Clinical Case Summary

Here we report the case of a 71-year-old man with alcohol-related gastric variceal bleeding (GVB) (50-year alcohol history, 150-200g/day) under management by endoscopic ultrasound (EUS) guided injection of coils, suggesting that the perforator embolization of intragastric varices would eventually complete obstruction of intraluminal gastric varices, leading to the era of the precision treatment of GVB.

Gastric varices are usually accompanied by porta-systemic collaterals¹. Isolated type 1 gastric varices, located in the fundus of the stomach, are a type of cardiofundal varices². Endoscopic injection of tissue adhesive (N-butyl-cyanoacrylate, CYA) is the first-line treatment, but is technically difficult with a high risk of ectopic embolization. Here we report a novel technique: EUS combined with computed tomographic angiography (CTA)-guided embolization of transmucosal cardiofundal varices, which takes advantage of EUS guidance and CTA-based radiological reconstruction of the varices, allowing visualisation of the feeding vessel of intragastric varices, significantly reducing coil consumption.

The vessel reconstruction implicated large cardiofundal varices around the stomach of this patient. We identified one transmucosal branch, and then confirmed the targeted transmucosal perforator branch supplying the complex of intragastric varices. The target gastric varices were accessed with a 19G needle, coils and cyanoacrylate were inserted through the needle into the branch under EUS. After implantation, EUS showed complete embolization of intragastric luminal varices. The CTA of the portal venous after 2 months showed the elimination of the cardiofundal varices. Follow-up endoscopy showed the gastric varix complex diminished while the esophageal varices became obvious; therefore, further endoscopic esophageal variceal ligation was performed. The complete elimination of gastric and esophageal varices was obtained after two sessions of endoscopic treatment.

References

1. Pillai AK, Andring B, Patel A, Trimmer C, Kalva SP. Portal hypertension: a review of portosystemic collateral pathways and endovascular interventions. Clin Radiol. 2015;70(10):1047-59.
2. Aleem A, Shah H. Gastric Varices. StatPearls. Treasure Island (FL) ineligible companies. Copyright © 2024, StatPearls Publishing LLC.; 2024.

Introduction

Endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) is primarily used for biliary drainage in patients with malignant distal biliary obstruction. A recent meta-analysis reported a reintervention rate of 15.8% with EUS-CDS. However, studies analyzing the factors associated with reintervention on follow-up after EUS-CDS are limited.

Aims & Methods

The study aimed to analyze the incidence and predictors of reintervention in patients with malignant biliary obstruction undergoing EUS-CDS. The present study is a retrospective analysis of data from eight tertiary care centers in India from January 2022 to January 2024. Patients aged 18-70 years with malignant distal biliary obstruction undergoing EUS-CDS, with a follow-up duration of more than eight weeks, were included. The study's primary outcome was reintervention, which was required in patients with failure of jaundice to improve due to stent migration or stent blockage during the follow‑up, presenting as the worsening of jaundice, with or without cholangitis. The secondary outcomes included clinical success and adverse events. Multivariate analysis using the logistic regression model was used to identify the independent predictors of reintervention.

Results

A total of 140 patients underwent EUS-CDS, out of which 134 patients completed the 8-week follow-up. The median age of the patients was 54.5 (range: 22-90) years, with 53% (71/134) being male. The most common indication for EUS-CDS was inaccessible papilla (59/134, 44.0%), followed by failed cannulation (57/134, 42.5%). The technical success rate was 97.8% (131/134), with placement of self-expanding metal stent (SEMS) in 86.6% (116/134) and lumen-apposing metal stent in 11.2% (15/134). Coaxial double pigtail plastic stent was placed in 19.4% (26/134) cases. Periprocedural adverse events (AE) were seen in 6% (8/134) cases, with severe AE in 0.7% (1/134) cases. Clinical success was achieved in 93.9% (123/131) of the cases with successful stent placement. Over a median follow-up of 20 weeks, reintervention was required in 8.4% of the cases after a median interval of 11 weeks. All patients requiring reintervention could be managed successfully with endoscopic or percutaneous techniques. On multivariate analysis (Table 1), cholangitis at presentation [Odd ratio (OR) 6.26, 95% confidence interval (CI) 1.03-38.09; p =.046] and the absence of coaxial stent with concomitant duodenal stent (OR 7.41, 95% CI: 1.44-38.05; p=.016) were independent predictors of reintervention in the overall cohort. On subgroup analysis of patients undergoing EUS-CDS with SEMS, the absence of coaxial stent with concomitant duodenal stent (OR 10.15, 95% CI: 1.80-57.29; p=.009) was an independent predictor of reintervention.

Conclusion

Reintervention on follow-up after EUS-CDS is required in around 8.4% of cases, with all cases being managed successfully. The absence of coaxial stent with concomitant duodenal stent was an independent predictor of reintervention in the overall cohort as well as in those undergoing EUS-CDS with SEMS.

Clinical Case Summary

Eosinophilic gastroenteritis is a rare digestive inflammation that can affect one or more layers of gastrointestinal wall
The subserosal form is the most common variety.
We report here a case of eosinophilic ascites diagnosed in the hepato-gastro-enterology department
Here we report a case of a 45-year-old man, admitted to our department for generalized abdominal pain evolving for 2 years. On physical examination, he presented a minimal ascites. Laboratory examinations revealed hypereosinophilia at 2480/mm³ with a normal blood smear, total IgE elevated at 125 U/ml, C reactive protein, albumin, liver and kidney functions were normal. The standard stool test showed no parasites but contained 35% of eosinophils.
Prick test was positive to mites, cats, shrimps, almonds, and peanuts.
Abdominal CT revealed a minimal ascites with infiltration of mesenteric fat and diffuse thickening bowel wall.
The gastroscopy and colonoscopy showed erythema in duodenum and recto-colic mucosa, an eosinophilic infiltration at 20 per HPF was found only at the colonic wall.
The laparoscopy found an inflammation of the bowel and peritoneum without visualization of nodules, the ascites was exudative and rich in eosinophils, the peritoneal biopsy didn’t show any specific fibro-inflammatory remodeling.
An Albendazole trial was instituted for 5 days at a dose of 400mg per day. The evolution was marked by the regression of abdominal pain and blood eosinophilic polynuclear cells decreased to 21/ mm³.
An ultrasound is planned after 3 months to affirm the ascites draying up.

Introduction

The immune regulatory proteins, such as cytotoxic T lymphocyte antigen (CTLA)-4 as well as programmed death (PD)−1 and its ligand PD-L1 are important immune regulatory proteins collectively referred to as immune checkpoint receptors. These pathways can be used by malignant tumors as a mechanism to avert antitumoral immune responses.
Immune checkpoint inhibitors (ICIs) target these immune checkpoint receptors. ICIs have demonstrated impressive clinical activity and are now approved for the treatment of diverse malignant neoplasms. However, inhibition of these regulatory receptors leads to loss of tolerance and a wide spectrum of inflammatory toxicities known as immune-related adverse events (ir-AEs). Colitis or enterocolitis are the most frequent GI irAEs, affecting 15%–20% of patients who undergo endoscopic evaluation. When severe, irAEs can necessitate ICI therapy interruption, discontinuation, and treatment escalation with powerful immunosuppressive agents.
Isolated ICI-associated duodenitis has been reported after treatment with different immunotherapies.
Interestingly, de novo celiac disease (CeD) specific antibodies (serum tTG antibodies) with
histological features consistent with CeD in the setting of treatment with ICIs have been reported.

Aims & Methods

A literature search in Pubmed and Scopus to identify original reports in which CeD was documented histologically in patients treated with ICIs. Clinical, endoscopic and histopathological and immunological background were reviewed.

Results

Eleven papers were identified, all case reports or case series. A total of 26 pts were described. Twelve patients had a serologic and histological diagnosis of CeD.
CeD has been rarely observed during treatment with ICIs and is morphologically similar to ICI-CeD
enteropathy. Endoscopically, duodenal congestion, nodularity, or erythema were seen in 67% of patients with ICI-duodenitis, compared with 33% of patients with ICI-CeD. Few patients had concomitant upper and lower GI tract mucosal inflammatory changes.
Correlation with medication history, the finding of typical histologic changes, and re-evaluation of pathologic changes after checkpoint receptor inhibitor therapy will help confirm if an injury is likely to be an irAE.
Patients with ICI-CeD were reported to improve on a gluten free diet (GFD) as the single therapy, while some patients required the addition of immunosuppression with variable improvement in symptoms.

Conclusion

Whether ICI-associated celiac disease (ICI-CeD) reflects new onset gluten sensitivity or unmasking of previously asymptomatic CeD remains to be answered.
There is some evidence that ICI-CeD is biologically similar to ICI-duodenitis, but treatment strategies differ. ICI-CeD often improves with GFD alone, whereas ICI-duodenitis may require systemic immunosuppression.
In patients with atypical digestive symptoms in the context of ICI treatment, there is a necessity of complementary/additional investigation. Celiac disease specific antibodies (tTG-IgA assay) and duodenal biopsy are required. In the case of morphological lesions resembling CeD, serological and genetic testing should be performed for differentiating true CeD from ICI-drug-induced villous atrophy.
It might be useful to check for CeD before scheduled ICI therapy in patients with known high susceptibility to CeD, such as a family history of CeD, dermatitis herpetiformis, or chronic unexplained bowel symptoms.

Introduction

Recently, sub-classification of steatotic liver disease (SLD) has been updated by revising non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated steatotic liver disease (MASLD). In this new nomenclature, emphasis was on the etiology of SLD, primarily at factors of metabolic syndrome and alcohol intake. However, associations between MASLD and gastrointestinal tract cancers other than liver cancer in relation to alcohol intake still require further analysis.

Aims & Methods

We investigated the relationship between the incidence of three gastrointestinal tract cancers (esophageal, stomach, and colorectal) and MASLD or alcohol related-SLD in diabetic patients. Using a retrospective screening cohort of National Health Insurance Service, individuals with type 2 diabetes from 2009 to 2012 were enrolled with their disease status being monitored until 2021. Fatty liver index (FLI) score described by Bedogni et al. (2006) was used to stratify the probability of hepatic steatosis. No steatosis (NS), indeterminate steatosis (IS), and steatosis-probable (PS) group were defined as FLI score 0 to < 30, 30< to ≤60, and >60, respectively. SLD was assumed if FLI score ≥ 30, and MASLD was defined as having at least 1 adult criteria provided by the American Association for the Study of Liver Diseases (AASLD). 2,746,079 subjects were classified into following subgroups: group 1: no steatosis, group 2: MASLD alone, group 3: MASLD with other liver disease, group 4: MASLD with heavy alcohol intake (metALD, 30-60g/d for men and 20-50g/d for women), and group 5: alcoholic liver disease (alcohol intake ≥ 60g/d for men and ≥50g/d for women) with metabolic syndrome. Adjusted hazard ratios (aHR) for each gastrointestinal tract cancer were estimated by incorporating multivariate Cox proportional hazards model.

Results

Compared with group 1 (reference), group 2 showed increased risks of stomach and colorectal cancers (aHR [95% confidence interval (CI)]: 1.06 [1.04-1.09] and 1.17 [1.14-1.19] respectively), but a decreased risk of esophageal cancer (0.81 [0.74-0.88]). In all gastrointestinal tract cancers, the risk of developing cancer compared to group 1 tended to increase from group 3 to group 5 (aHRs in groups 3, 4, 5: 1.40, 1.74, 2.36 in esophageal cancer; 1.13, 1.20, 1.22 in stomach cancer; 1.24, 1.33, 1.34 in colorectal cancer, respectively; all p for trend < 0.0001). Subgroup analysis by probability of steatosis in non-drinkers showed that stomach and colorectal cancer risk was positively correlated with higher likelihood of liver steatosis (aHR for NS, IS, PS: 1.00, 1.05, 1.11 for stomach cancer and 1.00, 1.15, 1.27 for colorectal cancer, respectively, p for trend < 0.05). However, this correlation was not demonstrated in esophageal cancer (aHR for NS, IS, PS:1.00, 0.95, 1.08 for esophageal cancer).

Conclusion

In patients with diabetes, MASLD itself is associated with an increased risk of stomach and colorectal cancers but is likely associated with a reduced risk of esophageal cancer. Hepatic steatosis may be associated with higher risk of stomach and colorectal cancers, but not esophageal cancer. Amount of alcohol consumption is confirmed to increase the risk of these cancers regardless of the presence of SLD.

References

1. Rinella, Mary E. "Examining the Nomenclature Change From NAFLD and NASH to MASLD and MASH." Gastroenterology & Hepatology 19.11 (2023): 697.
2. Bedogni, Giorgio, et al. "The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population." BMC gastroenterology 6 (2006): 1-7.
3. Dabo, Bashir, et al. "The association between diabetes and gastric cancer: results from the Stomach Cancer Pooling Project Consortium." European Journal of Cancer Prevention 31.3 (2022): 260-269.
4. Lee, Hokyou, et al. "Metabolic Dysfunction–Associated Fatty Liver Disease Increases Colon Cancer Risk: A Nationwide Cohort Study." Clinical and translational gastroenterology 13.1 (2022): e00435.

Introduction

Patients with Hypermobile Ehlers Danlos Syndrome (hEDS) have a high prevalence of Disorders of Gut-Brain Interaction (DGBI) and pose complex nutritional challenges in gastroenterology clinic. Despite this, little is known regarding nutrient intake and adequacy in hEDS.

Aims & Methods

Our aim was to assess nutrient intake and adequacy of patients with hEDS, as well as to determine which factors, including co-existent DGBI, are associated with poor intake. We conducted a cross sectional survey of patients with hEDS from two tertiary neurogastroenterology clinics as well as the Ehlers-Danlos Support UK. Inclusion criteria were adults with hEDS, exclusion criteria were those currently or previously using artificial nutrition. Patients completed the validated semi-quantitative Scottish Collaboration Group Food Frequency Questionnaire (FFQ) alongside questionnaires characterising: demographics, DGBIs (Rome IV), gastrointestinal, mood, somatic and autonomic symptoms, past history of eating disorders and screen for Avoidant Restrictive Food Intake Disorder (ARFID) using the Nine Item Avoidant-Restrictive Scale (NIAS). Nutrient intake was calculated from the FFQ and nutrient adequacy was calculated by comparison with UK daily reference values (DRVs) for age and sex. Unpaired t-tests were performed to compare nutrient intakes among patients with and without comorbidities, including the most common DGBIs.

Results

425 participants were included in the final analysis (mean: 41 years, 96% female). Only 48.5% reported BMI in the normal range, whereas 5.2% were underweight (BMI <18.5 kg/m²)and46.4% were overweight/obese (BMI >25 kg/m²). Only one third met their estimated average requirements (EAR) for energy (kcal/d). The majority met their reference nutrient intake (RNI) for protein (87.3%) and fat (72.5%), in contrast to only 21.2% for carbohydrate. Fibre intakes were very low (AOAC mean 23.7g/day (SD: 12.7) with only 24.7% meeting the RNI of 30 g/d. More than 58% of participants met/exceeded their DRV for micronutrients (zinc, magnesium, copper, manganese and selenium) and >95% for vitamins. Patients with functional nausea (n=157) were less likely to meet their protein requirements compared to those without (82.2% vs. 90.3%, p=0.015) and also had lower intakes for sodium (p=0.02), magnesium (p=0.02), calcium (p=0.01), zinc (p=0.002), selenium (p=0.03), folic acid (p=0.02) and vitamin C (p=0.05). Patients with previous eating disorders were less likely to meet nutrient requirements for thiamine (p=0.01) and vitamin B12 (p=0.04). Patients with ARFID (n=110) were less likely to meet requirements for all nutrients (except fat, calcium, vitamin D, vitamin B12) compared to patients without.

Conclusion

Patients with hEDS are rarely underweight and tend to consume high protein, high fat diets that are low in fibre. Functional nausea is the single most important DGBI impacting nutrient intake, as well as previous eating disorders and disordered eating (ARFID). These factors should be considered by clinicians and dietitians when assessing nutrient intake in this complex patient group.

Disclosure

RT, AF and QA have received a grant from EDS-UK to conduct this study. AF undergoes consulting work for Abbvie.
KW has received research funding from Almond Board of California, Danone, International Nut & Dried Fruit Council, and has a patent for volatile organic compounds in the detection and management of IBS.
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.