. pylori. Using

GastroPanel in targeted groups of at-risk patients could help to

direct referrals more effectively. As well as detecting cancers

at an earlier and more curable stage, reducing the number of

gastroscopies in lower risk patients would reduce both the cost

and volume burden on healthcare resources, without adversely

affecting patient care.

For more information about GastroPanel

contact: info@biohithealthcare.co.uk

1 . Kong YJ, Yi HG, Dai JC, Wei MX. Histological changes of gastric mucosa after Helicobacter pylori eradication: A systematic review and meta-analysis. World J Gastroenterol 2014; 20(19): 5903-5911

For the early diagnosis

of gastric cancer risk

Reduce endoscopy waiting lists and

improve the diagnostic pathway for

patients, through an earlier, faster

and more cost-effective approach.









Zhemin Shen 1 , Peilong Sun 1*† , Miao Jiang 2† , Zili Zhen 1 , Jingtian Liu 1 , Mu Ye 1 and Weida Huang 1

Shen et al. BMC Gastroenterology (2022) 22:63 https://doi.org/10.1186/s12876-022-02139-7





An increasing number of studies have shown the merits of endoscopic

retrograde appendicitis therapy (ERAT) in diagnosing and treating acute

uncomplicated appendicitis. However, no related prospective controlled

studies have been reported yet. Our aim is to assess the feasibility and

safety of ERAT in the treatment of acute uncomplicated appendicitis.


In this open-label, randomized trial, participants were randomly allocated

to the ERAT group, laparoscopic appendectomy (LA) group and open

appendectomy (OA) group. The primary outcome was the clinical success

rate of the treatment. Intention-to-treat analysis was used in the study.


The study comprised of 99 patients, with 33 participants in each

group. The clinical success rate was 87.88% (29/33), 96.97% (32/33)

and 100% (33/33) in the ERAT, LA and OA group, respectively. In the

ERAT group, 4 patients failed ERAT due to difficult cannulation. In LA

group, 1 patient failed because of abdominal adhesion. There were no

significant differences among the three treatment groups regarding the

clinical success rate (P=0.123). The median duration of follow-up was

22 months. There were no significant differences (P =0.693) among the

three groups in terms of adverse events and the final crossover rate of

ERAT to surgery was 21.21% (7/33).


ERAT can serve as an alternative and efficient method to treat acute

uncomplicated appendicitis.

Trial registration The study is registered with the WHO Primary Registry-

Chinese Clinical Trial Registry (ChiCTR1900025812).


Acute appendicitis, Endoscopic retrograde appendicitis therapy,

Appendectomy, Randomized controlled trial


Acute appendicitis is one of the most common causes of acute

abdominal pain clinically [1]. Appendectomy has long been standard

treatment for acute appendicitis. However, there are a series of potential

*Correspondence: sunpeilong@fudan.edu.cn

Peilong Sun and Miao Jiang contributed equally in the trial


Department of General Surgery, Jinshan Hospital, Fudan University, Shanghai, China

©The Author(s) 2022

postoperative complications, such as postoperative bleeding, wound

infection and intestinal obstruction [2, 3], and the overall complication

rate has been reported to be 8.2–31.4% [1]. Moreover, negative

appendectomy is also a nonnegligible problem [4]. As previous studies

suggested that perforation may not be an inevitable consequence of

acute appendicitis, there is a division of opinions on performing surgery

on patients with acute uncomplicated appendicitis [5]. Thus, developing

a safe and efficient nonoperative method has been an agenda for

treating acute uncomplicated appendicitis.

Endoscopic retrograde appendicitis therapy (ERAT) was firstly

reported by Liu et al. as being inspired by endoscopic retrograde

cholangiopancreatography (ERCP) [6]. ERAT is a novel, nonoperative and

minimally invasive method of treating acute uncomplicated appendicitis.

Recently, there has been additional studies of the use of ERAT for

treating acute uncomplicated appendicitis [7,8,9]. The results of these

3 trials indicated the clinical value of ERAT, including both diagnostic

and therapeutic aspects. Thus, ERAT has the potential to become an

alternative treatment method for acute appendicitis, especially in patients

who are deemed as high-risk candidates for surgery. However, these

previous studies were all retrospective, and no prospective study has

been reported yet. To address this issue, we conducted a prospective

randomized controlled trial to compare ERAT with laparoscopic

appendectomy (LA) and open appendectomy (OA), and evaluated the

feasibility and safety of ERAT in treating acute uncomplicated appendicitis.



The period of patient enrollment was between January 2018 and August

2019. A prospective, open-label, randomized controlled study was

conducted at Jinshan Hospital, Fudan University. Patients diagnosed

with acute uncomplicated appendicitis were enrolled in the study.

The inclusion criteria were as follows: (1) patient age over 18 years and

under 80 years; (2) Alvarado score >5 [1]; (3) suspicious (or could not

be excluded) acute appendicitis diagnosed by an abdominal CT scan,

which was indicated by a dilated appendix with a diameter greater than

6 mm, a thickened cecal wall, and periappendiceal fat inflammation, with

or without an appendicolith [10].

Exclusion criteria were as follows: (1) suspected acute complicated

appendicitis with perforation or gangrene; (2) appendiceal diameter


Fig. 1 Procedures of endoscopic retrograde appendicitis therapy (ERAT). a Congestion and edema around the mucosa of appendix orifice. b The

endoscopic retrograde appendicography (ERA) fluoroscopy showed filling defect in the appendix lumen (arrows), which indicated the presence

of appendicoliths. c Cannulation of catheter along the guidewire with sand-like appendicoliths excretion and pus drainage inside the appendix

lumen, confirming acute appendicitis. d Retracting the appendicoliths by the extraction basket. e After appendicolith being retracted, the appendix

lumen was fully filled with contrast media under ERA. f Stenting for keeping pus drainage

greater than 15 mm, which usually indicates malignancy [11]; (3)

patients under the age of 18 years or over 80 years; (4) patients

with the following contradictions for receiving colonoscopy, surgery

or anesthesia: (a) severe cardiopulmonary insufficiency, psychiatric

dysfunction or coma; (b) acute diffuse peritonitis, which is defined

as diffuse abdominal tenderness, rebound tenderness and muscular

tension; (c) acute gastroenteritis (dysentery, explosive ulcerative colitis);

(d) concurrent menses; (e) intestinal obstruction; (f) acute gastrointestinal

hemorrhage; (g) recent gastrointestinal or pelvic operation or

radiotherapy; (h) allergy to contrast medium; (i) hemorrhagic tendency

because of long-term use of corticosteroids or anticoagulant treatment;

(5) patients undergoing any other clinical trial.

Written informed consent was obtained from all participants. The study

was conducted according to the Declaration of Helsinki and approved

by the Ethics Committee of Jinshan Hospital, Fudan University (No.

2017–24) on May 17th, 2017. The study is registered with the WHO

Primary Registry-Chinese Clinical Trial Registry (ChiCTR1900025812)


Randomization was conducted by a computer-generated randomization

number (1:1:1) by statisticians. The final allocation was concealed in

an opaque envelope. The allocation was reported to the doctors and

patients immediately prior to the intervention.

Preintervention preparation

All patients intravenously received antibiotic treatment (1.5 g cefuroxime

with 100 ml normal saline, 0.5% metronidazole 100 ml) immediately

after being clinically diagnosed. In the ERAT group, the patients orally

took 328.8 g polyethylene glycol (PEG) electrolyte solution with 2000 ml

water before ERAT for bowel preparation. When the excrement became

a clear liquid, the patients were well prepared to undergo ERAT.

ERAT procedure

Similar to that in previous studies [7,8,9], the ERAT procedure was

performed as follows (Fig. 1):

First, a full and careful examination of the large intestine was performed

by a colonoscope (CF-H260AI, Olympus, Japan) with a transparent cap.

Then, the colonoscope was located to the appendiceal orifice to check

the appendiceal mucosa to determine whether there was inflammation

or any other abnormalities. With the help of a transparent cap, the tip

of the catheter (BDC-12/55–7/1810/55–7/18, Micro-Tech Co. Ltd.,

Nanjing, China) was placed in the appendiceal orifice, and a 0.035-inch




guidewire (MTN-BM-89/45-A, Micro-Tech Co. Ltd., Nanjing, China) was

gently and deeply inserted into the appendiceal lumen over the catheter.

Finally, the catheter moved forward into the appendiceal lumen along

the guidewire. To make a definite diagnosis, the appendiceal lumen

was filled with contrast medium (ioversol) for endoscopic retrograde

appendicography (ERA) fluoroscopy. Next, the appendiceal lumen was

flushed repeatedly with gentamicin (240,000 units with 100 ml normal

saline) and 0.5% metronidazole 100 ml to clear pus and other infectious

contents, such as sand-like appendicoliths. Then, an extraction basket

(SEB-A- 30/55–7/200, Micro-Tech Co., Ltd., Nanjing, China) was used

to extract the remaining appendicoliths if necessary. Finally, a plastic

stent (SPSOF7-7, Cook, USA) was placed routinely in the appendiceal

orifice to maintain pus drainage.

Surgical treatment

All operations were performed by surgeons from a same team. In the

LA group, the three-port technique (umbilical, 10 mm; suprapubic, 5

mm; right lower abdomen, 10 mm) was chosen. In the OA group, a

McBurney muscle-splitting incision technique was used.

and CRP level; the duration of diet resumption; the length of hospital

stay (LOS); the total cost of the primary hospital stay; adverse events

during follow-up period and final crossover rate of ERAT to surgery.


The clinical success of ERAT is defined as successful appendix

cannulation with complete resolution of symptoms and normalization

of inflammatory markers, including WBC count, neutrophil percentages

and CRP. Difficult appendix cannulation is defined as failure to achieve

successful appendix cannulation within 15 min. The assessment of

abdominal pain degree is based on visual analog scales (VAS). In the

VAS, scores of 0 and 10 represent no pain and most severe pain,

respectively. Complete relief of abdominal pain refers to a VAS score of


The diagnostic criteria of acute appendicitis by ERAT mainly consist

of ERA fluoroscopy images, inflammation of the appendiceal mucosa

observed under endoscopy and the presence of pus or appendicoliths

inside the appendiceal lumen [8].



Postintervention management

After ERAT or surgery was performed, patients were sent back to the

ward and monitored carefully. Patients continued to receive antiinflammatory

therapy when necessary. In the ERAT group, patients

were given a soft diet later on the same day and resumed a normal diet

when the soft diet was tolerated. In the LA and OA groups, a soft diet

was started 24 h after surgery, and a normal diet was given when the

soft diet was completely tolerated. All patients were asked about their

clinical presentation every day. Routine blood tests, including the white

blood cell (WBC) count, neutrophil percentages and C-reactive protein

(CRP) level, were performed on day 1, 3, and 5 in a similar fashion after

ERAT or surgery. Patients were discharged when all symptoms were

completely relieved and inflammatory markers (including the WBC count,

neutrophil percentages, and CRP level) returned to normal. If ERAT

failed or abdominal pain persisted after ERAT, LA or OA was performed



Fourteen days after ERAT, all patients in the ERAT group were scheduled

for outpatient services to inform doctors of their symptoms after

discharge. Patients then received an abdominal X-ray to check the

status of the stent. If the stent was not discharged spontaneously with

defecation, colonoscopy was recommended to retrieve the stent.

Follow-up was performed by telephone interview every 3 months for

the first half year, and then every 6 months till November 2020. In

the ERAT group, recurrence of abdominal pain or appendicitis after

ERAT, including the relevant treatment, was mainly investigated. In the

LA group and OA group, the survey mainly included postoperative

complications such as wound infection, persistent incision pain and

intestinal obstruction. Follow-up was performed until the end of the

study period.


The primary outcome was the clinical success of the treatment. The

secondary outcomes were as follows: the duration of complete relief of

abdominal pain and body temperature; the duration of normalization of

inflammatory markers including the WBC count; neutrophil percentages

In the ERAT group, adverse events mainly indicated the recurrence of

acute appendicitis. In the LA and OA groups, adverse events suggested

postoperative complications.

Statistical analysis

As this was a pilot trial, we did not perform a power calculation. On the

basis of our yearly caseload of approximately 240 cases and estimated

recruitment of one fifth of eligible cases, we aimed to enroll at least

96 patients within a 2-year period. Qualitative data are expressed as

numbers (n) and percentages (%) and were compared by using the χ 2

test or Fisher’s exact test when appropriate.

Quantitative data are expressed as the mean ±standard deviation

(SD) or median with 25th and 75th percentiles, as appropriate. For

normally distributed quantitative data (such as age, temperature, WBC

count), one-way analysis of variance (ANOVA) was used to compare

the differences among the three groups. For nonnormally distributed

quantitative data (neutrophil percentages, CRP, Alvarado scores, VAS

scores, the duration of normalization of inflammatory markers, the

duration of normal diet and body temperature, total cost and length of

hospitalization), the Kruskal–Wallis test followed by all pairwise multiple

comparisons was used to detect statistical significance. Bonferroni’s

correction was used for multiple hypothesis testing. The data were

analyzed by IBM SPSS software version 22 (SPSS, Chicago, Illinois,

USA). A P value


Fig. 2 Trial profile

Appendicoliths were present in 12 patients (36.36%) in the ERAT group,

16 patients (48.48%) in the LA group and 11 patients (33.33%) in the

OA group. There were no significant differences in appendicoliths among

the three groups (p =0.516).

Treatment success rate and efficacy of ERAT

Table 2 shows the clinical outcomes of the three groups. Successful

treatment was achieved in 29 patients (87.88%) in the ERAT group,

32 patients (96.97%) in the LA group and 33 patients (100%) in the

OA group. No significant differences were observed among the three

groups (P=0.123). Among the three groups, ERAT failed in four patients

(12.12%) due to difficult cannulation, and LA was performed in these

patients later on the same day, with uneventful recoveries. All these

four patients were found appendicoliths before ERAT. Appendicoliths

of the other 8 patients who were found to have appendicoliths by CT

scan were removed by ERAT. Stents were placed in 29 patients with

successful ERAT. In the LA group, a 63-year-old patient failed LA due

to extensive abdominal adhesion caused by surgical reduction for

intussusception 3 years ago. The patient was later converted to OA


Among 29 patients who underwent successful ERAT, most achieved

complete abdominal pain relief immediately after the procedure. The

duration of normalization of inflammatory markers, including the WBC

count, neutrophil percentages and CRP level, did not significantly differ

among the ERAT, LA and OA groups (P =0.351, P=0.607, P=0.147,

respectively). The overall cost in the LA group was significantly

higher (P


Table 1 Basic characteristics

ERAT group (n=33) LA group (n=33) OA group


P value

Age, mean (SD), years 44.12±16.95 43.24±15.41 45.45±18.04 0.866

Male, n (%) 18 (54.55) 17 (51.52) 19 (57.58) 0.967

Abdominal surgery history, n (%) 8 (24.24) 8 (24.24) 7 (21.21) > 0.999


Migrated right lower abdominal pain, n (%) 29 (87.88) 22 (66.67) 25 (75.76) 0.142

Nausea, n (%) 22 (66.67) 23 (69.70) 17 (51.52) 0.285

Vomiting, n (%) 5 (15.15) 4 (12.12) 9 (27.27) 0.345

Anorexia, n (%) 33 (100) 32 (96.97) 32 (96.97) > 0.999

Fever, n (%) 18 (54.55) 13 (39.39) 17 (51.52) 0.532

Temperature (℃) 37.37±0.77 37.13±0.57 37.22±0.58 0.317


Right lower abdominal tenderness, n (%) 33 (100) 33 (100) 33 (100)

Rebound tenderness, n (%) 17 (51.52) 15 (45.45) 20 (57.58) 0.654

Laboratory examination

WBC count (× 10 9 /L) 11.78±3.84 11.87±3.80 13.64±3.87 0.091

Neutrophil percentages, median (25th, 75th percentile) 0.84 (0.78, 0.87) 0.81 (0.76,0.85) 0.83 (0.76, 0.90) 0.233

CRP (mg/L) 0.749

0–20 18 (54.6) 20 (60.6) 25 (75.76)

21–50 7 (21.2) 7 (21.2) 6 (18.18)

> 50 8 (24.2) 6 (18.2) 2 (6.06)

CT scan

Local Cecal Wall thickening, n (%) 4 (12.12) 0 (0) 1 (3.03) 0.123

Periappendiceal fat inflammation, n (%) 25 (75.76) 27 (81.82) 29 (87.88) 0.496

Intraluminal appendicolith, n (%) 12 (36.36) 16 (48.48) 11 (33.33) 0.516

Alvarado scores, median (25th, 75th percentile) 8 (7, 9) 8 (6, 9) 8 (7, 9) 0.127

VAS scores, median (25th,75th percentile) 6 (5, 7) 7 (6, 7) 6 (6, 7) 0.054

ERAT, endoscopic retrograde appendicitis therapy; LA, laparoscopic appendectomy; OA, open appendectomy; SD, standard deviation; WBC, white blood cell; CRP,

C-reactive protein; VAS, visual analog scale


9 patients only received colonoscopy for one time. Moreover, for the 4

patients who failed ERAT, they also received two-times intervention since

they underwent both ERAT and LA. Table 3 summarizes the adverse

events which arose in the three groups. No significant differences

(P =0.693) were found among the three treatment groups. In the ERAT

group, three patients (9.09%) reported right lower abdominal pain and

were diagnosed with recurrent acute appendicitis. The recurrence time

was 4, 6 and 11 months, respectively. Two of them were found to have

intraluminal appendicoliths during primary hospitalization. These three

patients received LA later at the same day. Thus, there were totally 7

patients in the ERAT group who crossed over to the LA group, and

the final crossover rate is 21.21% (7/33). In the LA group, one patient

(3.03%) was found to have a fluid collection around the ileocecal

junction and the fluid collection gradually diminished later on. In the

OA group, three patients (9.09%) were found to have postoperative

complications. Two of them exhibited wound infections within one

month after surgery. Another patient complained of occasional incision

pain one month after OA, especially on rainy days.


In this pilot RCT, we have shown that ERAT is feasible and safe for

treating acute uncomplicated appendicitis. Overall, nearly 25% of

patients accepted to participate the trial, suggesting the potential

clinical extension of ERAT since it is a brand-new treating method and

no patient has ever heard of it before. Appendicoliths and infection are

considered as important causes of acute appendicitis and ERAT could

treat acute uncomplicated appendicitis by appendicolith extraction, pus

drainage and intraluminal pressure reduction to relieve the syndromes

and ultimately treat acute appendicitis [7, 12, 13]. Although this pilot trial

was not adequately powered to detect differences in treatment efficacy,

the results are useful to inform future clinical application of ERAT.

Although there are some complications associated to colonoscopy,

the adverse event rates were less than 1% and 0.2% for bleeding and

perforation respectively and there were no any adverse events related

to colonoscopy among the patients underwent ERAT treatment in our

study [14]. Moreover, ERAT compares favorably with the results of

surgery in terms of the postintervention recovery of patients. Regarding

the period of body temperature normalization, inflammatory markers

(including the WBC count, neutrophil percentages and CRP level)

and the length of hospitalization, our data did not indicate significant

differences among the three groups (P =0.194, P=0.351, P=0.607,

P=0.147, P=0.054, respectively), which showed that the clinical

efficacy of ERAT was similar to that of surgery. As for different surgical

methods, LA showed a similar clinical efficacy as OA, while LA yielded



Table 2 Clinical outcome

ERAT group

(n = 33)

LA group


OA group



Treatment Success, n (%) 29 (87.88) 32 (96.97) 33 (100) 0.123

Definite acute uncomplicated appendicitis, n (%) 33 (100) 33 (100) 33 (100)

Appendicoliths removal, n (%) 8 (66.67) NA NA

Stent d rainage, n(%) 29 (87.88) NA NA

Failed cannulation, n (%) 4 (12.12) NA NA

Transferred to surgery, n (%) 4 (12.12) NA NA

Normalization of WBC count, days 0.351

0–1 16 12 17

1–3 5 12 9

> 3 2 0 2

Normalization neutrophil percentages, days 0.607

0–1 15 11 7

1–3 11 14 19

> 3 4 2 2

Normalization of CRP, days 0.147

0–1 3 1 3

1–3 5 10 2

> 3 7 2 3

Normalization of temperature, median (25th, 75th 2 (1, 3) 1 (1, 2) 2 (1, 3) 0.194

percentile), days

LOS, median (25th, 75th percentile), days 5 (4, 6) 4 (3, 5) 4 (3, 5) 0.054

Total cost, median (25th, 75th percentile), RMB 10,983.25









< 0.001 0.001 < 0.001 < 0.001

ERAT, endoscopic retrograde appendicitis therapy; LA, laparoscopic appendectomy; OA, open appendectomy; NA, not applicable; WBC, white blood cell; CRP,

C-reactive protein; LOS, length of hospital stay

Table 3 Follow-up

ERAT group


LA group


OA group (n=33)

P value

Stent discharged, n (%) 29 (87.88) NA NA

Spontaneously discharged, n (%) 9 (31.03) NA NA

Retrieved, n (%) 20 (68.97) NA NA

Adverse events, n (%) 3 (9.09) 1 (3.03) 3 (9.09) 0.693

Recurrence, n (%) 3 (9.09) NA NA

Patients with appendicolith at first admission, n (%) 2 (6.06) NA NA

Patients without appendicolith at first admission, n (%) 1 (3.03) NA NA

Crossover rate (%) 21.21 3.03 NA


Wound infection, n (%) NA 0 2 (6.06)

Abdominal or incisional pain, n (%) NA 0 1 (3.03)

Abdominal fluid collection, n (%) NA 1 (3.03) 0

Obstructive symptoms, n (%) NA 0 0

ERAT, endoscopic retrograde appendicitis therapy; LA, laparoscopic appendectomy; OA, open appendectomy; NA, not applicable

fewer complications, although there was no statistical significance

(P =0.693) in the current study. OA, as the traditional treatment method,

is the most reliable therapy for acute appendicitis. However, OA seems

to cause more adverse events, such as wound infection, which reduces

the quality of life of patients.

protect beneficial or commensal microorganisms from contamination

with pathogenic organisms [15]. In addition, evidence has shown that

appendectomy may slightly increase the incidence of Crohn’s disease

[16]. In patients with acute uncomplicated appendicitis, ERAT may

preserve the function of the appendix with a satisfactory therapeutic

effect. To some extent, ERAT may be essential for intestinal immune

A previous study suggested that the appendix could preserve and function, which is another strength of the treatment.





Difficult biliary cannulation is defined as the inability to achieve selective

cannulation within 10 min or 5 attempts by a recent ERCP guideline

[17]. Taking the ERCP guideline as a reference, in our study, we set

the difficult appendix cannulation time to within 15 min regardless of

the number of cannulation attempts. In the present study, 4 patients

(12.12%) failed ERAT treatment. All of these failures were due to difficult

cannulation caused by a swollen mucosa and narrow lumen of the

appendix. In these patients, the guidewire failed to pass through the

swollen and convoluted appendiceal lumen. Unfortunately, difficult

appendiceal cannulation remains an unsolved issue. We believe that

there may be two ways to assist appendiceal cannulation in this

situation. One is to find new equipment that can overcome the severe

edema of the appendix mucosa. The other is to prolong the pre-ERAT

duration to acquire more sufficient anti-inflammatory effect by antibiotics

and thereby maximally reduce the inflammation of the appendiceal

mucosa. However, the second method would definitely increase the

overall hospitalization duration of patients. Subsequent studies will be

conducted to address difficult appendiceal cannulation. In the current

study, 4 patients who failed ERAT were found to have appendicoliths.

However, the reason of failure was due to the mucosal edema instead

of the obstruction of the appendicoliths. Apart from the 4 patients,

the other 8 patients with appendicoliths had a smooth recovery by

receiving ERAT alone. Hence, appendicolith should not be considered

as a contraindication of ERAT. Same as previous study [18], we think

the key to remove appendicoliths was based on the quality of the stone

and the technique of the endoscopist. A fragile stone, regardless of

its size, is more likely to be removed by the combination of irrigation

and extraction basket. If the stone is hard and large, the success of

retraction is more dependent on the experience and the technique of

the endoscopist. When a giant and irregular appendicolith is observed,

it is also feasible to squeeze the appendix and let the stone fall into

the intestine cavity. After that, the appendicolith can be removed via

the intestine by a stone basket. Previous studies showed that the

recurrence rates of acute appendicitis patients treated with ERAT ranges

from 6.1 to 15% [7,8,9]. In the present study, 3 patients (9.09%) had

recurrent appendicitis. This recurrence rate was consistent with previous

findings. The recurrence of acute appendicitis may be associated with

the appendiceal morphology since long and curved appendix is also

risk factor of acute appendicitis. Other factors, such as genetic and

environmental factors, may also have impact on recurrence. The final

crossover rate of ERAT group was 21.21%, which means more than 3/4

of all patients recovered successfully by receiving ERAT alone and those

who crossed over to surgery did not experience any adverse outcomes

due to the delay in appendectomy. However, the final crossover rate

may be underestimated due to short-term follow-up period and a

long-term follow-up is needed to be done in the future. Moreover, in a

previous study, spontaneous discharge of the stents was considered as

an adverse event [9]. However, in current study, the stents of 9 patients

spontaneously discharged and these 9 patients did not show symptoms

during the 14-day period. Thus, from our point of views, if the patients

do not show any discomfort, spontaneous discharge of the stents

should be considered as a benefit and convenience since these patients

will not have to undergo colonoscope a second time.

Another advantage of ERAT is its ability to facilitate a precise diagnosis

of acute appendicitis. Generally, endoscopy can serve as a diagnostic

tool for numerous diseases, such as ulcerative colitis and Crohn’s

disease [19, 20]. A previous study indicated that colonoscopy can

diagnose acute appendicitis with 100% sensitivity and 99% specificity

[21]. Li et al. further described the key points of diagnosing acute

appendicitis by ERAT by observing both the appendiceal mucosa

morphology and the appendiceal lumen imaging by fluoroscopy [8].

In our study, 33 patients with acute uncomplicated appendicitis in

the ERAT group were all confirmed by ERAT. In the future, ERAT may

become an essential diagnostic method for patients suspicious for acute

appendicitis who have atypical clinical manifestations.

One feature of our study was that an abdominal CT scan was performed

in all participants. Although CT scan is not a necessary diagnostic

criterion for acute appendicitis, using CT can enhance the accuracy of

diagnosing acute appendicitis and minimize the negative appendicitis

rate. Similar to this view, some previous trials showed that their study

design was limited due to the lack of CT scans performed in suspicious

patients [7]. Based on former experiences, all participants had to be

examined by abdominal CT scan in our study. Thus, we could accurately

enroll the patients with acute uncomplicated appendicitis in our trial by

both clinical manifestation and CT scan confirmation.

The study has several limitations. First, the success rate of ERAT largely

depends on the skills of endoscopists. Although our endoscopists are

experienced doctors, the lack of ERAT guidelines was still the main

problem when faced with difficult cannulation. Second, since this was

an RCT, we tried to perform ERAT on the first day of hospital admission,

which was similar to the timing of emergency surgery. The downside of

this strategy is that it may cause insufficient anti-inflammatory treatment

in patients, which may increase the difficulty of appendiceal cannulation.

Third, in the current study, the power was not calculated and the study

is more likely to commit a type II error. However, in this pilot study,

the safety and feasibility of ERAT were preliminarily estimated. Thus,

future studies involved with larger sample size are needed to be done.

Fourth, a double-blinded trial cannot be conducted due to the nature

of the study. Last, the need to prepare for colonoscopy in patients with

abdominal pain requires further study and is another limitation of the


In conclusion, ERAT was demonstrated to be a feasible and safe

treatment for acute uncomplicated appendicitis. However, difficult

appendiceal cannulation and acute appendicitis recurrence are the main

problems that remain to be solved. In the future, large-scale multicenter

RCTs are needed to further address the current challenges.


ERAT: Endoscopic retrograde appendicitis therapy; LA: Laparoscopic

appendectomy; OA: Open appendectomy; PEG: Polyethylene glycol;

SD: Standard deviation; ERA: Endoscopic retrograde appendicography;

WBC: White blood cell; CRP: C-reactive protein; LOS: Length of

hospital stay; VAS: Visual analog scales; ANOVA: Analysis of variance;

ITT: Intention-to-treat; CT: Computed tomography; RCT: Randomized

controlled trial; EMR: Endoscopic mucosal resection


We would like to thank American Journal Experts (https://www.aje.com/)

for English language editing. We also appreciate all members from the

Department of General Surgery, Jinshan hospital, Fudan University, for

helping with the study.



Authors’ contributions

PLS and MJ proposed the study and were accountable for all aspects of

the work. ZMS contributed to the article in the aspects of drafting work

as well as collecting, analyzing and interpreting the data; ZLZ, JTL, MY

and WDH all made essential contribution to the manuscript. All authors

read and approved the final manuscript.


This study was supported by Project of Shanghai Municipal Health

Commission of China (No. 201740041). All the funding was used to

conduct this trial.

Availability of data and materials

The datasets supporting the conclusions of this article are available in the

the ResMan original data sharing platform (IPD sharing platform) of the

Chinese Clinical Trial Registry, which can be viewed at the following website:


We expect to release the original data on December 2022.


Ethics approval and consent to participate

All procedures performed in studies involving human participants

were in accordance with the ethical standards of Ethics Committee of

Jinshan Hospital, Fudan University (No. 2017-24) on May 17th, 2017

and also with the 1964 Helsinki declaration and its later amendments

or comparable ethical standards. The experimental protocol was also

approved by Shanghai Municipal Health Commission and Project of

Shanghai Municipal Health Bureau in China (No. 201740041). Written

informed consent was obtained from all participants. The study is

registered with the WHO Primary Registry-Chinese Clinical Trial Registry


Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Author details


Department of General Surgery, Jinshan Hospital, Fudan University,

Shanghai, China. 2 Department of Gastroenterology, Jinshan Hospital,

Fudan University, Shanghai, China.

Received: 29 June 2021 Accepted: 3 February 2022

Published online: 13 February 2022


1. Bhangu A, Søreide K, Di Saverio S, Assarsson JH, Drake FT. Acute

appendicitis: modern understanding of pathogenesis, diagnosis,

and management. Lancet. 2015;386(10000):1278–87.

2. National Surgical Research Collaborative. Multicentre observational

study of performance variation in provision and outcome of

emergency appendicectomy. Br J Surg. 2013;100:1240–52.

3. Ahmed HO, Muhedin R, Boujan A, Aziz AHS, Abdulla AM, Hardi RA,

et al. A five-year longitudinal observational study in morbidity and

mortality of negative appendectomy in Sulaimani teaching Hospital/

Kurdistan Region/Iraq. Sci Rep. 2020;10:2028.

4. Andersson RE. The natural history and traditional management of

appendicitis revisited: spontaneous resolution and predominance

of prehospital perforations imply that a correct diagnosis is more

important than an early diagnosis. World J Surg. 2007;31:86–92.

5. Flum DR. Clinical practice. Acute appendicitis—appendectomy or

the “antibiotics first” strategy. N Engl J Med. 2015;372:1937–43.

6. Liu BR, Song JT, Han FY, Li H, Yin JB. Endoscopic retrograde

appendicitis therapy: a pilot minimally invasive technique (with

videos). Gastrointest Endosc. 2012;76:862–6.

7. Liu BR, Ma X, Feng J, Yang Z, Qu B, Feng ZT, et al. Endoscopic

retrograde appendicitis therapy (ERAT): a multicenter retrospective

study in China. Surg Endosc. 2015;29:905–9.

8. Li Y, Mi C, Li W, She J. Diagnosis of acute appendicitis by

endoscopic retrograde appendicitis therapy (ERAT): combination of

colonoscopy and endoscopic retrograde appendicography. Dig Dis

Sci. 2016;61:3285–91.

9. Ye LP, Mao XL, Yang H, He BL, Zhu LH, Zhang Y. Endoscopic

retrograde appendicitis techniques for the treatment of patients with

acute appendicitis. Z Gastroenterol. 2018;56:899–904.

10. Gaitini D. Imaging acute appendicitis: state of the art. J Clin Imaging

Sci. 2011;1:49.

11. Pickhardt PJ, Levy AD, Rohrmann CA Jr, Kende AI. Primary

neoplasms of the appendix manifesting as acute appendicitis: CT

findings with pathologic comparison. Radiology. 2002;224:775–81.

12. Williams SN, Bulstrode CJK, O’Connell PR. The vermiform

appendix. In: Bailey & Love’s short practice of surgery. 26th ed.

Boca Raton: CRC Press; 2013. p. 1201–2.

13. Liang MK, Andersson RE, Jaffe BM, Berger HD, et al. The appendix.

In: Brunicardi FC, Andersen DK, Billiar TR, et al., editors. Schwartz’s

principles of surgery. 9th ed. New York: McGraw-Hill; 2010. p. 1074–5.

14. Su YK, Kim HS, Hong JP. Adverse events related to colonoscopy:

global trends and future challenges. World J Gastroenterol.


15. Randal Bollinger R, Barbas AS, Bush EL, Lin SS, Parker W. Biofilms

in the large bowel suggest an apparent function of the human

vermiform appendix. J Theor Biol. 2007;249:826–31.

16. Kaplan GG, Pedersen BV, Andersson RE, Sands BE, Korzenik

J, Frisch M. The risk of developing Crohn’s disease after an

appendectomy: a population-based cohort study in Sweden and

Denmark. Gut. 2007;56:1387–92.

17. Liao WC, Angsuwatcharakon P, Isayama H, Dhir V, Devereaux B,

Khor CJ, et al. International consensus recommendations for difficult

biliary access. Gastrointest Endosc. 2017;85:295–304.

18. Song MY, Liu ZH, Zhao LX, Liu BR. Endoscopic retrograde

appendicitis therapy for treating a giant hard appendicolith

embedded in the appendiceal orifice: a case report. Asian J Surg.


19. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long

MD. ACG clinical guideline: ulcerative colitis in adults. Am J

Gastroenterol. 2019;114:384–413.

20. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB,

Sands BE. ACG clinical guideline: management of crohn’s disease in

adults. Am J Gastroenterol. 2018;113:481–517.

21. Chang HS, Yang SK, Myung SJ, Jung HY, Hong WS, Kim JH, et al.

The role of colonoscopy in the diagnosis of appendicitis in patients

with atypical presentations. Gastrointest Endosc. 2002;56:343–8.

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Zhiqiang Yi 1† , Cheng Chen 2† , Biguang Tuo 1 , Taolang Li 3 and Xuemei Liu 1*

Yi et al. BMC Gastroenterology (2022) 22:67 https://doi.org/10.1186/s12876-022-02138-8



Upper gastrointestinal (GI) bleeding is a severe acute disease of

gastroenterology department. Fish bone is the most common foodrelated

foreign body. However, fish bone piercing the esophagus,

causing the mediastinal abscess that corroded the left subclavian artery,

resulting delayed but high-risk massive upper gastrointestinal bleeding

is very rare.

Case presentation

A 54-year-old man was admitted to the hospital with a chief complaint

of hematemesis for 2 h. The color of hematemesis was bright red, and

the volume was over 1000 ml. He also had symptoms of palpitations,

fatigue and sweating. He had been on long-term glucocorticoids or

nonsteroidal anti-inflammatory drugs (NSAIDs) for gout for 3 years

before admission, had no previous history of liver disease or GI bleeding

disease, and had a history of drinking.


Case presentation

We report a 54-year-old man who was diagnosed with delayed but

high-risk massive upper GI bleeding that was the result of a fish bone

piercing the esophagus, causing a mediastinal abscess that corroded

the left subclavian artery. He was saved effectively by early and timely

multidisciplinary collaboration.


A fish bone-caused mediastinal abscess that corrodes the left

subclavian artery and induces delayed but high-risk massive upper GI

bleeding is very rare. In addition to routine consideration of upper GI

bleeding, medical history, endoscopy and CT are helpful for achieving

a diagnosis. Importantly, early and timely multidisciplinary collaboration

can effectively save critically ill patients.


Delayed but high-risk massive upper gastrointestinal bleeding, Fish

bone, Mediastinal abscess, Left subclavian artery (LSA), Early and timely

multidisciplinary collaboration


Upper gastrointestinal (GI) bleeding is a severe acute disease

associated with four main causes, namely, esophageal variceal

bleeding, peptic ulcer (PU) bleeding, gastric cancer bleeding

and acute erosive hemorrhagic gastritis, and prompt diagnosis

and treatment are mandatory [1, 2]. In adults, a fish bone is the

most common food-related foreign body [3, 4]. A fish bone can

unfortunately pierce the left subclavian artery (LSA) and cause a

pseudoaneurysm in rare cases, resulting in an LSA esophageal

fistula [3, 5]. Arterioesophageal fistula are rare, but they can cause

massive life-threatening bleeding [6, 7]. Here, we report an adult

case of a mediastinal abscess corroding the LSA, resulting in

delayed but high-risk massive upper GI bleeding.

On admission, the patient’s vital signs included a temperature of 36.4 °C,

blood pressure of 80/50 mmHg, and heart rate of 135 bpm. Laboratory

data showed routine blood tests: hemoglobin 72 g/L (normal, 130–175

g/L), white blood cells 13.41×10 9 /l (normal, 4–10*10 9 /L), total platelets

60×10 9 (normal, 100–300*10 9 /L); C-reactive protein 159.90 mg/l

(normal 0–8 mg/L); blood gas analysis: oxygen partial pressure 79.3

mmHg, CO 2

partial pressure 30.8 mmHg, pH value 7.281; and normal

liver and renal function and coagulation tests. Therefore, GI hemorrhage

was first considered, and esomeprazole was administered. Computed

tomography (CT) on admission showed a visible breach on the left side

of the esophageal wall, a low-density lesion was found between the

esophageal wall and the LSA, and the demarcation from the esophageal

wall and subclavian artery was unclear (Fig. 1). Because the patient had

no history of foreign body ingestion, we initially considered esophageal

diverticula with bleeding potential. However, the patient still presented

with repeated hematemesis with a large volume of bright red blood;

his vital signs could not be maintained, and he developed progressive

unconsciousness 30 min after admission to the hospital. We applied

a multidisciplinary approach; critical care doctors were included in the

treatment, and a member of the Department of Anesthesiology performed

an urgent consultation. Tracheal intubation-assisted respiration, aspiration

prevention, and anti-shock therapy were applied, and 6 units of red blood

cells were transfused. Additionally, urgent esophagogastroduodenoscopy

was performed in the operating room, which indicated active and massive

bleeding from the esophageal wall (Fig. 2). However, due to massive

bleeding, this patient suffered from two cardiac arrests, so a detailed

endoscopic examination could not be performed.

Urgent thoracotomy through the median sternal incision was performed

immediately, and an abscess cavity 4 cm in size was detected between

the LSA and the left common carotid artery. A stench of putrefaction

accompanied by a large gush of blood was present when the abscess

cavity was opened. The active bleeding point was found in the posterior

lateral wall of the LSA with a 3 mm rupture. During the repair of the LSA

and clean-up of the abscess cavity, an esophageal fistula was detected

and repaired on the other side of the abscess cavity. However, no foreign


*Correspondence: onlyoneliuxuemei@163.com

Zhiqiang Yi and Cheng Chen contributed equally and shared first authorship


Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China

©The Author(s) 2022


Fig. 1 Image from CT scan. CT showed that the local soft tissue

was Fig. thickened 1 Image in the from esophagus CT scan. CT at the showed cervicothoracic that the local junction, soft tissue

and was a gaseous thickened cavity in was the esophagus present on at the the left cervicothoracic posterior wall of junction, the

esophagus and a gaseous (red arrow), cavity approaching was present the on left the subclavian left posterior artery wall (white of the

arrow). esophagus Esophageal (red breach arrow), was approaching detected (black the left arrow) subclavian artery (white

arrow). Esophageal breach was detected (black arrow)

body was observed (Fig. 3a, b). With prompt and effective treatment, the

patient recovered. Revisiting family history indicated that chest pain and

discomfort occurred in this patient after eating fish 4 days prior.

Discussion and conclusions

Fig. 2 Image from the emergent endoscopy. Active and massive

bleeding Fig. 2was Image detected from from the emergent the esophageal endoscopy. wall by Active emergent and massive

endoscopy bleeding was detected from the esophageal wall by emergent


There are generally four main causes of upper GI bleeding, namely,

esophageal variceal bleeding, PU-caused bleeding, gastric cancercaused

bleeding and acute erosive hemorrhagic gastritis [1, 2].

In addition, there are also reports of NSAIDs causing esophageal

mucosal damage. These drugs may cause mucosal damage by

reducing the cytoprotective effect of prostaglandins on the mucosa

or aggravating reflux esophagitis [8, 9]. The clinical manifestations of

these patients are usually retrosternal pain, sore throat and dysphagia

[9]. Esophageal bleeding caused by NSAIDs is a rare nonfatal bleeding,

mostly secondary to superficial esophageal ulcer oozing, and some

bleeding can even be discovered during endoscopy [10, 11]. However,

Fig. 3 Image from the surgical operation. a The abscess cavity (white arrow) was located between the left subclavian artery (black arrow) and the

left common carotid artery (blue arrow). b Schematic diagram of surgical anatomy





in the present case, the patient’s condition progressed so rapidly and

dangerously that the challenge was to determine the cause of the

bleeding and how to treat it. Based on medical history, physiological

signs, examination and treatment, this case of delayed but high-risk

massive upper GI bleeding was the result of a fish bone piercing

the esophagus, causing the mediastinal abscess that corroded the

LSA. Fistulas between the subclavian artery and esophagus are rare

but can rapidly become life-threatening [12, 13]. Clinically, among

arterial-esophageal fistulas caused by esophageal foreign bodies,

the proportion of LSA esophageal fistulas is only 2% [3]. Most

mediastinal abscesses are related to infections of deep sternal wounds,

esophageal perforations, or descending necrotizing mediastinitis [14,

15]. Mediastinal abscess directly caused by taking glucocorticoids

has not been reported. It may be a contributing factor to the formation

of abscesses after mediastinal infection. Glucocorticoids have many

complex quantitative and qualitative immunosuppressive effects,

which can induce cellular immune deficiency and may increase the

susceptibility of the host to various viruses, bacteria, fungi and parasites

[16]. The patient’s risk of infection increases with increasing treatment

dose and treatment time. In patients exposed to low doses, even if the

cumulative dose is high, the risk of infection is often low. In addition, the

host’s underlying disease status also determines the changes in the risk

of infection in clinical practice [17]. Therefore, in this case, we believe

that the patient’s long-term use of glucocorticoids is not an independent

risk factor for mediastinal abscess.

Generally, fish bones or sharp foreign bodies can directly pierce the large

arteries in the mediastinum, causing fatal upper GI bleeding. For example,

some case reports have reported sharp foreign bodies such as fish

bones or chicken bones piercing the esophagus and mediastinal artery

[3, 18, 19]. Because the symptoms are initially not serious, they are often

ignored by patients and their families. Once the foreign body leaves the

artery, the patient will die suddenly due to acute upper GI bleeding [3, 18].

If the patient seeks medical attention in time and the foreign body does

not break away from the artery, the patient can be successfully cured by

surgery [19]. In contrast, in this rare case, the mediastinal abscess that

resulted from puncture of the esophagus by the fishbone corroded the

LSA, causing delayed but high-risk arterial hemorrhage.

This case suggests that in addition to routine consideration of upper GI

bleeding, medical history, endoscopy and CT are helpful for achieving

a diagnosis. Importantly, early and timely multidisciplinary collaboration

can effectively save critically ill patients. Emergency thoracotomy

remains a life-saving treatment.


GI: Gastrointestinal; NSAIDs: Nonsteroidal anti-inflammatory drugs; LSA:

Left subclavian artery; CT: Computed tomography; PU: Peptic ulcer.


The authors are grateful to Prof. Hua Zhang and Jiaxing Zhu

(Department of Gastroenterology, Affiliated Hospital of Zunyi Medical

University, Zunyi, Guizhou Province, China) for study support.

Authors’ contributions

ZQY collected and interpreted the data; ZQY and XML drafted the

manuscript; CC established the surgical plan; BGT analyzed the

radiological images; TLL and XML designed the study and revised

the draft; and XML supervised the study. All the authors listed have

approved the enclosed manuscript.


This research was supported by the National Natural Science

Foundation of China (81860103 and 82070536 to X.M.L., 81660098

and 82160505 to T.L.L., 81960532 to C.C., and 82073087 to B.G.T.),

the Guizhou Province International Science and Technology Cooperation

(Gastroenterology) Base (Qian Ke He Platform Talents-HZJD [2021] 001

to X.M.L.), the Guizhou Province Science Plan Program (Qian Ke He

Foundation-ZK [2021] General 461 to T.L.L.), the Cultivation of high-level

innovative talents in Guizhou Province [“Thousand” level] (fzc120200615

to T.L.L.), the 15851 Talent Projects of Zunyi City (2018 to T.L.L.), and

the Guizhou Province Science and Technology Plan (No. Qiankehe

Support [2021] General 073 to C.C.).

Availability of data and materials

All information about the patient came from the Affiliated Hospital of

Zunyi Medical University. The data used and analyzed during the current

study are included in this article.


Ethics approval and consent to participate

The study was reviewed and approved by the Ethics Committee of the

Affiliated Hospital of Zunyi Medical University.

Consent for publication

Written informed consent was obtained from the patient for publication

of this report and any accompanying images. A copy of the written

consent is available upon request.

Competing interests

The authors declare that they have no competing interests.

Author details


Department of Gastroenterology, Affiliated Hospital of Zunyi Medical

University, Zunyi 563003, Guizhou Province, China. 2 Department of

Thoracis Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi,

Guizhou Province, China. 3 Department of Thyroid and Breast Surgery,

Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province,


Received: 27 August 2021 Accepted: 3 February 2022

Published online: 15 February 2022


1. Gralnek I, Dumonceau J, Kuipers E, Lanas A, Sanders D, Kurien

M, et al. Diagnosis and management of nonvariceal upper

gastrointestinal hemorrhage: European Society of Gastrointestinal

Endoscopy (ESGE). Guideline. 2015;47(10):a1-46.

2. Gralnek I, Stanley A, Morris A, Camus M, Lau J, Lanas A, et al.

Endoscopic diagnosis and management of nonvariceal upper

gastrointestinal hemorrhage (NVUGIH): European Society of

Gastrointestinal Endoscopy (ESGE). Guideline Update 2021.




3. Zhao S, Tinzin L, Deng W, Tong F, Shi Q, Zhou Y. Sudden

unexpected death due to left subclavian artery-esophageal fistula

caused by fish bone. J Forensic Sci. 2019;64(6):1926–8.

4. Wang X, Zhao J, Jiao Y, Wang X, Jiang D. Upper gastrointestinal

foreign bodies in adults: a systematic review. Am J Emerg Med.


5. Stringari C, Sbraga P, Zaraca F. Endovascular treatment of a left

subclavian pseudoaneurysm induced by ingestion of a foreign body.

Ann Vasc Surg. 2013;27(5):672.e677-672.611.

6. Hollander JE, Quick G. Aortoesophageal fistula: a comprehensive

review of the literature. Am J Med. 1991;91(3):279–87.

7. Millar A, Rostom A, Rasuli P, Saloojee N. Upper gastrointestinal

bleeding secondary to an aberrant right subclavian arteryesophageal

fistula: a case report and review of the literature. Can J

Gastroenterol. 2007;21(6):389–92.

8. Noffsinger AE. Update on esophagitis: controversial and

underdiagnosed causes. Arch Pathol Lab Med. 2009;133(7):1087–95.

9. Zografos GN, Georgiadou D, Thomas D, Kaltsas G, Digalakis M.

Drug-induced esophagitis. Dis Esophagus. 2009;22(8):633–7.

10. Kikendall JW, Friedman AC, Oyewole MA, Fleischer D, Johnson

LF. Pill-induced esophageal injury. Case reports and review of the

medical literature. Dig Dis Sci. 1983;28(2):174–82.

11. Kim SH, Jeong JB, Kim JW, Koh S-J, Kim BG, Lee KL, et al. Clinical

and endoscopic characteristics of drug-induced esophagitis. World

J Gastroenterol. 2014;20(31):10994–9.

12. Kim S, Jeon KN, Bae K. Aberrant left subclavian artery-esophageal

fistula in a patient with a prolonged use of nasogastric tube: a case

report and literature review. Diagnostics (Basel). 2021;11(2):195.

13. Oliveira E, Anastácio M, Marques AJ. Aberrant right subclavian

artery-esophageal fistula: massive upper gastrointestinal

hemorrhage secondary to prolonged intubation. Braz J Anesthesiol.


14. Pastene B, Cassir N, Tankel J, Einav S, Fournier PE, Thomas P, et

al. Mediastinitis in the intensive care unit patient: a narrative review.

Clin Microbiol Infect. 2020;26(1):26–34.

15. Martínez Vallina P, Espinosa Jiménez D, Hernández Pérez L, Triviño

RA. Mediastinitis. Arch Bronconeumol. 2011;47(Suppl 8):32–6.

16. Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal

infections. Lancet. 2003;362(9398):1828–38.

17. Cutolo M, Seriolo B, Pizzorni C, Secchi ME, Soldano S, Paolino S,

et al. Use of glucocorticoids and risk of infections. Autoimmun Rev.


18. Russo SS, Taff ML, Ratanaproeksa O, Spitz WU. Sudden death

resulting from chicken bone perforation of the esophagus. Am J

Forensic Med Pathol. 1986;7(3):263–5.

19. Jiang D, Lu Y, Zhang Y, Hu Z, Cheng H. Aortic penetration due to a

fish bone: a case report. J Cardiothorac Surg. 2020;15(1):292.

Publisher’s Note

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Find out more at www.calprotectin.co.uk

[Figure 1: Edwards et al. ECCO 2021 P518]

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Healthcare survey highlights

the impact of the pandemic

on IBD patient care

Over 7,000 people responded to the

Crohn’s & Colitis UK Healthcare Survey,

providing an insight into how IBD patients

experienced healthcare during 2021.

The responses showed that health services

have continued to be disrupted by the

coronavirus pandemic and there’s been a big

impact on patient care. Difficulties accessing

GPs, specialists, medicines, tests, and

procedures have led to delays in diagnosis,

flares, and complications for people with

Crohn’s and Colitis. Mental wellbeing,

relationships, and ability to work have also

been affected.

Ruth Wakeman, Director of Services,

Advocacy & Evidence at Crohn’s & Colitis

UK says: ‘The results of the Healthcare

Survey highlight that the pandemic has

exacerbated existing issues with resourcing

of IBD services, which need to be addressed,

but also some opportunities as services

have adapted to the pandemic. We are

very grateful for the care and support that

healthcare professionals continue to give

to people with Crohn’s and Colitis in such

difficult circumstances.’

The results showed that whilst huge efforts

had been made to deliver excellent care for

people with Crohn’s and Colitis, prioritisation

and investment are vital to tackle increasingly

long waits for care. The recent Getting it Right

First Time (GIRFT) gastroenterology report

called for more proactive management of IBD,

with the aim of reducing admissions. It also

highlighted improvements that could be made

to triage to speed up diagnosis and early


This survey, which was conducted between

August and October 2021, asked questions

about experiences of healthcare during the

previous 6-12 months. It builds on previous

surveys by Crohn’s & Colitis UK, including

the Life in Lockdown Survey in 2020 and IBD

Patient Survey in 2019, all contributing to

build a comprehensive view of healthcare over

the last 3 years.

What people with living with Crohn’s and

Colitis said


Many said that getting a diagnosis during

the pandemic has been difficult, with 29% of

respondents diagnosed during the previous

12 months reporting that this had taken

over a year. This is an increase from 26% in

2019. Respondents also reported that it had

taken longer for treatment to start following

diagnosis. 41% said it took more than two

weeks for treatment to start, compared to

2019 when only 24% reported waiting more

than two weeks for treatment.

Access to healthcare professionals

The results also showed that people found

it harder to get through to IBD teams for

specialist advice, with 27% of those who tried

to contact their advice line saying they did not

get a response by the end of the next working


This was in addition to 41% of those who had

needed care from their GP during the previous

6 months saying they had been unable to get

the care they needed. Furthermore, 29% had

not been able to get the help they needed from

urgent care services.

Access to medicines, tests and procedures

The results indicate a particularly big disruption

to surgery and colonoscopy. 29% reported

cancelled surgery and 24% cancelled

colonoscopies, with many still waiting for a

new date.

Additionally, 18% had experienced disruption

to getting medication.

Impact of difficulties accessing health

services or treatment

22% of those who have needed health

services or treatment during the previous 6

months said that difficulties accessing this had

resulted in a flare of their condition. In addition

to this, 24% reported that their mental health

had been affected. Respondents relayed

how this has led to time off work, affected

relationships and ability to do everyday tasks.

Changes to how patients access care

The survey found that 72% of those who had

needed outpatient appointments during the

previous 6 months had mostly had these by

telephone, with only 3% having mostly video

appointments. Only 13% were offered a

choice. Comments highlighted the benefits of

remote appointments, but also preferences for

some face-to-face appointments. Whichever

method was used, quality of care and a

personalised approach were considered


Quality of care

Despite the challenges during this period, 56%

felt that their quality of care was the same as

before the pandemic, with a small proportion

(4%) considering it was better.

More information about the survey can be

found on the Crohn’s & Colitis UK website. If

you’re an IBD Nurse Specialist or Healthcare

Professional working in IBD, you may want

to use these results alongside your service’s

IBD UK Benchmarking reports as your service

refocuses, adapts, and redesigns for the

future. If you would like to seek feedback and

involve your IBD patients in service redesign,

the charity also has a Patient Engagement

Toolkit, also available on their website which

may be helpful.

Cause of inflammatory

bowel disease discovered

Interaction between gut bacteria and

mucus layer cells

Chronic inflammatory bowel disease (IBD)

is becoming increasingly widespread. Until

now, however, the underlying causes of

the inflammation responses were unclear.

Scientists at the Technical University

of Munich (TUM) have now identified a

mechanism that triggers a problematic

interaction between intestinal bacteria and

cells in the intestinal mucus layer in XLP2,

a condition associated with IBD. The team

believes that the results can be applied to

other intestinal diseases and could offer

approaches to the development of new


The billions of bacteria living in the human

gut – known collectively as the microbiome

– are of enormous importance. They help

with digestion, among other functions.

Consequently, the immune system in the gut

must be extremely well regulated: It should

fight only harmful pathogens without attacking

useful microorganisms. However, this fine

balance can be disrupted by various factors.

A defect in the gene XIAP, which causes

the rare disease XLP2, results in chronic

inflammation of the bowels in 30 percent of all



Dr Monica Yabal

cases, among other symptoms. Babies with this

genetic defect often display serious symptoms

such as diarrhea, abdominal pain, weakness

and weight loss soon after birth. Until now,

scientists have been unable to understand the

underlying mechanism or discover effective

treatments – apart from stem cell transplants,

which involve a high risk of mortality.

Overreaction of the innate immune system

Working with organoids – intestinal cells in a

Petri dish – and animal experiments, a team

headed by Dr. Monica Yabal, Adam Wahida and

Madeleine Müller of the Institute for Molecular

Immunology and the Clinic of Hematology

and Oncology of TUM’s university hospital,

Klinikum rechts der Isar, has now identified the

mechanism behind the inflammation response

and learned how it becomes chronic. “The

innate immune system overreacts to microbes

in the gut,” says Yabal. The immune system in

healthy people eliminates bacteria that cause

illness and then returns to its resting state. But

in some XLP2 patients, a fatal chain reaction


Every person has toll-like receptors (TLRs) that

use unique structures such as molecules in the

cell wall to identify harmful microbes. When a

TLR binds a molecule, the signaling substance

TNF and its TNFR1 and TNFR2 receptors

activate the immune system to eliminate the

pathogen. However, this does not work properly

in XLP2 patients. Instead, the binding of TNF to

the TNFR1 receptor on cells known as Paneth

cells causes these cells to die, resulting in a

vicious circle. That is because the Paneth cells

in the gut mucus layer produce antimicrobial

substances and thus ensure a bacterial balance

in the intestines. The loss of those cells changes

the composition of the microbiome. Beneficial

bacteria such as clostridia are attacked and can

no longer perform their Publication:

regulatory role. This Adam Wahida, Madeleine Müller, Andreas

again activates the Hiergeist, Bastian Popper, Katja Steiger,

immune system. Caterina Branca, Markus Tschurtschenthaler,

Thomas Engleitner, Sainitin Donakonda,

New drugs

Jordy De Coninck, Rupert Öllinger, Marie K.

could stop the Pfautsch, Nicole Müller, Miguel Silva, Sinem


Usluer, Erik Thiele Oberg, Jan P. Böttcher,


Nicole Pfarr, Martina Anton, Julia B. Slotta-

“We believe that this Huspenina, Andreas G. Nerlich, Tobias Madl,

principle might also Marijana Basic, André Bleich, Geert Berx,

be applicable to other Jürgen Ruland, Percy A. Knolle, Roland

inflammatory bowel Rad, Timon E. Adolph, Peter Vandenabeele,

diseases and not only Hirokazu Kanegane, André Gessner, Philipp

in XLP2 patients,” says J. Jost, Monica Yabal. XIAP restrains TNFdriven

intestinal inflammation and dysbiosis by

Prof. Percy Knolle,

the Director of the promoting innate immune responses of Paneth

Institute for Molecular Immunology at TUM. and dendritic cells (2021) Science Immunology,

Malfunctioning Paneth cells have also been Vol 6, Issue 65. DOI: 10.1126/sciimmunol.

observed in many patients with inflammatory abf7235.

bowel diseases with various causes.

More information:

These insights might open up important The study was funded by the European

avenues for the development of new drugs. Research Council (ERC), the German Research

Patients with chronic bowel inflammation Foundation (DFG), the Austrian Research

have been treated for many years with drugs Promotion Agency (FFG) and the German

that inhibit the TNF ScheBo_GastroToday_Aug_2020 Center for Multi-Ad_Address_Change

Infection Research (FFG).

receptors. However,

these molecules are

not very specific

and deactivate both

TNFR1 and TNFR2.

“Our experiments

show that it would

be better if we had a

selective inhibitor for

the TNFR1 receptor,”

says Yabal. It also

remains unclear

why some people

respond very well

to this treatment

while others show

no response at

all. Consequently,

the team would

now like to turn

its attention to the

adaptive immune

system, which

learns throughout an

individual’s lifetime

through contact

with pathogens

and forms special

antigens, and also

study its special role

in the gut.





Go with the Flow!

How the Rare Disease Collaborative

Network can support you in diagnosis and

management of refractory coeliac disease

Woodward JM 1 , Soilleux E 1 , Passmore R 2 ,

Sanders D 3

Coeliac disease that is refractory to the

withdrawal of gluten from the diet is rare,

and as a result prone to both over and under

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indistinguishable from non-responsive coeliac

disease (1) and may be due to the individual

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gluten remaining in the diet that would not

affect most people with the condition. ‘Type 2’

refractory coeliac disease (RCD2) progresses

to an aggressive T-cell lymphoma in as many

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distinguished from non-responsive coeliac

disease or RCD1 by the abnormal clonal

increase of an unusual population of intestinal

intra-epithelial lymphocytes (IELs) characterized

by the presence of the T-cell marker CD3

within the cytoplasm but not on the surface of

the cell (3). These cells also usually lack the

normal expression of another surface marker,

CD8. However, immunohistochemistry for T-cell

markers or polymerase chain reaction (PCR) for

T-cell receptor clonality are unreliable diagnostic

tests for RCD2 (3,4), whereas flow cytometry

to identify individual IELs isolated from fresh

intestinal biopsies is definitive (figure 1a).

It is important to distinguish RCD1 from other

causes of non-responsive coeliac disease

and from RCD2 as specific treatments exist

– for instance, the use of topical steroids or

azathioprine for RCD1 and cladribine and

autologous stem cell transplantation for

RCD2. In 2018, NHS England designated

Sheffield and Cambridge as the two national

centres in the first ever UK Rare Disease

Collaborative network in order to refine

diagnostic and therapeutic techniques, and

to develop a national database in order to

further the understanding of the conditions

and facilitate trials of treatment (5,6). The

ongoing development of flow cytometry of

intra-epithelial lymphocytes in the network

has unexpectedly also demonstrated the

utility of this technique in the diagnosis of

coeliac disease itself (7). A characteristic

change in the IEL composition occurs

following the development of coeliac disease

(8) and remains regardless of normalization

of duodenal histology and serological tests

on institution of a gluten free diet. Hence IEL

flow cytometry is the only existing accessible

test capable of confirming or refuting the

diagnosis of coeliac disease in a patient

following a strict gluten free diet. Referrals

to the national centres remain lower than the

expected prevalence of RCD (6) and indicates

ongoing failure to recognize the condition. The

following case studies demonstrate the utility

of referral to the specialist national centres.

Coeliac UK

have developed

resources on

refractory and


coeliac disease

to support

you and your

patients, scan

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find out more.

Case 1. Misdiagnosis of coeliac disease.

A 20-year old woman contacted Coeliac UK

for advice. Following a period of chronic

fatigue she presented to her GP who found a

very high anti-TTG antibody titre in her serum.

Indirect immunofluorescence was negative for

anti-endomysial antibodies. Following referral

to her local gastroenterologist she underwent

a gastroscopy and duodenal biopsies which

were reported as showing equivocal features

but consistent with coeliac disease. She

was commenced on a gluten free diet which

marginally improved her symptoms, however

on follow up her anti-TTG titres remained

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Duodenal biopsies were reported as showing

mild peptic duodenitis and flow cytometry

revealed no evidence of coeliac disease (fig

1a). Following reassurance that she did not

have coeliac disease she was able to tolerate

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demonstrates the variability of anti-TTG assays

between laboratories, and the potential flaws

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Case 2. Delayed diagnosis of RCD2.

A previously fit and well 56-year old man

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disease was elicited, and duodenal biopsies

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atrophy, however anti-TTG antibodies were

negative. He was therefore considered not

to have coeliac disease and was treated

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However, his symptoms progressed and 12

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duodenum with thickening of the distal jejunum

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jejunum in order to make a diagnosis. An

experienced clinician considered the possibility

of RCD2 and lymphoma and instead carried

out a gastroscopy and duodenal biopsy with

flow cytometry the day after receiving the

referral. The flow cytometry demonstrated

a large population of atypical IELs lacking

surface CD3 (fig 1b) in keeping with RCD2

and a presumptive diagnosis of enteropathy

associated lymphoma was made. Within

3 weeks of referral he was admitted for

establishment of home parenteral nutrition

and underwent laparotomy and resection

of the tumour, which was confirmed as a T

cell lymphoma. He subsequently underwent

CHOP chemotherapy and autologous

haematopoeitic stem cell transplant. In his

case earlier consideration of the diagnosis of

RCD and referral to a national centre could

have led to preventative treatment prior to

developing lymphoma.

Case 3. Overdiagnosis and overtreatment.

A 37-year old woman presented to her GP

in 2013 with diarrhoea and weight loss. A

positive anti-tissue transglutaminase (TTG)

antibody titre led to referral to the local

gastroenterologist and a diagnosis was

confirmed by the presence of sub-total

villous atrophy on duodenal biopsy. She

was commenced on a gluten free diet.

However, in 2016 the presence of ongoing

symptoms led to a repeat endoscopy which

demonstrated persistent villous atrophy in

the duodenal biopsies. She was told by her

local gastroenterologist that she had refractory

coeliac disease and that she needed to start

on steroids and azathioprine as she was

otherwise at risk of developing lymphoma. At

this stage she sought a referral for a second



Figure 1a Figure 1b Figure 1c

opinion through one of the national tertiary

centres. An experienced clinician elicited a

history of a shared kitchen with potential for

gluten contamination during food preparation,

and that the patient was consuming foods

that were labelled as ‘may contain traces of

gluten’. It was recommended that she did

not start steroids or azathioprine but made

the necessary changes to her lifestyle and

attend for a repeat duodenal biopsy after a

further 9 months. At endoscopy the patient

reported complete resolution of her symptoms,

biopsies were reported as entirely normal

while flow cytometry confirmed the underlying

diagnosis of coeliac disease (figure 1c). She

therefore avoided potentially harmful treatment,

considerable health anxiety and achieved rapid

resolution of her condition following referral.

Notably the referral came from herself via her

GP, not the local gastroenterologist.

Figure 1. Typical duodenal IEL flow cytometry

plots for a non-coeliac individual (a), a

patient with RCD2 (b), and a patient with

coeliac disease (c). Each dot on the plot

represents a separate cell, immunostained

for surface CD3 (y-axis) and cytoplasmic CD3

(x-axis). In addition, CD3+ T cells bearing the

gamma-delta type of TCR are in dark blue,

those with the alpha-beta TCR are in light

blue. Clearly defined population of IELs are

apparent based on the lack of expression of

CD3 (green), the expression of surface and

cytoplasmic CD3 (light and dark blue), or just

cytoplasmic CD3 (orange). Note that RCD1 is

not distinguishable from coeliac disease using

any available diagnostic tests (including flow

cytometry) (reference 2), whereas populations

of CD3+ and gamma delta TCR positive

cells are clearly increased in coeliac disease

compared to normal.


1. Rubio-Tapia A, Murray JA. Classification

and management of refractory coeliac

disease. Gut 2010 Apr;59(4):547-57.

2. Nijeboer P, van Wanrooij, van Gils T, et

al. Lymphoma development and survival

in refractory coeliac disease type II:

histological response as a prognostic

factor. United European Gastroenterol J

2017; 5(2): 208-217

3. Woodward JM. Improving outcomes of

refractory Celiac Disease: current and

emerging treatment strategies. Clinical

and Experimental Gastroenterology 2016;

9: 225-236

4. Liu H, Brais R, Lavergne-Slove A, et al.

Continual monitoring of intraepithelial

lymphocyte immunophenotype and clonality

is more important than snapshot analysis

in the surveillance of refractory coeliac

disease. Gut. 2010 Apr;59(4):452-60.

5. https://www.coeliac.org.uk/about-us/


6. Baggus E, Urwin H, Watson S, Woodward

JM, Sanders DS. How to manage

adult coeliac disease: The perspective

from the NHS England Rare Diseases

Collaborative Network for Non-Responsive

and Refractory Coeliac Disease. Frontline

Gastroenterol. 2019 Aug 8;11(3):235-242

7. Basu K, Creasey H, Bruggemann N,

Stevens J, Bloxham DM, Woodward

JM. The diagnosis of coeliac disease

by flow cytometry of intraepithelial

lymphocytes – a new ‘gold standard’?

Frontline Gastroenterology 2021 epub

ahead of print http://dx.doi.org/10.1136/


8. Mayassi T, Ladell K, Gudjonson H, et

al. Chronic inflammation permanently

reshapes tissue-resident immunity in celiac

disease. Cell 2019;176:967–81.

9. Abadie V, Sollid LM, Barreiro LB, et al.

Integration of genetic and immunological

insights into a model of celiac disease

pathogenesis. Annu Rev Immunol.



NHS Refractory Coeliac Disease Rare

Disease Collaborative Network

Box 133

Addenbrooke’s Hospital

Hills Road

Cambridge CB2 0QQ



*Corresponding author


Coeliac UK

Apollo Centre,

Desborough Road

High Wycombe

HP11 2QW


NHS Refractory Coeliac Disease Rare

Disease Collaborative Network

Academic unit of gastroenterology,

Royal Hallamshire Hospital,

Sheffield S10 2JF





Mother thanks doctors for

saving her and unborn baby

A Herefordshire mother has thanked

clinicians at University Hospitals of North

Midlands NHS Trust (UHNM) for life-saving

treatment she received.

Pregnant Lucy Rossiter was initially thought

to have irritable bowel syndrome (IBS) after

suffering for months with stomach pain, but

doctors in Hereford later found she had a bile

duct infection which posed a serious risk to her

and her baby.

“My doctors contacted Royal Stoke University

Hospital in Stoke-on-Trent and the entire

endoscopy team got together and agreed

that the necessary procedure could be carried

out at Stoke and would be scheduled for the

following morning.

“When I arrived at Stoke I was in terrible pain

and almost unable to stand, let alone walk.

I would have given anything to stop the pain

and make me feel better.

“I found the endoscopy team ready and

waiting for me at Royal Stoke. Everybody I

came into contact with was aware of who I

was and exactly why I was there.

The team were able to remove the bile duct

stone which was causing Lucy’s infection and

affecting her liver function.

Dr Hebbar said: “Lucy’s was an extremely

complicated case, made more challenging

by the fact that she was pregnant. The

endoscopic procedure to remove the stone

in the bile duct involves using X-ray to assess

the location of the stone and understand

the anatomy. In a pregnant lady in her first

trimester, the radiation is a significant risk to

the baby. An additional risk of this particular

procedure is pancreatitis - especially so

in young women - because the bile duct

and pancreas are close to each other. This

complication can be serious and even fatal.

34-year-old Lucy, a primary school teacher

from Kingsland in Herefordshire, was seven

weeks’ pregnant when her condition began to

rapidly deteriorate.

“When I left after having my procedure,

everybody was amazed that I could not only

stand but also walk out of hospital, the pain was

gone instantly. The change was just incredible

“Unfortunately other trusts were unable to

accept Lucy’s case because of the complexity

involved, so we were contacted.

Doctors at Hereford County Hospital scoured

the country to find clinicians with the expert

knowledge needed to treat the mother-of-two.

UHNM’s endoscopy team were contacted

and made such a difference to my condition, it

was as if someone had turned a tap off. William

commented that it was like a different person

who walked out of Royal Stoke.

“When I was ill I was having flare-ups a good

“If we had not done the procedure, there was

clearly a significant risk to Lucy because of

the infection but at the same time, we did not

want to put the baby at any risk because of the


and Lucy was taken to Royal Stoke University

Hospital for care.

Lucy said: “I started to experience abdominal

pains in early May 2020. My GP suspected I

had IBS but over time various remedies proved

to be ineffective and the flare-ups increased

few times a week, so trying to look after my

daughter Poppy was really hard. Now I have a

controlled diet but I can live more normally.

“I need to have my gall bladder removed and

might have to always be a bit more restricted in

what I eat, but I feel I will be able to manage it.

The team performed an endoscopic

ultrasound, which helps to identify internal

structures and can assess the pancreas and

bile duct in detail. Using this, they were able

to identify the location and size of the bile duct

stone and successfully remove it.

in intensity and frequency and on a number of

occasions I had to go to hospital.

“I had been living with these symptoms for about

12 months and during this time I discovered I

“Dr Hebbar and his team at Royal Stoke

were incredible. The care that I had, their

professionalism, just everything. I cannot thank

them enough.

Dr Hebbar continued: “As it turned out, we

did not need to use any x-ray in the end, so

the procedure was completed and the stone

removed with no risk to the baby.


was pregnant with my second child, Thomas.

“In April 2021 me and my partner William

became very worried. Not only did my

symptoms continue to get worse but I now

also had our unborn baby to worry about.

“Events finally came to a head one night when

I was in severe pain, vomiting and unable to

stand. William called 111 and I was bluelighted

to Hereford County Hospital. I then

spent the next few days as an inpatient waiting

for a diagnosis. It was horrible, I was desperate

to get home so that I could see my daughter.

“Eventually I was able to get home but my liver

function continued to get worse and I was

back in hospital in May, where my condition

deteriorated rapidly.

“Now I can get back to a more normal life.

We’re quite an active family and we like the

outdoors, we like spending time at the coast,

we spend quite a lot of time with our extended

family. We’ve got holidays booked as well.

When I was ill I couldn’t really enjoy them, so

it’s nice to have something to look forward to.

“I am very grateful to all the NHS for working

together to help me.”

Lucy lives with her partner William Wood, 37,

and is mum to two-year-old daughter Poppy

and new baby Thomas.

Consultant gastroenterologist Dr Srisha

Hebbar and his team cared for Lucy at Royal

Stoke University Hospital.

“Lucy was able to travel back to Hereford the

same day and was discharged the next day.”





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Gastroenterology Today welcomes the submission of

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