Gastroenterology Today Spring 2022

Gastroenterology Today Spring 2022

Gastroenterology Today Spring 2022


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Volume 32 No. 1<br />

<strong>Spring</strong> <strong>2022</strong><br />

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6 FEATURE Gastric polyps: a 10-year analysis of 18,496<br />

upper endoscopies<br />

14 FEATURE Endoscopic retrograde appendicitis therapy<br />

versus laparoscopic appendectomy versus open<br />

appendectomy for acute appendicitis: a pilot study<br />

22 FEATURE An extremely dangerous case of acute massive<br />

upper gastrointestinal bleeding: a case report<br />

26 NEWS<br />


This issue edited by:<br />

Hesam Ahmadi Nooredinvand<br />

c/o Media Publishing Company<br />

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

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


The views and opinions expressed in<br />

this issue are not necessarily those of<br />

the Publisher, the Editors or Media<br />

Publishing Company.<br />

Next Issue Summer <strong>2022</strong><br />

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GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />




GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

“COVID-19<br />

pandemic<br />

appears to<br />

be shifting<br />

towards an<br />

endemic<br />

disease<br />

with most<br />

healthcare<br />

services<br />

gradually<br />

returning<br />

to normal,<br />

the positive<br />

impact of<br />

which will<br />

certainly<br />

be felt by<br />

patients.”<br />

Disruption to the health service during the last couple of years as a result of the<br />

pandemic has undoubtedly had a detrimental impact on certain aspects of patient care.<br />

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

difficulty in accessing specialist advice and disruption to surgery and endoscopy services<br />

have had a negative impact on both physical and mental wellbeing of many patients with<br />

Inflammatory Bowel Disease (IBD).<br />

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

towards an endemic disease with most healthcare services gradually returning to normal,<br />

the positive impact of which will certainly be felt by patients.<br />

We have a number of fascinating articles included in this <strong>Spring</strong> edition of <strong>Gastroenterology</strong><br />

<strong>Today</strong> including,<br />

• Role of Endoscopic Retrograde Appendicitis Therapy (ERAT) as an alternative to surgical<br />

appendectomy in acute uncomplicated appendicitis<br />

• Scientists in Munich explore the mechanism that triggers problematic interaction between<br />

intestinal bacteria and cells in intestinal mucus layer in patients with IBD which could offer<br />

targets for development of new drug therapy<br />

• Coeliac UK highlights the role of the Rare Disease Collaborative Network in supporting<br />

with diagnosis and management of patients with refractory coeliac disease<br />

• Retrospective study looking at the frequency of gastric polyps and their association with<br />

certain factors<br />

• An interesting case report of massive gastrointestinal bleeding secondary to a fish bone!<br />

Hesam Ahmadi Nooredinvand,<br />

St George’s Hospital<br />


Prescribe Entocort ® CR by brand<br />

instead of prednisolone<br />

• Rapid induction of remission from 2 weeks with<br />

Entocort ® CR* 1<br />

• ~50% fewer corticosteroid-associated side effects<br />

than prednisolone 2,3<br />

• Unlike Entocort ® CR, prednisolone increases<br />

susceptibility to, and severity of, infections †2,4<br />

• Entocort ® CR is the only controlled-release<br />

oral budesonide indicated for Crohn’s disease 2<br />

Help keep your Crohn’s patients out of hospital...<br />

...and where they want to be<br />

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

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

ENTOCORT CR 3mg Capsules (budesonide) - Prescribing<br />

Information<br />

Please consult the Summary of Product Characteristics (SmPC) for full<br />

prescribing Information<br />

Presentation: Hard gelatin capsules for oral administration with an<br />

opaque, light grey body and an opaque, pink cap marked CIR 3mg in black<br />

radial print. Contains 3mg budesonide. Indications: Induction of remission<br />

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

the ascending colon. Induction of remission in patients with active<br />

microscopic colitis. Maintenance of remission in patients with microscopic<br />

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

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

weeks. When treatment is to be discontinued, dose should normally be<br />

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

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

daily in the morning, or the lowest effective dose. Paediatric population: Not<br />

recommended. Older people: No special dose adjustment recommended.<br />

Swallow whole with water. Do not chew. Contraindications:<br />

Hypersensitivity to the active substance or any of the excipients. Warnings<br />

and Precautions: Side effects typical of corticosteroids may occur. Visual<br />

disturbances may occur. If a patient presents with symptoms such as<br />

blurred vision or other visual disturbances they should be considered for<br />

referral to an ophthalmologist for evaluation of the possible causes.<br />

Systemic effects may include glaucoma and when prescribed at high doses<br />

for prolonged periods, Cushing’s syndrome, adrenal suppression, growth<br />

retardation, decreased bone mineral density and cataract. Caution in<br />

patients with infection, hypertension, diabetes mellitus, osteoporosis,<br />

peptic ulcer, glaucoma or cataracts or with a family history of diabetes or<br />

glaucoma. Particular care in patients with existing or previous history of<br />

severe affective disorders in them or their first degree relatives. Caution<br />

when transferring from glucocorticoid of high systemic effect to Entocort<br />

CR. Chicken pox and measles may have a more serious course in patients<br />

on oral steroids. They may also suppress the HPA axis and reduce the stress<br />

response. Reduced liver function may increase systemic exposure. When<br />

treatment is discontinued, reduce dose over last 2-4 weeks. Concomitant<br />

use of CYP3A inhibitors, such as ketoconazole and cobicistat-containing<br />

products, is expected to increase the risk of systemic side effects and<br />

should be avoided unless the benefits outweigh the risks. Excessive<br />

grapefruit juice may increase systemic exposure and should be avoided.<br />

Patients with fructose intolerance, glucose-galactose malabsorption or<br />

sucrose-isomaltase insufficiency should not take Entocort CR. Monitor<br />

height of children who use prolonged glucocorticoid therapy for risk of<br />

growth suppression. Interactions: Concomitant colestyramine may<br />

reduce Entocort CR uptake. Concomitant oestrogen and contraceptive<br />

steroids may increase effects. CYP3A4 inhibitors may increase systemic<br />

exposure. CYP3A4 inducers may reduce systemic exposure. May cause low<br />

values in ACTH stimulation test. Fertility, pregnancy and lactation: Only<br />

to be used during pregnancy when the potential benefits to the mother<br />

outweigh the risks for the foetus. May be used during breast feeding.<br />

Adverse reactions: Common: Cushingoid features, hypokalaemia,<br />

behavioural changes such as nervousness, insomnia, mood swings and<br />

depression, palpitations, dyspepsia, skin reactions (urticaria, exanthema),<br />

muscle cramps, menstrual disorders. Uncommon: anxiety, tremor,<br />

psychomotor hyperactivity. Rare: aggression, glaucoma, cataract, blurred<br />

vision, ecchymosis. Very rare: Anaphylactic reaction, growth retardation.<br />

Prescribers should consult the summary of product characteristics in<br />

relation to other adverse reactions. Marketing Authorisation Numbers,<br />

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

capsules: £37.53. Packs of 100 capsules: £75.05. Legal category: POM.<br />

Marketing Authorisation Holder: Tillotts Pharma UK Ltd, The Stables,<br />

Wellingore Hall, Wellingore, Lincoln, LN5 0HX. Date of preparation of PI:<br />

February 2020<br />

Adverse events should be reported.<br />

Reporting forms and information can be<br />

found at https://yellowcard.mhra.gov.uk.<br />

Adverse events should also be reported to<br />

Tillotts Pharma UK Ltd. Tel: 01522 813500.<br />

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

CR 3 mg capsules – Summary of Product Characteristics. 3. Rutgeerts<br />

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

– Summary of Product Characteristics.<br />

Date of preparation: August 2021. PU-00572.



ANALYSIS OF 18,496 UPPER<br />


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<br />

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

Abstract<br />

Background/aims<br />

Gastric polyps (GPs) are usually asymptomatic lesions of the upper<br />

gastrointestinal tract observed in 1–3% of esophagogastroduodenoscopies<br />

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

frequency of different types of gastric polyps in our population, and to<br />

analyze their possible association with other factors.<br />

Materials and methods<br />

A total of 18,496 consecutive patients undergoing EGD over a<br />

10-year period (between 2007 and 2018) in a tertiary hospital were<br />

retrospectively reviewed. Eighty-six patients diagnosed with gastric<br />

polyps were analysed. Demographics, medical history of the patients,<br />

and indication for gastroscopy were collected. Morphological,<br />

histological characteristics of polyps, and therapeutic management data<br />

were also collected.<br />

fundic gland are the most common in our country. The high frequency of<br />

Helicobacter pylori infection in our patients and in our area may explain<br />

the high frequency of HP.<br />

Keywords<br />

Stomach, Polyp, Polypectomy, Endoscopic mucosal resection<br />

Introduction<br />

Gastric polyps (GPs) are defined as luminal projections above<br />

the plane of the adjacent mucosa regardless of its histological<br />

type [1]. Gastric polyps are usually discovered incidentally during<br />

esophagogastroduodenoscopies (EGD) and their prevalence is<br />

estimated from 0.5 to 23% of all upper gastrointestinal endoscopies [2].<br />

Some polyps can occasionally present with bleeding, anemia, or gastric<br />

outlet obstruction [3].<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

Results<br />

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

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

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

average age was 58.1 years. One hundred and forty one polyps were<br />

included, and histopathology was obtained on 127 GPs. The most<br />

common location was the fundus (59.6%) and 48.9% were smaller than<br />

5 mm. The polyp was unique in 75.6% of cases. According to Paris<br />

classification, 80% of the polyps were sessile (Is). Hyperplastic polyps<br />

were the most common (55.9%), followed by sporadic fundic gland<br />

polyps observed in 23 patients (18.1%), 7 (5.5%) were adenomas and<br />

4 (3.1%) were neuroendocrine tumors type 1. The following factors<br />

were associated with hyperplastic polyps: anemia (p =0.022), single<br />

polyp (p=0.025) and size≥5 mm (p=0.048). Comparing hyperplastic<br />

polyps’ biopsies to resected polyps, no difference was found in the<br />

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

was associated with fundic gland polyps. Sixty polyps (47.2%) were<br />

treated by cold forceps, 19 (15%) treated by a mucosal resection and<br />

15 (11.8%) with diathermic snare. Five procedural bleeding incidents<br />

were observed (3.9%). Only the use of anticoagulant treatment was<br />

associated with a high bleeding risk (p=0.005). The comparative<br />

histological study between specimens of biopsied GPs and endoscopic<br />

polypectomy led to an overall agreement of 95.3%.<br />

Conclusion<br />

In our study, the GPs frequency was 0.36%. Hyperplastic polyps and<br />

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

malignancy or malignant transformation of gastric polyps depends on<br />

their histological nature. GPs have been associated with multiple factors,<br />

such as H. pylori infection for hyperplastic polyps and adenomas,<br />

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

The aim of this study was to precise the frequency of different types of<br />

gastric polyps in our population and to analyze their possible association<br />

with other factors to evaluate the results of curative endoscopic<br />

resection of gastric polyps and to study the evolutionary status of<br />

unresected gastric polyps.<br />

Methods<br />

Study design<br />

A retrospective study in which all consecutive patients with GPs were<br />

enrolled was performed at a tertiary-level hospital (Habib Thameur<br />

Hospital of Tunis) from 2008 to 2017. A total of 18,496 consecutive<br />

EGD over a 10-year period were retrospectively reviewed. Eightysix<br />

patients diagnosed with gastric polyps were analysed. Follow-up<br />

gastroscopies performed on the same patient were not excluded. This<br />

study was performed according to the Declaration of Helsinki, following<br />

the guidelines for good clinical practice. Habib Thameur Hospital ethics<br />

committee approved the study protocol.<br />

6<br />

*Correspondence: yacoubhaythem@hotmail.com<br />

1<br />

<strong>Gastroenterology</strong> and Hepatology Department, Habib Thameur Hospital, Tunis, Tunisia<br />

©The Author(s) <strong>2022</strong>


All cases of gastric polyps were identified from endoscopy reports.<br />

All data regarding patients were obtained from the electronic medical<br />

record. Demographic data (sex, age), relevant pathological history<br />

(colorectal cancer or hereditary polyposis syndrome, colon polyp,<br />

cirrhosis), routine hemograms, as well as data related to the EGD<br />

indication of gastroscopy, number and size of GPs, location, histological<br />

type, and the presence of chronic gastritis or H. pylori infection using<br />

the Hematoxylin eosin staining) were collected. The polyp size was<br />

estimated by comparing it with the opening size of the used biopsy<br />

forceps. In patients with multiple polyps, we collected the endoscopic<br />

characteristics of the four largest polyps. GP recurrence following<br />

resection were also collected (number, location, size, histological type<br />

and, recurrence interval after polypectomy) Patients whose hemoglobin<br />

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

considered with anemia.<br />

was based on endoscopic findings; the most common localization<br />

for gastric polyps was the fundus, followed by the antrum and the<br />

corpus (Table 2).<br />

Histopathologic diagnosis of polyps was obtained for 127 polyps.<br />

The histological study showed hyperplastic polyps in 71 of the polyps<br />

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

“other” category included pancreatic heterotopias, lipoma and polypoid<br />

foveolar hyperplasia.<br />

H. pylori infection identification was carried out with the hematoxylin<br />

eosin staining in 64 patients (patients with gastric mucosa<br />

abnormalities). H. pylori infection was detected in 45 patients<br />

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

hyperplastic polyps.<br />

Ethics approval and consent to participate<br />

This study was performed according to the Declaration of Helsinki,<br />

following the guidelines for good clinical practice. “Habib Thameur<br />

Hospital ethics committee” approved the study protocol. All methods<br />

were carried out in accordance with relevant guidelines and regulations.<br />

Informed consent to participate in the study was obtained from<br />

participants.<br />

Statistical analysis<br />

The data were analyzed on the Statistical Package for the Social<br />

Sciences (SPSS) version 23, IBM SPSS Inc.; Chicago, IL, USA). Results<br />

for the continuous variables that followed a normal distribution were<br />

expressed as mean±standard deviation and range while variables that<br />

did not follow a normal distribution were presented in median and the<br />

interquartile range.<br />

For comparisons, Student’s t-test was used for quantitative variables.<br />

A univariate analysis was conducted to identify the possible associated<br />

factors with the different histological types of GPs. A multivariate analysis<br />

was carried out with variables that achieved statistical significance. The<br />

level of statistical significance was established with a p value ≤ 0.05.<br />

The factors independently associated with hyperplastic polyps were<br />

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

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

GPs was summarized in Fig. 1.<br />

More than the three-quarters of the patients had single polyps.<br />

The average polyp diameter was 6 mm (range: 2–30 mm). The<br />

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

mm in 53 (37.6%) patients, 10–19 mm in 15 (10.7%) patients,<br />

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

Age (median years),(range, years) 58.1 ± 15.4, (18–84)<br />

Gender<br />

Male 22 (25.6)<br />

Female 64 (74.4)<br />

Personal history<br />

GERD 26 (30.2)<br />

Anemia 36 (44.2)<br />

Colon polyps 2 (2.3)<br />

Cirrhosis 11 (12.8)<br />

Gastrectomy 3 (3.5)<br />

Hereditary polyposis syndrome 0 (0)<br />

Indication<br />

Epigastric pain 30 (34.9)<br />

Dyspepsia 16 (18.6)<br />

Anemia 21 (24.4)<br />

UGIB 2 (2.3)<br />

Monitoring of PHT 13 (15.1)<br />

Other 4 (4.7)<br />

GP gastric polyps, GERD gastro-esophageal reflux disease, PHT portal<br />

hypertension, UGIB upper gastrointestinal bleeding<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />



Anticoagulant or anti-aggregating medication was significantly correlated<br />

with the onset of bleeding (p=0.002).<br />

Twenty-one polyps were biopsied and then resected. A comparison of<br />

the histological results between biopsy specimen and polypectomy was<br />

made.<br />

Adenomas analysis showed a 100% agreement between primary and<br />

final results. The agreement rate was 93% for hyperplastic polyps<br />

(13 polyps out of 14). The comparative histological study between<br />

specimens of biopsied GPs and endoscopic polypectomy led to an<br />

overall agreement of 95.3% (Table 7).<br />

Discussion<br />

One hundred and twenty-seven specimens, corresponding to eightysix<br />

patients, of the total of 18,496 upper gastrointestinal endoscopic<br />

procedures, taken from gastric polypoid lesions (0.46%) were reported.<br />

In the literature, a great variability was observed in the prevalence of<br />

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

of GPs is lesser than reported in literature. This can be explained by<br />

the fact that follow-up EGD performed on the same patient was not<br />

excluded.<br />

This is the first study that evaluates the GPs frequency in Tunisia. In our<br />

study, we found that the most common symptoms in patients with GPs<br />

were epgastric pain and anemia. We also found that GPs were localized<br />

mostly in the fundus, and mostly Is according to Paris classification and<br />

the hyperplastic type was the most common.<br />

Table 2 Morphological and histological characteristics of the<br />

141 polyps<br />

Parameter n (%)<br />

Table 2 Morphological and histological characteristics of the<br />

Patient with GPs 86 (100)<br />

141 polyps<br />

Single 65 (75.6)<br />

Parameter Multiple n (%) 21 (24.4)<br />

Location<br />

Patient with GPs 86 (100)<br />

Fundus 51 (59.3)<br />

Single 65 (75.6)<br />

Body 5 (5.8)<br />

Multiple 21 (24.4)<br />

Antrum 28 (32.6)<br />

Location<br />

Multiple location 2 (2.3)<br />

Fundus 51 (59.3)<br />

Size in mm<br />

Body 5 (5.8)<br />

1–4 mm 69 (48.9)<br />

Antrum 28 (32.6)<br />

5–9 mm 53 (33.6)<br />

Multiple location 2 (2.3)<br />

10–14 mm 8 (5.7)<br />

Size in mm<br />

15–19 mm 7 (5)<br />

1–4 mm 69 (48.9)<br />

> 20 mm 4 (2.8)<br />

5–9 mm 53 (33.6)<br />

Paris classification<br />

10–14 mm 8 (5.7)<br />

Ip 17 (12)<br />

15–19 mm 7 (5)<br />

Is 112 (80)<br />

> 20 mm 4 (2.8)<br />

IIa 11 (8)<br />

Paris classification<br />

IIb, IIc 0 (0)<br />

Ip 17 (12)<br />

Is GP gastric polyps<br />

112 (80)<br />

IIa 11 (8)<br />

IIb, IIc 0 (0)<br />

Hyperplastic polyps and fundic gland polyps together make up to 90%<br />

GP gastric polyps<br />

[6,7,8] followed by adenomas and other histological type, which are<br />

much less common. These rates are similar to those observed in our<br />

population with a predominance of hypeplastic type.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

Fig. 1 The age distribution of patients with gastric polyps<br />

Fig. 1 The age distribution of patients with gastric polyps<br />



Table Table 3 3 Histological analysis analysis of the of the 127 127 GP GP<br />

Table Table 5 5 Univariate analysis analysis of of associated factors factors with with fundic fundic<br />

Table 3 Histological analysis of the 127 GP<br />

gland Tablepolyps 5 Univariate analysis of associated factors with fundic<br />

Histological Table 3 type Histological type analysis of the 127 GP<br />

gland<br />

n (%) n (%) Tablepolyps 5 Univariate (n=127) analysis of associated factors with fundic<br />

gland polyps (n=127)<br />

Histological type n (%)<br />

Parameter gland polyps (n=127)<br />

Histological type n (%)<br />

Fundic Fundic gland gland polyps polyps Non-fundic p value p value<br />

Hyperplastic 71 (55.9) 71 (55.9)<br />

Parameter Fundic gland polyps gland Non-fundic gland polyps polyps<br />

Parameter Fundic gland polyps Non-fundic p value p value<br />

Fundic Hyperplastic Fundic Hyperplastic gland gland polyps polyps 23 71 (18.1) (55.9) 23 71 (18.1) (55.9)<br />

n (%) n (%) gland n (%) gland n (%) polyps polyps<br />

Adenoma Fundic Adenoma Fundic gland gland polyps polyps 237 (5.5) (18.1) 237 (5.5) (18.1)<br />

n (%) n (%) n (%) n (%)<br />

Age Age (years) (years) 53.3 53.3 ± 21.3 ± 21.3 58.8±14.1 0.303 0.303<br />

Adenoma Neuroendocrine Adenoma neoplasia neoplasia 47 (3.1) (5.5) 47 (3.1) (5.5)<br />

Age Gender (years) 53.3 ± 21.3 58.8±14.1 0.303 0.289<br />

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

Neuroendocrine neoplasia 4 (3.1)<br />

Male Gender Male 1 (11.1) 19 (27.5) 0.289<br />

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

Xanthelasma 1 (0.8)<br />

Male Female 18 (11.1) (88.9) 19 50 (27.5) (72.5)<br />

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)<br />

Inflammatory fibroid polyp 9 (7.2)<br />

Female 8 (88.9) 50 (72.5) 0.170<br />

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

No true polyp 7 (5.5)<br />

Single/multiple 5 (55.6) 53 (76.8)<br />

GP Other gastric polyps<br />

5 (3.9)<br />

Single/multiple 5 (55.6) 53 (76.8) 0.170 0.170<br />

GP Other gastric polyps<br />

5 (3.9)<br />

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)<br />

GP gastric GP gastric polyps polyps<br />

GERDMultiple 4 (44.4) 4 (44.4) 16 (23.2) 16 (23.2) 0.7 0.7<br />

Table Table 4 4 Univariate analysis analysis of of associated factors factors with with<br />

GERDYes GERD 5 (55.6) 5 (55.6) 20 (29) 20 (29) 0.7 0.7<br />

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)<br />

hyperplastic polyps (n = 127)<br />

Parameter hyperplastic polyps Hyperplastic (n = 127) polyps polyps Non-<br />

Nonhyperplastic<br />

p value p value No Anemia No Anemia 4 (44.4) 4 (44.4) 49 (71) 49 (71) 0.115 0.115<br />

p value Yes Anemia 8 (88.9) 43 (62.3) 0.115<br />

Parameter Hyperplastic polyps Nonhyperplastic<br />

polyps<br />

Parameter Hyperplastic polyps Nonhyperplastic<br />

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)<br />

p value<br />

Yes Anemia 8 (88.9) 43 (62.3) 0.115<br />

polyps<br />

n (%) n (%) n polyps (%) polyps n (%)<br />

No Location No Location 1 (11.1) 1 (11.1) 26 (37.7) 26 (37.7)<br />

n (%) n (%) n (%) n (%)<br />

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)<br />

Age Gender Age Gender (years) (years) 57.7 57.7 ± 13.4 ± 13.4 58.8 58.8 ± 17.4 ± 17.4 0.7<br />

0.7<br />

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)<br />

Male Gender Male Gender 12 (24.5) 12 (24.5) 8 (27.6) 8 (27.6) 0.7 0.7<br />

Non Size Non Size in fundus mm in fundus mm 0 (0) 0 (0) 48 (46.1) 48 (46.1) 0.013 0.013<br />

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)<br />

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

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)<br />

Single/multiple Single/multiple 40 (81.6) 40 (81.6) 11 (38) 11 (38) 0.05 0.05<br />

≥Paris 5 mm ≥Paris 5 mm classification 9 (39.1) 9 (39.1) 49 (47) 49 (47)<br />

Multiple Single Multiple Single 940 (18.4) (81.6) 940 (18.4) (81.6) 18 11 (62) (38) 18 11 (62) (38)<br />

Ip Paris Ip Paris classification classification 3 (13) 3 (13) 12 (11.5) 12 (11.5) 0.524 0.524<br />

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<br />

GERDYes GERD 15 (30.6) 15 (30.6) 10 (34.5) 10 (34.5) 0.7 0.7<br />

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<br />

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)<br />

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 –<br />

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) – –<br />

Yes Anemia Yes Anemia 28 (57.2) 28 (57.2) 3 (10.3) 3 (10.3) < 10 < –3<br />

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<br />

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)<br />

Significant Significant p value p value < 0.05 < 0.05 are in are bold in bold<br />

Location No Location No 21 (42.8) 21 (42.8) 26 (89.7) 26 (89.7) 0.009 0.009<br />

Table Table 6 Risk 6 Risk value value for the for the significant variables variables in the in the multivariate<br />

Antrum Location Antrum Location 34 (47.9) 34 (47.9) 43 (76.8) 43 (76.8) 0.009 0.009<br />

analysis Table analysis Table 6 Risk 6 Risk value value for the for the significant significant variables variables in the in the multivariate multivariate<br />

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)<br />

analysis<br />

Size Non Size in antrum mm in mm 37 (52.1) 13 (23.2) 0.002 0.002 Variable Variable analysis<br />

Non antrum 37 (52.1) 13 (23.2)<br />

Odds Odds ratio ratio 95% 95% CI CI p value p value<br />

< 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<br />

Variable Variable Hyperplastic polyps polyps<br />

Odds Odds ratio ratio 95% 95% CI CI p value p value<br />

≥< 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)<br />

Anemia Hyperplastic Anemia Hyperplastic polyps polyps 4.28 4.28 (1.39–13.17) 0.022 0.022<br />

Paris ≥ 5 mm Paris ≥ 5 mm classification 41 (47.7) 41 (47.7) 17 (30.4) 17 (30.4)<br />

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<br />

Ip Paris Ip Paris classification classification 10 (14) 10 (14) 5 (8.9) 5 (8.9) 0.371 0.371<br />

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<br />

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<br />

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<br />

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<br />

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) – –<br />

GP gastric GP gastric polyps, polyps, GERD GERD gastro-esophageal reflux reflux disease disease<br />

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<br />

Significant Significant p value p value < 0.05 < 0.05 are in are bold in bold<br />

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

the prevalence of hyperplastic polyps could be related to the high<br />

Argüello et al. reported the frequency of GP as 42.8% for<br />

hyperplastic polyps, and 37.7% for fundic gland polyps. The<br />

mean age of the patients was 65.6 years and 38% were males<br />

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

EGD. Fundic gland polyps were the most frequent polyp type,<br />

which accounted for 77% of all polyps of all polyps [6]. Fundic<br />

gland polyps were the second most common type (18.1%) of GPs<br />

lesions in our study. In the majority of series, hyperplastic polyps<br />

prevalence of H. pylori infection in our population (62.3%). Freeman<br />

et al. reported tendency of fundic gland polyps to arise in H. pylori<br />

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

findings were also reported in Carmack et al. study (OR 0.007,<br />

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

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

widespread of PPIs use and the low H. Pylori infection rate may be<br />

the most important reasons behind the large frequency of fundic<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />



gland polyps reported in American studies [6, 14]. Although in three<br />

Spanish series, hyperplastic polyps were the most common which<br />

is comparable to our study [8, 9, 16].<br />

Hyperplastic polyps are associated with chronic gastritis such<br />

as H. pylori gastritis, and particularly autoimmune gastritis.<br />

Patients with hyperplastic polyp have an increased risk of gastric<br />

adenocarcinoma [1, 17, 18].<br />

In our study, adenomas were detected in seven patients (5.5%).<br />

The majority of cases we reported were low-grade intestinal-type.<br />

These polyps constitute less than 10% and have a malignant<br />

potential. They are more common in communities where gastric<br />

cancer is frequent [19]. Malignant potential of adenomas is variable<br />

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

high-grade dysplasia, and size of the lesion [19].<br />

It has been reported that between 16 and 37.5% of cases, and<br />

despite the endoscopic appearance of a polyp, the final histological<br />

study shows normal mucosa [6, 16]. In our study the percentage of<br />

biopsies with normal mucosa was 5.5%.<br />

Although the majority of GP do not cause symptoms, they can be<br />

the cause of bleeding and gastric obstruction. Frequently, GP are<br />

detected during EGD performed to study gastrointestinal symptoms<br />

not attributable to polyps or asymptomatic patients examined for<br />

other reasons [6, 21].<br />

In our study, an association between hyperplastic polyps and<br />

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

the literature between anaemia and hyperplastic polyps, while the<br />

gastrointestinal reflux was associated with fundic gland polyps [22].<br />

A total of 94 polyps were resected with snare. Five patients had<br />

hemorrhage requiring endoscopic treatment and bleeding was<br />

60<br />

53<br />

Table 7 Agreement between polypectomy and biopsy<br />

specimen in different histological types<br />

Histological type<br />

Biopsy<br />

Polypectomy<br />

Table 7 Agreement between<br />

specimen (n)<br />

polypectomy<br />

(n)<br />

and biopsy<br />

specimen Adenomas in different histological types<br />

Histological With low grade typedysplasia Biopsy 4 Polypectomy<br />

4<br />

With high grade dysplasia specimen 1 (n) (n) 1<br />

Fundic gland polyps<br />

Adenomas<br />

1 1<br />

Hyperplastic polyps<br />

With low grade dysplasia<br />

13<br />

4<br />

14<br />

4<br />

Type I neuroendoscrine tumor<br />

With high grade dysplasia<br />

1<br />

1<br />

1<br />

1<br />

Inflammatory mucosa<br />

Fundic gland polyps<br />

1<br />

1<br />

0<br />

1<br />

Hyperplastic polyps 13 14<br />

Type I neuroendoscrine tumor 1 1<br />

controlled Inflammatory by mucosa endoscopic procedures. 1 Perforation did 0not occur in<br />

any of our patients. In the literature, bleeding as a complication of<br />

gastric polypectomy was reported in 3.5% [23].<br />

Relationship between long-term PPIs use and fundic gland polyps’<br />

occurring has not yet been fully established. Jalving et al. [4] found<br />

in their study a significant association only in the subgroup of<br />

patients treated with PPI for over 1 year. Our data do not support a<br />

relationship between PPI and fundic gland polyps.<br />

In patients with GP, evaluating H. pylori infection state by obtaining<br />

biopsies of the surrounding gastric mucosa is recommended and<br />

treatment is required if present [24, 25].<br />

Hyperplastic polyps should be biopsied according to the British<br />

society of gastroenterology and an examination of the whole<br />

stomach should be made. H pylori infection should be detected and<br />

eradicated when present [24]. GP of the non-adenomatous type<br />

are at a low risk of malignant transformation, therefore endoscopic<br />

resection is not necessary.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

50<br />

60<br />

53<br />

40<br />

50<br />

30<br />

40<br />

14 14<br />

20<br />

7<br />

30<br />

10<br />

14<br />

1<br />

14<br />

20<br />

7<br />

0<br />

10<br />

Cold snare Hot snare<br />

1<br />

EMR<br />

Monoblock Piece-meal<br />

0<br />

Fig. 2 The distribution of polypectomy. EMR endoscopic mucosal resection<br />

Cold snare Hot snare EMR<br />

Monoblock Piece-meal<br />

Fig. 2 The distribution of polypectomy. EMR endoscopic mucosal resection<br />

5<br />

5<br />



Guidelines on management of hyperplastic polyps, recommend<br />

resection of polyps greater than 5 mm [26, 27].<br />

Complete removal of the adenoma should be performed when safe to<br />

do according to the British recommendations [24].<br />

Polypectomy is not required for sporadic fundic gland polyps. Biopsy of<br />

probable fundic gland polyps is recommended to exclude dysplasia. In<br />

patients with multiple fundic gland polyps who are under 40 years-old,<br />

or where biopsies specimens show dysplasia, colonoscopy should be<br />

performed to exclude familial adenomatous polyposis [24].<br />

Szaloki et al. reported that there were important disagreements in 12<br />

cases of examined forceps biopsy specimens. In 14 neoplastic, and<br />

1 hyperplastic polyps, the degree of dysplasia seen on histological<br />

examination of the forceps biopsy specimens differed from that<br />

observed for the resected specimens. Complete agreement between<br />

the histological results on ectomized polyp, and the forceps biopsy<br />

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

analysis showed a 100% agreement between primary and final results.<br />

The agreement rate was 93% for hyperplastic polyps (13 polyps out of<br />

14). The overall agreement was of 95.3%.<br />

Ethics approval and consent to participate<br />

This study was performed according to the Declaration of Helsinki,<br />

following the guidelines for good clinical practice. “Habib Thameur<br />

Hospital ethics committee” approved the study protocol. All methods<br />

were carried out in accordance with relevant guidelines and regulations.<br />

Informed consent to participate in the study was obtained from<br />

participants.<br />

Consent for publication<br />

Not applicable.<br />

Competing interests<br />

The authors declare that they have no competing interests.<br />

Author details<br />

1<br />

<strong>Gastroenterology</strong> and Hepatology Department, Habib Thameur<br />

Hospital, Tunis, Tunisia. 2 Faculty of Medicine of Tunis, El Manar<br />

University, Tunis, Tunisia.<br />

Received: 8 July 2021 Accepted: 7 February <strong>2022</strong><br />

Published online: 19 February <strong>2022</strong><br />

Our study included the greatest number of EGD with patients diagnosed<br />

with GP in our country.<br />

Conclusion<br />

Gastric polyps’ frequency in our study was low (0.46%). Hyperplastic<br />

polyps are the most common gastric polyps in our country. In case of<br />

single polyps, biopsies are recommended to rule out a diagnosis of<br />

adenoma or hyperplastic polyps with dysplasia. Good knowledge of<br />

practical guidelines is important for the management of GP.<br />

Acknowledgements<br />

Not applicable.<br />

Authors’ contributions<br />

H.Y.: concept, design, definition of intellectual content, literature<br />

search, manuscript preparation, manuscript editing, manuscript review.<br />

N.B.: concept, design, definition of intellectual content, manuscript<br />

preparation, manuscript review. M.S.: definition of intellectual content,<br />

manuscript preparation. N.B.: design. A.O.: design, manuscript<br />

review. D.T.: manuscript review. D.G.: definition of intellectual content,<br />

manuscript review. All authors read and approved the final manuscript.<br />

Funding<br />

Not applicable.<br />

Availability of data and materials<br />

The data that support the findings of this study are available on<br />

request from the corresponding author, [HY]. The data are not publicly<br />

available due to [restrictions e.g. their containing information that could<br />

compromise the privacy of research participants].<br />

Declarations<br />

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GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

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Gastric cancer is typically diagnosed at a very late stage,<br />

leading to a poor prognosis for the patient, and the strain<br />

on healthcare services through the COVID-19 pandemic<br />

has only made things worse. However, detection of precancerous<br />

conditions – such as atrophic gastritis (AG) and<br />

gastric intestinal metaplasia (GIM) – before endoscopy could<br />

potentially support diagnostic pathways, allowing doctors<br />

in primary care to identify and prioritise patients for whom<br />

endoscopy would be useful, streamlining NHS resources and<br />

improving patient outcomes.<br />

What are AG and GIM?<br />

AG is a chronic inflammatory condition of the gastric mucosa.<br />

It can be an autoimmune disorder, but most commonly arises<br />

following prolonged inflammation caused by Helicobacter<br />

pylori<br />

infection. This disrupts the mucus barrier that helps<br />

to protect the cells of the stomach lining from digestive<br />

juices, causing them to be slowly destroyed. AG significantly<br />

increases the risk of stomach cancer, with 18 % of cases<br />

progressing to cancer within 10 years. However, studies<br />

suggest that in some cases the progression of AG can be<br />

halted, and even improved, reinforcing the importance of early<br />

diagnosis and monitoring. 1<br />

GIM is common in cases of AG and occurs when the cells<br />

of the stomach lining are replaced with cells similar to the<br />

lining of the intestines. Again, H. pylori is often implicated in<br />

this process, which predisposes individuals to intestinal-type<br />

gastric adenocarcinoma and neuroendocrine tumours (NETs).<br />

Patients with GIM are often over 50 years of age, and the risk<br />

is further increased by factors such as smoking or having a<br />

first-degree relative with gastric cancer.<br />

Challenges of diagnosis<br />

The current gold standard for diagnosing AG and GIM is<br />

gastroscopy with targeted biopsies, which relies on referral<br />

of patients from primary care. However, AG and GIM are often<br />

asymptomatic – or present with very general symptoms such as<br />

stomach pain, loss of appetite, nausea or vomiting, anaemia and<br />

stomach ulcers – making them hard to detect. Tests for<br />

H. pylori infection, along with blood tests for levels of<br />

pepsinogens and gastrin-17, may help to identify some patients<br />

for whom a referral would be beneficial. However, current<br />

practice is not to actively look for AG and GIM cases before<br />

endoscopy, and so patients may remain undiagnosed in primary<br />

care for prolonged periods if they do not qualify for referral.<br />

Rapid detection of AG and GIM<br />

GastroPanel from BIOHIT is a simple, non-invasive blood test<br />

that can be used in primary care settings for effective diagnosis<br />

of AG and GIM. It gives detailed information on the structure<br />

and function of the stomach mucosa, by quantifying pepsinogen<br />

I, pepsinogen II and gastrin-17, and can also differentiate the<br />

cause of AG by identifying IgG antibodies to H. pylori. Using<br />

GastroPanel in targeted groups of at-risk patients could help to<br />

direct referrals more effectively. As well as detecting cancers<br />

at an earlier and more curable stage, reducing the number of<br />

gastroscopies in lower risk patients would reduce both the cost<br />

and volume burden on healthcare resources, without adversely<br />

affecting patient care.<br />

For more information about GastroPanel<br />

contact: info@biohithealthcare.co.uk<br />

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<br />

For the early diagnosis<br />

of gastric cancer risk<br />

Reduce endoscopy waiting lists and<br />

improve the diagnostic pathway for<br />

patients, through an earlier, faster<br />

and more cost-effective approach.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

www.biohithealthcare.co.uk<br />







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

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

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

14<br />

Abstract<br />

Background<br />

An increasing number of studies have shown the merits of endoscopic<br />

retrograde appendicitis therapy (ERAT) in diagnosing and treating acute<br />

uncomplicated appendicitis. However, no related prospective controlled<br />

studies have been reported yet. Our aim is to assess the feasibility and<br />

safety of ERAT in the treatment of acute uncomplicated appendicitis.<br />

Methods<br />

In this open-label, randomized trial, participants were randomly allocated<br />

to the ERAT group, laparoscopic appendectomy (LA) group and open<br />

appendectomy (OA) group. The primary outcome was the clinical success<br />

rate of the treatment. Intention-to-treat analysis was used in the study.<br />

Results<br />

The study comprised of 99 patients, with 33 participants in each<br />

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

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

ERAT group, 4 patients failed ERAT due to difficult cannulation. In LA<br />

group, 1 patient failed because of abdominal adhesion. There were no<br />

significant differences among the three treatment groups regarding the<br />

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

22 months. There were no significant differences (P =0.693) among the<br />

three groups in terms of adverse events and the final crossover rate of<br />

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

Conclusion<br />

ERAT can serve as an alternative and efficient method to treat acute<br />

uncomplicated appendicitis.<br />

Trial registration The study is registered with the WHO Primary Registry-<br />

Chinese Clinical Trial Registry (ChiCTR1900025812).<br />

Keywords<br />

Acute appendicitis, Endoscopic retrograde appendicitis therapy,<br />

Appendectomy, Randomized controlled trial<br />

Introduction<br />

Acute appendicitis is one of the most common causes of acute<br />

abdominal pain clinically [1]. Appendectomy has long been standard<br />

treatment for acute appendicitis. However, there are a series of potential<br />

*Correspondence: sunpeilong@fudan.edu.cn<br />

†<br />

Peilong Sun and Miao Jiang contributed equally in the trial<br />

1<br />

Department of General Surgery, Jinshan Hospital, Fudan University, Shanghai, China<br />

©The Author(s) <strong>2022</strong><br />

postoperative complications, such as postoperative bleeding, wound<br />

infection and intestinal obstruction [2, 3], and the overall complication<br />

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

appendectomy is also a nonnegligible problem [4]. As previous studies<br />

suggested that perforation may not be an inevitable consequence of<br />

acute appendicitis, there is a division of opinions on performing surgery<br />

on patients with acute uncomplicated appendicitis [5]. Thus, developing<br />

a safe and efficient nonoperative method has been an agenda for<br />

treating acute uncomplicated appendicitis.<br />

Endoscopic retrograde appendicitis therapy (ERAT) was firstly<br />

reported by Liu et al. as being inspired by endoscopic retrograde<br />

cholangiopancreatography (ERCP) [6]. ERAT is a novel, nonoperative and<br />

minimally invasive method of treating acute uncomplicated appendicitis.<br />

Recently, there has been additional studies of the use of ERAT for<br />

treating acute uncomplicated appendicitis [7,8,9]. The results of these<br />

3 trials indicated the clinical value of ERAT, including both diagnostic<br />

and therapeutic aspects. Thus, ERAT has the potential to become an<br />

alternative treatment method for acute appendicitis, especially in patients<br />

who are deemed as high-risk candidates for surgery. However, these<br />

previous studies were all retrospective, and no prospective study has<br />

been reported yet. To address this issue, we conducted a prospective<br />

randomized controlled trial to compare ERAT with laparoscopic<br />

appendectomy (LA) and open appendectomy (OA), and evaluated the<br />

feasibility and safety of ERAT in treating acute uncomplicated appendicitis.<br />

Method<br />

Patients<br />

The period of patient enrollment was between January 2018 and August<br />

2019. A prospective, open-label, randomized controlled study was<br />

conducted at Jinshan Hospital, Fudan University. Patients diagnosed<br />

with acute uncomplicated appendicitis were enrolled in the study.<br />

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

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

be excluded) acute appendicitis diagnosed by an abdominal CT scan,<br />

which was indicated by a dilated appendix with a diameter greater than<br />

6 mm, a thickened cecal wall, and periappendiceal fat inflammation, with<br />

or without an appendicolith [10].<br />

Exclusion criteria were as follows: (1) suspected acute complicated<br />

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<br />

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

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

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

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

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

patients under the age of 18 years or over 80 years; (4) patients<br />

with the following contradictions for receiving colonoscopy, surgery<br />

or anesthesia: (a) severe cardiopulmonary insufficiency, psychiatric<br />

dysfunction or coma; (b) acute diffuse peritonitis, which is defined<br />

as diffuse abdominal tenderness, rebound tenderness and muscular<br />

tension; (c) acute gastroenteritis (dysentery, explosive ulcerative colitis);<br />

(d) concurrent menses; (e) intestinal obstruction; (f) acute gastrointestinal<br />

hemorrhage; (g) recent gastrointestinal or pelvic operation or<br />

radiotherapy; (h) allergy to contrast medium; (i) hemorrhagic tendency<br />

because of long-term use of corticosteroids or anticoagulant treatment;<br />

(5) patients undergoing any other clinical trial.<br />

Written informed consent was obtained from all participants. The study<br />

was conducted according to the Declaration of Helsinki and approved<br />

by the Ethics Committee of Jinshan Hospital, Fudan University (No.<br />

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

Primary Registry-Chinese Clinical Trial Registry (ChiCTR1900025812)<br />

(09/09/2019).<br />

Randomization was conducted by a computer-generated randomization<br />

number (1:1:1) by statisticians. The final allocation was concealed in<br />

an opaque envelope. The allocation was reported to the doctors and<br />

patients immediately prior to the intervention.<br />

Preintervention preparation<br />

All patients intravenously received antibiotic treatment (1.5 g cefuroxime<br />

with 100 ml normal saline, 0.5% metronidazole 100 ml) immediately<br />

after being clinically diagnosed. In the ERAT group, the patients orally<br />

took 328.8 g polyethylene glycol (PEG) electrolyte solution with 2000 ml<br />

water before ERAT for bowel preparation. When the excrement became<br />

a clear liquid, the patients were well prepared to undergo ERAT.<br />

ERAT procedure<br />

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

performed as follows (Fig. 1):<br />

First, a full and careful examination of the large intestine was performed<br />

by a colonoscope (CF-H260AI, Olympus, Japan) with a transparent cap.<br />

Then, the colonoscope was located to the appendiceal orifice to check<br />

the appendiceal mucosa to determine whether there was inflammation<br />

or any other abnormalities. With the help of a transparent cap, the tip<br />

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

Nanjing, China) was placed in the appendiceal orifice, and a 0.035-inch<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />



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

gently and deeply inserted into the appendiceal lumen over the catheter.<br />

Finally, the catheter moved forward into the appendiceal lumen along<br />

the guidewire. To make a definite diagnosis, the appendiceal lumen<br />

was filled with contrast medium (ioversol) for endoscopic retrograde<br />

appendicography (ERA) fluoroscopy. Next, the appendiceal lumen was<br />

flushed repeatedly with gentamicin (240,000 units with 100 ml normal<br />

saline) and 0.5% metronidazole 100 ml to clear pus and other infectious<br />

contents, such as sand-like appendicoliths. Then, an extraction basket<br />

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

to extract the remaining appendicoliths if necessary. Finally, a plastic<br />

stent (SPSOF7-7, Cook, USA) was placed routinely in the appendiceal<br />

orifice to maintain pus drainage.<br />

Surgical treatment<br />

All operations were performed by surgeons from a same team. In the<br />

LA group, the three-port technique (umbilical, 10 mm; suprapubic, 5<br />

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

McBurney muscle-splitting incision technique was used.<br />

and CRP level; the duration of diet resumption; the length of hospital<br />

stay (LOS); the total cost of the primary hospital stay; adverse events<br />

during follow-up period and final crossover rate of ERAT to surgery.<br />

Definition<br />

The clinical success of ERAT is defined as successful appendix<br />

cannulation with complete resolution of symptoms and normalization<br />

of inflammatory markers, including WBC count, neutrophil percentages<br />

and CRP. Difficult appendix cannulation is defined as failure to achieve<br />

successful appendix cannulation within 15 min. The assessment of<br />

abdominal pain degree is based on visual analog scales (VAS). In the<br />

VAS, scores of 0 and 10 represent no pain and most severe pain,<br />

respectively. Complete relief of abdominal pain refers to a VAS score of<br />

0.<br />

The diagnostic criteria of acute appendicitis by ERAT mainly consist<br />

of ERA fluoroscopy images, inflammation of the appendiceal mucosa<br />

observed under endoscopy and the presence of pus or appendicoliths<br />

inside the appendiceal lumen [8].<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

16<br />

Postintervention management<br />

After ERAT or surgery was performed, patients were sent back to the<br />

ward and monitored carefully. Patients continued to receive antiinflammatory<br />

therapy when necessary. In the ERAT group, patients<br />

were given a soft diet later on the same day and resumed a normal diet<br />

when the soft diet was tolerated. In the LA and OA groups, a soft diet<br />

was started 24 h after surgery, and a normal diet was given when the<br />

soft diet was completely tolerated. All patients were asked about their<br />

clinical presentation every day. Routine blood tests, including the white<br />

blood cell (WBC) count, neutrophil percentages and C-reactive protein<br />

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

ERAT or surgery. Patients were discharged when all symptoms were<br />

completely relieved and inflammatory markers (including the WBC count,<br />

neutrophil percentages, and CRP level) returned to normal. If ERAT<br />

failed or abdominal pain persisted after ERAT, LA or OA was performed<br />

immediately.<br />

Follow-up<br />

Fourteen days after ERAT, all patients in the ERAT group were scheduled<br />

for outpatient services to inform doctors of their symptoms after<br />

discharge. Patients then received an abdominal X-ray to check the<br />

status of the stent. If the stent was not discharged spontaneously with<br />

defecation, colonoscopy was recommended to retrieve the stent.<br />

Follow-up was performed by telephone interview every 3 months for<br />

the first half year, and then every 6 months till November 2020. In<br />

the ERAT group, recurrence of abdominal pain or appendicitis after<br />

ERAT, including the relevant treatment, was mainly investigated. In the<br />

LA group and OA group, the survey mainly included postoperative<br />

complications such as wound infection, persistent incision pain and<br />

intestinal obstruction. Follow-up was performed until the end of the<br />

study period.<br />

Outcomes<br />

The primary outcome was the clinical success of the treatment. The<br />

secondary outcomes were as follows: the duration of complete relief of<br />

abdominal pain and body temperature; the duration of normalization of<br />

inflammatory markers including the WBC count; neutrophil percentages<br />

In the ERAT group, adverse events mainly indicated the recurrence of<br />

acute appendicitis. In the LA and OA groups, adverse events suggested<br />

postoperative complications.<br />

Statistical analysis<br />

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

basis of our yearly caseload of approximately 240 cases and estimated<br />

recruitment of one fifth of eligible cases, we aimed to enroll at least<br />

96 patients within a 2-year period. Qualitative data are expressed as<br />

numbers (n) and percentages (%) and were compared by using the χ 2<br />

test or Fisher’s exact test when appropriate.<br />

Quantitative data are expressed as the mean ±standard deviation<br />

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

normally distributed quantitative data (such as age, temperature, WBC<br />

count), one-way analysis of variance (ANOVA) was used to compare<br />

the differences among the three groups. For nonnormally distributed<br />

quantitative data (neutrophil percentages, CRP, Alvarado scores, VAS<br />

scores, the duration of normalization of inflammatory markers, the<br />

duration of normal diet and body temperature, total cost and length of<br />

hospitalization), the Kruskal–Wallis test followed by all pairwise multiple<br />

comparisons was used to detect statistical significance. Bonferroni’s<br />

correction was used for multiple hypothesis testing. The data were<br />

analyzed by IBM SPSS software version 22 (SPSS, Chicago, Illinois,<br />

USA). A P value


Fig. 2 Trial profile<br />

Appendicoliths were present in 12 patients (36.36%) in the ERAT group,<br />

16 patients (48.48%) in the LA group and 11 patients (33.33%) in the<br />

OA group. There were no significant differences in appendicoliths among<br />

the three groups (p =0.516).<br />

Treatment success rate and efficacy of ERAT<br />

Table 2 shows the clinical outcomes of the three groups. Successful<br />

treatment was achieved in 29 patients (87.88%) in the ERAT group,<br />

32 patients (96.97%) in the LA group and 33 patients (100%) in the<br />

OA group. No significant differences were observed among the three<br />

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

(12.12%) due to difficult cannulation, and LA was performed in these<br />

patients later on the same day, with uneventful recoveries. All these<br />

four patients were found appendicoliths before ERAT. Appendicoliths<br />

of the other 8 patients who were found to have appendicoliths by CT<br />

scan were removed by ERAT. Stents were placed in 29 patients with<br />

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

to extensive abdominal adhesion caused by surgical reduction for<br />

intussusception 3 years ago. The patient was later converted to OA<br />

successfully.<br />

Among 29 patients who underwent successful ERAT, most achieved<br />

complete abdominal pain relief immediately after the procedure. The<br />

duration of normalization of inflammatory markers, including the WBC<br />

count, neutrophil percentages and CRP level, did not significantly differ<br />

among the ERAT, LA and OA groups (P =0.351, P=0.607, P=0.147,<br />

respectively). The overall cost in the LA group was significantly<br />

higher (P


Table 1 Basic characteristics<br />

ERAT group (n=33) LA group (n=33) OA group<br />

(n=33)<br />

P value<br />

Age, mean (SD), years 44.12±16.95 43.24±15.41 45.45±18.04 0.866<br />

Male, n (%) 18 (54.55) 17 (51.52) 19 (57.58) 0.967<br />

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

Symptoms<br />

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

Nausea, n (%) 22 (66.67) 23 (69.70) 17 (51.52) 0.285<br />

Vomiting, n (%) 5 (15.15) 4 (12.12) 9 (27.27) 0.345<br />

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

Fever, n (%) 18 (54.55) 13 (39.39) 17 (51.52) 0.532<br />

Temperature (℃) 37.37±0.77 37.13±0.57 37.22±0.58 0.317<br />

Signs<br />

Right lower abdominal tenderness, n (%) 33 (100) 33 (100) 33 (100)<br />

Rebound tenderness, n (%) 17 (51.52) 15 (45.45) 20 (57.58) 0.654<br />

Laboratory examination<br />

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

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<br />

CRP (mg/L) 0.749<br />

0–20 18 (54.6) 20 (60.6) 25 (75.76)<br />

21–50 7 (21.2) 7 (21.2) 6 (18.18)<br />

> 50 8 (24.2) 6 (18.2) 2 (6.06)<br />

CT scan<br />

Local Cecal Wall thickening, n (%) 4 (12.12) 0 (0) 1 (3.03) 0.123<br />

Periappendiceal fat inflammation, n (%) 25 (75.76) 27 (81.82) 29 (87.88) 0.496<br />

Intraluminal appendicolith, n (%) 12 (36.36) 16 (48.48) 11 (33.33) 0.516<br />

Alvarado scores, median (25th, 75th percentile) 8 (7, 9) 8 (6, 9) 8 (7, 9) 0.127<br />

VAS scores, median (25th,75th percentile) 6 (5, 7) 7 (6, 7) 6 (6, 7) 0.054<br />

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

C-reactive protein; VAS, visual analog scale<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

9 patients only received colonoscopy for one time. Moreover, for the 4<br />

patients who failed ERAT, they also received two-times intervention since<br />

they underwent both ERAT and LA. Table 3 summarizes the adverse<br />

events which arose in the three groups. No significant differences<br />

(P =0.693) were found among the three treatment groups. In the ERAT<br />

group, three patients (9.09%) reported right lower abdominal pain and<br />

were diagnosed with recurrent acute appendicitis. The recurrence time<br />

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

intraluminal appendicoliths during primary hospitalization. These three<br />

patients received LA later at the same day. Thus, there were totally 7<br />

patients in the ERAT group who crossed over to the LA group, and<br />

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

(3.03%) was found to have a fluid collection around the ileocecal<br />

junction and the fluid collection gradually diminished later on. In the<br />

OA group, three patients (9.09%) were found to have postoperative<br />

complications. Two of them exhibited wound infections within one<br />

month after surgery. Another patient complained of occasional incision<br />

pain one month after OA, especially on rainy days.<br />

Discussion<br />

In this pilot RCT, we have shown that ERAT is feasible and safe for<br />

treating acute uncomplicated appendicitis. Overall, nearly 25% of<br />

patients accepted to participate the trial, suggesting the potential<br />

clinical extension of ERAT since it is a brand-new treating method and<br />

no patient has ever heard of it before. Appendicoliths and infection are<br />

considered as important causes of acute appendicitis and ERAT could<br />

treat acute uncomplicated appendicitis by appendicolith extraction, pus<br />

drainage and intraluminal pressure reduction to relieve the syndromes<br />

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

was not adequately powered to detect differences in treatment efficacy,<br />

the results are useful to inform future clinical application of ERAT.<br />

Although there are some complications associated to colonoscopy,<br />

the adverse event rates were less than 1% and 0.2% for bleeding and<br />

perforation respectively and there were no any adverse events related<br />

to colonoscopy among the patients underwent ERAT treatment in our<br />

study [14]. Moreover, ERAT compares favorably with the results of<br />

surgery in terms of the postintervention recovery of patients. Regarding<br />

the period of body temperature normalization, inflammatory markers<br />

(including the WBC count, neutrophil percentages and CRP level)<br />

and the length of hospitalization, our data did not indicate significant<br />

differences among the three groups (P =0.194, P=0.351, P=0.607,<br />

P=0.147, P=0.054, respectively), which showed that the clinical<br />

efficacy of ERAT was similar to that of surgery. As for different surgical<br />

methods, LA showed a similar clinical efficacy as OA, while LA yielded<br />



Table 2 Clinical outcome<br />

ERAT group<br />

(n = 33)<br />

LA group<br />

(n=33)<br />

OA group<br />

(n=33)<br />

P value ERAT-LA ERAT-OA LA-OA<br />

Treatment Success, n (%) 29 (87.88) 32 (96.97) 33 (100) 0.123<br />

Definite acute uncomplicated appendicitis, n (%) 33 (100) 33 (100) 33 (100)<br />

Appendicoliths removal, n (%) 8 (66.67) NA NA<br />

Stent d rainage, n(%) 29 (87.88) NA NA<br />

Failed cannulation, n (%) 4 (12.12) NA NA<br />

Transferred to surgery, n (%) 4 (12.12) NA NA<br />

Normalization of WBC count, days 0.351<br />

0–1 16 12 17<br />

1–3 5 12 9<br />

> 3 2 0 2<br />

Normalization neutrophil percentages, days 0.607<br />

0–1 15 11 7<br />

1–3 11 14 19<br />

> 3 4 2 2<br />

Normalization of CRP, days 0.147<br />

0–1 3 1 3<br />

1–3 5 10 2<br />

> 3 7 2 3<br />

Normalization of temperature, median (25th, 75th 2 (1, 3) 1 (1, 2) 2 (1, 3) 0.194<br />

percentile), days<br />

LOS, median (25th, 75th percentile), days 5 (4, 6) 4 (3, 5) 4 (3, 5) 0.054<br />

Total cost, median (25th, 75th percentile), RMB 10,983.25<br />

(10,210.26,<br />

13,028.25)<br />

14,517.22<br />

(12,991.05,<br />

15,528.25)<br />

8246.82<br />

(6819.71,<br />

9530.22)<br />

< 0.001 0.001 < 0.001 < 0.001<br />

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

C-reactive protein; LOS, length of hospital stay<br />

Table 3 Follow-up<br />

ERAT group<br />

(n=33)<br />

LA group<br />

(n=33)<br />

OA group (n=33)<br />

P value<br />

Stent discharged, n (%) 29 (87.88) NA NA<br />

Spontaneously discharged, n (%) 9 (31.03) NA NA<br />

Retrieved, n (%) 20 (68.97) NA NA<br />

Adverse events, n (%) 3 (9.09) 1 (3.03) 3 (9.09) 0.693<br />

Recurrence, n (%) 3 (9.09) NA NA<br />

Patients with appendicolith at first admission, n (%) 2 (6.06) NA NA<br />

Patients without appendicolith at first admission, n (%) 1 (3.03) NA NA<br />

Crossover rate (%) 21.21 3.03 NA<br />

Complications<br />

Wound infection, n (%) NA 0 2 (6.06)<br />

Abdominal or incisional pain, n (%) NA 0 1 (3.03)<br />

Abdominal fluid collection, n (%) NA 1 (3.03) 0<br />

Obstructive symptoms, n (%) NA 0 0<br />

ERAT, endoscopic retrograde appendicitis therapy; LA, laparoscopic appendectomy; OA, open appendectomy; NA, not applicable<br />

fewer complications, although there was no statistical significance<br />

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

is the most reliable therapy for acute appendicitis. However, OA seems<br />

to cause more adverse events, such as wound infection, which reduces<br />

the quality of life of patients.<br />

protect beneficial or commensal microorganisms from contamination<br />

with pathogenic organisms [15]. In addition, evidence has shown that<br />

appendectomy may slightly increase the incidence of Crohn’s disease<br />

[16]. In patients with acute uncomplicated appendicitis, ERAT may<br />

preserve the function of the appendix with a satisfactory therapeutic<br />

effect. To some extent, ERAT may be essential for intestinal immune<br />

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

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />



GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

Difficult biliary cannulation is defined as the inability to achieve selective<br />

cannulation within 10 min or 5 attempts by a recent ERCP guideline<br />

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

the difficult appendix cannulation time to within 15 min regardless of<br />

the number of cannulation attempts. In the present study, 4 patients<br />

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

cannulation caused by a swollen mucosa and narrow lumen of the<br />

appendix. In these patients, the guidewire failed to pass through the<br />

swollen and convoluted appendiceal lumen. Unfortunately, difficult<br />

appendiceal cannulation remains an unsolved issue. We believe that<br />

there may be two ways to assist appendiceal cannulation in this<br />

situation. One is to find new equipment that can overcome the severe<br />

edema of the appendix mucosa. The other is to prolong the pre-ERAT<br />

duration to acquire more sufficient anti-inflammatory effect by antibiotics<br />

and thereby maximally reduce the inflammation of the appendiceal<br />

mucosa. However, the second method would definitely increase the<br />

overall hospitalization duration of patients. Subsequent studies will be<br />

conducted to address difficult appendiceal cannulation. In the current<br />

study, 4 patients who failed ERAT were found to have appendicoliths.<br />

However, the reason of failure was due to the mucosal edema instead<br />

of the obstruction of the appendicoliths. Apart from the 4 patients,<br />

the other 8 patients with appendicoliths had a smooth recovery by<br />

receiving ERAT alone. Hence, appendicolith should not be considered<br />

as a contraindication of ERAT. Same as previous study [18], we think<br />

the key to remove appendicoliths was based on the quality of the stone<br />

and the technique of the endoscopist. A fragile stone, regardless of<br />

its size, is more likely to be removed by the combination of irrigation<br />

and extraction basket. If the stone is hard and large, the success of<br />

retraction is more dependent on the experience and the technique of<br />

the endoscopist. When a giant and irregular appendicolith is observed,<br />

it is also feasible to squeeze the appendix and let the stone fall into<br />

the intestine cavity. After that, the appendicolith can be removed via<br />

the intestine by a stone basket. Previous studies showed that the<br />

recurrence rates of acute appendicitis patients treated with ERAT ranges<br />

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

recurrent appendicitis. This recurrence rate was consistent with previous<br />

findings. The recurrence of acute appendicitis may be associated with<br />

the appendiceal morphology since long and curved appendix is also<br />

risk factor of acute appendicitis. Other factors, such as genetic and<br />

environmental factors, may also have impact on recurrence. The final<br />

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

of all patients recovered successfully by receiving ERAT alone and those<br />

who crossed over to surgery did not experience any adverse outcomes<br />

due to the delay in appendectomy. However, the final crossover rate<br />

may be underestimated due to short-term follow-up period and a<br />

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

previous study, spontaneous discharge of the stents was considered as<br />

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

spontaneously discharged and these 9 patients did not show symptoms<br />

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

do not show any discomfort, spontaneous discharge of the stents<br />

should be considered as a benefit and convenience since these patients<br />

will not have to undergo colonoscope a second time.<br />

Another advantage of ERAT is its ability to facilitate a precise diagnosis<br />

of acute appendicitis. Generally, endoscopy can serve as a diagnostic<br />

tool for numerous diseases, such as ulcerative colitis and Crohn’s<br />

disease [19, 20]. A previous study indicated that colonoscopy can<br />

diagnose acute appendicitis with 100% sensitivity and 99% specificity<br />

[21]. Li et al. further described the key points of diagnosing acute<br />

appendicitis by ERAT by observing both the appendiceal mucosa<br />

morphology and the appendiceal lumen imaging by fluoroscopy [8].<br />

In our study, 33 patients with acute uncomplicated appendicitis in<br />

the ERAT group were all confirmed by ERAT. In the future, ERAT may<br />

become an essential diagnostic method for patients suspicious for acute<br />

appendicitis who have atypical clinical manifestations.<br />

One feature of our study was that an abdominal CT scan was performed<br />

in all participants. Although CT scan is not a necessary diagnostic<br />

criterion for acute appendicitis, using CT can enhance the accuracy of<br />

diagnosing acute appendicitis and minimize the negative appendicitis<br />

rate. Similar to this view, some previous trials showed that their study<br />

design was limited due to the lack of CT scans performed in suspicious<br />

patients [7]. Based on former experiences, all participants had to be<br />

examined by abdominal CT scan in our study. Thus, we could accurately<br />

enroll the patients with acute uncomplicated appendicitis in our trial by<br />

both clinical manifestation and CT scan confirmation.<br />

The study has several limitations. First, the success rate of ERAT largely<br />

depends on the skills of endoscopists. Although our endoscopists are<br />

experienced doctors, the lack of ERAT guidelines was still the main<br />

problem when faced with difficult cannulation. Second, since this was<br />

an RCT, we tried to perform ERAT on the first day of hospital admission,<br />

which was similar to the timing of emergency surgery. The downside of<br />

this strategy is that it may cause insufficient anti-inflammatory treatment<br />

in patients, which may increase the difficulty of appendiceal cannulation.<br />

Third, in the current study, the power was not calculated and the study<br />

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

the safety and feasibility of ERAT were preliminarily estimated. Thus,<br />

future studies involved with larger sample size are needed to be done.<br />

Fourth, a double-blinded trial cannot be conducted due to the nature<br />

of the study. Last, the need to prepare for colonoscopy in patients with<br />

abdominal pain requires further study and is another limitation of the<br />

study.<br />

In conclusion, ERAT was demonstrated to be a feasible and safe<br />

treatment for acute uncomplicated appendicitis. However, difficult<br />

appendiceal cannulation and acute appendicitis recurrence are the main<br />

problems that remain to be solved. In the future, large-scale multicenter<br />

RCTs are needed to further address the current challenges.<br />

Abbreviations<br />

ERAT: Endoscopic retrograde appendicitis therapy; LA: Laparoscopic<br />

appendectomy; OA: Open appendectomy; PEG: Polyethylene glycol;<br />

SD: Standard deviation; ERA: Endoscopic retrograde appendicography;<br />

WBC: White blood cell; CRP: C-reactive protein; LOS: Length of<br />

hospital stay; VAS: Visual analog scales; ANOVA: Analysis of variance;<br />

ITT: Intention-to-treat; CT: Computed tomography; RCT: Randomized<br />

controlled trial; EMR: Endoscopic mucosal resection<br />

Acknowledgements<br />

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

for English language editing. We also appreciate all members from the<br />

Department of General Surgery, Jinshan hospital, Fudan University, for<br />

helping with the study.<br />



Authors’ contributions<br />

PLS and MJ proposed the study and were accountable for all aspects of<br />

the work. ZMS contributed to the article in the aspects of drafting work<br />

as well as collecting, analyzing and interpreting the data; ZLZ, JTL, MY<br />

and WDH all made essential contribution to the manuscript. All authors<br />

read and approved the final manuscript.<br />

Funding<br />

This study was supported by Project of Shanghai Municipal Health<br />

Commission of China (No. 201740041). All the funding was used to<br />

conduct this trial.<br />

Availability of data and materials<br />

The datasets supporting the conclusions of this article are available in the<br />

the ResMan original data sharing platform (IPD sharing platform) of the<br />

Chinese Clinical Trial Registry, which can be viewed at the following website:<br />

http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=5600.<br />

We expect to release the original data on December <strong>2022</strong>.<br />

Declarations<br />

Ethics approval and consent to participate<br />

All procedures performed in studies involving human participants<br />

were in accordance with the ethical standards of Ethics Committee of<br />

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

and also with the 1964 Helsinki declaration and its later amendments<br />

or comparable ethical standards. The experimental protocol was also<br />

approved by Shanghai Municipal Health Commission and Project of<br />

Shanghai Municipal Health Bureau in China (No. 201740041). Written<br />

informed consent was obtained from all participants. The study is<br />

registered with the WHO Primary Registry-Chinese Clinical Trial Registry<br />

(ChiCTR1900025812).<br />

Consent for publication<br />

Not applicable.<br />

Competing interests<br />

The authors declare that they have no competing interest.<br />

Author details<br />

1<br />

Department of General Surgery, Jinshan Hospital, Fudan University,<br />

Shanghai, China. 2 Department of <strong>Gastroenterology</strong>, Jinshan Hospital,<br />

Fudan University, Shanghai, China.<br />

Received: 29 June 2021 Accepted: 3 February <strong>2022</strong><br />

Published online: 13 February <strong>2022</strong><br />

References<br />

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appendicitis: modern understanding of pathogenesis, diagnosis,<br />

and management. Lancet. 2015;386(10000):1278–87.<br />

2. National Surgical Research Collaborative. Multicentre observational<br />

study of performance variation in provision and outcome of<br />

emergency appendicectomy. Br J Surg. 2013;100:1240–52.<br />

3. Ahmed HO, Muhedin R, Boujan A, Aziz AHS, Abdulla AM, Hardi RA,<br />

et al. A five-year longitudinal observational study in morbidity and<br />

mortality of negative appendectomy in Sulaimani teaching Hospital/<br />

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

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appendicitis revisited: spontaneous resolution and predominance<br />

of prehospital perforations imply that a correct diagnosis is more<br />

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

5. Flum DR. Clinical practice. Acute appendicitis—appendectomy or<br />

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

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appendicitis therapy: a pilot minimally invasive technique (with<br />

videos). Gastrointest Endosc. 2012;76:862–6.<br />

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retrograde appendicitis therapy (ERAT): a multicenter retrospective<br />

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8. Li Y, Mi C, Li W, She J. Diagnosis of acute appendicitis by<br />

endoscopic retrograde appendicitis therapy (ERAT): combination of<br />

colonoscopy and endoscopic retrograde appendicography. Dig Dis<br />

Sci. 2016;61:3285–91.<br />

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

retrograde appendicitis techniques for the treatment of patients with<br />

acute appendicitis. Z Gastroenterol. 2018;56:899–904.<br />

10. Gaitini D. Imaging acute appendicitis: state of the art. J Clin Imaging<br />

Sci. 2011;1:49.<br />

11. Pickhardt PJ, Levy AD, Rohrmann CA Jr, Kende AI. Primary<br />

neoplasms of the appendix manifesting as acute appendicitis: CT<br />

findings with pathologic comparison. Radiology. 2002;224:775–81.<br />

12. Williams SN, Bulstrode CJK, O’Connell PR. The vermiform<br />

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

Boca Raton: CRC Press; 2013. p. 1201–2.<br />

13. Liang MK, Andersson RE, Jaffe BM, Berger HD, et al. The appendix.<br />

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

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

14. Su YK, Kim HS, Hong JP. Adverse events related to colonoscopy:<br />

global trends and future challenges. World J Gastroenterol.<br />

2019;25(02):190–204.<br />

15. Randal Bollinger R, Barbas AS, Bush EL, Lin SS, Parker W. Biofilms<br />

in the large bowel suggest an apparent function of the human<br />

vermiform appendix. J Theor Biol. 2007;249:826–31.<br />

16. Kaplan GG, Pedersen BV, Andersson RE, Sands BE, Korzenik<br />

J, Frisch M. The risk of developing Crohn’s disease after an<br />

appendectomy: a population-based cohort study in Sweden and<br />

Denmark. Gut. 2007;56:1387–92.<br />

17. Liao WC, Angsuwatcharakon P, Isayama H, Dhir V, Devereaux B,<br />

Khor CJ, et al. International consensus recommendations for difficult<br />

biliary access. Gastrointest Endosc. 2017;85:295–304.<br />

18. Song MY, Liu ZH, Zhao LX, Liu BR. Endoscopic retrograde<br />

appendicitis therapy for treating a giant hard appendicolith<br />

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2020;44(2):488–9.<br />

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Publisher’s Note<br />

<strong>Spring</strong>er Nature remains neutral with regard to jurisdictional claims in<br />

published maps and institutional affiliations.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />






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

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

Abstract<br />

Background<br />

Upper gastrointestinal (GI) bleeding is a severe acute disease of<br />

gastroenterology department. Fish bone is the most common foodrelated<br />

foreign body. However, fish bone piercing the esophagus,<br />

causing the mediastinal abscess that corroded the left subclavian artery,<br />

resulting delayed but high-risk massive upper gastrointestinal bleeding<br />

is very rare.<br />

Case presentation<br />

A 54-year-old man was admitted to the hospital with a chief complaint<br />

of hematemesis for 2 h. The color of hematemesis was bright red, and<br />

the volume was over 1000 ml. He also had symptoms of palpitations,<br />

fatigue and sweating. He had been on long-term glucocorticoids or<br />

nonsteroidal anti-inflammatory drugs (NSAIDs) for gout for 3 years<br />

before admission, had no previous history of liver disease or GI bleeding<br />

disease, and had a history of drinking.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

Case presentation<br />

We report a 54-year-old man who was diagnosed with delayed but<br />

high-risk massive upper GI bleeding that was the result of a fish bone<br />

piercing the esophagus, causing a mediastinal abscess that corroded<br />

the left subclavian artery. He was saved effectively by early and timely<br />

multidisciplinary collaboration.<br />

Conclusion<br />

A fish bone-caused mediastinal abscess that corrodes the left<br />

subclavian artery and induces delayed but high-risk massive upper GI<br />

bleeding is very rare. In addition to routine consideration of upper GI<br />

bleeding, medical history, endoscopy and CT are helpful for achieving<br />

a diagnosis. Importantly, early and timely multidisciplinary collaboration<br />

can effectively save critically ill patients.<br />

Keywords<br />

Delayed but high-risk massive upper gastrointestinal bleeding, Fish<br />

bone, Mediastinal abscess, Left subclavian artery (LSA), Early and timely<br />

multidisciplinary collaboration<br />

Background<br />

Upper gastrointestinal (GI) bleeding is a severe acute disease<br />

associated with four main causes, namely, esophageal variceal<br />

bleeding, peptic ulcer (PU) bleeding, gastric cancer bleeding<br />

and acute erosive hemorrhagic gastritis, and prompt diagnosis<br />

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

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

unfortunately pierce the left subclavian artery (LSA) and cause a<br />

pseudoaneurysm in rare cases, resulting in an LSA esophageal<br />

fistula [3, 5]. Arterioesophageal fistula are rare, but they can cause<br />

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

case of a mediastinal abscess corroding the LSA, resulting in<br />

delayed but high-risk massive upper GI bleeding.<br />

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

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

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

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

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

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

mmHg, CO 2<br />

partial pressure 30.8 mmHg, pH value 7.281; and normal<br />

liver and renal function and coagulation tests. Therefore, GI hemorrhage<br />

was first considered, and esomeprazole was administered. Computed<br />

tomography (CT) on admission showed a visible breach on the left side<br />

of the esophageal wall, a low-density lesion was found between the<br />

esophageal wall and the LSA, and the demarcation from the esophageal<br />

wall and subclavian artery was unclear (Fig. 1). Because the patient had<br />

no history of foreign body ingestion, we initially considered esophageal<br />

diverticula with bleeding potential. However, the patient still presented<br />

with repeated hematemesis with a large volume of bright red blood;<br />

his vital signs could not be maintained, and he developed progressive<br />

unconsciousness 30 min after admission to the hospital. We applied<br />

a multidisciplinary approach; critical care doctors were included in the<br />

treatment, and a member of the Department of Anesthesiology performed<br />

an urgent consultation. Tracheal intubation-assisted respiration, aspiration<br />

prevention, and anti-shock therapy were applied, and 6 units of red blood<br />

cells were transfused. Additionally, urgent esophagogastroduodenoscopy<br />

was performed in the operating room, which indicated active and massive<br />

bleeding from the esophageal wall (Fig. 2). However, due to massive<br />

bleeding, this patient suffered from two cardiac arrests, so a detailed<br />

endoscopic examination could not be performed.<br />

Urgent thoracotomy through the median sternal incision was performed<br />

immediately, and an abscess cavity 4 cm in size was detected between<br />

the LSA and the left common carotid artery. A stench of putrefaction<br />

accompanied by a large gush of blood was present when the abscess<br />

cavity was opened. The active bleeding point was found in the posterior<br />

lateral wall of the LSA with a 3 mm rupture. During the repair of the LSA<br />

and clean-up of the abscess cavity, an esophageal fistula was detected<br />

and repaired on the other side of the abscess cavity. However, no foreign<br />

22<br />

*Correspondence: onlyoneliuxuemei@163.com<br />

†<br />

Zhiqiang Yi and Cheng Chen contributed equally and shared first authorship<br />

1<br />

Department of <strong>Gastroenterology</strong>, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China<br />

©The Author(s) <strong>2022</strong>


Fig. 1 Image from CT scan. CT showed that the local soft tissue<br />

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

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

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

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

arrow). Esophageal breach was detected (black arrow)<br />

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

patient recovered. Revisiting family history indicated that chest pain and<br />

discomfort occurred in this patient after eating fish 4 days prior.<br />

Discussion and conclusions<br />

Fig. 2 Image from the emergent endoscopy. Active and massive<br />

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

endoscopy bleeding was detected from the esophageal wall by emergent<br />

endoscopy<br />

There are generally four main causes of upper GI bleeding, namely,<br />

esophageal variceal bleeding, PU-caused bleeding, gastric cancercaused<br />

bleeding and acute erosive hemorrhagic gastritis [1, 2].<br />

In addition, there are also reports of NSAIDs causing esophageal<br />

mucosal damage. These drugs may cause mucosal damage by<br />

reducing the cytoprotective effect of prostaglandins on the mucosa<br />

or aggravating reflux esophagitis [8, 9]. The clinical manifestations of<br />

these patients are usually retrosternal pain, sore throat and dysphagia<br />

[9]. Esophageal bleeding caused by NSAIDs is a rare nonfatal bleeding,<br />

mostly secondary to superficial esophageal ulcer oozing, and some<br />

bleeding can even be discovered during endoscopy [10, 11]. However,<br />

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

left common carotid artery (blue arrow). b Schematic diagram of surgical anatomy<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />



GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

in the present case, the patient’s condition progressed so rapidly and<br />

dangerously that the challenge was to determine the cause of the<br />

bleeding and how to treat it. Based on medical history, physiological<br />

signs, examination and treatment, this case of delayed but high-risk<br />

massive upper GI bleeding was the result of a fish bone piercing<br />

the esophagus, causing the mediastinal abscess that corroded the<br />

LSA. Fistulas between the subclavian artery and esophagus are rare<br />

but can rapidly become life-threatening [12, 13]. Clinically, among<br />

arterial-esophageal fistulas caused by esophageal foreign bodies,<br />

the proportion of LSA esophageal fistulas is only 2% [3]. Most<br />

mediastinal abscesses are related to infections of deep sternal wounds,<br />

esophageal perforations, or descending necrotizing mediastinitis [14,<br />

15]. Mediastinal abscess directly caused by taking glucocorticoids<br />

has not been reported. It may be a contributing factor to the formation<br />

of abscesses after mediastinal infection. Glucocorticoids have many<br />

complex quantitative and qualitative immunosuppressive effects,<br />

which can induce cellular immune deficiency and may increase the<br />

susceptibility of the host to various viruses, bacteria, fungi and parasites<br />

[16]. The patient’s risk of infection increases with increasing treatment<br />

dose and treatment time. In patients exposed to low doses, even if the<br />

cumulative dose is high, the risk of infection is often low. In addition, the<br />

host’s underlying disease status also determines the changes in the risk<br />

of infection in clinical practice [17]. Therefore, in this case, we believe<br />

that the patient’s long-term use of glucocorticoids is not an independent<br />

risk factor for mediastinal abscess.<br />

Generally, fish bones or sharp foreign bodies can directly pierce the large<br />

arteries in the mediastinum, causing fatal upper GI bleeding. For example,<br />

some case reports have reported sharp foreign bodies such as fish<br />

bones or chicken bones piercing the esophagus and mediastinal artery<br />

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

ignored by patients and their families. Once the foreign body leaves the<br />

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

If the patient seeks medical attention in time and the foreign body does<br />

not break away from the artery, the patient can be successfully cured by<br />

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

resulted from puncture of the esophagus by the fishbone corroded the<br />

LSA, causing delayed but high-risk arterial hemorrhage.<br />

This case suggests that in addition to routine consideration of upper GI<br />

bleeding, medical history, endoscopy and CT are helpful for achieving<br />

a diagnosis. Importantly, early and timely multidisciplinary collaboration<br />

can effectively save critically ill patients. Emergency thoracotomy<br />

remains a life-saving treatment.<br />

Abbreviations<br />

GI: Gastrointestinal; NSAIDs: Nonsteroidal anti-inflammatory drugs; LSA:<br />

Left subclavian artery; CT: Computed tomography; PU: Peptic ulcer.<br />

Acknowledgements<br />

The authors are grateful to Prof. Hua Zhang and Jiaxing Zhu<br />

(Department of <strong>Gastroenterology</strong>, Affiliated Hospital of Zunyi Medical<br />

University, Zunyi, Guizhou Province, China) for study support.<br />

Authors’ contributions<br />

ZQY collected and interpreted the data; ZQY and XML drafted the<br />

manuscript; CC established the surgical plan; BGT analyzed the<br />

radiological images; TLL and XML designed the study and revised<br />

the draft; and XML supervised the study. All the authors listed have<br />

approved the enclosed manuscript.<br />

Funding<br />

This research was supported by the National Natural Science<br />

Foundation of China (81860103 and 82070536 to X.M.L., 81660098<br />

and 82160505 to T.L.L., 81960532 to C.C., and 82073087 to B.G.T.),<br />

the Guizhou Province International Science and Technology Cooperation<br />

(<strong>Gastroenterology</strong>) Base (Qian Ke He Platform Talents-HZJD [2021] 001<br />

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

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

innovative talents in Guizhou Province [“Thousand” level] (fzc120200615<br />

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

the Guizhou Province Science and Technology Plan (No. Qiankehe<br />

Support [2021] General 073 to C.C.).<br />

Availability of data and materials<br />

All information about the patient came from the Affiliated Hospital of<br />

Zunyi Medical University. The data used and analyzed during the current<br />

study are included in this article.<br />

Declarations<br />

Ethics approval and consent to participate<br />

The study was reviewed and approved by the Ethics Committee of the<br />

Affiliated Hospital of Zunyi Medical University.<br />

Consent for publication<br />

Written informed consent was obtained from the patient for publication<br />

of this report and any accompanying images. A copy of the written<br />

consent is available upon request.<br />

Competing interests<br />

The authors declare that they have no competing interests.<br />

Author details<br />

1<br />

Department of <strong>Gastroenterology</strong>, Affiliated Hospital of Zunyi Medical<br />

University, Zunyi 563003, Guizhou Province, China. 2 Department of<br />

Thoracis Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi,<br />

Guizhou Province, China. 3 Department of Thyroid and Breast Surgery,<br />

Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province,<br />

China.<br />

Received: 27 August 2021 Accepted: 3 February <strong>2022</strong><br />

Published online: 15 February <strong>2022</strong><br />

References<br />

1. Gralnek I, Dumonceau J, Kuipers E, Lanas A, Sanders D, Kurien<br />

M, et al. Diagnosis and management of nonvariceal upper<br />

gastrointestinal hemorrhage: European Society of Gastrointestinal<br />

Endoscopy (ESGE). Guideline. 2015;47(10):a1-46.<br />

2. Gralnek I, Stanley A, Morris A, Camus M, Lau J, Lanas A, et al.<br />

Endoscopic diagnosis and management of nonvariceal upper<br />

gastrointestinal hemorrhage (NVUGIH): European Society of<br />

Gastrointestinal Endoscopy (ESGE). Guideline Update 2021.<br />

2021;53(3):300–32.<br />



3. Zhao S, Tinzin L, Deng W, Tong F, Shi Q, Zhou Y. Sudden<br />

unexpected death due to left subclavian artery-esophageal fistula<br />

caused by fish bone. J Forensic Sci. 2019;64(6):1926–8.<br />

4. Wang X, Zhao J, Jiao Y, Wang X, Jiang D. Upper gastrointestinal<br />

foreign bodies in adults: a systematic review. Am J Emerg Med.<br />

2021;50:136–41.<br />

5. Stringari C, Sbraga P, Zaraca F. Endovascular treatment of a left<br />

subclavian pseudoaneurysm induced by ingestion of a foreign body.<br />

Ann Vasc Surg. 2013;27(5):672.e677-672.611.<br />

6. Hollander JE, Quick G. Aortoesophageal fistula: a comprehensive<br />

review of the literature. Am J Med. 1991;91(3):279–87.<br />

7. Millar A, Rostom A, Rasuli P, Saloojee N. Upper gastrointestinal<br />

bleeding secondary to an aberrant right subclavian arteryesophageal<br />

fistula: a case report and review of the literature. Can J<br />

Gastroenterol. 2007;21(6):389–92.<br />

8. Noffsinger AE. Update on esophagitis: controversial and<br />

underdiagnosed causes. Arch Pathol Lab Med. 2009;133(7):1087–95.<br />

9. Zografos GN, Georgiadou D, Thomas D, Kaltsas G, Digalakis M.<br />

Drug-induced esophagitis. Dis Esophagus. 2009;22(8):633–7.<br />

10. Kikendall JW, Friedman AC, Oyewole MA, Fleischer D, Johnson<br />

LF. Pill-induced esophageal injury. Case reports and review of the<br />

medical literature. Dig Dis Sci. 1983;28(2):174–82.<br />

11. Kim SH, Jeong JB, Kim JW, Koh S-J, Kim BG, Lee KL, et al. Clinical<br />

and endoscopic characteristics of drug-induced esophagitis. World<br />

J Gastroenterol. 2014;20(31):10994–9.<br />

12. Kim S, Jeon KN, Bae K. Aberrant left subclavian artery-esophageal<br />

fistula in a patient with a prolonged use of nasogastric tube: a case<br />

report and literature review. Diagnostics (Basel). 2021;11(2):195.<br />

13. Oliveira E, Anastácio M, Marques AJ. Aberrant right subclavian<br />

artery-esophageal fistula: massive upper gastrointestinal<br />

hemorrhage secondary to prolonged intubation. Braz J Anesthesiol.<br />

2016;66(3):318–20.<br />

14. Pastene B, Cassir N, Tankel J, Einav S, Fournier PE, Thomas P, et<br />

al. Mediastinitis in the intensive care unit patient: a narrative review.<br />

Clin Microbiol Infect. 2020;26(1):26–34.<br />

15. Martínez Vallina P, Espinosa Jiménez D, Hernández Pérez L, Triviño<br />

RA. Mediastinitis. Arch Bronconeumol. 2011;47(Suppl 8):32–6.<br />

16. Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal<br />

infections. Lancet. 2003;362(9398):1828–38.<br />

17. Cutolo M, Seriolo B, Pizzorni C, Secchi ME, Soldano S, Paolino S,<br />

et al. Use of glucocorticoids and risk of infections. Autoimmun Rev.<br />

2008;8(2):153–5.<br />

18. Russo SS, Taff ML, Ratanaproeksa O, Spitz WU. Sudden death<br />

resulting from chicken bone perforation of the esophagus. Am J<br />

Forensic Med Pathol. 1986;7(3):263–5.<br />

19. Jiang D, Lu Y, Zhang Y, Hu Z, Cheng H. Aortic penetration due to a<br />

fish bone: a case report. J Cardiothorac Surg. 2020;15(1):292.<br />

Publisher’s Note<br />

<strong>Spring</strong>er Nature remains neutral with regard to jurisdictional claims in<br />

published maps and institutional affiliations.<br />

Find out more at www.calprotectin.co.uk<br />

[Figure 1: Edwards et al. ECCO 2021 P518]<br />

Improved Compliance for Faecal Calprotectin<br />

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NEWS<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

Healthcare survey highlights<br />

the impact of the pandemic<br />

on IBD patient care<br />

Over 7,000 people responded to the<br />

Crohn’s & Colitis UK Healthcare Survey,<br />

providing an insight into how IBD patients<br />

experienced healthcare during 2021.<br />

The responses showed that health services<br />

have continued to be disrupted by the<br />

coronavirus pandemic and there’s been a big<br />

impact on patient care. Difficulties accessing<br />

GPs, specialists, medicines, tests, and<br />

procedures have led to delays in diagnosis,<br />

flares, and complications for people with<br />

Crohn’s and Colitis. Mental wellbeing,<br />

relationships, and ability to work have also<br />

been affected.<br />

Ruth Wakeman, Director of Services,<br />

Advocacy & Evidence at Crohn’s & Colitis<br />

UK says: ‘The results of the Healthcare<br />

Survey highlight that the pandemic has<br />

exacerbated existing issues with resourcing<br />

of IBD services, which need to be addressed,<br />

but also some opportunities as services<br />

have adapted to the pandemic. We are<br />

very grateful for the care and support that<br />

healthcare professionals continue to give<br />

to people with Crohn’s and Colitis in such<br />

difficult circumstances.’<br />

The results showed that whilst huge efforts<br />

had been made to deliver excellent care for<br />

people with Crohn’s and Colitis, prioritisation<br />

and investment are vital to tackle increasingly<br />

long waits for care. The recent Getting it Right<br />

First Time (GIRFT) gastroenterology report<br />

called for more proactive management of IBD,<br />

with the aim of reducing admissions. It also<br />

highlighted improvements that could be made<br />

to triage to speed up diagnosis and early<br />

treatment.<br />

This survey, which was conducted between<br />

August and October 2021, asked questions<br />

about experiences of healthcare during the<br />

previous 6-12 months. It builds on previous<br />

surveys by Crohn’s & Colitis UK, including<br />

the Life in Lockdown Survey in 2020 and IBD<br />

Patient Survey in 2019, all contributing to<br />

build a comprehensive view of healthcare over<br />

the last 3 years.<br />

What people with living with Crohn’s and<br />

Colitis said<br />

Diagnosis<br />

Many said that getting a diagnosis during<br />

the pandemic has been difficult, with 29% of<br />

respondents diagnosed during the previous<br />

12 months reporting that this had taken<br />

over a year. This is an increase from 26% in<br />

2019. Respondents also reported that it had<br />

taken longer for treatment to start following<br />

diagnosis. 41% said it took more than two<br />

weeks for treatment to start, compared to<br />

2019 when only 24% reported waiting more<br />

than two weeks for treatment.<br />

Access to healthcare professionals<br />

The results also showed that people found<br />

it harder to get through to IBD teams for<br />

specialist advice, with 27% of those who tried<br />

to contact their advice line saying they did not<br />

get a response by the end of the next working<br />

day.<br />

This was in addition to 41% of those who had<br />

needed care from their GP during the previous<br />

6 months saying they had been unable to get<br />

the care they needed. Furthermore, 29% had<br />

not been able to get the help they needed from<br />

urgent care services.<br />

Access to medicines, tests and procedures<br />

The results indicate a particularly big disruption<br />

to surgery and colonoscopy. 29% reported<br />

cancelled surgery and 24% cancelled<br />

colonoscopies, with many still waiting for a<br />

new date.<br />

Additionally, 18% had experienced disruption<br />

to getting medication.<br />

Impact of difficulties accessing health<br />

services or treatment<br />

22% of those who have needed health<br />

services or treatment during the previous 6<br />

months said that difficulties accessing this had<br />

resulted in a flare of their condition. In addition<br />

to this, 24% reported that their mental health<br />

had been affected. Respondents relayed<br />

how this has led to time off work, affected<br />

relationships and ability to do everyday tasks.<br />

Changes to how patients access care<br />

The survey found that 72% of those who had<br />

needed outpatient appointments during the<br />

previous 6 months had mostly had these by<br />

telephone, with only 3% having mostly video<br />

appointments. Only 13% were offered a<br />

choice. Comments highlighted the benefits of<br />

remote appointments, but also preferences for<br />

some face-to-face appointments. Whichever<br />

method was used, quality of care and a<br />

personalised approach were considered<br />

important.<br />

Quality of care<br />

Despite the challenges during this period, 56%<br />

felt that their quality of care was the same as<br />

before the pandemic, with a small proportion<br />

(4%) considering it was better.<br />

More information about the survey can be<br />

found on the Crohn’s & Colitis UK website. If<br />

you’re an IBD Nurse Specialist or Healthcare<br />

Professional working in IBD, you may want<br />

to use these results alongside your service’s<br />

IBD UK Benchmarking reports as your service<br />

refocuses, adapts, and redesigns for the<br />

future. If you would like to seek feedback and<br />

involve your IBD patients in service redesign,<br />

the charity also has a Patient Engagement<br />

Toolkit, also available on their website which<br />

may be helpful.<br />

Cause of inflammatory<br />

bowel disease discovered<br />

Interaction between gut bacteria and<br />

mucus layer cells<br />

Chronic inflammatory bowel disease (IBD)<br />

is becoming increasingly widespread. Until<br />

now, however, the underlying causes of<br />

the inflammation responses were unclear.<br />

Scientists at the Technical University<br />

of Munich (TUM) have now identified a<br />

mechanism that triggers a problematic<br />

interaction between intestinal bacteria and<br />

cells in the intestinal mucus layer in XLP2,<br />

a condition associated with IBD. The team<br />

believes that the results can be applied to<br />

other intestinal diseases and could offer<br />

approaches to the development of new<br />

drugs.<br />

The billions of bacteria living in the human<br />

gut – known collectively as the microbiome<br />

– are of enormous importance. They help<br />

with digestion, among other functions.<br />

Consequently, the immune system in the gut<br />

must be extremely well regulated: It should<br />

fight only harmful pathogens without attacking<br />

useful microorganisms. However, this fine<br />

balance can be disrupted by various factors.<br />

A defect in the gene XIAP, which causes<br />

the rare disease XLP2, results in chronic<br />

inflammation of the bowels in 30 percent of all<br />


NEWS<br />

Dr Monica Yabal<br />

cases, among other symptoms. Babies with this<br />

genetic defect often display serious symptoms<br />

such as diarrhea, abdominal pain, weakness<br />

and weight loss soon after birth. Until now,<br />

scientists have been unable to understand the<br />

underlying mechanism or discover effective<br />

treatments – apart from stem cell transplants,<br />

which involve a high risk of mortality.<br />

Overreaction of the innate immune system<br />

Working with organoids – intestinal cells in a<br />

Petri dish – and animal experiments, a team<br />

headed by Dr. Monica Yabal, Adam Wahida and<br />

Madeleine Müller of the Institute for Molecular<br />

Immunology and the Clinic of Hematology<br />

and Oncology of TUM’s university hospital,<br />

Klinikum rechts der Isar, has now identified the<br />

mechanism behind the inflammation response<br />

and learned how it becomes chronic. “The<br />

innate immune system overreacts to microbes<br />

in the gut,” says Yabal. The immune system in<br />

healthy people eliminates bacteria that cause<br />

illness and then returns to its resting state. But<br />

in some XLP2 patients, a fatal chain reaction<br />

begins:<br />

Every person has toll-like receptors (TLRs) that<br />

use unique structures such as molecules in the<br />

cell wall to identify harmful microbes. When a<br />

TLR binds a molecule, the signaling substance<br />

TNF and its TNFR1 and TNFR2 receptors<br />

activate the immune system to eliminate the<br />

pathogen. However, this does not work properly<br />

in XLP2 patients. Instead, the binding of TNF to<br />

the TNFR1 receptor on cells known as Paneth<br />

cells causes these cells to die, resulting in a<br />

vicious circle. That is because the Paneth cells<br />

in the gut mucus layer produce antimicrobial<br />

substances and thus ensure a bacterial balance<br />

in the intestines. The loss of those cells changes<br />

the composition of the microbiome. Beneficial<br />

bacteria such as clostridia are attacked and can<br />

no longer perform their Publication:<br />

regulatory role. This Adam Wahida, Madeleine Müller, Andreas<br />

again activates the Hiergeist, Bastian Popper, Katja Steiger,<br />

immune system. Caterina Branca, Markus Tschurtschenthaler,<br />

Thomas Engleitner, Sainitin Donakonda,<br />

New drugs<br />

Jordy De Coninck, Rupert Öllinger, Marie K.<br />

could stop the Pfautsch, Nicole Müller, Miguel Silva, Sinem<br />

inflammation<br />

Usluer, Erik Thiele Oberg, Jan P. Böttcher,<br />

response<br />

Nicole Pfarr, Martina Anton, Julia B. Slotta-<br />

“We believe that this Huspenina, Andreas G. Nerlich, Tobias Madl,<br />

principle might also Marijana Basic, André Bleich, Geert Berx,<br />

be applicable to other Jürgen Ruland, Percy A. Knolle, Roland<br />

inflammatory bowel Rad, Timon E. Adolph, Peter Vandenabeele,<br />

diseases and not only Hirokazu Kanegane, André Gessner, Philipp<br />

in XLP2 patients,” says J. Jost, Monica Yabal. XIAP restrains TNFdriven<br />

intestinal inflammation and dysbiosis by<br />

Prof. Percy Knolle,<br />

the Director of the promoting innate immune responses of Paneth<br />

Institute for Molecular Immunology at TUM. and dendritic cells (2021) Science Immunology,<br />

Malfunctioning Paneth cells have also been Vol 6, Issue 65. DOI: 10.1126/sciimmunol.<br />

observed in many patients with inflammatory abf7235.<br />

bowel diseases with various causes.<br />

More information:<br />

These insights might open up important The study was funded by the European<br />

avenues for the development of new drugs. Research Council (ERC), the German Research<br />

Patients with chronic bowel inflammation Foundation (DFG), the Austrian Research<br />

have been treated for many years with drugs Promotion Agency (FFG) and the German<br />

that inhibit the TNF ScheBo_Gastro<strong>Today</strong>_Aug_2020 Center for Multi-Ad_Address_Change<br />

Infection Research (FFG).<br />

receptors. However,<br />

these molecules are<br />

not very specific<br />

and deactivate both<br />

TNFR1 and TNFR2.<br />

“Our experiments<br />

show that it would<br />

be better if we had a<br />

selective inhibitor for<br />

the TNFR1 receptor,”<br />

says Yabal. It also<br />

remains unclear<br />

why some people<br />

respond very well<br />

to this treatment<br />

while others show<br />

no response at<br />

all. Consequently,<br />

the team would<br />

now like to turn<br />

its attention to the<br />

adaptive immune<br />

system, which<br />

learns throughout an<br />

individual’s lifetime<br />

through contact<br />

with pathogens<br />

and forms special<br />

antigens, and also<br />

study its special role<br />

in the gut.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />


NEWS<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

Go with the Flow!<br />

How the Rare Disease Collaborative<br />

Network can support you in diagnosis and<br />

management of refractory coeliac disease<br />

Woodward JM 1 , Soilleux E 1 , Passmore R 2 ,<br />

Sanders D 3<br />

Coeliac disease that is refractory to the<br />

withdrawal of gluten from the diet is rare,<br />

and as a result prone to both over and under<br />

diagnosis. Two types are described: ‘Type 1’ is<br />

indistinguishable from non-responsive coeliac<br />

disease (1) and may be due to the individual<br />

being highly sensitized to trace amounts of<br />

gluten remaining in the diet that would not<br />

affect most people with the condition. ‘Type 2’<br />

refractory coeliac disease (RCD2) progresses<br />

to an aggressive T-cell lymphoma in as many<br />

as 67% of cases over 5 years (2). RCD2 is<br />

distinguished from non-responsive coeliac<br />

disease or RCD1 by the abnormal clonal<br />

increase of an unusual population of intestinal<br />

intra-epithelial lymphocytes (IELs) characterized<br />

by the presence of the T-cell marker CD3<br />

within the cytoplasm but not on the surface of<br />

the cell (3). These cells also usually lack the<br />

normal expression of another surface marker,<br />

CD8. However, immunohistochemistry for T-cell<br />

markers or polymerase chain reaction (PCR) for<br />

T-cell receptor clonality are unreliable diagnostic<br />

tests for RCD2 (3,4), whereas flow cytometry<br />

to identify individual IELs isolated from fresh<br />

intestinal biopsies is definitive (figure 1a).<br />

It is important to distinguish RCD1 from other<br />

causes of non-responsive coeliac disease<br />

and from RCD2 as specific treatments exist<br />

– for instance, the use of topical steroids or<br />

azathioprine for RCD1 and cladribine and<br />

autologous stem cell transplantation for<br />

RCD2. In 2018, NHS England designated<br />

Sheffield and Cambridge as the two national<br />

centres in the first ever UK Rare Disease<br />

Collaborative network in order to refine<br />

diagnostic and therapeutic techniques, and<br />

to develop a national database in order to<br />

further the understanding of the conditions<br />

and facilitate trials of treatment (5,6). The<br />

ongoing development of flow cytometry of<br />

intra-epithelial lymphocytes in the network<br />

has unexpectedly also demonstrated the<br />

utility of this technique in the diagnosis of<br />

coeliac disease itself (7). A characteristic<br />

change in the IEL composition occurs<br />

following the development of coeliac disease<br />

(8) and remains regardless of normalization<br />

of duodenal histology and serological tests<br />

on institution of a gluten free diet. Hence IEL<br />

flow cytometry is the only existing accessible<br />

test capable of confirming or refuting the<br />

diagnosis of coeliac disease in a patient<br />

following a strict gluten free diet. Referrals<br />

to the national centres remain lower than the<br />

expected prevalence of RCD (6) and indicates<br />

ongoing failure to recognize the condition. The<br />

following case studies demonstrate the utility<br />

of referral to the specialist national centres.<br />

Coeliac UK<br />

have developed<br />

resources on<br />

refractory and<br />

non-responsive<br />

coeliac disease<br />

to support<br />

you and your<br />

patients, scan<br />

the QR code to<br />

find out more.<br />

Case 1. Misdiagnosis of coeliac disease.<br />

A 20-year old woman contacted Coeliac UK<br />

for advice. Following a period of chronic<br />

fatigue she presented to her GP who found a<br />

very high anti-TTG antibody titre in her serum.<br />

Indirect immunofluorescence was negative for<br />

anti-endomysial antibodies. Following referral<br />

to her local gastroenterologist she underwent<br />

a gastroscopy and duodenal biopsies which<br />

were reported as showing equivocal features<br />

but consistent with coeliac disease. She<br />

was commenced on a gluten free diet which<br />

marginally improved her symptoms, however<br />

on follow up her anti-TTG titres remained<br />

high and she was repeatedly told by her<br />

hospital team that this meant that she was<br />

continuing to ingest gluten, which was a cause<br />

of significant anxiety for her and contributed<br />

to her fatigue. The patient was advised to<br />

request a second opinion from a tertiary<br />

centre. Further blood tests at the national<br />

centre revealed a negative anti-TTG titre<br />

and non-compatible HLA (human leucocyte<br />

antigen) haplotype for coeliac disease (9).<br />

Duodenal biopsies were reported as showing<br />

mild peptic duodenitis and flow cytometry<br />

revealed no evidence of coeliac disease (fig<br />

1a). Following reassurance that she did not<br />

have coeliac disease she was able to tolerate<br />

a normal diet without symptoms. This case<br />

demonstrates the variability of anti-TTG assays<br />

between laboratories, and the potential flaws<br />

of current diagnostic techniques.<br />

Case 2. Delayed diagnosis of RCD2.<br />

A previously fit and well 56-year old man<br />

presented via his GP to the local hospital<br />

following a business trip to the tropics with<br />

diarrhoea. A strong family history of coeliac<br />

disease was elicited, and duodenal biopsies<br />

at gastroscopy demonstrated sub-total villous<br />

atrophy, however anti-TTG antibodies were<br />

negative. He was therefore considered not<br />

to have coeliac disease and was treated<br />

empirically for tropical parasitic infections.<br />

However, his symptoms progressed and 12<br />

months later he was reinvestigated and found<br />

to have ongoing severe villous atrophy in the<br />

duodenum with thickening of the distal jejunum<br />

on magnetic resonance enterography. He was<br />

referred to one of the national tertiary centres<br />

for enteroscopy and biopsy of the thickened<br />

jejunum in order to make a diagnosis. An<br />

experienced clinician considered the possibility<br />

of RCD2 and lymphoma and instead carried<br />

out a gastroscopy and duodenal biopsy with<br />

flow cytometry the day after receiving the<br />

referral. The flow cytometry demonstrated<br />

a large population of atypical IELs lacking<br />

surface CD3 (fig 1b) in keeping with RCD2<br />

and a presumptive diagnosis of enteropathy<br />

associated lymphoma was made. Within<br />

3 weeks of referral he was admitted for<br />

establishment of home parenteral nutrition<br />

and underwent laparotomy and resection<br />

of the tumour, which was confirmed as a T<br />

cell lymphoma. He subsequently underwent<br />

CHOP chemotherapy and autologous<br />

haematopoeitic stem cell transplant. In his<br />

case earlier consideration of the diagnosis of<br />

RCD and referral to a national centre could<br />

have led to preventative treatment prior to<br />

developing lymphoma.<br />

Case 3. Overdiagnosis and overtreatment.<br />

A 37-year old woman presented to her GP<br />

in 2013 with diarrhoea and weight loss. A<br />

positive anti-tissue transglutaminase (TTG)<br />

antibody titre led to referral to the local<br />

gastroenterologist and a diagnosis was<br />

confirmed by the presence of sub-total<br />

villous atrophy on duodenal biopsy. She<br />

was commenced on a gluten free diet.<br />

However, in 2016 the presence of ongoing<br />

symptoms led to a repeat endoscopy which<br />

demonstrated persistent villous atrophy in<br />

the duodenal biopsies. She was told by her<br />

local gastroenterologist that she had refractory<br />

coeliac disease and that she needed to start<br />

on steroids and azathioprine as she was<br />

otherwise at risk of developing lymphoma. At<br />

this stage she sought a referral for a second<br />


NEWS<br />

Figure 1a Figure 1b Figure 1c<br />

opinion through one of the national tertiary<br />

centres. An experienced clinician elicited a<br />

history of a shared kitchen with potential for<br />

gluten contamination during food preparation,<br />

and that the patient was consuming foods<br />

that were labelled as ‘may contain traces of<br />

gluten’. It was recommended that she did<br />

not start steroids or azathioprine but made<br />

the necessary changes to her lifestyle and<br />

attend for a repeat duodenal biopsy after a<br />

further 9 months. At endoscopy the patient<br />

reported complete resolution of her symptoms,<br />

biopsies were reported as entirely normal<br />

while flow cytometry confirmed the underlying<br />

diagnosis of coeliac disease (figure 1c). She<br />

therefore avoided potentially harmful treatment,<br />

considerable health anxiety and achieved rapid<br />

resolution of her condition following referral.<br />

Notably the referral came from herself via her<br />

GP, not the local gastroenterologist.<br />

Figure 1. Typical duodenal IEL flow cytometry<br />

plots for a non-coeliac individual (a), a<br />

patient with RCD2 (b), and a patient with<br />

coeliac disease (c). Each dot on the plot<br />

represents a separate cell, immunostained<br />

for surface CD3 (y-axis) and cytoplasmic CD3<br />

(x-axis). In addition, CD3+ T cells bearing the<br />

gamma-delta type of TCR are in dark blue,<br />

those with the alpha-beta TCR are in light<br />

blue. Clearly defined population of IELs are<br />

apparent based on the lack of expression of<br />

CD3 (green), the expression of surface and<br />

cytoplasmic CD3 (light and dark blue), or just<br />

cytoplasmic CD3 (orange). Note that RCD1 is<br />

not distinguishable from coeliac disease using<br />

any available diagnostic tests (including flow<br />

cytometry) (reference 2), whereas populations<br />

of CD3+ and gamma delta TCR positive<br />

cells are clearly increased in coeliac disease<br />

compared to normal.<br />

References<br />

1. Rubio-Tapia A, Murray JA. Classification<br />

and management of refractory coeliac<br />

disease. Gut 2010 Apr;59(4):547-57.<br />

2. Nijeboer P, van Wanrooij, van Gils T, et<br />

al. Lymphoma development and survival<br />

in refractory coeliac disease type II:<br />

histological response as a prognostic<br />

factor. United European Gastroenterol J<br />

2017; 5(2): 208-217<br />

3. Woodward JM. Improving outcomes of<br />

refractory Celiac Disease: current and<br />

emerging treatment strategies. Clinical<br />

and Experimental <strong>Gastroenterology</strong> 2016;<br />

9: 225-236<br />

4. Liu H, Brais R, Lavergne-Slove A, et al.<br />

Continual monitoring of intraepithelial<br />

lymphocyte immunophenotype and clonality<br />

is more important than snapshot analysis<br />

in the surveillance of refractory coeliac<br />

disease. Gut. 2010 Apr;59(4):452-60.<br />

5. https://www.coeliac.org.uk/about-us/<br />

media-centre/news/first-rare-diseasecollaborative-network-on-refractorycoeliac/<br />

6. Baggus E, Urwin H, Watson S, Woodward<br />

JM, Sanders DS. How to manage<br />

adult coeliac disease: The perspective<br />

from the NHS England Rare Diseases<br />

Collaborative Network for Non-Responsive<br />

and Refractory Coeliac Disease. Frontline<br />

Gastroenterol. 2019 Aug 8;11(3):235-242<br />

7. Basu K, Creasey H, Bruggemann N,<br />

Stevens J, Bloxham DM, Woodward<br />

JM. The diagnosis of coeliac disease<br />

by flow cytometry of intraepithelial<br />

lymphocytes – a new ‘gold standard’?<br />

Frontline <strong>Gastroenterology</strong> 2021 epub<br />

ahead of print http://dx.doi.org/10.1136/<br />

flgastro-2021-101838<br />

8. Mayassi T, Ladell K, Gudjonson H, et<br />

al. Chronic inflammation permanently<br />

reshapes tissue-resident immunity in celiac<br />

disease. Cell 2019;176:967–81.<br />

9. Abadie V, Sollid LM, Barreiro LB, et al.<br />

Integration of genetic and immunological<br />

insights into a model of celiac disease<br />

pathogenesis. Annu Rev Immunol.<br />

2011;29:493-525<br />

1<br />

NHS Refractory Coeliac Disease Rare<br />

Disease Collaborative Network<br />

Box 133<br />

Addenbrooke’s Hospital<br />

Hills Road<br />

Cambridge CB2 0QQ<br />

01223-596231<br />

(jeremy.woodward@nhs.net)<br />

*Corresponding author<br />

2<br />

Coeliac UK<br />

Apollo Centre,<br />

Desborough Road<br />

High Wycombe<br />

HP11 2QW<br />

3<br />

NHS Refractory Coeliac Disease Rare<br />

Disease Collaborative Network<br />

Academic unit of gastroenterology,<br />

Royal Hallamshire Hospital,<br />

Sheffield S10 2JF<br />

(david.sanders1@nhs.net)<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />


NEWS<br />

Mother thanks doctors for<br />

saving her and unborn baby<br />

A Herefordshire mother has thanked<br />

clinicians at University Hospitals of North<br />

Midlands NHS Trust (UHNM) for life-saving<br />

treatment she received.<br />

Pregnant Lucy Rossiter was initially thought<br />

to have irritable bowel syndrome (IBS) after<br />

suffering for months with stomach pain, but<br />

doctors in Hereford later found she had a bile<br />

duct infection which posed a serious risk to her<br />

and her baby.<br />

“My doctors contacted Royal Stoke University<br />

Hospital in Stoke-on-Trent and the entire<br />

endoscopy team got together and agreed<br />

that the necessary procedure could be carried<br />

out at Stoke and would be scheduled for the<br />

following morning.<br />

“When I arrived at Stoke I was in terrible pain<br />

and almost unable to stand, let alone walk.<br />

I would have given anything to stop the pain<br />

and make me feel better.<br />

“I found the endoscopy team ready and<br />

waiting for me at Royal Stoke. Everybody I<br />

came into contact with was aware of who I<br />

was and exactly why I was there.<br />

The team were able to remove the bile duct<br />

stone which was causing Lucy’s infection and<br />

affecting her liver function.<br />

Dr Hebbar said: “Lucy’s was an extremely<br />

complicated case, made more challenging<br />

by the fact that she was pregnant. The<br />

endoscopic procedure to remove the stone<br />

in the bile duct involves using X-ray to assess<br />

the location of the stone and understand<br />

the anatomy. In a pregnant lady in her first<br />

trimester, the radiation is a significant risk to<br />

the baby. An additional risk of this particular<br />

procedure is pancreatitis - especially so<br />

in young women - because the bile duct<br />

and pancreas are close to each other. This<br />

complication can be serious and even fatal.<br />

34-year-old Lucy, a primary school teacher<br />

from Kingsland in Herefordshire, was seven<br />

weeks’ pregnant when her condition began to<br />

rapidly deteriorate.<br />

“When I left after having my procedure,<br />

everybody was amazed that I could not only<br />

stand but also walk out of hospital, the pain was<br />

gone instantly. The change was just incredible<br />

“Unfortunately other trusts were unable to<br />

accept Lucy’s case because of the complexity<br />

involved, so we were contacted.<br />

Doctors at Hereford County Hospital scoured<br />

the country to find clinicians with the expert<br />

knowledge needed to treat the mother-of-two.<br />

UHNM’s endoscopy team were contacted<br />

and made such a difference to my condition, it<br />

was as if someone had turned a tap off. William<br />

commented that it was like a different person<br />

who walked out of Royal Stoke.<br />

“When I was ill I was having flare-ups a good<br />

“If we had not done the procedure, there was<br />

clearly a significant risk to Lucy because of<br />

the infection but at the same time, we did not<br />

want to put the baby at any risk because of the<br />

procedure.”<br />

and Lucy was taken to Royal Stoke University<br />

Hospital for care.<br />

Lucy said: “I started to experience abdominal<br />

pains in early May 2020. My GP suspected I<br />

had IBS but over time various remedies proved<br />

to be ineffective and the flare-ups increased<br />

few times a week, so trying to look after my<br />

daughter Poppy was really hard. Now I have a<br />

controlled diet but I can live more normally.<br />

“I need to have my gall bladder removed and<br />

might have to always be a bit more restricted in<br />

what I eat, but I feel I will be able to manage it.<br />

The team performed an endoscopic<br />

ultrasound, which helps to identify internal<br />

structures and can assess the pancreas and<br />

bile duct in detail. Using this, they were able<br />

to identify the location and size of the bile duct<br />

stone and successfully remove it.<br />

in intensity and frequency and on a number of<br />

occasions I had to go to hospital.<br />

“I had been living with these symptoms for about<br />

12 months and during this time I discovered I<br />

“Dr Hebbar and his team at Royal Stoke<br />

were incredible. The care that I had, their<br />

professionalism, just everything. I cannot thank<br />

them enough.<br />

Dr Hebbar continued: “As it turned out, we<br />

did not need to use any x-ray in the end, so<br />

the procedure was completed and the stone<br />

removed with no risk to the baby.<br />

GASTROENTEROLOGY TODAY - SPRING <strong>2022</strong><br />

was pregnant with my second child, Thomas.<br />

“In April 2021 me and my partner William<br />

became very worried. Not only did my<br />

symptoms continue to get worse but I now<br />

also had our unborn baby to worry about.<br />

“Events finally came to a head one night when<br />

I was in severe pain, vomiting and unable to<br />

stand. William called 111 and I was bluelighted<br />

to Hereford County Hospital. I then<br />

spent the next few days as an inpatient waiting<br />

for a diagnosis. It was horrible, I was desperate<br />

to get home so that I could see my daughter.<br />

“Eventually I was able to get home but my liver<br />

function continued to get worse and I was<br />

back in hospital in May, where my condition<br />

deteriorated rapidly.<br />

“Now I can get back to a more normal life.<br />

We’re quite an active family and we like the<br />

outdoors, we like spending time at the coast,<br />

we spend quite a lot of time with our extended<br />

family. We’ve got holidays booked as well.<br />

When I was ill I couldn’t really enjoy them, so<br />

it’s nice to have something to look forward to.<br />

“I am very grateful to all the NHS for working<br />

together to help me.”<br />

Lucy lives with her partner William Wood, 37,<br />

and is mum to two-year-old daughter Poppy<br />

and new baby Thomas.<br />

Consultant gastroenterologist Dr Srisha<br />

Hebbar and his team cared for Lucy at Royal<br />

Stoke University Hospital.<br />

“Lucy was able to travel back to Hereford the<br />

same day and was discharged the next day.”<br />





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