Clinical Case Summary

Introduction: Despite advantages in diagnostic procedures and treatment possibilities, recurrent obscure gastrointestinal (GI) bleeding remains a clinical challenge in up to 5% of all patients presenting with GI bleeding. Challenge is even more significant in complex patients with comorbidities limiting more aggressive therapeutic approach.
Case: We present a case of 54-year-old male patient with obscure GI bleeding. He has a history of alcoholic chronic pancreatitis with cystic lesion in pancreatic head and subocclusive stenosis of portal vein (PV) causing prehepatic portal hypertension. In December 2021, he underwent a surgery in which hepaticojejunal anastomosis was performed due to obstructive jaundice caused by compression of main bile duct by enlarged pancreatic head.
From September 2022 to December 2022 he was hospitalized repeatedly for melena and severe symptomatic anemia. Extensive workup was performed (4 esophagogastroduodenoscopies, 2 colonoscopies, small bowel capsule endoscopy and computorized tomography (CT) angiography of mesenteric vessels) founding no apparent cause of bleeding. CT scan revealed significant PV stenosis with distal esophageal, gastric, main bile duct and duodenal varices.
Patient was thoroughly discussed and since PV occlusion with developed venous collaterals was the only apparent possible cause of bleeding we could intervene on we decided to perform PV stenting. After diagnostic angiography confirming the stenosis a patient underwent percutaneous transhepatic PV stent placement using self-expanding nitinol stent (60 mm length, 12 mm diameter). After the procedure anticoagulant therapy was initiated. Patient has been monthly clinically checked and stent patency has been assessed using colour Doppler ultrasonography. He has been stable for the last 4 months with no signs of bleeding.
Conclusion: Portal vein stenting can be considered as an option in treating patients with obscure GI bleeding and confirmation of portal vein stenosis.

References

Image 1. CT image of portal vein stenosis and developed venous collaterals
Image 2. CT image after stent placement showing disappearance of blood flow in collaterals

Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with substantial impact on quality of life, and increasing incidence and prevalence. Dupilumab, a fully human monoclonal antibody, blocks IL-4 and IL-13, central drivers of type 2 inflammation, and is approved in the US and EU for the treatment of EoE.

Aims & Methods

We aimed to assess the effect of dupilumab on EoE outcomes in subgroups of patients from the Phase 3 LIBERTY EoE TREET (NCT03633617) study categorized by weight or body mass index (BMI).
Data were pooled from patients in Parts A and B who received dupilumab 300 mg or placebo qw (weekly) for 24 weeks (W24). The proportion of patients achieving ≤6 or <15 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score (EREFS), and Histologic Scoring System (HSS) grade/stage scores were assessed. Outcomes were compared between pre-specified weight (<60kg and ≥60kg) and BMI groups (<25kg/m², ≥25–<30kg/m², and ≥30kg/m²). As this is a post hoc analysis, all p-values are nominal.

Results

122 patients received dupilumab and 118 placebo. At baseline, subgroups comprised: Weight <60kg (N=51) and ≥60kg (N=189); BMI <25kg/m² (N=121), ≥25–<30kg/m² (N=73), and ≥30kg/m² (N=46). Baseline demographics and disease characteristics were generally similar across subgroups. Dupilumab was efficacious regardless of baseline weight. At W24 dupilumab treatment resulted in a greater proportion of patients achieving ≤6 eos/hpf compared with placebo (weight <60kg 47% vs 5%, p=0.0031, ≥60kg 63% vs 6%, p<0.0001), and improved DSQ score (LS mean difference [LSMD] [95% CI]: weight <60kg –8.74 [–18.77, 1.30], p=0.0878, ≥60kg –10.36 [–14.57, –6.15], p<0.0001). Dupilumab-treated patients improved at W24 vs placebo in EREFS total score (LSMD [95% CI]: –2.47 [–3.89, –1.06], p=0.0006, –3.66 [–4.50, –2.81], p<0.0001), and HSS mean grade (–0.608 [–0.837, –0.380], p<0.0001, –0.737 [–0.839, –0.636], p<0.0001) and stage scores (–0.588 [–0.811, –0.365], p<0.0001, –0.730 [–0.826, –0.633], p<0.0001). Furthermore, dupilumab treatment resulted in a greater proportion of patients achieving <15 eos/hpf compared with placebo (weight <60kg 70% vs 10%, p=0.0006, ≥60kg 78% vs 7%, p<0.0001). Similar results were observed across BMI subgroups (Table).

Table: EoE endpoints in patients categorized by weight or BMI at Week 24

Conclusion

Patients with EoE improved in measures of histology, symptoms, and endoscopy, including an increased proportion achieving peak esophageal intraepithelial eosinophil count ≤6 and <15, along with reductions in DSQ score, HSS grade and stage scores, and EREFS total score at W24 with dupilumab 300 mg qw vs placebo regardless of baseline weight or BMI. Dupilumab was well tolerated, and the safety profile was similar to the overall treatment population.

Disclosure

Hirano I: Allakos, Pfizer/Arena Pharmaceuticals, Aslan, AstraZeneca, Calyx/Parexel, Ellodi/Adare Pharma Solutions, EsoCap, Gossamer Bio, Phathom, Nexstone Immunology, Receptos/BMS, Sanofi/Regeneron Pharmaceuticals Inc., Shire/Takeda – consultant; Adare Pharma Solution, Allakos, AstraZeneca, Pfizer/Arena, Meritage Pharma, Receptos/BMS, Regeneron Pharmaceuticals Inc., Shire/Takeda – research funding; Sanofi/Regeneron Pharmaceuticals Inc. – speaking.
Chehade M: Adare Pharma Solutions, Allakos, AstraZeneca, BMS, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda – consultant; Adare Pharma Solutions/Ellodi Pharmaceuticals, Allakos, AstraZeneca, Danone, Regeneron Pharmaceuticals Inc., Shire/Takeda – research funding.
Dellon ES: Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron Pharmaceuticals Inc., Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio– consultant; Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron Pharmaceuticals Inc., Revolo, Shire/Takeda – research funding; Allakos, Holoclara, Invea– educational grant.
Schoepfer AM: Adare Pharma Solutions, Aptalis, Dr. Falk – consultant; AstraZeneca, Aptalis, Dr. Falk, GSK, Nestlé, Novartis, Receptos/BMS, Regeneron Pharmaceuticals Inc. – research funding.
Xia C, Shabbir A: Regeneron Pharmaceuticals Inc. – employees and shareholders.
Glotfelty L: Sanofi – employees, may hold stock and/or stock options in the company.

Introduction

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal and extra-intestinal cancers. Specific therapies used to control inflammation in IBD may have a different impact on cancer risk. However, there are no long-term studies investigating cancer risk in patients with IBD.

Aims & Methods

In the present study we aimed to quantify the overall risk for of developing cancer and to identify specific risk factors for the occurrence of intestinal and extra-intestinal cancers in 560 consecutive patients with Crohn's disease (CD, N=310) or ulcerative colitis (UC, N=250) referred to our outpatient department between January 2021 and February 2022. Demographic data, smoking status, alcohol consumption, age at IBD diagnosis, disease location and course, therapies, and cancer development after IBD diagnosis were recorded. Odds ratios (OR) were estimated by logistic regression analysis. Standardized Incidence Ratios (SIRs) were estimated compared with the general population.

Results

During a median follow-up interval or time of 10 years (range 1-26 years), 6.6% of patients (37/550, female 65 %, mean age 51 years) developed cancer (SIR 1.94, 95%CI 1.4-2.6). The most common cancers were colorectal (12.3%), skin (8.2%), and breast cancer (7.2%). Female patients had an increased risk for all cancers (SIR 3.11, 95%CI 2.06-4.3), melanoma (SIR 5.6, 95%CI 1.14-16.2) and colorectal cancer (SIR 7.59, 95%CI 3-15.4). Male patients had an increased risk of lymphoma (SIR 26.15, 95%CI 3.2-95.7). Younger age at diagnosis of CD (A1 Montreal classification, OR 37.9, 95%CI 10-14), immunosuppressive monotherapy (OR 5.5, 95%CI 2.65- 11) or in combination with anti-TNFα (OR 9.9, 95%CI 3.3-29.09) were associated with an increased risk of cancer in the study population.

Conclusion

We have identified subgroups of IBD patients who would particularly benefit from screening programs. Our findings need to be validated in independent cohorts.

Introduction

Cholecystectomy (CCE) is commonly performed for treatment of gallstone disease. However, CCE may result in post-CCE syndrome (PCS) and diarrhea (PCD) in a subgroup of patients. In addition, epidemiological association of CCE with colorectal cancer (CRC) and metabolic-associated fatty liver disease (MAFLD) has raised concerns. CCE is expected to affect the enterohepatic circulation and result in gut microbiome changes. Such changes may account for clinical symptoms and risk for CRC and MAFLD. However, the spectrum and type of gut microbiome changes post-CCE has not been fully quantified and results have been inconsistent.

Aims & Methods

This systematic review aimed to clarify the effect of CCE on gut microbiome composition and the clinical impact. A systematic search was conducted on PubMed, Web of Science and Scopus in March 2024, combining keywords such as “cholecystectomy” or “post-cholecystectomy” with “gut microbiome” or “gut dysbiosis”. Reference and citation searches were conducted on included articles. Original articles irrespective of study design that described gut microbiome changes post-CCE were included. Articles were independently reviewed by two authors and data were extracted and synthesized using narrative review. The quality of studies was assessed using the Newcastle-Ottawa scale.

Results

A total of 1373 articles (after excluding duplicates) were initially selected, and after review of the titles and abstracts, 14 eligible studies were identified and the full text reviewed. There were 3 prospective cohort and 11 cross-sectional/ case control cohort studies, of which 13 examined the bacteria microbiome using 16S rRNA gene sequencing, and 1 cross-sectional study examined the fungal microbiome using ITS1 rDNA gene sequencing. Changes in microbiome diversity indices and relative abundances were inconsistent. Among 3 prospective cohort studies, an increase in phylum Bacteroidetes was observed in a study with post-CCE interval more than 3 months, but not in the study with 3-month post-CCE interval. One study reported no change at the phylum level, but an effect for the class Clostridia and the orders Clostridiales and Coriobacteriales within 3 days of CCE. An increase in phylum Bacteroidetes post-CCE was also seen in 3 other cross-sectional studies. Five studies attempted to correlate post-CCE microbiome changes with symptoms. A decreased Firmicutes/ Bacteroidetes (F/B) ratio was observed in patients with PCS/ PCD in 3 out of 5 studies. Although changes in relative abundances of taxa correlated with symptoms, these were inconsistent, with an increase in genus Prevotella being the only common finding in 2 out of these 5 studies. Other significant observations post-CCE included a decrease of the potentially beneficial genus Faecalibacterium and an increase in the opportunistic pathogen Escherichia/Shigella, as well as an attenuated aging-associated intestinal microbiota. The single cross-sectional study that examined post-CCE fungal microbiome changes found that the relative abundance of Candida glabrata and Aspergillus were enriched, and Candida albicans was depleted.

Conclusion

CCE is associated with significant changes in gut microbiome diversity and relative abundances of taxa. Such changes have been correlated with clinical symptoms. These microbiome changes may potentially explain the risk of CRC and MAFLD noted in epidemiological studies. Discordant results between studies may relate to differences in patient populations and study methodologies.

Introduction

High-resolution manometry (HRM) is routinely performed in an outpatient clinic setting. If intubation is not tolerated or if the LOS is not traversed, the test is often abandoned with no viable alternative option, thus impacting on therapeutic decisions. This study explores the option of intubating the catheter during endoscopy under the comfort of sedation and direct vision.

Aims & Methods

All patients who had HRM catheter insertion during endoscopy at a tertiary referral centre in London between Jan 2020 and April 2023 were collated and analysed. A consecutive equivalent number of standard unsedated HRM studies, as well as patients having standard diagnostic endoscopy at the same centre between Nov and Dec 2022 were included for comparison. Demographic data, symptom presentation, endoscopic technique and manometry diagnosis were analysed. All HRM studies attempted a full protocol of single water swallows and rice meal, undertaken only after confirmation that sedation had abated. The median integrated relaxation pressure (IRP) of single water swallows was used to categorise patients into those with and without a disorder of outflow. Oesophageal body function was defined according to the Chicago Classification of motility disorders¹.

Results

Of the 47 patients (68.1% F; 17-86 yrs) who were referred for endoscopic insertion (EI) of the HRM catheter, 42 (89.3%) were successfully intubated to the stomach. Of those, 33 (78.6%) were observed to pass through the pharynx and LOS with the endoscope, 4 (9.5%) required manual guidance through the oesophagus and LOS, whilst 5 (11.9%) required only observation of catheter passage through the pharynx. Overall, 41 (87.2%) patients completed the full swallow protocol. Indications for referral for EI included intolerance to standard insertion through the nares (52.4%), inability to breach the LOS resulting in a curled catheter (26.2%) and other reasons including septal deviation and psychiatric burden (21.4%). Similarly, of the contemporaneous 47 patients who had standard insertion (SI) of the HRM catheter in the outpatient setting (67.3% F, 23-80 yrs), 39 (82.9%) were successfully intubated and 33 (67.3%) completed the full swallow protocol. Symptoms were reproduced during the test protocol in both cohorts similarly (69.0% EI, n=42; 59.0% SI, n=39). EI patients required higher doses of sedation compared to a consecutive cohort of patients who attended for routine diagnostic endoscopy; mean Fentanyl 112.5µg (n=36) vs 78.7µg (n=47) p<.001, and Midazolam 4.9mg vs 3.4mg p<.001, respectively. The IRP was not significantly different between EI and SI regardless of LOS morphology; mean IRP in patients with no LOS outflow disorder (8.01mmHg, n=28 vs 6.05mmHg, n=35; p=.08), compared to those with an outflow obstruction (28.0mmHg, n=12 vs 23.1mmHg, n=5; p=.35). Overall motility diagnoses between the two cohorts are presented in Table 1.

Table 1: Diagnoses for HRM

Conclusion

Inserting the HRM catheter during endoscopy under sedation and direct vision enables oesophageal physiology testing for patients who might not have otherwise been able to receive motility assessment. The procedure is safe, feasible and is associated with no complications or adverse risk to date. Just as wireless pH monitoring can be a salvage for those who are unable to tolerate the pH catheter, this technique can fill an important gap in the investigation algorithm where motility testing would have otherwise been abandoned.

References

¹Yadlapati, Rena et al. “Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0^©.” Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society vol. 33,1 (2021): e14058. doi:10.1111/nmo.14058

Introduction

Helicobacter pylori treatment´s effectiveness decreases as treatment eradication attempts fail.

Aims & Methods

To evaluate the use and effectiveness of empirical rescue therapies on third and subsequent lines in Europe.
Sub-study of the the European Registry on H. pylori Management (Hp-EuReg), an international, multicenter, prospective, non-interventionist registry starting in 2013 aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists (32 countries, 300 researchers). All infected adult patients were systematically registered at AEG-REDCap e-CRF until January 2023, all cases with three or more eradication attempts were extracted. Only the empirically prescribed therapies were analyzed. Data were subject to quality review.

Results

In total, 2,254 rescue treatments were included: 1,624, 424, 150 and 56 in third-, fourth-, fifth- and sixth-line treatments, respectively. Mean age was 52 years, 67% of patients were women and 5% were allergic to penicillin. Sixty-three different therapy regimens were used, being three-in-one single-capsule bismuth quadruple therapy the most commonly prescribed, as shown in the table. Overall effectiveness was 73% by modified intention-to-treat (mITT), and 74% by per-protocol (PP) analyses. Bismuth quadruple therapy as single-capsule provided the highest mITT cure rate (86%).One regimen achieved an optimal eradication rate (≥90%, by mITT): quadruple PPI-bismuth-tetracycline-metronidazole, only when high-dose PPIs and 14 days’ prescriptions were used. The use of doxycycline instead of tetracycline was associated with lower eradication rates in classical bismuth quadruple therapies (p<0.05).

Conclusion

Empirical rescue treatments in third and subsequent lines obtain, in general, suboptimal eradication rates in Europe; however, bismuth quadruple therapy as single-capsule obtained encouraging results. Only the optimised bismuth quadruple therapy with tetracycline-metronidazole achieved ≥90% effectiveness.

Disclosure

Olga P. Nyssen received research funding from Mayoly and Allergan.
Javier P. Gisbert served as speaker, consultant, and advisory member for or received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.