Advanced Gallbladder Cancer Research Articles

Mo1417 – Adjuvant Treatment for Advanced Gallbladder Cancer; Does External Beam Radiation Therapy Play a Role?

Mo1417 – Adjuvant Treatment for Advanced Gallbladder Cancer; Does External Beam Radiation Therapy Play a Role?

28. Robotic Radical Cholecystectomy for Locally Advanced Carcinoma Gall Bladder – A Case Report

Background and Aims: Gallbladder cancer is the most common malignant tumor of biliary system. The only potentially curative option for patients with gallbladder cancer is radical resection. We aim to describe the robotic radical cholecystectomy with segment 4b and 5 resection in a locally advanced gallbladder cancer. Case Summary: A 46-year gentleman presented with dull aching right hypochondrial pain for 1 month. His per abdomen examination, liver function and renal function tests were normal. CECT abdomen showed locally advanced mass in gallbladder infiltrating segment 4b and 5. With this he was diagnosed to have locally advanced gallbladder carcinoma. Robotic radical cholecystectomy was contemplated with lymphadenectomy. On staging laparoscopy no evidence of intra-abdominal metastasis was found. Cystic duct arose from right hepatic duct. Frozen section of cystic duct showed no evidence of malignancy. Segment 4b and 5 of liver resected with CUSA and bipolar diathermy. A right sub hepatic drain was placed. The procedure was successfully completed in 320 min. Blood loss was 150 ml. There were no intraoperative complications and drain was removed on postoperative day 5, and then discharged on the same day. Histopathology report revealed – moderately differentiated squamous cell carcinoma with no malignancy in 7 lymph nodes examined (pT3N0M0). He was subjected for adjuvant therapy. On 1-year follow-up he had no recurrence. Conclusions: Robotic radical cholecystectomy is safe and feasible in locally advanced carcinoma gallbladder. The authors have none to declare.

Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy

BackgroundGallbladder cancer is the most common biliary tract malignancy and not sensitive to chemotherapy. Autophagy is an important factor prolonging the survival of cancer cells under chemotherapeutic stress. We aimed to investigate the role of long non-coding RNAs (lncRNAs) in autophagy and chemoresistance of gallbladder cancer cells.MethodsWe established doxorubicin (Dox)-resistant gallbladder cancer cells and used microarray analysis to compare the expression profiles of lncRNAs in Dox-resistant gallbladder cancer cells and their parental cells. Knockdown or exogenous expression of lncRNA combined with in vitro and in vivo assays were performed to prove the functional significance of lncRNA. The effects of lncRNA on autophagy were assessed by stubRFP-sensGFP-LC3 and western blot. We used RNA pull-down and mass spectrometry analysis to identify the target proteins of lncRNA.ResultsThe drug-resistant property of gallbladder cancer cells is related to their enhanced autophagic activity. And we found a lncRNA ENST00000425894 termed gallbladder cancer drug resistance-associated lncRNA1 (GBCDRlnc1) that serves as a critical regulator in gallbladder cancer chemoresistance. Furthermore, we discovered that GBCDRlnc1 is upregulated in gallbladder cancer tissues. Knockdown of GBCDRlnc1, via inhibiting autophagy at initial stage, enhanced the sensitivity of Dox-resistant gallbladder cancer cells to Dox in vitro and in vivo. Mechanically, we identified that GBCDRlnc1 interacts with phosphoglycerate kinase 1 and inhibits its ubiquitination in Dox-resistant gallbladder cancer cells, which leads to the down-regulation of autophagy initiator ATG5-ATG12 conjugate.ConclusionsOur findings established that the chemoresistant driver GBCDRlnc1 might be a candidate therapeutic target for the treatment of advanced gallbladder cancer.

An Approach to Soft Tissue Mass In The Gall Bladder

Background: Soft tissue mass in gall bladder (GB) is a radiologic finding commonly encountered in surgical practice. It needs proper evaluation as there is a fair chance that it can be a malignant lesion. Gall bladder cancer (GBC) is considered an incurable disease with an extremely poor prognosis. However, there is good chance of survival if it can be diagnosed in earlier stages (stage Ib, II, selective III).
 Methods: All consecutive cases of soft tissue mass lesions of GB found in ultrasonogram of abdomen and admitted in Hepato-Biliary-Pancreatic Surgery (HBPS) unit of BIRDEM hospital, from January 2009- September 2016, were included in this study. Detailed history and thorough clinical examination was done in all cases. Pre-operative evaluations were done by ultrasound, Tumor marker (CA19.9) & CT scan,. CT scan was a crucial investigation for all the patients, as depending on the findings, decision was made whether a patient is eligible for a possible curative surgery or not. On-table frozen section biopsy or imprint cytology was done for tissue diagnosis. Radical resection was done for the histology/ cytology proved malignancy of gallbladder (stage Ib, II, selective III). Post-cholecystectomy patients also underwent full thickness excision of the umbilical port. In benign cases only cholecystectomy was done. Advanced GBC cases underwent FNAC for tissue diagnosis followed by palliative chemotherapy. Some needed endoscopic or surgical palliation in the form of percutaneous external biliary drainage, endobiliary prosthesis, triple bypass, hepaticojejunostomy, left duct anastomosis, gastrojejunostomy, ileotransverse anastomosis, external biliary drainage etc before chemotherapy. All the GBC patients were regularly followed according to a schedule.
 Results: We are reporting 334 cases of soft tissue mass lesions of GB. Female 191 (57.2%) and male 143 (42.81%), M : F = 1 : 1.3 ,,between the ages of 32 and 88 years. Of these, 81 patients (24.2%) turned out to be benign; another 81 patients (24.2%) were in early stage (Ib, II selective III). The rest of 172 patients (51.5%) showed signs of advanced malignancy in USG & CT scan. Post-operative complications occurred in 27 cases (8.1%). During follow-up, 34 patients (42%) have crossed their 5 years of disease free survival after curative surgery. Rest of the patients (44 cases), after curative surgery, are still under follow-up. The 172 patients in Stage III & IV disease who underwent some sort of palliative procedure, had a mean survival of 7.2 months.
 Conclusion: Soft tissue mass in gall bladder picked up by imaging has a very high chance to be malignant. Among these malignant patients, a good number has a chance of curative resection if evaluated and managed properly.
 Bangladesh Crit Care J March 2019; 7(1): 29-34

Pretreatment with Gemcitabine/5-Fluorouracil Enhances the Cytotoxicity of Trastuzumab to HER2-Negative Human Gallbladder Cancer Cells In Vitro and In Vivo.

The effects of standard clinical therapies including surgery and chemotherapy are poor in advanced gallbladder cancer (GBC). There are a few reported cases of human epidermal growth factor receptor 2 (HER2)-positive GBC that responded well to trastuzumab. But trastuzumab has not yet been used to treat HER2-negative GBC. In this study, we investigated the cytotoxic effects of different combined therapies with trastuzumab and gemcitabine and/or 5-fluorouracil on HER2-negative GBC cell lines in vitro and in vivo. Trastuzumab alone showed almost no cytotoxicity to GBC cells with originally low HER2 gene amplification. Sequential therapy with chemotherapy followed by trastuzumab showed superiority over reverse sequential chemotherapy (P<0.05), concurrent combined chemotherapy (P<0.05), chemotherapy alone (P<0.05), and trastuzumab alone (P<0.05) in terms of cytotoxicity. Sequential therapy with chemotherapy followed by trastuzumab nearly completely inhibited cell viability in HER2-negative GBC cells. Similar results were observed with regard to apoptosis. Western blot analysis showed that gemcitabine/5-fluorouracil increased the expressions of total and phosphorylated forms of HER2, thus enhancing the cytotoxicity of trastuzumab. In vivo study verified the results of in vitro study by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis. Moreover, not only the lightest tumor bearing but also the best survival state was detected in sequential therapy with chemotherapy followed by trastuzumab group compared with other groups. Our in vivo and in vitro data suggest that sequential therapy with gemcitabine/5-fluorouracil followed by trastuzumab represents a novel and promising therapeutic strategy against HER2-negative GBC. The upregulation of phosphorylated HER2 and phosphorylated-AKT induced by gemcitabine/5-fluorouracil treatment shows that HER2/AKT pathway is triggered.

The imortant role of adjuvant treatment in advanced gallblader cancer

Background: The role of adjuvant treatment has been well established in cholangiocarcinoma, Gallbladder cancer (GC) is a rare and less studied tumor. Methods: We retrospectively analyzed all patients with gallbladder malignancy that underwent surgical removal of the gallbladder in our health system from 2007 to 2017. We compared clinical and oncological outcomes for two groups of patients: a group that received adjuvant treatment and a group that did not receive adjuvant treatment. The adjuvant treatment group was composed of patients who received either chemotherapy alone (19 patients) or chemo-radiation (21 patients). Results: Overall 69 patients with advanced (TNM stage III/IVa) gallbladder cancer (GBC) underwent resection for curative purposes. Among them, 40 patients (58%) were in the adjuvant treatment group and 29 patients (42%) were in the NO adjuvant treatment group. Gender (female, 58% vs 60%), ASA score (%) (I – 22 vs. 24, II - 39 vs. 37, III- 32 vs. 39, IV, 7 vs. 0), TNM stage IV (%, 17 vs. 10), and neoadjuvant chemotherapy administration (10% vs. 12%) were comparable (p = NS). The patients in theadjuvant treatment group were significantly younger (mean, years, 63 vs. 70, p = 0.03). Intraoperatively, surgical approach (laparoscopic, %, 28 vs. 25), incidental finding (%, 52 vs. 48), and tumor max dimension (mean, mm, 44 vs. 45) were all similar. Significantly more patients in the adjuvant treatment group underwent radical cholecystectomy (%, 69 vs. 98, p = 0.01). At median follow-up of 20 months, 43 patients recurred. Patients in adjuvant treatment group had significantly better survival (months, 25 vs. 10, p = 0.01). Similarly, the median disease-free survival was improved for patients in adjuvant treatment group (months, 18 vs. 8), although this didn’t reach statistical significance (p = 0.16). Conclusion: Adjuvant treatment has significant survival benefits for patients with advanced GBC and should be offered to patients with acceptable performance status. Despite these data, the application of adjuvant therapy after resection is not universally applied.

AB010. S2-4. Hepatopancreatoduodenectomy (HPD) for cholangiocarcinoma

: Major hepatectomy combined with pancreatoduodenectomy [hepatopancreatoduodenectomy (HPD)], is indicated for laterally advanced cholangiocarcinoma. Since Takasaki et al. first introduced HPD for the treatment of locally advanced gallbladder cancer in 1980, many Japanese surgeons and a small number of Western surgeons have employed this extended procedure for the treatment of biliary cancer. However, limited number of patients and high rate of mortality hindered our ability to reach to definitive conclusion regarding the survival benefit of this procedure. Even today, HPD for biliary cancer remains controversial and is the most challenging operation. In 2012, we reported the surgical outcome of 85 patients with cholangiocarcinoma who underwent HPD. The main tumor location was perihilar in 59 patients and distal in 26 patients. The types of hepatectomy performed included right-sided hepatectomy in 55 patients, left-sided hepatectomy in 23 patients, and central hepatectomy in 7 patients. Combined portal vein resection was performed in 24 patients, and hepatic artery resection was performed in 7 patients. Despite this aggressiveness, mortality rate was only 2.4%, and overall 5-year survival rate was 37.4%. Survival rate of 57 patients with pM0 disease who underwent R0 resection was 54.3%. Our data demonstrate that HPD can be performed with low-mortality rate and offers improved chance of long-term survival in selected patients. We stress that HPD is an important procedure for treating extensively spreading cholangiocarcinoma that is otherwise unresectable, and it is now the fourth standard procedure following hepatectomy, bile duct resection, and pancreatoduodenectomy. The current challenge is super-extended resection, i.e., hepato-ligamento-pancreatoduodenectomy (HLPD), in which HPD is performed with an en bloc resection of the hepatoduodenal ligament requiring the simultaneous resection of the portal vein and hepatic artery. Till date, we have performed this super-extended surgery in 9 patients. I will mention its outcome in this lecture.

Clinical efficacy of GEMOX regimen combined with targeted therapy for advanced gallbladder cancer

Objective To evaluate the clinical efficacy of gemcitabine-oxaliplatin (GEMOX) regimen combined with targeted therapy for advanced gallbladder cancer. Methods The retrospective descriptive study was conducted. The clinical data of 21 patients with advanced gallbladder cancer who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January 2016 and December 2017 were collected, including 8 males and 13 females, aged from 28 to 80 years, with the age of (58±12)years. Patients received GEMOX regimen combined with targeted therapy. According to the results of gene test, patients selected tageted therapy with Cetuximab, Herceptin or Apatinib. Observation indicators: (1) gene test situations; (2) situations of GEMOX regimen combined with targeted therapy; (3) adverse reactions of GEMOX regimen combined with targeted therapy. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute number or percentage. The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method. The survival analysis was done using the Log-rank test. Results (1) Gene test situations: of 21 patients, 19 were confirmed as K-ras wild type, including 13 of single K-ras wild type, 4 of K-ras wild type combined with human epidermal growth factor receptor 2 (HER2), 2 of K-ras wild type combined with vascular endothelial growth factor receptor 2(VEGFR2); 5 were detected positive HER2, including 1 of single positive HER2, 4 of positive HER2 combined with K-ras wild type; 3 were detected positive VEGFR2, including 1 of single positive VEGFR2, 2 of positive VEGFR2 combined with K-ras wild type. Two and 19 patients had 0 and 1 of Eastern Cooperative Oncology Group score. (2) Situations of GEMOX regimen combined with targeted therapy: all the 21 patients underwent ≥ 2 courses of GEMOX regimen combined with targeted therapy. Among the 21 patients, 0, 4, 9 and 8 were respectively detected in the complete remission (CR), partial remission (PR), stable disease (SD) and disease progression (PD). Fourteen patients (13 of single K-ras wild type and 1 of K-ras wild type combined with positive VEGFR2) received GEMOX regimen combined with Cetuximab therapy, including 0 with CR, 4 with PR, 5 with SD and 5 with PD; 5 patients (1 of single positive HER2 and 4 of positive HER2 combined with K-ras wild type) received GEMOX regimen combined with Herceptin therapy, including 0 with CR, 0 with PR, 2 with SD and 3 with PD; 2 patients (1 of single positive VEGFR2 and 1 of positive VEGFR2 combined with K-ras wild type) received GEMOX regimen combined with Apatinib therapy, including 0 with CR, 0 with PR, 2 with SD and 0 with PD. The objective response rate was 19.0%(4/21) and disease control rate was 61.9%(13/21) in the 21 patients. The median onset time was 1.8 months in the 21 patients. The 3-, 6- and 9-month progression free survival (PFS) rates and median PFS time were respectively 90.5%, 71.4%, 58.5% and 10.7 months. The 6- and 12-month overall survival rates were respectively 90.2% and 58.6%, and median overall survival (OS) time was 15.5 months in the 21 patients. The PFS and OS time were 8.4 months and 10.4 months in the 7 patients combined with jaundice, 10.5 months and 14.8 months in the 14 patients without jaundice, with no statistically significant difference (χ2=0.868, 0.774, P>0.05). (3) Adverse reactions of GEMOX regimen combined with targeted therapy: the most common adverse events were skin rash and digestive tract reactions. No serious adverse event occurred during the therapy. All the adverse events were improved after symptomatic treatments. Conclusion GEMOX regimen combined with targeted therapy for advanced gallbladder cancer has good outcomes, less adverse reactions and higher safety. Key words: Biliary tract neoplasms; Gallbladder cancer; Chemotherapy; Targeted therapy; Efficacy; Safety

Major hepatectomy with or without pancreatoduodenectomy for advanced gallbladder cancer.

The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P =0·015) and periaortic nodal metastasis (P =0·006), but were less likely to receive adjuvant therapy (P =0·006). HPD was associated with a high incidence of grade III or higher complications (P =0·002) and death (P =0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996-2006) (P =0·002), pathological T4 disease (P =0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P =0·002) with longer overall survival. Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint.

Roles of Pin1 as a Key Molecule for EMT Induction by Activation of STAT3 and NF-κB in Human Gallbladder Cancer.

Despite developments in multidisciplinary treatment, the prognosis for advanced gallbladder cancer (GBC) still is poor because of its rapid progression. Epithelial-mesenchymal transition (EMT) plays a central role in promoting tumor invasion and metastasis in malignancies thorough signal transducer and activator of transcription-3 (STAT3) and nuclear factor κB (NF-κB) activation. Whereas Pin1 mediates STAT3 and NF-κB activation, the involvement of Pin1 in GBC progression is unclear. Factors regulating Pin1-related STAT3 and NF-κB activation were evaluated using surgical specimens collected from 76 GBC patients, GBC cells, and orthotopic GBC xenograft mice. In the patients with GBC, high Pin1 expression in GBC was associated with aggressive tumor invasion and increased tumor metastasis, and was an independent factor for a poor prognosis. Pin1 expression was correlated with phosphorylation of STAT3(Ser727) and NF-κB-p65(Ser276), thereby activating STAT3 and NF-κB in GBC. Pin1-mediated STAT3 and NF-κB activation induced EMT in GBC. When Pin1 knockdown was performed in GBC cells, the phosphorylation of STAT3(Ser727) and NF-κB-p65(Ser276) was inhibited, and STAT3 and NF-κB activation was suppressed. Inactivation of STAT3 and NF-κB in Pin1-depleted cells decreased snail and zeb-2 expression, thereby reducing the rate of mesenchymal-like cells, suggesting that EMT was inhibited in GBC cells. PiB, a Pin1-specific inhibitor, inhibited EMT and reduced tumor cell invasion by inactivating STAT3 and NF-κB in vitro. Moreover, PiB treatment inhibited lymph node metastasis and intrahepatic metastasis in orthotopic GBC xenograft tumor in vivo. Pin1 accelerates GBC invasion and metastasis by activating STAT3 and NF-κB. Therefore, Pin1 inhibition by PiB is an excellent therapy for GBC by safely inhibiting its metastasis.

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer - A systematic review

Abstract Background Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival. Aim To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC. Methods Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival. Results 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0–10.8 months for non-resected group. Conclusions There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.

Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using ¹⁸F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma.

PurposeThis study aimed to determine the prognostic value of new quantitative parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC).Materials and MethodsIn total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent 18F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors.ResultsIn univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUVmt max (the highest SUV among the metastatic lesions) (p=0.040) and MTVtotal (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTVtotal (hazard ratio: 2.07; 95% confidence interval: 1.23–3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039).ConclusionIn locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTVtotal, were found to be useful for the identification of patients with poor prognosis.

Symptom Palliation in Advanced GallBladder Cancer: An Institutional Experience.

Aim:Palliation of symptoms of patients with advanced carcinoma gallbladder (GB).Materials and Methods:Sixty-two newly diagnosed patients of unresectable advanced and metastatic GB cancers were enrolled, and following clinicoradiological assessment patients were considered for palliative symptom management.Results:The most common presenting symptom was pain in 57 (92%) patients. Obstructive jaundice was observed in 29 (46.7%) patients. Patients were considered for percutaneous biliary drainage/internal stenting, therapeutic ascitic tapping, and pain control. Patients with good performance status were considered for palliative chemotherapy.Conclusion:Patients with advanced carcinoma GB were managed with various palliative procedures with the aim to improve the quality of life of patients because of jaundice, loss of appetite, nausea, pain, etc. Symptoms are distressing for patients.

Portal vein embolization combined with nact followed by radical surgery for locally advanced gall bladder cancer

Portal vein embolization combined with nact followed by radical surgery for locally advanced gall bladder cancer

Long term outcomes and prognostic factors of resected pancreatic neuroendocrine tumors

Introduction: Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors. For PNETs, the predictive factors for survival and prognosis are not well known. The aim of the present study was to investigated the clinicopathological and prognosis of the patients with resected pancreatic neuroendocrine tumors (PNET). Method: 42 patients with PNET underwent surgical treatment from April 1992 to June 2017. Data regarding the clinicopathologic factors of these patients were collected retrospectively. Factors influencing the prognosis of advanced gallbladder cancer after resection were analyzed by univariate and multivariate analysis. Result: The patients comprised of 18 men and 24 women. The mean age of the patients was 53.98±12.75 years. Nine cases (21.4%) were functional tumors and 33 cases (78.6%) were non-functional tumors. The mean tumor size was 2.99±2.08 cm. The most common location was tail (38.1%) and head (35.7%), followed body (21.4%), and body & tail(4.8%) in pancreas. The differences in the disease specific survival time as grading system based on Ki-67 and mitotic count were only statistically significant (P=0.015). The 5-year disease specific survival rates of patients with Grade 3 tumor was 0%. The T category (P=0.115), N category (P=0.299), TNM staging system (P=0.458), lymphovascular invasion (P=0.479), and perineural invasion (0.527) were not statistically significant factors. Conclusion: Patient with grade 3 PNET have worse postoperative prognosis. Therefore, we need careful monitoring after surgery.

Extended resection for xanthogranulomatous choleystitis mimicking gallbladder carcinoma: review of cases and diagnostic approach

Background: Xanthogranulomatous cholecystitis is a rare variant of chronic cholecystitis which may involve adjacent organs including liver, colon and duodenum mimicking gallbladder cancer. Preoperative differentiation of xanthogranulomatous cholecystitis from gallbladder cancer is often difficult and the final diagnosis is usually made on histopathology of the resected specimen. Methods: We report four cases of xanthogranulomatous cholecystitis which were misdiagnosed as cases of advanced gallbladder cancer based on presentation and radiological findings. Results: All the four patients presented with history of upper abdominal pain while two patients had history of associated weight loss. Radiological features were strongly suggestive of gallbladder cancer with involvement of adjacent organs in all cases. Based on the imaging findings, these patients underwent radical resections but the final histopathology was a diagnostic surprise. Conclusion: Xanthogranulomatous cholecystitis is still a diagnostic challenge as no clinical and imaging modality has been helpful to make a definitive diagnose of this entity. We review the role of available diagnostic modalities in this challenging area of uncertainty. Radical resection may be justified in patients who present with the features mimicking gallbladder cancer.

Five year experience of gallbladder polyp surveillance and cost effective analysis against new European consensus guidelines

BackgroundGallbladder polyp (GBP) surveillance seeks to identify early neoplasms, but practice varies amongst surgical units. Recent European consensus guidelines have recommended an evidence-based GBP surveillance strategy. In a tertiary centre Hepato-Pancreato-Biliary unit we examine GBP surveillance, malignant yield, and assess cost-effectiveness of the new European consensus guidelines. MethodsRespective data were collected from all patients with ultrasonography-detected GBPs between January 2008 and January 2013. Results558 patients had GBPs detected on ultrasonography. Following initial ultrasonography, 304 (54.5%) had further ultrasonography surveillance of which 168 were in a formal GBP surveillance programme. Pre-malignant/malignant pathology yield was 1.97% with an annual detection rate of 12.0 cases per 1000 GBPs surveyed. Cost-effectiveness analysis of European consensus guidelines calculated annual savings of £209 163 per 1000 GBPs surveyed. Compliance with these guidelines would result in an additional 12.5% of patients under surveillance requiring cholecystectomy. ConclusionGBP surveillance uptake was suboptimal at 32.8%. The incidence of pre-malignant/malignant lesions in GBPs emphasises the importance of surveillance for early detection and management with a view to avoiding the poor outcomes associated with more advanced gallbladder cancer. Adherence to the new European consensus guidelines would be clinically cost-effective with significant potential savings demonstrated in this study.

Scalp Metastases as a Rare Primary First Manifestation of Gallbladder Cancer

Gallbladder cancer (GBC) with cutaneous metastases is a rare entity. Metastases on the scalp is even rarer and an unusual metastatic pattern of GBC. Only 12 cases have been reported so far. We herein report a case of a 52-year-old woman who presented with subcutaneous nodule over the scalp with pain in the right upper abdomen. Fine-needle aspiration cytology (FNAC) of this nodule revealed metastatic adenocarcinoma. Contrast-enhanced computed tomography scan of the abdomen showed an advanced GBC confirmed by FNAC from the gallbladder mass. She was put on palliative combination chemotherapy but rapidly developed multiple scalp nodules and jaundice with dramatic deterioration. This report highlights the possible scalp metastasis from advanced GBC that portends an ominous prognosis.

Gemcitabine-oxaliplatin first-line chemotherapy in locally advanced and metastatic gallbladder cancer - results from a tertiary centre in North India

Introduction: In view of encouraging results of ABC-02 trial in advanced biliary tract cancer, we aimed to evaluate efficacy of gemcitabine-oxaliplatin chemotherapy in our patients with locally advanced/ metastatic gallbladder cancer (GBC). Methods: Retrospective analysis of prospectively maintained database of patients with locally advanced and metastatic GBC(July 2015- December 2017) was performed. Inclusion criteria - histologically proven locally advanced GBC(≥T3 or N2 disease) or metastatic GBC, no prior chemotherapy, ECOG status≤2, normal hematologic, renal and hepatic functions. Chemotherapy regimen included injection Gemcitabine 1250mg/m2 infusion on days 1 and 8 and oxaliplatin 100mg/m2 on day 1 every 3 weeks. Primary endpoints were overall survival(OS), progression-free survival(PFS) and R0 resection rate in those given preoperative chemotherapy. Secondary endpoints were response rate and toxicity of chemotherapy regimen. Results: Total of 52 patients received chemotherapy(mean age: 52 years, 73% females) of which preoperative chemotherapy was given in 38.5 %(n=20) and palliative chemotherapy in 61.5%(n=32). Median OS was 8.3 months and median PFS was 4.7 months. Complete response was seen in 1.9%, partial response in 11.5%, stable disease in 21.2% and progression in 65.4%.In locally advanced group, 30%(n= 6/20) underwent R0 resection. R0 resection was possible in 85.7% (6/7) patients who showed response to chemotherapy. Patients who underwent surgery had significantly better OS(p< 0.01) and PFS(p=0.01). Conclusion: Combination chemotherapy with gemcitabine-oxaliplatin showed good response rate in a select subgroup of patients. Curative surgery was feasible in majority of those who had good response. Patients who underwent curative resection had significant improvement in survival.

Outcomes of surgical resection of gallbladder cancer in patients presenting with jaundice: A systematic review and meta-analysis.

Preoperative jaundice is considered a relative contraindication to radical gallbladder cancer (GBC) resection due to poor prognosis and high postoperative morbidity. Recent reports have indicated that aggressive surgery may improve long-term survival for patients with advanced GBC who present with obstructive jaundice. The current systematic review and meta-analysis aimed to compare postoperative outcomes among jaundiced and non-jaundiced patients with resectable GBC. An electronic search was performed using several Medical Subject Headings terms: cholecyst, gallbladder, tumor, cancer, carcinoma, adenocarcinoma, neoplasia, neoplasm, jaundice, and icterus. Overall survival after surgery was the primary outcome; resectability and postoperative morbidity were the secondary outcomes. Overall survival was shorter among patients who presented with jaundice (Hazard ratio [HR]: 2.21, 95% confidence interval [CI], 1.64-2.97; P < 0.001). Patients with jaundice were less likely to have resectable disease (odds ratio: 0.27, 95% CI, 0.17-0.43; P < 0.001). The jaundice group had higher odds of postoperative morbidity, bile-leak, and posthepatectomy failure versus the non-jaundiced control group. Radical surgery for GBC resection for patients presenting with obstructive jaundice was associated with reduced overall survival and increased postoperative morbidity. Jaundiced patients with advanced GBC should be considered for surgical resection but need careful evaluation and counseling before undertaking extensive surgical resection.