Introduction

Although Endoscopic Retrograde Cholangiopancreatography (ERCP) has played an important role in the diagnosis and treatment of biliary and pancreatic diseases since its inception, the gallbladder is still considered a “blind spot” or inaccessible area for ERCP.

Aims & Methods

This study was intended to evaluate the technical success rate, safety, and clinical application value of per-oral cholangioscopy-guided transpapillary cystic duct approach for Gb-NOEES, and to explore the feasibility of Natural Orifice Endoluminal Endoscopic Surgery (NOEES) in the diagnosis and treatment of gallbladder diseases.
Patients with gallbladder diseases who received Gb-NOEES treatment from January 2023 to November 2024 were retrospectively included in a single-center study. Inclusion criteria: Patients are preoperatively diagnosed with gallstones, gallstones combined with common bile duct stones, gallstones combined with intrahepatic stones, acute cholecystitis, and gallbladder polyps. Exclusion criteria: patients with asymptomatic gallstones, patients with gallbladder cancer, and patients at risk of gallbladder cancer. All procedures were performed by experts with ≥10 years of experience in digestive endoscopy, and postoperative follow-up period ranged from 2 to 26 months.

Results

A total of 100 patients were included (58 males and 42 females, with an average age of 47±15.1). The disease distribution is shown in Table 1. The technical success rate of Gb-NOEES was 99% (99/100), and the average operative time was 130±59 minutes. The complication rate was 4%: 3 cases of gallbladder perforation (1 case of successful conservative treatment, and 2 cases of conversion to laparoscopic surgery), and 1 case of postoperative bleeding (successful conservative treatment). No severe pancreatitis or death occurred. Treatment outcomes: Gallstone clearance rate was 98% (78/80), with the largest stone measuring 4.0 cm, and up to 52 stones removed in a single operation. Complete excision rate of gallbladder polyps was achieved in 100% (15/15), with long diameter of polyps ranging from 4 mm to 15 mm, and up to 8 polyps excised in a single operation. Drainage success rate for acute cholecystitis was 100% (4/4). One case of early-stage gallbladder cancer was incidentally detected. During the follow-up period, the recurrence rate of stones was 2.5% (2/80), and there was no recurrence of polyps.

Conclusion

Gb-NOEES demonstrated favorable safety profile (complication rate was 4%) and high efficacy (overall success rate was 98%) in the diagnosis and treatment of gallbladder diseases. This technique has advantages of both lesion removal and organ preservation, offering a new minimally-invasive treatment option for gallbladder diseases. However, its clinical application value requires further validation through multi-center studies.

Table 1. Disease Distribution of Patients

Disclosure

There is no conflict of interest.

Introduction

Gender differences are gaining increasing attention in autoimmune diseases, such as autoimmune atrophic gastritis (AAG). AAG is a chronic inflammatory pre-neoplastic condition that leads to atrophy of the oxyntic mucosa, resulting in hypochlorhydria and potentially leading to gastric neoplastic lesions. Recently, also the human microbiota has gained interest in the scientific community. Previous studies showed that AAG may be associated with modifications in the gastric microbiota composition likely due to hypochlorhydria, that makes plausible the overgrowth of intragastric bacteria. To our knowledge, data on gender differences in gastric microbiota are lacking.

Aims & Methods

In this study we aimed to investigate gender differences in the gastric microbiota composition in subjects with healthy stomachs and patients affected by AAG. This is a post-hoc analysis conducted on 52 adult subjects undergoing gastroscopy for dyspepsia: median age 61 years, range 18- 83, 32 females and 20 males; 30 (57.7%) with healthy stomach and 22 (42.3%) with AAG. Gastric biopsies were obtained for both histopathology and genomic DNA extraction. Gastric microbiota was assessed by sequencing hypervariable regions of the 16SrRNA gene. Bacterial profile at phylum and genus level was reported as relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for female and male gender separately in healthy subjects and AAG patients.

Results

Healthy women had a significantly higher bacterial abundance compared to men; differently, in AAG patients, gastric bacterial abundance was similar in both genders (at 13333 reads, 704.65 in healthy women vs 470.40 in healthy males, p= 0.03; 467.2 in AAG females vs 433 in AAG males, p=0.32). In healthy subjects, the gastric microbiota showed a significantly lower biodiversity in females compared to males (3.2 vs 3.4, p=0.003). In contrast, in AAG patients, the gastric microbiota showed a significantly lower biodiversity in males than in females (Shannon index 2.3 vs 3.5, p<0.0001). Compared to healthy subjects, in AAG patients, the biodiversity of the gastric microbiota was significantly lower in males (2.3 vs 3.4, p<0.001), while it was higher in females (3.5 vs 3.2, p=0.002). Taxa frequency at phylum level in females and males is shown in the table. Concerning taxa frequency at genus level, Streptococcus was the most prevalent being higher in healthy females compared to males (11.26 vs 7.88, p=0.03), but similar in both genders in AAG (15.94 vs 15.49, p= 0.77).

Conclusion

Gastric microbiota gender differences in healthy subjects, seem to be reset in AAG, likely due to hypochlorhydria. Differences between genders on taxa frequency at phylum and genus level were observed in healthy subjects and AAG patients. The impact of these findings on the gender-specific natural history of AAG remains to be elucidated.

Introduction

Chronic pancreatitis (CP), influenced by both genetic and environmental factors, poses a significant health burden with its progressive nature. While excessive alcohol consumption is a prominent risk factor, non-alcoholic chronic pancreatitis (NACP) presents challenges due to less overt precipitating factors.

Aims & Methods

We aimed to assess the impact of rs7057398 and rs12688220 variants at the RIPPLY1-CLDN2-MORC4 locus and rare functionally deficient TRPV6 variants in NACP susceptibility.
Systematic search weas conducted on PubMed, Embase, and Web of Science databases on November 2, 2023, aiming to assess non-alcoholic acute recurrent pancreatitis (ARP) and CP cases, excluding conference abstracts and preprints. The protocol was prospectively registered (CRD42023438777). Utilizing a random-effect model with REML estimation, odds ratios (OR) with 95% confidence intervals (CI) were computed using the allelic model (rs7057398: C vs T; rs12688220: T vs C) for the total population and hemizygotes as well, the homozygote (rs7057398: CC vs TT; rs12688220: TT vs CC) and heterozygote model (rs7057398: CT vs TT; rs12688220: TC vs CC). Minor allele frequnecy (MAF) was calculated for both variants. In the analysis of functionally deficient rare TRPV6 variants were collectively pooled and compared to cases without mutations affecting TRPV6 function, calculating OR with 95% CI. Subgroup analysis, stratified by age, set the threshold for early-onset CP at 30 years in all cases. Statistical heterogeneity was evaluated using Chi² tests and I² values. Due to limited study numbers, funnel plots and Egger’s test were deemed inappropriate. Risk of bias was assessed using the Joanna Briggs Institute's tool.

Results

Six studies were included in the quantitative analyses for SNPs rs7057398 and rs12688220. MAF for rs7057398 was 0.49 (CI 0.31 to 0.67) in cases and 0.38 (CI 0.27 to 0.50) in controls. For rs12688220, MAF was 0.46 (CI 0.27 to 0.67) in cases compared to 0.35 (CI 0.24 to 0.47) in controls. MAF was notably higher in Indian and Asian studies compared to European cohorts. Both risk alleles were significantly associated with NACP in homozygotes, heterozygotes and hemizygotes, respectively (see Table). In the allelic model, minor allele carriers displayed significantly increased odds for NACP for rs7057398 (OR 1.54, CI 1.17 to 2.01, p=0.009) and rs12688220 (OR 1.64, CI: 1.10 to 2.45, p=0.025). Limited data was available on early-onset cases, therefore definitive conclusions cannot be drawn. Functionally deficient TRPV6 variants were associated with a 35-fold increased odds of developing NACP compared to individuals without these variants (OR = 35.32, CI 20.72 to 60.22, across 4 cohorts, 2236 cases and 2748 controls). Risk of bias was generally jugded to be high in the included studies.

Conclusion

Our meta-analysis highlights the significant association of variants rs7057398 and rs12688220 of the RIPPLY1-CLDN2-MORC4 locus, along with functionally deficient TRPV6 variants, with NACP. These findings emphasize the importance of genetic screening for identifying individuals at risk of NACP and inform personalized intervention strategies.