Predictors of Toxicity in a Randomized Study of Consolidation Chemoradiation Versus Observation After First Line Chemotherapy in Advanced Gall Bladder Cancers.

Purpose: Gall bladder cancers (GBC) usually presents in advanced stage. First-line chemotherapy (CT) is the standard of care, and there is no other option for responders than to wait for disease progression. We conducted a randomized study of consolidation chemoradiation (CTRT) versus observation in responders to first line CT (NCT05493956), which showed an improvement in overall survival by 6 months and therefore is practice changing. We are reporting the toxicity and factors predicting toxicity due to CTRT so that it informs appropriate patient selection. Methods and Materials: Responders to first line CT (partial response, stable disease) were randomized to CTRT versus observation after 4 cycles. CTRT was delivered by 3D conformal radiotherapy (along-with concurrent capecitabine at 1250 mg/m2) to a dose of 45 Gy in 25 fractions to GBC and lymphatics followed by a boost of 9 Gy in 5 fractions to the GBC. Toxicities documented during CTRT were recorded using the Radiation Therapy Oncology Group criteria. Dose volume data were correlated with the radiation induced side effects. Results: Among 135 patients enrolled both arms are well balanced demographically, and 58% patients had T4 tumors, 42% had N2 and 15% had paraaortic lymph node, and 27% underwent upfront stenting. Grade 3 adverse events, such as anemia, dyspepsia, hepatotoxicity (Child Pugh B), and gastrointestinal bleed due to CTRT was observed in 9%, 1.5%, 13%, and 5.8%, respectively. Age >58 years (P = .02), planning target volume (PTV) 1 volume (>919 cc, P = .02), PTV2 volume (>380 cc, P = .01), mean liver dose (>28 Gy, P = .07), and liver V40 (>50%, P = .02) predicted radiation-induced liver disease. A receiver operating curve analysis revealed a cut-off value of PTV1 volume of 800 cc (sensitivity and specificity of 75% and 54%) and PTV2 volume of 300 cc (sensitivity and specificity of 81% and 65%) for prediction of hepatotoxicity. Duodenum V45 >45% (P = .02) predicted grade 3 anemia. Numerically high V15 duodenum (98%, P = .11), large PTV2 volume >484 cc (P = .06) and prior stenting had predilection for gastrointestinal bleed. Conclusions: Consolidation CTRT is tolerable in those with PTV1 volume less than 800 cc.

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.

Raised carbohydrate antigen 19-9 levels detect recurrences and impacts overall and disease-free survival in radically resected gallbladder cancer: A simple surveillance marker?

Background: There are no established markers which can be used for surveillance after curative resection in gallbladder carcinoma (GBC). Though carbohydrate antigen 19-9 (CA 19-9) has low specificity as a diagnostic marker, its role as a surveillance marker has not been explored. The aim of this study is to evaluate the predictive ability of CA 19-9 as a surveillance marker to detect recurrences on follow-up. Methods: A retrospective analysis of a prospectively maintained database of radically resected GBC who were either on observation or completed adjuvant therapy (chemotherapy or chemoradiation) were followed up 3 monthly with CA 19-9 and ultrasound (US) abdomen for the first 2 years and 6 monthly CA 19-9 and US for further 3 years. Patients with raised CA 19-9 and a recurrent lesion on US abdomen were confirmed with contrast-enhanced computed tomography (CECT) abdomen and fine-needle aspiration cytology (FNAC) of recurrent lesion to establish the diagnosis of recurrence. The performance of CA 19-9 levels (20 and more units/mL) for prediction of recurrence and its impact on survival was estimated. Results: Out of sixty patients on follow-up, 40% recurred: loco-regional (16.7%) and distant metastases (23.4%). The sensitivity, specificity, positive predictive value, and negative predictive value of CA 19-9 in detecting recurrence were 79.1%, 97.2%, 95%, and 87.5%, respectively. The median disease-free survival was 56 months versus 15 months (P = 0.008, hazard ratio [HR]: 7.4 [1.3-40]) and the median overall survival was not reached versus 20 months (P = 0.000, HR: 10.7 [confidence interval 4.2-27.3]) for CA 19-9 levels less than and more than 20 ng/mL. Conclusions: Based on the high positive and negative predictive value in our dataset, CA 19-9 can be used as a surveillance biomarker for follow-up of radically resected GBC. Raised levels of >20 ng/mL should be correlated with imaging findings and any suspicious lesion should be confirmed for recurrence by FNAC and CECT abdomen. Levels >20 ng/mL should be taken as a threshold for suspecting recurrence.

Chemotherapy or chemotherapy followed by consolidation chemoradiation in postoperative (simple cholecystectomy) gall bladder cancer with residual disease, unsuitable for revision surgery? Risk stratification and outcomes.

Background: Revision surgery (RS) is the standard of care for gallbladder cancer (GBC) after simple cholecystectomy (SC). Often these patients are unsuitable for RS due to late referral or unresectable disease. Do such patients benefit with chemotherapy (CT) alone or dual-modality (CT followed by consolidation chemoradiotherapy [CTRT])? In the absence of any guidelines, we reviewed our data with CT or CTRT to inform us regarding adequate therapy. Materials and Methods: Patients of GBC post-SC referred to us (January 2008 to December 2016) were risk-stratified into three categories based on a diagnostic CT scan: No residual disease (NRD), limited volume residual disease (LR1: Residual/recurrent disease in GB bed with or without N1 nodal station involvement), advanced residual disease (LR2: Residual/recurrent disease involving GB bed with N2 nodal station involvement) and treated with CT or CT followed by CTRT. Response to therapy (RECIST), overall survival (OS), and adverse prognostic factors affecting OS were evaluated. Results: Out of 176 patients, 87were nonmetastatic (NRD = 17, LR1 = 33 and LR 2 = 37). 31 received CT, 49 CTRT and 8 defaulted. At a median follow up of 21 months, the median OS with CT versus consolidation CTRT was not reached in NRD (P = 0.57), 19 months versus 27 months in LR1 (P = 0.003) and 14 months versus 18 months in LR 2 (P = 0.29), respectively. On univariate analysis, residual disease burden, type of treatment (CT vs. CTRT), N stage, and response to treatment were found statistically significant. Conclusion: Our data suggest that CT followed by CTRT improves outcomes in patients with limited volume disease.

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.

Multifocal Small Bowel Angioectasias: Managed with Innovative, Nonresectional Surgical Procedure.

Gastrointestinal (GI) angioectasias/angiodysplasias are the most frequent vascular lesions of GI tract, responsible for ∼5 to 6% of GI bleedings. It commonly involves the small bowel, making it difficult to diagnose and manage endoscopically. Though medical management has been used to prevent bleeding, it has only a limited role in acute severe hemorrhage. In such cases, surgical resection remains the only practical option. However, multiple lesions pose a unique challenge, as resection may not be advisable for long length of bowel involvement. Here, we report a case of recurrent GI bleeding due to multifocal small bowel angioectasias who was managed by a novel technique of full-thickness transmural sutures under intraoperative enteroscopic guidance. At 6 months follow-up, no new bleeding episodes were observed.

Does Timing of Completion Radical Cholecystectomy Determine the Survival Outcome in Incidental Carcinoma Gallbladder: A Single-Center Retrospective Analysis.

Introduction Incidental discovery of gallbladder cancer (GBC) on postoperative histopathology or intra-operative suspicion is becoming increasingly frequent since laparoscopic cholecystectomy became the standard of care for gallstone disease. Incidental GBC (IGBC) portends a better survival than primarily detected GBC. Various factors affect the outcome of re-resection with the timing of re-intervention an important determinant of survival. Methods All patients of IGBC who underwent curative resection from January 2009 to December 2018 were considered for analysis. Details of demographic profile, index surgery, and operative findings on re-resection, histopathology and follow-up were retrieved from the prospectively maintained database. Patients were evaluated in three groups based on the interval between index cholecystectomy and re-resection: Early (<4 weeks), Intermediate (4-12 weeks) and Late (>12 weeks), using appropriate statistical tests. Results Ninety-one patients were admitted with IGBC during the study period of which 48 underwent re-resection with curative intent. The median age of presentation was 55 years (31-77 years). The median duration of follow-up was 40.6 months (Range: 1.2-130.6 months). Overall and disease-free survival among the above-mentioned three groups was the best in the early group (104 and 102 months) as compared to the intermediate (84 and 83 months) and late groups (75 and 73 months), though the difference failed to achieve statistical significance (p=0.588 and 0.581). On univariate analysis, factors associated with poor outcome were node metastasis, need for common bile duct (CBD) excision and high-grade tumor. However, on multivariate analysis, poor differentiation was the only independent factor affecting survival. Conclusion Early surgery, preferably within four weeks, possibly entails better survival in incidentally detected GBC. The grade of a tumor, however, is the most important determinant of survival in IGBC.

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.

Post-endoscopic retrograde cholangiopancreatography perforation managed by surgery or percutaneous drainage.

PURPOSE: Post-endoscopic retrograde cholangiopancreatography (ERCP) perforation usually resolves conservatively; however, intervention is sometimes needed, and there is a paucity of literature regarding the best management approach. We evaluated our experience of managing post-ERCP perforations to help define the role of surgery with percutaneous drainage (PCD). METHODS: A retrospective chart review revealed 14 cases of post-ERCP perforation with intra-abdominal sepsis referred for intervention. We analyzed data pertaining to clinical details, management, and outcome. RESULTS: There were 12 patients with duodenal perforation and 2 with biliary perforation. Most (10/14; 72%) had symptom onset within 48 h, but delayed diagnosis or referral resulted in a mean delay until intervention of 6.6 days (range 1-18 days). Computed tomography revealed localized collections in 9 (64%) patients. Seven patients with localized collections and no or minimal contrast leak underwent PCD and rest, and 7 underwent surgery. The indications for surgery were free perforation, generalized peritonitis, and major contrast leak. Overall morbidity was 50% and there was one early postoperative death, caused by severe sepsis. CONCLUSION: There should be a high index of suspicion of perforation when abdominal signs and symptoms develop after ERCP. Computed tomography is the investigation of choice for diagnosis and guiding therapy. With judicious selection of surgery or PCD based on clinical and imaging features, patients can be managed with acceptable morbidity and low mortality.

Economics and safety of continuous and interrupted suture hepaticojejunostomy: An audit of 556 surgeries.

BACKGROUNDS/AIMS: Hepaticojejunostomy (HJ) for bilioenteric continuity is generally performed with interrupted sutures. This study compares the safety, economics, short- and long-term outcomes of continuous suture hepaticojejunostomy (CSHJ) and interrupted suture hepaticojejunostomy (ISHJ). METHODS: A retrospective cohort analysis involving all HJs between January 2014 and December 2018 was conducted. Patients with type IV or V biliary strictures, duct diameter < 8 mm and/or associated vascular injury, and liver transplant recipients were excluded. Patient demographics, preoperative parameters including diagnosis, intra-operative parameters including type and number of sutures, suture time, and postoperative morbidity (based on Clavien-Dindo classification) were recorded. Patients were followed up to 60 months. McDonald's Grade A and B outcomes were considered favorable. Cost according to suture type and number (polydioxanone 3-0/5-0 mean cost, US$ 9.26/length; polyglactin 3-0/4-0 mean cost, US$ 6.56/length), and operation room charge (US$ 67.47/hour) were compared between the two techniques. Statistical analysis was performed using IBM SPSS ver. 22 software. RESULTS: A total of 556 eligible patients (468 patients undergoing ISHJ and 88 undergoing CSHJ; 47% [n = 261] with malignant and 53% [n = 295] with benign pathology) were analyzed. The two groups were similar. Number of sutures, cost, time, and postoperative bile leak were significantly higher in the ISHJ group. Bile leak occurred in 54 patients (6 CSHJ, 48 ISHJ). Septic shock-induced death occurred in 16 cases (3 CSHJ, 13 ISHJ). Morbidity and the anastomotic stricture rates were comparable in both groups. CONCLUSIONS: CSHJ is a safe, economical, and worthy of routine use.

Determinants of curative resection in incidental gallbladder carcinoma with special reference to timing of referral.

BACKGROUNDS/AIMS: Re-resection of incidental gallbladder carcinoma (IGBC) is possible in a select group of patients. However, the optimal timing for re-intervention lacks consensus. METHODS: A retrospective analysis was performed for a prospective database of 91 patients with IGBC managed from 2009 to 2018. Patients were divided into three groups based on the duration between the index cholecystectomy and re-operation or final staging: Early (E), < 4 weeks; Intermediate (I), > 4 weeks and < 12 weeks; and Late (L), > 12 weeks. Demographic data, tumor characteristics, and operative details of patients were analyzed to determine factors affecting the re-resectability of IGBC. RESULTS: Twenty-two patients in 'E', 48 in 'I', and 21 in 'L' groups were evenly matched. Nearly two thirds were asymptomatic. Curative resection was possible in 48 (52.7%) patients. Metastasis was detected during staging laparoscopy (SL)/laparotomy in 26 (28.6%) patients. The yield of SL was more in the 'L' group (30.8%) than in the 'I' (11.1%) or 'E' (nil) group, avoiding unnecessary laparotomy in 13.6%. Only 28.5% of patients in the 'L' group could undergo curative resection (R0/R1 resection), significantly less than that in the 'E' (50.0%) or 'I' group (64.6%) (both p < 0.001). On multivariate analysis, presentation in intermediate period and tumor differentiation increased the chance of curative resection (p < 0.05). CONCLUSIONS: Asymptomatic patients in the 'I' group with well differentiated IGBC have the best chance of obtaining a curative resection.

Incidence, pattern and management of bile duct injuries during cholecystectomy: experience from a single center.

BACKGROUND: The incidence and pattern of bile duct injury (BDI) may be underreported because of the heterogeneous referral from multiple institutions. METHODS: Retrospective analysis of data from 5,782 cholecystectomies performed between 1989 and 2007 was done. BDI were categorized into Strasberg types. RESULTS: Fifty-seven (1%) patients sustained BDI. Ten of 57 (18%) patients had minor BDI (type A-10), 25/57 (44%) had major BDI (type C-3, type D-14, type E-8) and BDI could not be classified in the remaining 22/57 (39%) patients. Twenty-one of 25 (84%) major BDI were detected at operation - 21/57 (37%) injuries were detected and repaired intra-operatively. The other 36/57 (63%) injuries were detected after operation - 11 were managed expectantly, 5 had endoscopic stenting, 3 underwent percutaneous drainage of bilioma, 1 had a laparoscopic clipping of the subvesical duct, 4 underwent laparotomy and 12 required a combination of interventions. Five of the 57 (9%) patients died. At follow-up, 1 patient developed bile duct stricture which was managed endoscopically. All other patients were doing well at the last follow-up. CONCLUSIONS: In experienced centers, most of the major BDI can be detected and managed during cholecystectomy. Good results can be achieved by judicious selection of a combination of interventions in the majority of patients.

Peri-operative outcomes for pancreatoduodenectomy in India: a multi-centric study.

BACKGROUND: There have been an increasing number of reports world-wide relating improved outcomes after pancreatic resections to high volumes thereby supporting the idea of centralization of pancreatic resectional surgery. To date there has been no collective attempt from India at addressing this issue. This cohort study analysed peri-operative outcomes after pancreatoduodenectomy (PD) at seven major Indian centres. MATERIALS AND METHODS: Between January 2005 and December 2007, retrospective data on PDs, including intra-operative and post-operative factors, were obtained from seven major centres for pancreatic surgery in India. RESULTS: Between January 2005 and December 2007, a total of 718 PDs were performed in India at the seven centres. The median number of PDs performed per year was 34 (range 9-54). The median number of PDs per surgeon per year was 16 (range 7-38). Ninety-four per cent of surgeries were performed for suspected malignancy in the pancreatic head and periampullary region. The median mortality rate per centre was four (range 2-5%). Wound infections were the commonest complication with a median incidence per centre of 18% (range 9.3-32.2%), and the median post-operative duration of hospital stay was 16 days (range 4-100 days). CONCLUSIONS: This is the first multi-centric report of peri-operative outcomes of PD from India. The results from these specialist centers are very acceptable, and appear to support the thrust towards centralization.

Xanthogranulomatous inflammatory strictures of extrahepatic biliary tract: presentation and surgical management.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a benign, invasive variant of chronic cholecystitis. Invasion of common bile duct (CBD), termed as xanthogranulomatous choledochitis, may mimic malignancy. We describe clinico-pathological features and management of xanthogranulomatous inflammatory biliary strictures. METHODS: A review of a prospectively maintained database for XGC was performed. RESULTS: Out of 6,150 cholecystectomies performed, 620 patients had XGC (10% incidence). Four patients had biliary strictures with xanthogranulomatous choledochitis on final histology. All four patients presented with jaundice and history of cholangitis. Ultrasonography revealed gallstones and thick-walled gallbladder in all. Two patients had hilar strictures: one had mid-CBD stricture and one had a lower-CBD stricture with a dilated pancreatic duct. In all four patients, preoperative diagnosis of malignancy was entertained. Three patients underwent resection-CBD excision for mid-CBD stricture, pancreaticoduodenectomy for lower-end stricture, and right hepatectomy for hilar stricture with atrophy-hypertrophy complex. One patient with unresectable hilar stricture underwent hepaticojejunostomy. CONCLUSION: Xanthogranulomatous choledochitis may be considered as one of the differential diagnosis in patients with biliary stricture especially in a geographical area with a high incidence of XGC, when a patient harbors gall stones and had thick-walled gall bladder on imaging. This stricture can be found anywhere in the biliary tree from hepatic hilum to the lower end. However, preoperative imaging and cytology are unreliable both in confirming the diagnosis or ruling out malignancy. Therefore, resection of the stricture should be attempted wherever feasible.

Liver histology in benign biliary stricture: fibrosis to cirrhosis . . . and reversal?

BACKGROUND: Secondary biliary cirrhosis is a potential complication of post-cholecystectomy bile duct stricture (PCBDS). This study addresses the factors that determine the severity of pathological changes on liver biopsy and the correlation with long-term outcome following repair. METHODS: Liver biopsies obtained at surgery for repair of PCBDS in 71 patients were reviewed and pathological changes were scored from 0 to 3. Patients with fibrosis score 0-2 were categorized as the non-cirrhotic group and those with score 3 (secondary biliary cirrhosis) were categorized as the cirrhotic group. Clinical and biochemical parameters, stricture type and outcome were analyzed by univariate and multivariate analysis for correlation with degree of fibrosis. Follow-up liver biopsies (3-60 months) after stricture repair were obtained in five patients. RESULTS: There were 58 patients in the non-cirrhotic group and 13 in the cirrhotic group. On univariate analysis, portal hypertension and prolonged injury-repair duration correlated with secondary biliary cirrhosis. Patients with a fair outcome in the cirrhotic group (4/13) had derangements in liver function tests but had patent biliary enteric anastomosis on evaluation. Of the five patients in whom liver biopsies were obtained at follow up, two had regression, two were static, and one had progression. CONCLUSION: All patients with PCBDS had varying degrees of fibrosis. Prolonged injury-repair interval and portal hypertension were the important parameters correlating with secondary biliary cirrhosis. Early repair of biliary stricture is recommended to prevent liver fibrosis. A successful relief of biliary obstruction may halt and/or reverse pathological changes in the liver.

Post-cholecystectomy biliary strictures: not always benign.

BACKGROUND: Post-cholecystectomy malignant biliary obstruction masquerading as benign biliary stricture (BBS) has not been reported in the literature; it presents a diagnostic and management challenge. METHODS: Of the 349 post-cholecystectomy BBS managed at a tertiary care hospital in northern India between 1989 and 2004, 11 patients were found to have biliary malignancy. Records of these 11 patients were analyzed retrospectively for the purpose of this study. RESULTS: Mean age of patients with malignant biliary strictures was significantly higher (52 vs 38 years, P = 0.000); they were more likely to have jaundice (100% vs 78%, P = 0.008) and pruritus (82% vs 48%, P = 0.03). Unlike most patients with BBS referred from elsewhere to us, they had had a smooth postoperative course uncomplicated by bile leak, had a longer cholecystectomy-presentation interval, and were more likely to have high strictures ((Bismuth type III/IV) 91% vs 49%, P = 0.008). CONCLUSIONS: Post-cholecystectomy biliary obstruction is not always benign. High bilirubin levels and hilar strictures, especially after an uneventful cholecystectomy, in a middle-aged patient should raise a suspicion of underlying missed malignancy.

Does CA 19-9 Have Prognostic Relevance in Gallbladder Carcinoma (GBC)?

BACKGROUND: There is a scarce data on prognostic relevance of carbohydrate antigen (CA 19-9). This retrospective study was undertaken to evaluate its prognostic relevance in different prognostic subsets of gallbladder carcinoma (GBC). MATERIALS AND METHODS: One hundred forty-one patients of GBC treated between January 2012 and December 2014 were the subjects of this retrospective analysis. Baseline CA 19-9 levels of four cohorts of patients: extended cholecystectomy (EC), simple cholecystectomy (SC) with residual or recurrent disease, locally advanced disease (LAGBC) and metastatic disease were ascertained. The difference in its median baseline values among above groups was ascertained. The effect of clinicopathological variables, treatment-related variables and CA 19-9 on overall survival (OS) was also evaluated. AUC curve was computed to evaluate its performance. RESULTS: The median baseline levels of CA 19-9 were significantly different [10 units/ml, 24 units/ml, 48 units/ml and 75 units/ml in EC (n = 33), SC (n = 21), LAGBC (n = 38) and metastatic disease (n = 49), respectively, (p value 0.001)]. The median OS was also significantly different [24, 15, 7 and 6 months in EC, SC, LAGBC and metastatic disease, respectively, (p value 0.001)]. Univariate analysis revealed a significant influence of log transformed value of CA 19-9, CA 19-9 levels < or >20 units or 35 units, surgery vs. none and chemoradiation vs. chemotherapy on OS. On multivariate analysis, only treatment-related variables were significant (HR 1.1, 95% CI 1.026-1.19, p = 0.009). AUC curve was 0.63 for all patients and 0.72 for EC group. CONCLUSIONS: The median values of baseline CA 19-9 predict the burden of disease. Raised levels of serum CA 19-9 beyond 20 units/ml should be used for prognostication purposes after EC. A level beyond 35 units has a trend towards prognostication in other prognostic groups and needs to be evaluated in large subset of patients.

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.

Association of apolipoprotein A1-C3 gene cluster polymorphisms with gallstone disease.

INTRODUCTION: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease. AIM: To determine the association between apolipoprotein A1 (APOA1) -75 guanine [G] to adenine [A] and +83/84 M2(+/-), MspI) and apolipoprotein C3 (APOC3) (SstI) polymorphisms with gallstone disease. METHODS: MspI polymorphisms of the APOA1 gene and SstI polymorphisms of APOC3 were analyzed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. All statistical analyses were performed using SPSS version 11.5 (SPSS, USA) and Arlequin version 2.0 (Arlequin, Switzerland). RESULTS: The APOA1 -75 G/A polymorphism was significantly associated with gallstone disease. Patients with the GG genotype (P=0.015) and G allele carriers (P=0.004) had a significantly higher risk of gallstone disease (1.087-fold and 1.561-fold, respectively), whereas patients with AA genotypes (P=0.011) and A allele carriers (P=0.004) were protected (OR 0.230 and 0.641, respectively) against gallstone disease. APOA1 +83 M2(+/-) and APOC3 SstI polymorphisms were not associated with gallstone disease. Case-control analysis of haplotypes showed a significant association in males only. G-M2(+)-S1 conferred risk for gallstone disease (P=0.036; OR 1.593, 95% CI 1.029 to 2.464), while A-M2(+)-S1 was protective (P=0.002; OR 0.370, 95% CI 0.197 to 0.695) against gallstone disease. In APOA1(-75)-APOA1(+83) bilocus haplotypes, G-M2(+) was associated (P=0.0001) with very high risk (OR 3.173, 95% CI 1.774 to 5.674) for gallstone disease in males only. APOA1(-75)-APOC3(SstI) haplotypes also showed significant association while APOA1(+83)-APOC3(SstI) haplotypes showed no association with gallstone disease. CONCLUSIONS: The APOA1 -75 G/A polymorphism is associated with gallstone disease and shows sex-specific differences. On the other hand, APOA1 M2(+/-) and APOC3 SstI polymorphisms may not be associated with gallstone disease. Haplotype analysis is a better predictor of risk for gallstone disease.