Surgery versus no surgery in stage IV gallbladder carcinoma: A propensity score-matched analysis.

Objectives: Patients with stage IV gallbladder cancer (GBC) have a dismal prognosis. Mostly, they are not amenable to surgical treatment. However, in some of them, a potentially curative surgical resection is possible. There is paucity of the literature comparing survival of patients with surgically resectable stage IV GBC to the patients with unresectable stage IV GBC. Material and Methods: This retrospective study was conducted on patients with AJCC stage IV GBC who were managed by a surgical unit at a tertiary care center from May 2009 to March 2021. Patients were grouped into either surgery group (cases) or no surgery group (control). Cases were compared to controls for demographic characteristics, clinical parameters, and survival rates. A comparison was made in both unmatched and matched (propensity score matching 1:1 with covariates age, gender, ECOG, chemotherapy, and TNM staging) groups. Results: The total number of patients with stage IV GBS was 120, out of that, 29 were cases, and 91 were controls. After matching, each group had 28 cases (28 + 28= 56). Post-matching AJCC stage, chemotherapy, and other parameters were equally distributed between the groups (p= 1.00). However, cases had more patients with N2 metastasis (p <0.001), and controls had more patients with distant metastasis (p <0.001). Cases vs. controls, overall survival before matching was 22 vs. seven months (p= 0.001) and after matching was 22 vs. 11 months (p= 0.005). Conclusion: Patients with stage IV GBC amenable to potentially curative surgical resection (R0) have significantly better survival than patients with non-surgical treatment. Therefore, it may be more appropriate to classify these group differently.

A clinicoepidemiological and management profile of metastatic carcinoma gallbladder in the northeast part of Indian patients in a tertiary care center.

Introduction: Metastatic gallbladder cancer (GBC) is a highly fatal malignancy and it is difficult to treat the advanced stage of GBC. In India, northern and northeastern states are the worst affected by this disease. We, hereby, report the clinicoepidemiological and management profile of 242 patients of metastatic carcinoma of GB. Materials and Methods: In this study, a total of 242 cases of metastatic GBC (detected either on the first presentation or during follow-up) were managed at the Department of Medical Oncology tertiary care oncology center in the northeast part of India from May 2018 to September 2019. On presentation, all patients were subjected to detailed history and clinical examination, followed by requisite investigations and were treated as per the existent guidelines. Results: One-hundred and forty-two patients were female, while 100 patients were male out of 242 patients. Female patients with metastatic GBC presented with the mean age of 54, while for males, 51.4 years. The most common presentation was pain abdomen (81.8%), while the second most common was anorexia (77.2%), followed by weight loss (62.8%) and mass per abdomen (60.7%). The most common site of metastasis recorded in our study was the liver (79.7%), followed by nonregional abdominal lymph node (69.4%) and ascites (64.4%). Out of the 242 patients, 24 patients had presented in poor Eastern Cooperative Oncology Group Performance Status (≥3) hence were deemed unfit for any oncological interventions. About 136 (56.1%) patients had presented with features of obstructive jaundice, however only 108 patients were subjected to biliary drainage procedure. After the biliary drainage procedures, only one-third (38 out of 136; 35.1%) of patients were finally able to receive chemotherapy. Conclusion: In India, unfortunately, many patients present very late during the course of their illness. There is a need for the development of effective chemotherapy or targeted therapy and also there is an unmet need for patients' education. There has been an increase in the incidence of this malignancy, especially in the Northeast part of India; hence, it is the need of the hour to study various epidemiological and causative factors of the disease. Furthermore, the development of therapies for the effective management of this malignancy is really required.

Misdiagnosis of carcinoma gall bladder in endemic regions.

BACKGROUND: Incidental carcinoma gall bladder and benign disease in radical cholecystectomy specimen is the cause of concern. We attempted to find out the incidence and reasons thereof in the present study. METHODS: Present study is a retrospective analysis of a prospectively maintained database between July 2002 and July 2019. All patients with a diagnosis of carcinoma gall bladder admitted for surgery were included. RESULTS: Out of 148 patients, 110 patients had carcinoma gall bladder (CAGB), while 38 patients (25.7%) had incidental carcinoma (under-diagnosis). Radical resection was done in 61/110 (55.4%) patients with clinical CAGB, where 15 (24.6%) patients had benign pathology ("over-diagnosis"). Overdiagnosis was due to xanthogranulomatous cholecystitis (n = 9), chronic cholecystitis (n = 2), tuberculosis (n = 2) and IgG4 related cholecystitis (n = 2). Among 61 patients, a history of weight loss and anorexia were significantly associated with malignancy. Asymmetrical wall thickness was significantly more common in benign mimickers. Among patients with incidental carcinoma, preoperative ultrasonography reported normal wall thickness of gall bladder in 28 (73.7%), thickened gall bladder wall in 6, and polyp in 3 patients. The resectability rate among incidental carcinoma was 27/38 (71.05%). CONCLUSION: Over-diagnosis of the carcinoma gall bladder was present in 24.6%. On the other hand, incidental carcinoma comprised 25.7% of all admissions for carcinoma gall bladder with resectability of 71%.

Effect of cell migration-inducing hyaluronidase 1 on biological function of gallbladder cancer GBC-SD cells and its mechanism / 中华肝胆外科杂志

Objective:To investigate the effect of cell migration-inducing hyaluronidase 1 (CEMIP) on biological function of gallbladder cancer GBC-SD cells and its possible mechanism.Methods:The expression of CEMIP in biliary epithelial cell line HIBEC and gallbladder cancer cell line NOZ and GBC-SD was detected by Western blot. GBC-SD cells in logarithmic growth phase were divided into blank control group, negative control group (transfection with nonsense siRNA), siCEMIP-1 group (transfection with siCEMIP-1) and siCEMIP-2 group (transfection with siCEMIP-2). The expression of CEMIP and binding immunoglobulin protein (Bip) and calreticulin (CRT) in GBC-SD cells was detected by Western blot after culturing for 48h in blank control group, negative control group, siCEMIP-1 and siCEMIP-2 group. The relative survival rate was determined by CCK-8 assay. The wound healing rate and apoptotic rate was detected by wound healing assay and flow cytometry. The migration and invasion abilities were evaluated by Transwell chamber assay. Twelve 5-week-old BALB/c-nude mice were selected and divided into control group and experimental group (6 mice in each group). GBC-SD cells and GBC-SD cells with silenced CEMIP were subcutaneously injected into the right armpit (forelimb) of the two groups of mice, respectively. The volume and weight of transplanted tumor were compared 33 days later.Results:Compared with HIBEC cells, the relative protein level of CEMIP in gallbladder cancer GBC-SD cells [(0.750±0.034) vs. (0.120±0.002)] and NOZ cells [(0.690±0.013) vs. (0.120±0.002)] was significantly higher ( P<0.05). Compared with blank control group and negative control group, the relative protein level of CEMIP, Bip and CRT in siCEMIP-1 group and siCEMIP-2 group was significantly lower ( P<0.05). Compared with blank control group and negative control group, the relative survival rate and wound healing rate and number of migration cells and invading cells in siCEMIP-1 group and siCEMIP-2 group were also significantly lower ( P<0.05). While the apoptotic rate in siCEMIP-1 group and siCEMIP-2 group were higher than that in blank control group and negative control group ( P<0.05). Compared with control group, the average tumor volume [(543.6±114.7) vs. (801.5±256.3) mm 3] and tumor weight [(0.453±0.093) vs. (0.728±0.278) g ] of the experimental group was significantly decreased ( P<0.05). Conclusions:CEMIP was up-regulated in gallbladder cancer cell line GBC-SD and NOZ. Silencing CEMIP inhibited cell proliferation, wound healing rate, migration and invasion, and promoted apoptosis in gallbladder cancer GBC-SD cells, which may be related to the inhibition of endoplasmic reticulum chaperone Bip and CRT expression.

Combination of portal vein embolization and neoadjuvant chemotherapy for locally advanced gallbladder cancer requiring extended hepatectomy - A novel approach.

BACKGROUND: Locally advanced gallbladder cancer (GBC) may require extended hepatectomy. Portal vein embolization (PVE) can lead to hypertrophy of future liver remnant (FLR), and neoadjuvant chemotherapy (NACT) can be used in this cohort, with additional advantage of downstaging tumors as well as preventing progression while waiting for liver regeneration. Here, we share our experience of combining NACT along with PVE in locally advanced GBC requiring major hepatectomy. METHODS: Retrospective analysis of prospectively maintained database was conducted for patients with locally advanced GBC who underwent PVE and received NACT between 2012 and 2018. RESULTS: Fourteen patients with locally advanced GBC underwent PVE and NACT. Median baseline FLR volume was 25.09% with a median degree of hypertrophy of 8.8% after PVE. Out of 14 patients, 7 (50%) underwent curative resection. Median overall survival in resectable and unresectable patients was 27 months and 15 months respectively. CONCLUSION: PVE along with NACT made curative surgery feasible in half of the patients who were deemed unresectable initially.

Utility of Contrast-Enhanced Ultrasound in Differentiation between Benign Mural Lesions and Adenocarcinoma of Gallbladder.

BACKGROUND: Mural lesions of gallbladder on ultrasound (US) are often difficult to characterize as benign or malignant. PURPOSE: The aim of the study was to evaluate the role of contrast-enhanced US (CEUS) in characterization of gallbladder (GB) wall lesions and making distinction between benign wall thickening and GB adenocarcinoma, utilizing both quantitative and qualitative parameters. METHODS: A total of 26 patients with GB wall lesions detected on sonography underwent CEUS. Lesions were evaluated on the basis of morphological imaging features, enhancement pattern, dynamic real-time contrast uptake, and intralesional vascularity. RESULTS: Overall, 19 patients had final diagnosis of GB adenocarcinoma, whereas seven patients had benign etiology. CEUS has enabled the differentiation of nonenhancing tumefactive sludge from enhancing mural lesions, thus improving the accuracy of morphological assessment of lesions. The intactness of outer wall was better assessed on CEUS. The dynamic postcontrast assessment showed that carcinoma showed early washout of contrast compared to benign thickening (P = 0.002). Nonlayered mural enhancement or thick enhancing inner layer with nonenhancing thin outer layer was associated with adenocarcinoma. The classification of intralesional vascularity on CEUS was not helpful in distinguishing benign lesions and adenocarcinoma. CONCLUSION: CEUS can increase the diagnostic confidence in differentiation between benign mural lesions and adenocarcinoma of GB.

Incidental Carcinoma Gallbladder: Incidence, Risk Factors, and Factors Affecting Survival-5-Year Experience from a Tertiary Care Institute.

INTRODUCTION: Carcinoma gallbladder is a very lethal disease. It can get detected incidentally after laparoscopic cholecystectomy. The overall outcome of incidentally detected carcinoma gallbladder is a matter of debate in literature. AIM: To estimate the overall incidence of the incidental gallbladder carcinoma, the various risk factors associated with it and factors affecting overall survival in patients who underwent laparoscopic cholecystectomy with eventual histology turning out to be carcinoma gallbladder. METHODS: Data of all the patients undergoing laparoscopic cholecystectomies in one surgical unit under the Department of Surgery at All India Institute of Medical Sciences, New Delhi, India, between January 2014 and December 2018 was retrospectively analyzed. All patients with incidental carcinoma gallbladder were followed up and completion radical cholecystectomy was performed. The demographic profile, preoperative imaging, intra-operative finding, histopathology of primary surgery, and median interval between two surgeries were analyzed to look for various risk factors associated with incidental carcinoma gallbladder and factors affecting overall survival. RESULTS: Incidence of the incidental carcinoma gallbladder was 0.51% with a female/male ratio of 4:1 and mean age of 47.2 years. Preoperative imaging of most of them was suggestive of chronic cholecystitis; however, one patient had multiple gallbladder polyps. Six patients had uneventful laparoscopic cholecystectomy, while four had bile spillages intraoperatively. All the patients had adenocarcinoma on histopathology. Pathological staging of four patients was pT1b and six patients had pT2 tumor. The median interval between cholecystectomy and completion radical cholecystectomy in this series was 8 weeks. At the end of 19-month median follow-up, overall survival was 55.5%. CONCLUSION: Incidence of incidental carcinoma gallbladder is 0.51%, most commonly affecting middle-aged females. Risk factors associated with incidental carcinoma gallbladder were found to be multiple gallbladder calculi, single large stone, and gallbladder polyps. Survival is better in males, young patients with uneventful primary surgery and better-differentiated pathology.

Strategies for Differentiating Gallbladder Carcinoma from Xanthogranulomatous Cholecystitis-a Tertiary Care Centre Experience.

Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis, characterized by focal or diffuse destructive inflammatory process. The importance of XGC is that it mimics gallbladder carcinoma (GBC) both preoperatively and intra-operatively, since it can present with pericholecystic infiltration, hepatic involvement and lymphadenopathy. As a result of this misdiagnosis which is not infrequent, the patient may need to undergo an unnecessary radical cholecystectomy rather than only a cholecystectomy which is associated with greater morbidity and mortality. Patients who underwent gallbladder and gallbladder-related operations during period of 5 years between 2010 and 2014 were reviewed (n = 462). A comparison of clinical, biochemical, radiological and operative features were made between patients with carcinoma gallbladder (n = 101) and xanthogranulomatous cholecystitis (n = 22). Patient with a long history of recurrent abdominal pain with leucocytosis and who on imaging are found to have a diffusely thickened gallbladder wall (p < 0.01), with cholelithiasis, choledocholithiasis and sub-mucosal hypoattenuated nodules (p < 0.05) are likely to have XGC while those with anorexia, weight loss, focal thickening of the gallbladder wall on imaging (p < 0.01) and dense local organ infiltration are more likely to have GBC. The presence of lymph nodes on imaging and the loss of fat plane interface between the liver and gallbladder are not differentiating factors. Differentiating XGC from GBC in preoperative setting is necessary to avoid radical procedures being done for a benign process. Certain clinical, radiological and intra-operative features aid in differentiating these benign and malignant process. However, the definitive diagnosis still remains a histopathological examination to avoid radical resection in patients who have a benign condition.

Porcelain Gallbladder.

Porcelain gallbladder or calcified gallbladder is a rare entity and is considered as the end stage of chronic cholecystitis. This disease is rarely diagnosed preoperatively and usually mimics carcinoma gallbladder. Hereby, we present a rare and interesting case of porcelain gallbladder that was diagnosed preoperatively and managed by cholecystectomy. How to cite this article: Goel A, Agarwal A, Gupta S, Bhagat TS, Kumar G, Gupta AK. Porcelain Gallbladder. Euroasian J Hepato-Gastroenterol 2017;7(2):181-182.

Modified palliative biliary stenting in situs inversus totalis patient with carcinoma gallbladder: feasibility and technical details.

Knowledge of the anatomical variants is essential for all invasive hepatobiliary procedures such as endoscopy, surgery and radiologic interventions. Modification in standard therapeutic interventions may be required based on variant anatomy. We report a technical modification in a 75-year-old female with known situs inversus (SI) totalis with carcinoma gallbladder. Present case highlights the finer technical details of the modified percutaneous transhepatic biliary drainage (PTBD) procedure and biliary stenting in a SI patient with carcinoma gallbladder causing malignant biliary obstruction.

Predictors of curative resection and long term survival of gallbladder cancer - A retrospective analysis.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy. We analysed factors predicting resectability and survival of patients with GBC and the impact of surgical obstructive jaundice (SOJ). METHODS: Four hundred and thirty-seven patients with suspected GBC were analysed (52 excluded: benign pathology n = 35, missed GBC n = 17). The remaining 385 patients were divided into non-SOJ (n = 234) and SOJ (n = 151) groups. Predictors of resectability and long term survival were analysed and compared with their subgroups. RESULTS: Patients with gastric outlet obstruction, abdominal lump, weight loss and SOJ were more likely to be unresectable (p:0.04, 0.024, 0.003 and 0.003, respectively). TNM stage, node positivity and adjacent organ involvement were predictors of survival (p < 0.001, 0.008 and <0.001). Metastatic (36.7% vs 47.7%), inoperable (1.7% vs 12.6%) and unresectable disease (9.8% vs 24.5%) were more in the SOJ group and had lower curative resection rates (51.7% vs 15.2%; p < 0.0001). The 1,2 and 5-year survival rates were higher in patients in the non-SOJ than SOJ group (79.6%, 65% and 52.9% vs 48.6, 32.4% and 0%; p < 0.001). CONCLUSION: GBC with SOJ is more likely to be unresectable. SOJ, nodal involvement, adjacent organ infiltration and higher TNM stage predict poor survival.

Xanthogranulomatous cholecystitis: What every radiologist should know.

Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis characterized by xanthogranulomatous inflammation of the gallbladder. Intramural accumulation of lipid-laden macrophages and acute and chronic inflammatory cells is the hallmark of the disease. The xanthogranulomatous inflammation of the gallbladder can be very severe and can spill over to the neighbouring structures like liver, bowel and stomach resulting in dense adhesions, perforation, abscess formation, fistulous communication with adjacent bowel. Striking gallbladder wall thickening and dense local adhesions can be easily mistaken for carcinoma of the gallbladder, both intraoperatively as well as on preoperative imaging. Besides, cases of concomitant gallbladder carcinoma complicating XGC have also been reported in literature. So, we have done a review of the imaging features of XGC in order to better understand the entity as well as to increase the diagnostic yield of the disease summarizing the characteristic imaging findings and associations of XGC. Among other findings, presence of intramural hypodense nodules is considered diagnostic of this entity. However, in some cases, an imaging diagnosis of XGC is virtually impossible. Fine needle aspiration cytology might be handy in such patients. A preoperative counselling should include possibility of differential diagnosis of gallbladder cancer in not so characteristic cases.

Gallbladder tuberculosis camouflaging as gallbladder cancer - case series and review focussing on treatment.

INTRODUCTION: Gallbladder tuberculosis, in an endemic region, is a common infectious etiology affecting a rare organ. The high prevalence of carcinoma gallbladder in the endemic regions of tuberculosis, like India, poses diagnostic dilemma. CASE SERIES: We are reporting three cases of gallbladder tuberculosis mimicking carcinoma gallbladder of which the first two cases were operated with a presumptive diagnosis of malignancy. The third case presented to us after laparoscopic cholecystectomy elsewhere and on evaluation was found to have disseminated tuberculosis. DISCUSSION: The lack of pathognomonic clinical and radiological characters results in histological surprise of gallbladder tuberculosis following surgery performed for other indications like malignancy. In preoperatively diagnosed patients medical management plays pivotal role in management. Surgery is required in symptomatic patients. On the other hand, histologically proven cases following surgical resection require antitubercular therapy. CONCLUSION: Previous history of tuberculosis or concomitant tuberculosis at other sites may provide clue to the diagnosis of biliary tuberculosis. Antitubercular treatment after surgery plays an important role in preventing further dissemination.

Porcelain Gallbladder Mimicking Carcinoma Gallbladder-a Case Report and Review of Literature.

Porcelain gallbladder, inspite of its rare occurence, assumes importance because of its risk of malignant transformation. Here, we report a case which mimicked carcinoma during surgery and on histopathological examination was reported as Porcelain gallbladder. This report focuses on the rarity of occurence of Porcelain gallbladder, its differentiating histopathological features with respect to carcinoma, risk of malignancy and its treatment.