Metagenomic Analysis of Biliary Microbial Flora in Patients with Gallbladder Cancer or Gallstones-Associated Chronic Cholecystitis.

Biliary dysbiosis is associated with gallbladder cancer (GBC). We aimed to look for biliary bacteria specifically detected in GBC patients. We used 16S rRNA-based metagenomic analysis to elucidate biliary microbiota in 30 GBC and 30 gallstones-associated chronic cholecystitis patients. Relative abundance of five genera, Streptococcus, Enterococcus, Halomonas, Escherichia and Caulobacter was significantly associated with GBC. Of 15-species, 7 were detected significantly higher in GBC, Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius, Actinomyces bowdenii, Actinomyces israelii, Actinomyces gerencseriae, and Escherichia fergusonii were biosafety level-2 infectious bacteria; other 8 species were biosafety level-1 bacteria. These bacterial species may be involved in pathogenesis of GBC.

Post Cholecystectomy Bile Duct Injury in an Acute Setting: Categorization, Triaging, and Management Algorithm.

Background Postcholecystectomy bile duct injury (BDI) is a management challenge with significant morbidity, mortality, and effects on long-term quality of life. Early referral to a specialized hepatobiliary center and appropriate early management are crucial to improving outcomes and overall quality of life. In this retrospective analysis, we examined patients who were managed at our center over the past 10 years and proposed a triage and management algorithm for BDI in acute settings. Methods Patients referred to our center with BDI from January 2011 to December 2020 were reviewed retrospectively. The primary objective of initial management is to control sepsis and minimize BDI-related morbidity and mortality. All the patients were resuscitated with intravenous fluid, antibiotics (preferably culture-based), correction of electrolyte deficiencies, and organ support if required. A triage module and management algorithm were framed based on our experience. All the patients were triaged based on the presence or absence of bile leaks. Each group was further subdivided into red, yellow, and green zones (depending on the presence of sepsis, organ failure, and associated injuries), and the results were analyzed as per the proposed algorithm. Results One hundred twenty-eight patients with acute BDI were referred to us during the study period, and 116 patients had BDI with a bile leak and 12 patients were without a bile leak. Out of bile leak patients, 106 patients (91.38%) had sepsis with or without organ failure (red and yellow zone) and required invasive intervention in the form of PCD insertion (n=99, 85.34%) and/or laparotomy, lavage, and drainage (n=7, 6.03%). Another 10 patients (8.62%) had controlled external biliary fistula (green zone), of which four were managed with antibiotics, four underwent endoscopic retrograde cholangiopancreatography stenting, and only two (1.7%) patients could undergo Roux-en-Y hepaticojejunostomy upfront due to late referral. Among patients with BDI without bile leaks, nine (75%) had cholangitis (red and yellow zones). Out of these, five required PTBD along with antibiotics and four were managed with antibiotics alone. Only three (25%) patients in this group could undergo definitive repair without any restriction on the timing of referral and were sepsis-free at presentation (green zone). A total of nine patients had a vascular injury, and four of them required digital subtraction angiography and coil embolization. There were three (2.34%) mortalities; all were in the red zone of rest and had successful initial management. In total, five patients were managed with early repair in the acute setting, and the rest underwent definitive intervention at subsequent admissions after being converted to green zone patients with initial management. Conclusion The presented categorization, triaging, and management algorithm provides optimum insight to understand the severity, simplify these complex scenarios, expedite the decision-making process, and thus enhance patient outcomes in early acute settings following BDI.

Clinicopathological and prognostic significance of VEGF, PDGF-B, and HER2/neu expression in gallbladder cancer.

AIM: Gallbladder cancer (GBC) is usually diagnosed in advanced stages with poor survival. The molecular mechanisms of GBC still remain unexplored. Several angiogenesis factors play a pivotal role in tumor progression. We aimed to study the expression of VEGF, PDGF-B, and human epidermal growth factor receptor 2 (HER2/neu) and its association with clinicopathological features and survival in GBC. MATERIALS AND METHODS: VEGF, PDGF-B, and HER2/neu expression was studied by immunohistochemistry (IHC) after histological evaluation in 91 GBC cases. The relationship between these markers and clinicopathological features and survival was explained through the Cox regression model and Kaplan-Meier method. RESULTS: VEGF, PDGF-B, and HER2/neu overexpressed in 45, 79, and 68% GBC cases, respectively. VEGF was significantly overexpressed in GBC without gall stones (GS) (p = 0.007) and with moderately and poorly differentiated tumors (p = 0.012). HER2/neu was significantly overexpressed in GBC with GS (p = 0.022). Median overall survival (OS) was 39 months (95% CI: 23-55). In univariate analysis, histological type (adenocarcinoma and papillary) vs. others (signet ring/mucinous/adenosquamous) (p = 0.004), depth of tumor infiltration (p = 0.017), distant metastasis (p = 0.012), and adjuvant therapies (chemotherapy/radiotherapy) (p = 0.083) were associated with poor prognosis. Multivariate survival analysis showed histological type (p = 0.004) and distant metastasis (p = 0.032) to be independent prognostic factors for OS. Histological type (p = 0.002), distant metastasis (p = 0.003), and depth of tumor infiltration (T3-T4) (p = 0.012) showed poor median survival. Poor survival was seen in VEGF and HER2/neu positive cases. CONCLUSION: Overexpression of VEGF, PDGF-B, and HER2/neu might be possible prognostic biomarkers in GBC. Poor survival of VEGF and HER2/neu positive cases indicates the possibilities of using their blockers as therapeutic agents.