Introduction

Few population-based studies have investigated rates and management of perianal disease and long-term perianal surgery rates in Crohn’s disease (CD). The present study is a continuation of the Veszprem IBD population based cohort with a follow-up osince 1977.

Aims & Methods

Our aim was to analyze the long-term rates of perianal surgical procedures over different therapeutic eras in a prospective population-based database from Veszprem Province, including incident CD patients. Patient inclusion was between January 1, 1977 and December 31, 2018; follow-up ended December 31, 2020. Both in-hospital and outpatient records were collected. Perianal surgical procedure was defined as any perianal surgical procedure including fistulotomy, abscess drainage or seton placement. Surgery rates were examined in three different eras based on time of diagnosis: cohort-A, 1977-1995; cohort-B, 1996-2008; and cohort-C, 2009-2018.

Results

Data of 946 incident CD patients were analyzed (male/female: 496/450; median age at diagnosis: 28 years(y) [IQR: 22-40]). Median follow-up time for the entire cohort was 15 years (IQR: 9-21). Perianal disease at diagnosis was present in 17.4% (n=165) of the total cohort, and in 24.7%/ 18.5%/ 13.2% in cohorts A/B/C, respectively. By the end of follow-up, an additional 9.3% (n=88) of the total cohort developed perianal disease. Cumulative immunosuppressive and biologic therapy exposure increased by time. Cumulative probability of biological therapy after diagnosis in patients with perianal disease was 0.0±0% / 15.1±3.2% / 42.5±6.2% at 5 years after diagnosis between cohorts A/B/C. Biologic use was higher in patients with perianal disease compared to the overall population. [pLogRank<0.001]. The overall rate of perianal surgical procedures was 44.7% (113/253) in patients with perianal disease during the total follow-up. The cumulative probability of perianal surgical procedure in patients with perianal disease was 28.3±2.9% after 10 years, 41.0±3.5% after 20 years, and 64.1±5.1% after 30 years. No statistically significant differences have been observed in the cumulative probability of perianal intervention between cohorts A/B/C: 24.2±5.4%/ 19.9±3.5%/ 29.4±5.8% after 5 years; 33.9±6.0%/ 23.6±3.8%/ 31.7±6.1% after 10 years; [pLogRank=0.594]. Cox-regression multivariate analysis showed that stenosing or penetrating disease (B2/B3) behavior (HR 1.81; 95%CI 1.19-2.75; p=0.005) was independent predictor of perianal surgical procedure. Table 1.

Table 1. Predictive factors for first perianal surgical procedure in incident CD patients diagnosed between 1977 and 2018 – Cox-regression analysis

Conclusion

The burden of perianal disease and perianal surgical interventions was high in this cohort. Patients with perianal CD had higher exposure to biologicals. No difference was observed in perianal surgical intervention rates despite the increasing use of immunosuppressives and biologicals over time, however these procedures may partly represent a medical decision and the complex management of perianal disease.

Clinical Case Summary

We present the case of a 43-year-old black male with a relevant medical history of arterial hypertension, alcoholism, and epilepsy. He was admitted to the emergency department for cough with purulent sputum, shortness of breath and chest pain for the past week. On observation, he presented several perianal fistula openings with bloody and purulent discharge. A computed tomography (CT) revealed perirectal densification, fistulous tracts to the ischioanal fossae, ascites, mesenteric fat densification and necrotic inguinal adenopathies. Due to the presence of hematochezia, a rectosigmoidoscopy was performed which showed deep ulceration causing destruction of the posterior wall of the distal rectum, involving one third of its luminal circumference, with bloody and purulent discharge. The patient developed septic and hemorrhagic shock and was admitted to the intensive care unit. He underwent urgent surgery for hemostasis of the rectal ulcer, partial fistulectomy, seton placement in the other three fistulous tracts, and loop colostomy. Analysis of the perianal discharge detected Mycobacterium tuberculosis by polymerase chain reaction. Sputum acid-fast bacilli smear was also positive, and a thoracic CT scan showed cavitating consolidations in the upper pulmonary lobes and a tree-in-bud pattern reflecting active tuberculosis (TB) with endobronchial spread. Remarkably, the patient was HIV-negative and did not have other causes for immunosuppression besides the chronic alcoholism. He was started on antitubercular medication and evolved favorably.
Gastrointestinal TB represents less than 1% of all tuberculosis cases. Anorectal involvement is even rarer, being present in 1% of all cases of gastrointestinal TB. Its most common presentation is complex perianal fistulizing disease. In most cases, pulmonary TB is also present. Although it is more prevalent in immunosuppressed patients, it should be included in the differential diagnosis of complex perianal fistulizing disease.

References

1- Photographs of perianal fistulizing disease with purulent discharge;
2- CT scan suggesting disseminated TB;
3- Rectosigmoidoscopy showing destruction of the distal rectal wall.

Introduction

Several factors affect the difficulty of endoscopic retrograde cholangiopancreatography (ERCP) (Facciorusso et al.). This study aimed to evaluate whether the intra- and peri-diverticular location of the papilla has an impact on the results of ERCP for common bile duct stones.

Aims & Methods

Retrospective evaluation of patients without previous sphincterotomy undergoing ERCP for common bile duct stones between August 2020 and February 2023. Data on the patient (age, sex, comorbidities), procedure (elective/urgent, location and type of papilla, techniques used, successful cannulation, diagnosis, immediate complications), and outcomes (complications at 3, 30, and 90 days, need for repeating ERCP) were collected.

Results

Of the 769 patients undergoing ERCP during this period, 224 met the inclusion criteria (median age 76 years, 58% female). The papilla had an intra-diverticular location in 20 and a peri-diverticular location in 45, while it was not dependent on the diverticula in the remaining 159. Regarding the endoscopic classification (SADE; Haraldsson et al.), most were type 1 (55%) or type 2 (20%). The cannulation rate was 93%, with precut being used in 18% (fistulotomy/papillotomy n=22; transpancreatic precut n=14). The cannulation rate was significantly lower in patients with intra-diverticular and peri-diverticular papilla (75% and 87%, respectively, versus 97%; p<0.01), being the precut use also higher (20% and 31%, p=0.038). The ability to completely remove stones in the index ERCP (efficacy) was lower in patients with intra- or peri-diverticular papilla (71% and 70% versus 85%, p=0.04). There were no differences in intraprocedural complications (n=8, p=0.42), at 3 (n=20, p>0.05), 30, and 90 days (n=1). However, the need for repeating ERCP was different between groups (38% peri-diverticular, 25% intra-diverticular, versus 15%; p<0.01).

Conclusion

The intra- or peri-diverticular location of the papilla limits the cannulation rate and efficacy of ERCP, requiring more frequent use of advanced cannulation techniques and repeat procedures. However, it should be noted that no more complications occurred in these locations.

References

Haraldsson, E., et al. Endoscopic classification of the papilla of Vater. Results of an inter-and intraobserver agreement study. United European Gastroenterology Journal 5.4 (2017): 504-510.
Facciorusso A, et al. Comparative efficacy of different methods for difficult biliary cannulation in ERCP: systematic review and network meta-analysis. Gastrointest Endosc. 2022;95(1):60-71.

Introduction

A male patient in his twenties presented with clinical aspects of primary sclerosing cholangitis (PSC), chronic cholestatic liver disease, and hypothyroidism. PSC is a rare, chronic cholestatic liver disease characterized by biliary strictures and peribiliary fibrosis (1). Susceptible loci were identified in GWAS but the correlation between genetic background and disease pathogenesis needs further investigation (2). In the index patient we identified a heterozygote candidate variant in the ABCC6 gene (c.2279G>A, p.(Arg760Gln)). Dysfunctional ABCC6 was described to cause ABCB11 and ABCG5/G8 genes overexpression, leading to imbalanced bile composition resulting in gallstone formation and cholestasis (3). ABCC6 variants were previously described in cases with low phospholipid-associated cholelithiasis (LPAC) and intrahepatic cholestasis of pregnancy (ICP)(4-6) . Subsequently, we aimed to investigate rare variants in ABCC6 gene in whole exome sequencing (WES) results from patients with suspected cholestatic liver disease.

Aims & Methods

Variant evaluation and annotation analysis was carried out on WES data, with focus on loss of function and missense variants, presenting allele frequency (AF) of ≤1% based on gnomAD database (https://gnomad.broadinstitute.org). Variants were filtered to include only those in genes relevant to the patients’ clinical phenotype. For each rare variant, a comprehensive in silico assessment was performed using tools such as REVEL, AlphaMissense, EVE, SIFT, and MetaLR to evaluate potential pathogenicity. Filtered were prioritized and interpreted using ACMG-AMP guidelines. This systematic approach ensured a clinically meaningful and evidence-based evaluation of the identified variants.

Results

Nine different rare heterozygote variants were identified in fifteen samples of 247 WES results. Among these, the missense variants c.179G>A, p.(Arg60Gln) and c.3139C>T, p.(Arg1047Cys) were found in two LPAC patients. Additionally, the c.1171A>G, p.(Arg391Gly) variant was observed in two related cases: a mother with ICP and her child with elevated gamma-glutamyl transferase (GGT) levels and jaundice. Moreover, this variant was also detected in another patient with elevated transaminases. c.3871G>A, p.(Ala1291Thr) and c.955A>G, p.(Ile319Val) were seen in patients with ICP and cholestasis, respectively. Three other variants were also identified in patients with liver disease of unknown etiology (c.1540G>A, p.(Val514Ile) and c.2707G>C, p.(Glu903Gln) and c.4397G>A, p.CYS1466Tyr). Additionally one splicing variant (c.37-1G>A, p,?) was also detected in a patient with cholangiocarcinoma (CCA). All variants were observed in heterozygote state and classified as variants of uncertain significance (VUS).

Conclusion

An in-depth analysis of WES data led to the identification of several potentially disease-relevant variants in the ABCC6 gene. These variants may play a contributory role in the observed hepatic phenotypes, suggesting a broader functional involvement of ABCC6 beyond its well-established association with pseudoxanthoma elasticum (PXE). Our findings highlight the importance of integrating genetic data with detailed clinical phenotyping to enhance understanding of genotype–phenotype correlations and reveal novel roles for known genes in atypical or organ-specific presentations.

References

1. Reich M, Spomer L, Klindt C, Fuchs K, Stindt J, et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis. J Hepatol. 2021;75(3):634-46.
2. Goode EC, Fachal L, Panousis N, Moutsianas L, McIntyre RE, Bai BYH, et al. Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci. Nat Commun. 2024;15(1):9594.
3. Ibold B, Faust I, Tiemann J, Gorgels T, Bergen AAB, Knabbe C, et al. Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues. Lipids Health Dis. 2019;18(1):2.
4. Liu X, Lai H, Xin S, Li Z, Zeng X, Nie L, et al. Whole-exome sequencing identifies novel mutations in ABC transporter genes associated with intrahepatic cholestasis of pregnancy disease: a case-control study. BMC Pregnancy Childbirth. 2021;21(1):110.
5. Liu X, Zheng J, Xin S, Zeng Y, Wu X, Zeng X, et al. Whole-exome sequencing expands the roles of novel mutations of organic anion transporting polypeptide, ATP-binding cassette transporter, and receptor genes in intrahepatic cholestasis of pregnancy. Front Genet. 2022;13:941027.
6. Romeo M, Dallio M, Federico A. Is it time to reconsider the MRP6 role in bile secretion and LPAC genetic signature? J Hepatol. 2023;79(4):e152-e4.

Disclosure

The authors declare that they have no conflict of interest.

Introduction

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) offers advantages over duodenal stenting and surgical bypass. EUS-GE technique, however, remains non-standardized. A parallel enteric tube (PET) facilitates luminal distention, a critical step during EUS-GE.

Aims & Methods

We primarily aimed at standardizing PET-assisted EUS-GE, secondarily assessing reproducibility and outcomes.
Prospective multicenter study on consecutive adult patients with unresectable malignant gastric outlet obstruction undergoing primary EUS-GE between August 2019-April 2021. Hierarchical task analysis predefined procedural steps into tasks and subtasks. Subtasks were further categorized into essential (performed in all centers and in over 85% of the procedures) or optional. Subtask methodology was considered established if performed similarly in all centers or variable if not. Procedure times, injected fluid volume, luminal diameters obtained, accessories used, and clinical outcomes were recorded.

Results

Seven endoscopists performed EUS-GE in 65 patients (50.8% male, median [IQR] age 77.5 [65.7-86.5] years). EUS-GE was categorized into 4 tasks and 10 subtasks (Table 1). Five essential subtasks involved an established methodology (guidewire and PET placement, endoscope exchange, delivery system insertion and LAMS deployment).
Technical and clinical success rates were 98.5% and 83.3%, respectively. AEs occurred in 10 (15.4%) patients (2 mild, 7 moderate, 1 severe). Success and AE rates were not different between expert and non-experts. Median (IQR) procedure time was 26.2 (19.7-37.1) min. The short and long axis of the targeted small bowel loop was 27 (23-30) x 40 (33-60) mm. Procedure time was longer (35 [30.6-43.7] vs 21.8 [16.4-29.5] min, p<0.001) and injected fluid volume higher (510 [439-870] vs 415 [255-480] ml, p=0.01) in non-experts.

Table 1. Proposed taxonomy for the PET-assisted EUS-GE

Conclusion

PET-assisted EUS-GE was standardized, identifying its key steps and technique variants. PET-assisted EUS-GE appears to be a reproducible procedure among advanced endoscopists with different levels of experience. (Clinical Trials Identification Number: NCT04660695).

Disclosure

Carlos Chavarríareceived research and training support by a grant from The Foundation of the Institute of Health Sciences Studies of Castilla y León (IECSCYL).
Vanessa Martín-Álvarezhas nothing to declare.
José Ramón Aparicio is a consultant for Boston Scientific.
Jose Carlos Subtil has nothing to declare.
Francisco Javier Garcia-Alonso has nothing to declare.
Juan J. Vila is a consultant for Boston Scientific and speaker for Cook Endoscopy and Olympus.
Belén Martínez-Moreno has nothing to declare.
Victoria Busto-Bea has nothing to declare.
Ramon Sanchez-Ocaña has nothing to declare.
Carlos de la Serna-Higuera has nothing to declare.
Manuel Perez-Miranda Miranda is a consultant and speaker for Boston Scientific, Olympus, and M.I.Tech.

Introduction

The role of prophylactic biliary stenting after clearance of common bile duct stones (CBDS) in patients awaiting cholecystectomy for concomitant gallstones is controversial.

Aims & Methods

Aim: To study the effect of prophylactic biliary stenting after achieving biliary clearance in reducing CBDS recurrence and biliary complications in patients awaiting cholecystectomy.
Methods: Patients with concomitant gallstones and CBDS were included and those who had evidence of clearance of CBDS that was documented on occlusion cholangiogram during endoscopic retrograde cholangiography (ERC) were randomized to prophylactic biliary stenting (group A) or no stenting (group B). After clearance, the patients were advised to undergo cholecystectomy as early as possible. The patients were followed up at 1 week, 1, 2, and 3 months after clearance, and at 3 months or after cholecystectomy (whichever was early) they were assessed for recurrence of CBDS by either endoscopic ultrasound or MRCP or ultrasound abdomen and liver function test whichever was convenient for the patient. During each follow-up visit patients were assessed for symptoms and were requested to do a hemogram and liver function test. The primary outcome was to compare the CBDS recurrence rate, while the secondary outcomes were to compare the biliary complications and the need for repeat/ emergency ERC. Statistical analysis was performed using IBM SPSS version 22. Quantitative variables were analysed by mean and standard deviation (SD) while categorical variables were analysed by frequency and proportion. Median and interquartile range (IQR) were used for non-normally distributed quantitative variables. Comparison of categorical outcomes was done between study groups using Chi-square test/Fisher's Exact test. At different time periods, categorical variables were compared using the McNemar test. For quantitative parameters with normal distribution, the mean values were compared between study groups using an independent sample t-test (2 groups). Change in the quantitative parameters before and after the intervention was assessed by paired t-test. P value < 0.05 was considered statistically significant.

Results

Between September 2021 to July 2022, 70 patients were randomized into Group A-stenting (n-35) and Group B- no stenting (n-35). Sixty-six patients were included in the final analysis. The baseline characteristics were comparable between the 2 groups. Ten (15.15%) patients had a recurrence of CBDS and it was comparable between the 2 groups [7/34 (20.59%) and 3/32 (9.38%), p=0.306]. Two patients in the stent group developed biliary complication (cholecystitis) while none of the patients in the no stent group developed any biliary complication. Three patients in the stent group while none in the no-stent group developed post-ERC pancreatitis (p=0.085). None of the patients in both the groups needed emergency ERC during the follow-up.

Conclusion

This randomized trial shows no advantage of prophylactic stenting in preventing CBDS recurrence or biliary complications in patients waiting for cholecystectomy after biliary clearance. (CTRI registration number: CTRI/2021/09/036538)