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

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)

Introduction

Pancreatic cancer (PC) screening can improve survival in high-risk patients by detecting preneoplastic lesions or early-stage tumors.
Surveillances is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, little has been described regarding the possibility of finding other morphological changes that may be also important.

Aims & Methods

The aim of the study is to evaluate all the findings described in screening test and to analyze the correlation between these two screening techniques.
Descriptive observational single-center study that includes high-risk PC patients either due to family history (familial pancreatic cancer) or because they belong to hereditary syndromes, who have been undergone pancreatic cancer screening at our center from 2015 to 2023. Demographic variables and findings described in the EUS or MRI were collected.

Results

Thirty-five patients were included, with a mean age of 57.3 ± 8.2 years and a predominance of females (65.7%). Four patients (11.4%) were smokers, two were diabetic (5.7%), and one had a history of chronic pancreatitis (2.9%). The median follow-up time was 23 months (interquartile range 8-59 months).
The most frequent hereditary syndrome was hereditary breast and ovarian cancer syndrome (n=19, 54.3%), followed by familial atypical multiple mole melanoma syndrome (n=4; 11.4%). The BRCA2 mutation was the most common identifiable genetic factor (34.8%).
Regarding screening test findings, solid tumors were detected in three patients (8.6%) (Two stage I and IV adenocarcinomas and one stage I neuroendocrine tumor). In two individuals (5.7%) branch-duct intraductal papillary mucinous neoplasm were observed. Other pancreatic abnormalities were detected in 18 patients (51.4%) that include chronic pancreatitis-like parenchymal changes (34.3%), peripancreatic lymph nodes and fatty pancreas (5.7%). Finally, in 12 patients (34.3%) the screening tests were normal.
In relation to the concordance between MRI and EUS, in ten patients (28.6%) there was no agreement between these two techniques. EUS detected more parenchymal changes (n=5), pancreatic steatosis (n=2) and one neuroendocrine tumor that were not described on MRI. In contrast, MRI detected a cystic lesion and a pseudonodular enhancement that were not found on EUS.

Conclusion

Pancreatic cancer screening in high-risk individuals, detects neoplastic and preneoplastic lesions at a high rate.
Other findings, such as chronic pancreatitis-like parenchymal changes, peripancreatic lymph nodes or fatty pancreas, were also common in these patients
MRI and EUS have a good correlation, but EUS detects more parenchymal changes.

References

1. Goggins M, Overbeek KA, Brand R et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 2020; 69 (1): 7-17
2. Bogdanski AM, van Hooft JE, Boekestijn B, Bonsing BA, Wasser MNJM, Klatte DCF, van Leerdam ME. Aspects and outcomes of surveillance for individuals at high‑risk of pancreatic cancer. Fam Cancer 2024; 23(3):323-339.
3. Blackford AL, Canto MI, Dbouk M, Hruban RH, Katona BW, Chak A et al. Pancreatic Cancer Surveillance and Survival of High-Risk Individuals. JAMA Oncol. 2024;10(8):1087-1096.
4. Maurer E, Lehman B, Matthäi E, Denzer U, Figiel J, Jseinghaus M et al. Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant‐negative familial pancreatic cancer families. United European Gastroenterol J 2024; 12 (9): 1211-1221