Introduction

Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis has been effective for patients with ascites and bleeding tendencies. However, the success rate of ETGBD is lower than that of other endoscopic retrograde cholangiopancreatography-related procedures, and it is often difficult to complete the procedure.

Aims & Methods

This study aimed to investigate the outcomes of ETGBD in the management of acute cholecystitis at our hospital while offering some technical recommendations for the procedure. This was a retrospective study of 41 patients who had undergone ETGBD for acute cholecystitis at our hospital between January 2015 and July 2021.

Results

There were 28 males and 13 females, with a median age of 80 years (range, 58–91). Of these patients, 27 (65.9%) had mild ETGBD, 13 (31.7%) had moderate ETGBD, and one (2.4%) had severe ETGBD. The cases of intra-gallbladder, cholecystic duct, and common bile duct stones were found in 30 (73.2%), 13 (31.7%), and 16 (39.0%) patients, respectively. The types of cystic duct branching were merging of the upper (n = 36) and lower sides (n = 5), toward the head (n = 35) and foot sides (n = 6), and merging of the right (n = 34) and left sides (n = 7). The technical success rate was 95.1% (39 out of 41) (endoscopic nasobiliary stenting [n = 34] and endoscopic nasobiliary gallbladder drainage [n = 5]), and the clinical success rate was 100% (n = 39). The median treatment time was 30 minutes (range, 11–72). In the present study, difficult intubation was defined as failure to intubate the gallbladder using conventional devices. Among the 12 patients who experienced intrabiliary intubation difficulties, seven of them were able to be cannulated into the gallbladder with the SwingTip^TM cannula (Olympus, Tokyo, Japan), which features a controllable catheter tip angle. In two patients whose bile duct stenosis was still difficult even with the SwingTip^TM cannula, the long-tapered cannula (StarTipV^TM, Olympus) was used to break through the stenosis. In one patient whose cholecystogram could not be obtained, a retrieval balloon for the above contrast was used to obtain a cholecystogram, and endoscopic transpapillary balloon sphincteroplasty was finally performed. Regarding factors influencing the difficulty of intubation of the gallbladder, multivariate analysis showed that "dilation of the common bile ducts (>10 mm)" was a significantly difficult factor.

Conclusion

Even though ETGBD is difficult in patients with dilated common bile ducts (≥10 mm), it could be performed relatively safely and effectively by using dedicated devices.

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

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

The endoscopic retrograde cholnagio-pancreatography (ERCP) with endoscopic sphincterotomy results in a complete bile duct stones (CBDSs) clearance in about 80-90%. However, in case of incomplete CBDSs clearance, an endoprosthesis could be placed. A plastic stent is commonly used, with a success rate after a previous ERCP, ranging from 44% to 96%. However, there are no comparative studies between plastic and metal stent. Moreover, data concerning the safety and efficacy of antimigration Fully covered Metal stents – flare type (aFCMS) are lacking.

Aims & Methods

In this single-center retrospective study we collected data concerning all patients who underwent ERCP with antimigration metal stent placement for incomplete removal of CBDSs between January 2021 to January 2023. All patients were contacted in order to program stent remotion within 3-6 months (considering their general clinical condition) or to evaluate their clinical status. We aim to estimate the incidence of migration rate, and adverse events, and complete biliary clearance after 3-6 months from the index ERCP.

Results

Out of 34 patients included patients, 20 underwent a second ERCP after a median of 164 (±78) days. The reasons for the lack of a second ERCP evaluation are reported in the table. In 11/20 (55%) a distal migration occurred. Only one proximal migration was reported. Among the 34 included patients only one presented a clinical recurrence linked to the proximal migration of aFCMS. 19/20 patients achieved a complete clearance after the second ERCP. No serious adverse events were reported.

Conclusion

The aFCMS represents an effective and safe therapeutic chance in case of incomplete CBDSc clearance in particular in case of difficult CBDSs. Moreover, the very low incidence of stent proximal migration makes this device particularly useful in the case of this clinical condition.

Disclosure

None

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)