Advanced Gallbladder Cancer Research Articles

Clinical application of hepatopancreatoduodenectomy in treatment of advanced gallbladder cancer

Clinical application of hepatopancreatoduodenectomy in treatment of advanced gallbladder cancer

P-166 - Downstaging with neoadjuvant chemotherapy in locally advanced gall bladder cancers, improves outcomes

Introduction: The management of locally advanced, non metastatic gall bladder cancers (GBC) is traditionally palliative chemotherapy. Down staging with neoadjuvant chemotherapy and attempting curative resection is an emerging option in this subset of tumors. Methods: A prospectively maintained GBC database was screened for locally advanced disease, satisfying pre-defined criteria. Patients required histological proof of adenocarcinoma before entry into study. All patients with metastatic disease were excluded by performance of pre-treatment CT scans or PET-CT scans. Patients were treated with neoadjuvant chemotherapy (NACT) with Gemcitabine-Platinum doublet and assessed for response and potential resection after 3-4 cycles of chemotherapy. Prognostic factors for survival, response rates (RR), clinical benefit rate (CBR), resection rates, progression free survival (PFS) and overall survival (OS) were calculated. Results: 160 patients were available for analysis in the time period between January 2010 and February 2016. Median age of the cohort was 52 years (range: 26-73), with a female predominance. 105 patients (65%) had node positive disease. Reasons for initial unresectability included pyloric infiltration in 10(6.3%), duodenal infiltration in 42 (26.3%), hepatic flexure in 25(15.6%), liver infiltration > 2cm in 119 (75%), bile duct invasion in 31 (19.4%), vascular invasion in 8 (5%), nodal disease in 105 (65%) and doubtful margin status if resected in 26(16%), respectively. Median number of cycles administered as NACT was 4. RR and CBR after NACT was 52.5% and 70% respectively. 93 patients (58%) under surgical exploration after NACT, of which 48 patients underwent a radical cholecystectomy (30%), 18 underwent revision cholecystectomy (11%), while the remaining 27 patients were deemed unresectable intra-operatively (17%). Resection status was R0 in 63 patients (95%) and R+ in 3 patients (5%). Of the 67 patients who did not undergo surgical exploration, 10 were deemed unresectable on scans (6.3%), 43 had progressed on NACT (27%), while 14 patients (9%) defaulted/refused/progressed clinically prior to surgical assessment. 52 patients of those underwent resection (79%), received adjuvant therapy. With a median follow-up of 33 months, the median OS of the entire cohort was 13 months (95% CI: 8.7 to 17.2 months), with those having undergone curative surgery having a statistically superior OS as compared to those who did not (49 vs. 7 months; p = 0.0001). The median PFS of the entire cohort was 8 months (95% CI: 7 to 8.9 months). Patients having undergone curative surgery had a statistically superior PFS as compared to those who did not (25 months vs. 5 months; p = 0.0001). On multivariate analysis, pre-NACT higher T stage (T3,4> T0,1,2) and CA 19-9 (>37 IU/ml) remained significant factors with poorer PFS and OS. Conclusion: The strategy of neoadjuvant chemotherapy with potential down staging and attempted curative resection appears feasible in a selected group of ‘locally advanced’ GBC with improved survival outcomes as opposed to continuing palliative intent chemotherapy alone.

Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis.

Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO.

Treatment of advanced Gall bladder cancer in the real world-can continuation chemotherapy improve outcomes?

Gemcitabine-Platinum doublet chemotherapy is the standard of care in patients with locally advanced inoperable and metastatic (LA/M) Gall bladder cancers (GBC). Consecutive patients with LA/M GBC treated with Gemcitabine-Cisplatin (GC) or Gemcitabine-Oxaliplatin (GO) as first line palliative chemotherapy from January 2013 to June 2015 were retrospectively analysed. Patients who were able to continue chemotherapy beyond 6-8 cycles were separately compared to those who were potential candidates for this approach, but chose not to continue chemotherapy. A total of 396 patients received first line palliative chemotherapy during the period of analysis, 276 patients (69.6%) were unable to complete 6-8 cycles of chemotherapy, while 120 patients (30.4%) were potential candidates for continuing chemotherapy. Seventy patients (n=120; 58.3%) received a median of 4 cycles of continuation chemotherapy. Median overall survival (OS) for the entire cohort was 7.65 months [95% confidence interval (CI), -7.14 to 8.16], while median event free survival (EFS) was 4.53 months (95% CI, -4.23 to 4.83). Patients receiving continuation chemotherapy had a statistically improved median OS compared to all other patient cohorts, 14.88 months (95% CI, -12.48 to 17.27; P=0.005 on multivariate analysis). Burden/number of sites of metastases, receiving of continuation chemotherapy, fit and able to receive second line chemotherapy (CT2) were identified on multivariate analysis as prognostic factors for OS. OS in our study appeared lower than published literature, but a group of patients were identified whose survival could be prolonged by continuing chemotherapy. Easily available factors can predict prognosis of GBC undergoing first line palliative chemotherapy.

Tu1504 - Minimally Invasive Versus Open Resection of Advanced Gallbladder Cancer: A National Assessment of Short and Long-Term Outcomes

Tu1504 - Minimally Invasive Versus Open Resection of Advanced Gallbladder Cancer: A National Assessment of Short and Long-Term Outcomes

Neutrophil/lymphocyte & platelet/lymphocyte ratios as predictor markers for advanced gallbladder cancer, is there a value?

Neutrophil/lymphocyte & platelet/lymphocyte ratios as predictor markers for advanced gallbladder cancer, is there a value?

A case of pancreaticobiliary maljunction with a connecting duct without a long common channel

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall, usually forming an abnormally long common channel. In PBM, since the long common channel defeats the effect of the sphincter of Oddi, pancreatobiliary reflux frequently occurs, resulting in high rates of biliary tract cancers. We present the case of a 68-year-old female with advanced gallbladder cancer concomitant with bile duct cancer associated with PBM without biliary dilatation that had an extremely rare configuration showing a connecting duct without a long common channel. Pancreatography in the selectively cannulated main pancreatic duct showed the terminal portion of the common bile duct via an abnormal connecting duct. Cholangiography in the selectively cannulated lower bile duct showed the main and accessory pancreatic ducts via the connecting duct. The bile amylase level was markedly elevated. This case of a rare configuration of PBM with a connecting duct without a long common channel is the first such reported case in the English literature.

Correlation of Radiotherapy Doses with Toxicities in Patients Undergoing Neoadjuvant Chemoradiation for Locally Advanced Gall Bladder Cancer

Correlation of Radiotherapy Doses with Toxicities in Patients Undergoing Neoadjuvant Chemoradiation for Locally Advanced Gall Bladder Cancer

Epigenetic Downregulation of PTEN in Gallbladder Cancer.

Gallbladder cancer (GBC) is becoming a global health problem. Phosphatase and tensin homolog (PTEN), also known as guardian gene of cancer, encodes a protein, which dephosphorylates phosphatidylinositol (3,4,5) triphosphate {PtdIns (3,4,5) P3 } into phosphatidylinositol (4,5) diphosphate {PtdIns (4,5) P2} that results in the inhibition of AKT/PKB signaling pathway. PTEN plays a key role in the pathogenesis of various cancers. However, its role in GBC is still obscure. The present study was aimed to identify the epigenetic role of PTEN in GBC and GSD. PTEN promoter methylation was studied by methylation-specific PCR in 50 GBC and 30 GSD tissues. Transcript level expression of PTEN was analyzed by reverse transcriptase PCR and quantitative PCR in 20 GBC and 20 GSD tissue samples. Immunohistochemistry was performed on tissue microarrays of 136 GBC samples to correlate the methylation pattern with the pattern of in situ expression of PTEN protein. Student's t test was performed to test the significant level of difference between case and control samples. Values showing p≤0.05 were considered significant. MS PCR showed PTEN promoter methylation in 30% (15/50) GBC (p=0.0486) and 22.86% (8/30) GSD (p=0.0530) cases. RT-PCR and qPCR revealed downregulation of PTEN in advanced GBC cases (p<0.0001), but, not in GSD (p=0.901). Immunohistochemistry of GBC tissue microarray scored 1+ in 20.29% (p=0.0028) and zero or negative in 50% (p<0.0001) GBC cores. Thus, PTEN may be considered asa useful biomarker for the management of GBC, however, needs larger sample size to validate it further.

Gemcitabine and Carboplatin in Inoperable, Loco-Regionally Advanced and Metastatic Gallbladder Cancer- A Study from Northern Indian Cancer Institute

Gemcitabine and Carboplatin in Inoperable, Loco-Regionally Advanced and Metastatic Gallbladder Cancer- A Study from Northern Indian Cancer Institute

進行胆嚢癌と鑑別が困難だった門脈血栓症併発無石性慢性胆嚢炎の1例

進行胆嚢癌と鑑別が困難だった門脈血栓症併発無石性慢性胆嚢炎の1例

Locally advanced gallbladder cancer: a management dilemma

Gallbladder cancer is an aggressive malignancy that is associated with a poor prognosis. While surgical resection provides the only curative option, the majority of patients are not considered resectable due to the presence of metastatic disease at the time of presentation. As systemic therapeutic options improve, a treatment dilemma can arise in patients treated with upfront chemotherapy with responsive disease and regionally metastatic disease that is resectable. We present a patient with regionally metastatic gallbladder cancer to segment IVb of the liver with responsive disease after gemcitabine/cisplatin treatment who underwent a radical cholecystectomy and central hepatectomy resulting in a prolonged disease-free interval.

Resection in a case of locally advanced gallbladder cancer with refractory staphylococcus blood stream infection

Resection in a case of locally advanced gallbladder cancer with refractory staphylococcus blood stream infection

226P Neoadjuvant chemotherapy in locally advanced gall bladder cancer: A retrospective tertiary care centre experience

226P Neoadjuvant chemotherapy in locally advanced gall bladder cancer: A retrospective tertiary care centre experience

241P NAB-paclitaxel as third-line therapy after failure of gemcitabine and 5-fluorouracil (5-FU) based combinations in advanced gall bladder cancer patients

241P NAB-paclitaxel as third-line therapy after failure of gemcitabine and 5-fluorouracil (5-FU) based combinations in advanced gall bladder cancer patients

226P Neoadjuvant chemotherapy in locally advanced gall bladder cancer: A retrospective tertiary care centre experience

226P Neoadjuvant chemotherapy in locally advanced gall bladder cancer: A retrospective tertiary care centre experience

Long-Term Outcomes and Prognostic Factors in Advanced Gallbladder Cancer: Focus on the Advanced T Stage.

BackgroundRadical resection is an effective therapeutic method to increase the survival rate of patients with gallbladder cancer (GBC). In addition to the surgical approach, the relationships between various clinicopathologic factors and the outcome of patients with GBC remain controversial.MethodsClinical and laboratory examination characteristics, pathological and surgical data, and post-operative survival time of 338 patients with advanced GBC who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University, China from January 2008 to December 2012 were analyzed retrospectively. Factors influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analysis.ResultsThe overall survival rates for curative resection patients were significantly greater than those for non-curative resection patients (1-,3-,5-year survival rate and mean-survival time: 59.0%, 47.3%, 44.3% and 22.0 months vs. 12.7%, 8.3%, 7.7% and 3.0 months) (P < 0.001). For the curative resection patients, positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites were all independent risk factors for poor prognosis. For patients with T3 stage, neither segmentectomy of IVb and V nor common bile duct resection improved the prognosis (P = 0.867 and P = 0.948). For patients with T4 stage, aggressive curative resection improved the prognosis (P = 0.007).ConclusionsAn advanced T stage does not preclude curative resection. Positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites are all independent risk factors for poor prognosis in the curative intent resection patients. The range of liver resection and whether common bile duct resection is performed do not influence the prognosis as long as R0 resection is achieved.

Is Major Hepatectomy with Portal Vein Resection or Pancreatoduodenectomy for Advanced Gallbladder Cancer Justified?

Introduction: The clinical impact of major hepatectomy with portal vein resection or pancreatoduodenectomy (PD) for advanced gallbladder cancer remains unclear. Methods: A total of 96 patients underwent resection for Stage II, III, or IV gallbladder cancer between 2003 and 2012. Of these, 29 patients who underwent major hepatectomy (major Hx group; resecting two or more sections) were enrolled in this study. During the same period, resection was not undertaken after laparotomy in 15 patients (unresectable group) because they had unsuspected distant metastases. Of these, 12 patients underwent non-surgical chemotherapy treatments. We analyzed whether major Hx with portal vein resection (PVR) or PD are justified for patients with advanced gallbladder cancer. Results: In the major Hx group, nine patients underwent PVR and nine patients underwent major hepatopancreatoduodenectomy (HPD). Mortality was zero in the major Hx group. The median survival time (MST) and the 5-year survival rate (5yrOS) in the major Hx group were 17.7 months and 27.8%, respectively, compared to 11.4 months and 0.0%, respectively, in the unresectable group. The patients in the major Hx group had a significantly better prognosis than those in the unresectable group (p=0.003, Fig. 1); there were five long-term survivors of more than five years in the major Hx group. In the subgroup analysis of the major Hx group, the OS in the patients who underwent PVR (n=9, MST 16.3 months, 5yrOS 33.3%, p=0.872, Fig. 2a) or major HPD (n=9, MST 29.8 months, 5yrOS 41.7%, p=0.440, Fig. 2b) was comparable with that seen in the subjects who did not undergo PVR (n=20) or major HPD (n=20). The multivariate analysis revealed that liver metastasis (n=3, p=0.038) and hepatic arterial invasion (n=6, p=0.017) were independently associated with the poor survival. In the comparison with the unresectable group, the OS in the patients with liver metastasis (p=0.572) and hepatic arterial invasion (p=0.776, Fig. 2c) were comparable with those seen in the unresectable group. However, the OS in the patients with lymph node metastasis (n=20, p=0.062, Fig. 2d), PVR (p=0.054), or major HPD (p=0.011) was better than those seen in the unresectable group.Figure 1Figure 2Table 1: Results of univariate and multivariate analyses regarding the prognostic factors associated with overall survival in the 29 patients treated with major hepatectomy for gallbladder cancerConclusion: Even in patients with lymph node metastasis and/or a need for PVR or major HPD, the surgeon can consider aggressive surgery with lymphadenectomy and combined PVR or combined PD, especially in selected patients without liver metastasis or hepatic arterial invasion.Figure 3

Gallbladder cancer: South American experience.

Large differences in terms of incidence and mortality due to gallbladder cancer (GBC) have been reported worldwide. Moreover, it seems that GBC has unique characteristics in South America. We surveyed the literature looking for information about the epidemiology, basic and translational research, and clinical trials performed in South America in order to critically analyze the magnitude of this health problem in the region. Compared to other geographic areas, age-standardized mortality rates (ASMR) for GBC in women are very high, particularly in many western areas of South America. Genetic, as well as dietary and environmental factors likely contribute to the pathogenesis of this disease in the area. Compared to other regions the profile of abnormalities of key genes such as KRAS and TP53 in GBC seems to slightly differ in South America, while the clinical behavior appears to be similar with a median overall survival (OS) of 6.5 to 8 months in advanced GBC. In contrast to Europe and USA, prophylactic cholecystectomy is a common practice in western areas of South America. GBC particularly affects women in South America, and represents a significant public health problem. It appears to have peculiarities that pose an urgent need for additional research aimed to discover risk factors, molecular events associated with its development and new treatment options for this lethal disease.

700P - NAB-PACLITAXEL as third-line therapy after failure of gemcitabine and 5-FU based combinations in advanced gall bladder cancer patients

700P - NAB-PACLITAXEL as third-line therapy after failure of gemcitabine and 5-FU based combinations in advanced gall bladder cancer patients