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.

Portosystemic Shunt Surgery for Extrahepatic Portal Venous Obstruction Beyond Endoscopic Variceal Eradication: Two Decades of Pediatric Surgical Experience.

Background: This exclusively surgical series on pediatric extrahepatic portal venous obstruction (EHPVO) defines surgical indications beyond endoscopic eradication of esophageal varices (EEEV), the selection of an appropriate surgical procedure, and the long-term post-surgical outcome. Methods: EHPVO management protocol at the reporting institute has been endotherapy until esophageal variceal eradication and surgery for select adverse sequelae manifesting after EEEV. Results: One hundred and thirty-nine EHPVO cases underwent surgery for the following indications in combination: i) massive splenomegaly with severe hypersplenism (n = 132, 95%); ii) growth retardation (GR, n = 95, 68%); iii) isolated gastric (IGV) and ectopic varices (n = 49, 35%); iv) Portal cavernoma cholangiopathy (PCC) (n = 07, 5%). A portosystemic shunt (PSS) was performed in 119 (86%) cases. Types of PSS performed were as follows: central end-to-side splenorenal shunt with splenectomy (n = 104); side-to-side splenorenal shunt (n = 4); mesocaval shunt (n = 1); inferior mesenteric vein (IMV) to left renal vein shunt (n = 2); IMV to inferior vena cava shunt (n = 3); H-graft interposition splenorenal shunt (n = 1); spleno-adrenal shunt (n = 3); makeshift shunt (n = 1). Esophagogastric devascularization (n = 20, 14%) was opted for only for non-shuntable anatomy. At a median follow-up (FU) of 41 (range: 6-228) months, PSS block was detected in 13 (11%) cases, with recurrent variceal bleeding in 4 cases. PCC-related cholestasis regressed in 5 of 7 cases. Issues of splenomegaly were resolved, and growth z-scores improved significantly. Conclusions: Endotherapy for secondary prophylaxis until EEEV has resulted in a shift in surgical indications for EHPVO. Beyond EEEV, surgery was indicated predominantly for non-variceal sequelae, namely massive splenomegaly with severe hypersplenism, GR, and PCC. Varices warranted surgery infrequently but more often from sites less amenable to endotherapy, i.e., IGV and ectopic varices. The selection of PSS was tailored to anatomy and surgical indications. On long-term FU post surgery, PSS block was detected in 13% of patients. PCC-related cholestasis regressed in 71%, and issues of splenomegaly resolved with significantly improved growth Z scores.

NMR spectroscopy-based analysis of gallstones of cancerous and benign gallbladders from different geographical regions of the Indian subcontinent.

Analysis of the chemical composition of gallstones is vital for the etiopathogenesis of gallstone diseases that can ultimately help in the prevention of its formation. In the present study, gallstones from seven different regions of India were analyzed to highlight the major difference in their composition. Also, gallstones of different pathological conditions i.e., benign (chronic cholecystitis, CC) and malignant gallbladder disease (gallbladder cancer GBC) were characterized. The type of polymorphs of cholesterol molecules was also studied to provide insight into the structure of gallstones. 1H solution state NMR spectroscopy 1D experiments were performed on a total of 94 gallstone (GS) samples collected from seven different geographical regions of India. Solid-State NMR spectroscopy 13C cross-polarization magic angle spinning (CPMAS) experiments were done on the 20 CC GS samples and 20 GBC GS samples of two regions. 1H NMR spectra from the solution state NMR of all the stones reveal that cholesterol was a major component of the maximum stones of the north India region while in south Indian regions, GS had very less cholesterol. 13C CPMAS experiments reveal that the quantity of cholesterol was significantly more in the GS of CC in the Lucknow region compared with GBC stones of Lucknow and Chandigarh. Our study also revealed that GS of the Lucknow region of both malignant and benign gallbladder diseases belong to the monohydrate crystalline form of cholesterol while GS of Chandigarh region of both malignant and benign gallbladder diseases exists in both monohydrate crystalline form with the amorphous type and anhydrous form. Gallstones have a complicated and poorly understood etiology. Therefore, it is important to understand the composition of gallstones, which can be found in various forms and clinical conditions. Variations in dietary practices, environmental conditions, and genetic factors may influence and contribute to the formation of GS. Prevention of gallstone formation may help in decreasing the cases of gallbladder cancer.

Surgery for symptomatic hepatic hemangioma: Resection vs. enucleation, an experience over two decades.

Backgrounds/Aims: Hemangiomas are the most common benign liver lesions; however, they are usually asymptomatic and seldom require surgery. Enucleation and resection are the most commonly performed surgical procedures for symptomatic lesions. This study aims to compare the outcomes of these two surgical techniques. Methods: A retrospective analysis of symptomatic hepatic hemangiomas (HH) operated upon between 2000 and 2021. Patients were categorized into the enucleation and resection groups. Demographic profile, intraoperative bleeding, and morbidity (Clavien-Dindo Grade) were compared. Independent t-test and chi-square tests were used for continuous and categorical variables respectively. p-value of < 0.05 was considered significant. Results: Sixteen symptomatic HH patients aged 30 to 66 years underwent surgery (enucleation = 8, resection = 8) and majority were females (n = 10 [62.5%]). Fifteen patients presented with abdominal pain, and one patient had an interval increase in the size of the lesion from 9 to 12 cm. The size of hemangiomas varied from 6 to 23 cm. The median blood loss (enucleation: 350 vs. resection: 600 mL), operative time (enucleation: 5.8 vs. resection: 7.5 hours), and postoperative hospital stay (enucleation: 6.5 vs. resection: 11 days) were greater in the resection group (statistically insignificant). In the resection group, morbidity was significantly higher (62.6% vs. 12.5%, p = 0.05), including one mortality. All patients remained asymptomatic during the follow-up. Conclusions: Enucleation was simpler with less morbidity as compared to resection in our series. However, considering the small number of patients, further studies are needed with comparable groups to confirm the superiority of enucleation over resection.

Unconventional Shunts in Extrahepatic Portal Venous Obstruction-A Retrospective Review.

Background: Proximal splenorenal shunt (PSRS) is one of the most commonly performed portosystemic shunt (PSS) in extrahepatic portal venous obstruction (EHPVO) for portal decompression. Sometimes various anatomical and surgical factors related to the splenic vein and/or left renal vein may make the construction of a PSRS difficult or impossible. Unconventional shunts are required to tide over such conditions. Methods: From January 2008 to December 2018, 189 patients with EHPVO underwent PSS, of which, the 10 patients who underwent unconventional shunts form the study group of this paper. Results: The ten unconventional shunts included 8 proximal splenoadrenal shunts, one collateral-renal shunt, and one inferior mesenteric vein to inferior vena cava (IMV-Caval) shunt. The mean percentage drop in omental pressure was 34.2% post-shunt with a mean anastomotic diameter of 13.7 ± 3.1 mm. Three patients experienced some form of postoperative complication. With a mean follow-up period of 32.3 months (maximum of 111 months) all patients had patent shunts on follow-up Doppler. None of the patients had variceal bleed, or features of biliopathy and hepatic encephalopathy in follow-up. Conclusion: Unconventional shunts can be used safely and effectively with good postoperative outcomes in EHPVO.

The Utility of Biliary Manometry in Assessing Early Catheter Removal After Percutaneous Balloon Dilatation of Hepaticojejunostomy Strictures.

Background and objective Percutaneous balloon dilatation followed by long-term internal-external biliary catheter (IEBC) placement is the standard radiological management for postoperative hepaticojejunostomy (HJ) strictures. The treatment is considered successful when cholangiography shows a free flow of contrast across the anastomosis and the patient passes a "clinical test". However, these tests may not be suitable predictors of long-term successful treatment outcomes. The purpose of this study was to assess the utility of biliary manometry in the evaluation of successful treatment outcomes after HJ stricture dilatation and IEBC placement and its efficacy as a tool for early catheter removal. Patients and methods A total of 14 patients underwent percutaneous balloon dilatation of HJ strictures with IEBC placement. A two-to-three-month interval was maintained between sessions of exchanging or upsizing IEBCs. Biliary manometry was performed after a mean duration of 6.3 months. Intra-biliary pressure of <15 mmHg was considered as the success threshold. Results Among the 14 patients, 11 patients passed initial manometry and had their IEBCs removed and were followed up for a mean duration of 47.8 months. Of these, one patient developed biliary obstruction after six months and underwent repeat HJ stricture dilatation and long-term IEBC placement. Three patients failed manometry and underwent re-dilatation of HJ strictures with IEBC placement. Using Kaplan-Meier survival analysis, the probability of patients remaining stricture-free after HJ stricture dilatation was found to be 100% at three months and 91% at six, 12, 18, 24, 36, and 47.8 months. Conclusion Biliary manometry prevents subjective variations in determining treatment endpoints and helps to assess early catheter removal after percutaneous balloon dilatation of HJ strictures.

Gallbladder reporting and data system (GB-RADS) for risk stratification of gallbladder wall thickening on ultrasonography: an international expert consensus.

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0-5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management.

Retroperitoneal Lymph Node Metastasis in Gallbladder Cancer: As Bad as Distant Metastasis.

Ashish SinghBackground Regarding gallbladder cancer (GBC) there is conflicting evidence in the literature whether retroperitoneal lymph nodal metastases (RLNM) should be considered as regional nodal metastasis or as distant metastasis (DM) and the jury is out on radical curative surgery in presence of RLNM. This is an analysis of GBC patients, to see the effect of RLNM on survival and to compare with that of patients with DMs. Methods A retrospective analysis of a prospective database of patients of GBC with RLNM (interaortocaval and paraaortic) or DM on frozen section biopsy at surgery, between January 2013 and December 2018. Data was analyzed using the Statistical Package for the Social Sciences software (version 22.0). Survival in these two groups (RLNM and DM) was compared with log-rank test. A p -value of < 0.05 was considered significant. Results A total of 235 patients with ostensibly resectable GBC underwent surgical exploration. The planned curative resection was abandoned in 91 (39%) patients because of RLNM ( n = 20, 9%) or DM ( n = 71, 30%) on frozen section biopsy. Demographic profile and blood parameters were similar. The median survival for RLNM and DM groups were 5 (range 2-26) and 6 (range 2-24) months, respectively, with no significant difference on log-rank test ( p = 0.64). There was no 3-year or longer survivor in either group. Conclusion Due to similar poor survival in presence of RLNM or DM, RLNM should be considered as the equivalent of DM. This study strengthens evidence to avoid curative surgery in patients with RLNM. These lymph nodes should be sampled preoperatively, if suspicious on imaging, for fine-needle aspiration cytology and at surgery, as a routine for frozen section histological examination before initiating curative resection to avert a futile exercise.

Roles of Salmonella typhi and Salmonella paratyphi in Gallbladder Cancer Development.

BACKGROUND: Typhoid (Salmonella typhi and paratyphi) carriers and gall bladder cancer (GBC) are endemic in northern India. Results of previous studies about association of typhoid carriers with GBC are inconsistent. We studied antibodies against Salmonella typhi and paratyphi in serum samples of patients with GBC. METHODS: We performed modified Widal test for antibodies against Salmonella typhi (Vi and O) and Salmonella paratyphi (AO and BO) antigens in patients with GBC (n=100), xanthogranulomatous cholecystitis (XGC, n=24), chronic cholecystitis (CC, n=200) and healthy controls (HC, n=200). RESULTS: Serum antibodies against Salmonella were more frequently positive in GBC (22%) and XGC (29%), particularly in males in age ≥50 years (GBC: 47% and XGC: 50%) vs. HC (0) (p <0.01). Vi antibody was more common in GBC (13%, OR:9.8) and XGC (8%, OR:5.9) than HC (2%). O antibody was more common in GBC (8%, OR: 8.6) and XGC (8%, OR: 9.0) than HC (1%). O antibody was also more common in males with GBC (12%) than CC (1%) and HC (1%) (P=0.02 and p <0.001, respectively). AO (6%) and BO (4%) antibodies were detected in GBC, particularly in males, than HC (0), (p <0.01). Salmonella antibodies were more frequent in GBC with GS than those without GS (50% vs. 20%, OR=3.94, P=0.01). CONCLUSIONS: Salmonella carrier state was more common in GBC and XGC, particularly in elderly males than HC. The Vi antibody was more common in GBC and XGC than HC. Salmonella infection was more common in GBC with GS than those without GS.

Risk factors for gallbladder cancer development in northern India: A gallstones-matched, case-control study.

Background & objectives: A high incidence of gallbladder cancer (GBC) is observed in northern India. This study was aimed to identify the factors involved in developing GBC in this region. Methods: A gallstones-matched, case-control study was conducted in northern India. Ninety nine patients with GBC and gallstones (33 men and 66 women, mean age of 51.4 yr) comprised the case group, while 99 patients with cholelithiasis (40 men and 59 women, mean age of 45.7 yr) comprised the control group. All participants were interviewed to complete 183 questionnaire items that included 105 food items. Potential risk factors were identified using a multivariate analysis adjusted for age and sex. Significant risk factors were identified using a stepwise logistic-regression analysis. Results: Age (≥50 yr), education (illiterate), socioeconomic status (≤below poverty line), bowel habits (≤once a day), hypertension history, hypotensive drug use, non-vegetarian diet, use of firewood for cooking, tap water drinking, hand pump water drinking and high consumption of coffee and sweets were identified as the potential risk factors. In women, factors included menarche (<13 yr), number of pregnancies (≥3 pregnancies) and parity (≥3 babies). Of these factors, age, education, bowel habits, tap water drinking and multiple pregnancy and/or multiparity were identified as significant risk factors, whereas a high consumption of coffee and sweets or hypotensive drug use and/or hypertension history were protective factors. Interpretation & conclusions: Poor bowel habits and drinking unsafe water appear to be the main risk factors for developing GBC. These are, however, modifiable factors which are capable of decreasing the risk of GBC in the north Indian population.

Bile duct injury during laparoscopic cholecystectomy: An Indian e-survey.

BACKGROUNDS/AIMS: In the absence of national registry of laparoscopic cholecystectomy (LC) or its complications, it is impossible to determine incidence of bile duct injury (BDI) in India. We conducted an e-survey among practicing surgeons to determine prevalence and management patterns of BDI in India. Our hypothesis was that majority of surgeons would have experienced a BDI during LC despite large experience and that most surgeons who have a BDI tend to manage it themselves. METHODS: An 18-question e-survey of practicing laparoscopic surgeons in India was done. RESULTS: 278/727 (38%) surgeons responded. 240/278 (86%) respondents admitted to a BDI during LC and 179/230 (78%) affirmed to more than one BDI. A total of 728 BDIs were reported. 36/230 (15%) respondents experienced their first BDI even after ＞10 years of practice and 40% had their first BDI even after having performed ＞100 LCs. 161/201 (80%) of the respondents decided to manage the BDI themselves, including 56/99 (57%) non-biliary surgeons and 44/82 (54%) surgeons working in non-biliary center. 37/201 (18%) respondents admitted to having a mortality arising out of a BDI; the mortality rate of BDI was 37/728 (5%) in this survey. Only 13/201 (6%) respondents have experienced a medico-legal case related to a BDI during LC. CONCLUSIONS: Prevalence of BDI is high in India and occurs despite adequate experience and volume. Even inexperienced non-biliary surgeons working in non-biliary centers attempt to repair the BDI themselves. BDI is associated with significant mortality but litigation rates are fortunately low in India.

Outcome of portosystemic shunt surgery on pre-existing cholangiopathy in children with extrahepatic portal vein obstruction.

BACKGROUND: This study was performed to assess the effect of portosystemic shunt surgery (PSS) on portal cavernoma cholangiopathy (PCC) in children with extrahepatic portal vein obstruction (EHPVO). METHODS: Children with EHPVO and PCC (unfit for Meso-Rex shunt) underwent magnetic resonance cholangiogram (MRC) and magnetic resonance portovenogram (MRPV) before non-selective PSS. PCC was graded by modified Llop classification. Those with patent shunt were re-evaluated at least 6 months after surgery with MRC, MRPV and compared with pre-shunt images. RESULTS: Twenty-five children underwent PSS (central end to side splenorenal shunt with splenectomy [n = 24], mesocaval shunt [n = 1]). Pre-surgery MRC showed PCC grade I in 11, grade II in 1 and grade III in 13. MRPV showed superior mesenteric vein (SMV) block in 20. Re-assessment for PCC 18 (6 to 54) months after surgery showed grade I in 6 and grade III in 19. Thus, PCC was progressive in 6 and static in 19. Density of peribiliary collaterals decreased in 5 (SMV patent, static PCC), increased in 3 and remained unchanged in 17. Splenomegaly-related problems, gastroesophageal varices and other intra-abdominal (esophageal, perisplenic and perigastric) collaterals ameliorated in all. CONCLUSION: Non-selective PSS decompresses esophago-gastro-splenic venous circuit effectively but fails to ameliorate cholangiopathy and peribiliary collaterals. Persistence of cholangiopathy is attributable to SMV block.

Carcinogen Metabolism Pathway and Tumor Suppressor Gene Polymorphisms and Gallbladder Cancer Risk in North Indians: A Hospital-Based Case-Control Study.

BACKGROUND: Carcinogen metabolism pathway and tumor suppressor gene polymorphisms have been reported to be associated with increased gallbladder cancer risk. However, the association of genetic variants and gallbladder cancer risk in Indians are not well studied. We examined whether genetic polymorphisms of metabolic enzymes cytochrome P450 1A1 and glutathione S-transferase and tumor suppressor gene p53 (TP53) are associated with an increased risk of gallbladder cancer in North Indians. METHODS: This hospital-based case-control study was conducted in 96 gallbladder cancer patients with gallstones (cases) and 93 cholelithiasis patients (controls) at the Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India from July 2014 through May 2017. Genomic DNA was extracted from white blood cells of each patient using a simple salting-out procedure. The genotypic frequencies of CYP1A1 rs4646903, CYP1A1 rs1048943, and TP53 rs1042522 polymorphisms were investigated using TaqMan SNP Genotyping Assay and GSTM1 and GSTT1 polymorphisms were analyzed using the multiplex PCR assay. RESULTS: The frequency of CC genotype of TP53 rs1042522 polymorphism was 27.1% (26/96) in cases and 12.9% (12/93) in controls. The CC genotype was associated with an increased risk of gallbladder cancer in North Indians (age- and sex-adjusted odds ratio, 2.81; 95% confidence interval, 1.19-6.61; P = 0.02). No significant differences in genotypic and allelic frequencies of the metabolic pathway gene polymorphisms were found between cases and controls. CONCLUSIONS: Our data provide preliminary evidence that the CC genotype of the TP53 rs1042522 polymorphism may be associated with an increased risk of gallbladder cancer in North Indians.

Non-variceal gastrointestinal bleed in children: surgical experience with emphasis on management challenges.

PURPOSE: This exclusively surgical series on pediatric non-variceal gastrointestinal bleed (NVGIB) defines three levels of bleed site and describes etiology, bleed severity, diagnostic algorithm, and surgical management for each bleed site. Management challenges are detailed. METHODS: Patients aged ≤ 18 years treated surgically for NVGIB were analysed. RESULTS: Bleed site (n = 87) was classified as: upper gastrointestinal bleed (UGIB; n = 11); small bowel bleed (SBB: n = 52); and lower GIB (n = 24). Four etiology-based groups were identified: lesions with ectopic gastric mucosa (EGM; n = 33), tumours (n = 23), ulcers (n = 21), and vascular pathology (n = 8). Bleed severity spectrum was: acute severe bleed (n = 12); subacute overt bleed (n = 59); and occult GIB (n = 16). Preoperative diagnosis was obtained in all UGIB and LGIB lesions. Eighty-two percent of surgical SB lesions were diagnosed preoperatively on Tc99m pertechnetate scan, computed tomography enterography-angiography, and capsule endoscopy; remaining 18% were diagnosed at laparotomy with intra-operative enteroscopy (IOE). Surgical management was tailored to bleed site, severity, and etiology. Indications of IOE and approach to management challenges are detailed. CONCLUSIONS: The commonest site-specific bleed etiologies were duodenal ulcers for UGIB, EGM lesions for SBB, and tumours for LGIB. SBB presented diagnostic challenge. Diagnostic algorithm was tailored to bleed site, age-specific etiology, bleed severity, and associated abdominal/systemic symptoms. Management challenges were acute severe bleed, occult GIB, SBB, obscure GIB, and rare etiologies. IOE has a useful role in SBB management.

Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome.

BACKGROUND: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. OBJECTIVE: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. METHODS: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. RESULTS: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5µM) in combination with Jab1-siRNA. CONCLUSION: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.

Plasma Helicobacter pylori Antibody Titers and Helicobacter pylori Infection Positivity Rates in Patients with Gallbladder Cancer or Cholelithiasis: a Hospital-Based Case-Control Study

Objective: Gallbladder cancer is the commonest gastrointestinal cancer in northern Indian women. Some studies have examined the association between Helicobacter pylori infection and gallbladder cancer risk, but findings have been inconsistent. We aimed to examine the association between H. pylori infection and gallbladder cancer in Indian people. Materials and Methods: We conducted a hospital-based case-control study including 100 gallbladder cancer patients with gallstones who were 32 to 79 years old (cases; 72 women and 28 men), and 100 cholelithiasis patients aged 14 to 75 years (controls; 65 women and 35 men). All patients had a diagnosis of gallbladder cancer or cholelithiasis at the Sanjay Gandhi Post Graduate Institute of Medical Sciences in Lucknow having a high gallbladder cancer incidence in northern India, from May 2014 through July 2017. Plasma samples were collected from all patients before surgical treatment. Plasma H. pylori antibody titer was measured by the latex agglutination method and an autoanalyzer. H. pylori infection was defined as antibody titer ≥10 U/mL. Plasma antibody titers and H. pylori infection positivity rates were compared between cases and controls. Results: Mean plasma antibody titers (standard deviation, range) were 11.1 U/mL (11.6, 0­78) in cases and 13.6 U/mL (23.0, 1­164) in controls. H. pylori infection positivity rates were 41% and 42% in cases and controls, respectively. No significant differences in antibody titers or H. pylori infection positivity rates were found between cases and controls. Conclusions: We found no evidence of H. pylori infection as an important risk factor for gallbladder cancer in Indian people.

Management of residual gall bladder: A 15-year experience from a north Indian tertiary care centre.

BACKGROUNDS/AIMS: A residual gallbladder (RGB) following a partial/subtotal cholecystectomy may cause symptoms that require its removal. We present our large study regarding the problem of a RGB over a 15 year period. METHODS: This study involved a retrospective analysis of patients managed for symptomatic RGB from January 2000 to December 2015. RESULTS: A RGB was observed in 93 patients, who had a median age of 45 (25-70) years, and were comprised of 69 (74.2%) females. The most common presentation was recurrence pain (n=64, 68.8%). Associated choledocholithiasis was present in 23 patients (24.7%). An ultrasonography (USG) failed to diagnose RGB calculi in 10 (11%) patients; whereas, magnetic resonance cholangio-pancreatography (MRCP) accurately diagnosed RGB calculi in all the cases except for 2 (4%) and, additionally, detected common bile duct (CBD) stones in 12 patients. Completion cholecystectomy was performed in all patients (open 45 [48.4%]; laparoscopic 48 [51.6%] and 19 [20.4%] patients required a conversion to open). The RGB pathology included stones in 90 (96.8%), Mirizzi's syndrome in 10 (10.8%) and an internal fistula in 9 (9.7%) patients. Additional procedures included CBD exploration (n=6); Choledocho-duodenostomy (n=4) and Roux-en-Y hepatico-jejunostomy (n=3). The mortality and morbidity were nil and 11% (all wound infection), respectively. Two patients developed incisional hernia during follow up. The mean follow up duration was 23.1 months (3-108) in 65 patients and the outcome was excellent and good in 97% of the patients. CONCLUSIONS: Post-cholecystectomy recurrent biliary colic should raise suspicion of RGB. MRCP is a useful investigation for the diagnosis and assessment of any associated problems and provides a roadmap for surgery. Laparoscopic completion cholecystectomy is feasible, but is technically difficult and has a high conversion rate.

Splenic tuberculosis in an immunocompetent patient can be managed conservatively: a case report.

Tuberculosis is a significant health problem in developing countries. Splenic tuberculosis usually occurs as a part of miliary tuberculosis, and ranks third after lung and liver involvement, respectively. Splenic involvement is more common in immunocompromised patients and is very rarely found in immunocompetent patients. Here we report a case of splenic tuberculosis in an immunocompetent patient, which was managed successfully with conservative treatment.