Associations between external beam radiotherapy and overall survival in patients with gallbladder cancer: A population-based study.

Background: There is a lack of studies regarding radiotherapy (RT) in patients with gallbladder cancer (GBC) on the survival benefit after surgery and nonsurgical treatment. Therefore, this study evaluated the impact of external beam RT on the overall survival (OS) of patients with GBC in a real-world setting. Methods: Patients with GBC enrolled from the Surveillance, Epidemiology, and End Results (SEER) database were examined through Kaplan-Meier survival curves and multivariable Cox regression analyses. Results: A total of 7,866 patients with GBC were screened for the current analysis, of whom 2,130 (27.1%) did not undergo RT or surgery, 209 (2.7%) underwent RT, 4,511 (57.3%) underwent surgery, and 1,016 (12.9%) underwent both RT and surgery. The median OS times were 4 months, 8 months, 16 months, and 22 months (p < 0.0001). OS was significantly different between adjuvant RT (p = 0.0002) and palliative RT (p < 0.0001). Multifactorial analysis (controlling for age, sex, year of diagnosis, marital status, race, grade, and stage) showed that both adjuvant RT (surgery and adjuvant RT vs. surgery alone; HR, 0.75; 95% CI, 0.69-0.82, p < 0.001) and palliative RT (RT alone vs. no treatment; HR, 0.80; 95% CI, 0.69-0.92, p = 0.003) had a significant impact on patient OS. The results remained stable following sensitivity analyses. Conclusion: The study results indicate that adjuvant and palliative radiation treatment was associated with a survival benefit. GBC patients can derive a survival benefit from external beam RT.

Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy. METHODS: Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis. RESULTS: The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis. CONCLUSION: The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.

Benefit of adjuvant radiotherapy for gallbladder cancer: a comparability-based meta-analysis.

BACKGROUND AND PURPOSE: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. METHODS: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). RESULTS: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. CONCLUSION: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. PROTOCOL REGISTRATION: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).

Radiotherapy for locally advanced unresectable gallbladder cancer - A way forward: Comparative study of chemotherapy versus chemoradiotherapy.

Background: For nonmetastatic locally advanced gallbladder cancer (LAGBC) which remains unresectable and nonmetastatic after chemotherapy, there is no consensus on whether to continue chemotherapy or add local radiotherapy (RT) for improving outcomes. Materials and Methods: Forty-five patients of surgically unresectable nonmetastatic LAGBC were analyzed. Twenty patients did not receive RT (no RT cohort) and received only chemotherapy, while 25 patients received RT (RT cohort) with conformal techniques along with concurrent gemcitabine-based chemotherapy. No RT and RT cohorts were compared for disease-related outcomes and toxicities. Results: Median follow-up of the entire cohort was 11.5 months. Two-year progression-free survival (18.6% vs. 0%, P = 0.0001) and overall survival (37.3% vs. 5%, P = 0.0001) were significantly better in the RT cohort as compared to a no RT cohort. More number of patients had locoregional progression in the no RT cohort (85% vs. 32%, P = 0.0002). Radiation-induced acute and late gastrointestinal toxicity ≥ RTOG Grade 3 were seen in one and two patients, respectively. Conclusion: Addition of local RT to chemotherapy improves the survival outcomes and can be considered as a definite treatment modality for nonmetastatic LAGBC patients not amenable to surgery who have responded to chemotherapy.

Consolidation chemoradiation (cCTRT) improves survival in responders to first-line chemotherapy (CT) in locally advanced gallbladder cancer (LA-GBC): A new standard of care?

Introduction: Chemotherapy (CT) is the standard of care in advanced gallbladder cancer (GBC). Should locally advanced GBC (LA-GBC) with response to CT and good performance status (PS) be offered as consolidation chemoradiation (cCTRT) to delay progression and improve survival? There is a scarcity of literature on this approach in the English literature. We present our experience with this approach in LA-GBC. Materials and Methods: After obtaining ethics approval, we reviewed the records of consecutive GBC patients from 2014 to 2016. Out of 550 patients, 145 were LA-GBC who were initiated on chemotherapy. A contrast-enhanced computed tomography (CECT) abdomen was done to evaluate the response to treatment, according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. All responders to CT (PR and SD) with good PS but unresectable were treated with cCTRT. Radiotherapy was given to GB bed, periportal, common hepatic, coeliac, superior mesenteric, and para-aortic lymph nodes up to a dose of 45 to 54 Gy in 25 to 28 fractions along with concurrent capecitabine at the rate of 1,250 mg/m2. Treatment toxicity, overall survival (OS), and factors affecting OS were computed based on Kaplan-Meier and Cox regression analysis. Results: ">The median age of patients was 50 years (interquartile range [IQR] = 43-56 years), and men to women ratio was 1:3. A total of 65% and 35% patients received CT and CT followed by cCTRT, respectively. The incidence of Grade 3 gastritis and diarrhea was 10% and 5%, respectively. Responses were partial response (PR; 65%), stable disease (SD; 12%), progressive disease (PD; 10%), and nonevaluable (NE; 13%) because they did not complete six cycles of CT or were lost to follow-up. Among PR, 10 patients underwent radical surgery (six after CT and four after cCTRT). At a median follow-up of 8 months, the median OS was 7 months with CT and 14 months with cCTRT (P = 0.04). The median OS was 57 months, 12 months, 7 months, and 5 months for complete response (CR) (resected), PR/SD, PD, and NE (P = 0.008), respectively. OS was 10 months and 5 months for Karnofsky performance status (KPS) >80 and <80 (P = 0.008), respectively. PS (hazard ratio [HR] = 0.5), stage (HR = 0.41), and response to treatment (HR = 0.05) were retained as independent prognostic factors. Conclusions: CT followed by cCTRT appears to improve survival in responders with good PS.

Nafamostat mesilate, a nuclear factor kappa B inhibitor, enhances the antitumor action of radiotherapy on gallbladder cancer cells.

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 µg/mL and 40 µg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.

Postsurgical radiotherapy in stage IIIB gallbladder cancer patients with one to three lymph nodes metastases: A propensity score matching analysis.

BACKGROUND: The effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB. METHODS: The data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT. RESULTS: 726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup. CONCLUSIONS: PSRT provides no survival benefit for IIIB GBC.

Lumbar vertebral osteoradionecrosis: a rare case report with 10-year follow-up and brief literature review.

BACKGROUND: Osteoradionecrosis (ORN) is a complication that occurs after radiotherapy for head or neck malignancies. ORN of the spine is rare, with only few cases affecting the cervical spine reported to date. To our knowledge, no case of lumbar ORN has been reported. We report a rare case of ORN in the lumbar spine that occurred 2 years after radiotherapy and perform a literature review. CASE PRESENTATION: We present a case of lumbar ORN that occurred 2 years after radiotherapy for gallbladder carcinoma. The patient was successfully treated conservatively and followed up for > 10 years. CONCLUSIONS: ORN of the spine is a rare complication of radiotherapy. Spinal ORN is clinically described as a chronic disease with a slow onset. The most common presenting symptom of spinal ORN is pain. However, as ORN progresses, spinal kyphosis and instability can lead to neurological compression and thus to induced myelopathy or radiculopathy. Treatment of spinal ORN is comprehensive, including orthosis, medication, hyperbaric oxygen therapy, surgery, and new treatment combinations of pentoxifylline and tocopherol. The surgical rate for spinal ORN is relatively high.

A meta-analysis of the efficacy of postoperative adjuvant radiotherapy versus no radiotherapy for extrahepatic cholangiocarcinoma and gallbladder carcinoma.

OBJECTIVE: The benefit of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma (EHCC) and gallbladder carcinoma (GBC) is unclear, with conflicting results from nonrandomized studies. We reported a meta-analysis to determine the impact of adjuvant radiotherapy on survival. METHODS: PubMed, EMBASE, Cochrane Library and CNKI databases were searched to identify clinical trials of postoperative ART versus no radiotherapy for EHCC and GBC. The obtained data were analyzed using RevMan 5.3 and Stata 14.0 statistical software. Differences between two groups were estimated by calculating the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 21 clinical trials involving 1465 EHCC and GBC patients were selected according to the inclusion and exclusion criteria and included in this meta-analysis. The meta-analysis showed the following: The 5-year overall survival (OS) rate was higher in the ART group than in the no radiotherapy group (OR = 0.63; 95% CI = 0.50-0.81, p = 0.0002). The 5-year OS rate was significantly higher for those with lymph node-positive disease (OR = 0.15; 95% CI 0.07-0.35; p < 0.00001) and margin-positive disease (OR = 0.40; 95% CI 0.19-0.85; p = 0.02) in the ART group than in the no radiotherapy group. ART had a tendency to bring benefit to the 5-year OS of patients with margin-negative disease but the difference was not statistically significant (OR = 0.57, 95% CI 0.30-1,07, p = 0.08). The local recurrence rate was significantly lower in the ART group than in the no radiotherapy group (OR = 0.54; 95% CI = 0.38-0.76, p = 0.0004), and there was no significant difference in the distant metastasis rate between the two groups (OR = 1.33; 95% CI = 0.95-1.87, p = 0.10). CONCLUSIONS: A meta-analysis of the existing study results showed that compared with no radiotherapy, ART is an effective postoperative treatment for EHCC and GBC.

Contemporary perspectives on the use of radiation therapy for locally advanced gallbladder cancer.

Locally advanced gallbladder cancer poor prognosis due to a high distant metastatic rate and poor overall disease control. The impact of standard therapeutic options is unfortunately modest. Due to the rarity of the disease, evidence-based management continues to evolve. The goal of this review is to highlight the contemporary landscape of radiation therapy for gallbladder cancer. First, the rationale for radiation therapy is described. This includes the risk of locoregional recurrence following resection based on patterns-of-failure data, along with the high locoregional disease burden being a frequent cause morbidity and mortality in unresected cases. Additionally, improvements in systemic therapy over the next decade could shift contemporary patterns of failure more towards proportionally higher locoregional recurrence rates. Second, clinical data of radiation therapy for gallbladder cancer are discussed. These include consideration of postoperative chemoradiotherapy for margin- and/or node-positive cases. Patients with localized unresectable disease could benefit from ablative radiation therapy, based on promising data in non-gallbladder cancer pancreaticobiliary neoplasms. The use of advanced radiation therapy technologies such as proton beam therapy, as a means to deliver ablative radiation therapy in a potentially safer manner, is also mentioned. Lastly, the emerging concept of neoadjuvant therapy for gallbladder cancer is also described, in efforts to allow more patients to receive curative resection.

Interventional radiology's role in the diagnosis and management of patients with gallbladder carcinoma.

Gallbladder carcinoma is a rare, aggressive biliary tract malignancy, with a 5-year survival of less than 5%. It is the 6th most common gastrointestinal malignancy in the United States and more commonly found in women. While some risk factors include gallstones, porcelain gallbladder, and smoking, gallbladder carcinoma is often found incidentally following cholecystectomy or percutaneous image guided biopsy. Patients frequently present in a late disease state when they are no longer surgical candidates and minimally invasive image guided-interventions therefore play a critical role in the management and treatment of these patients. This review will discuss some of the key procedures and roles interventional radiologists play in the diagnosis and management of patients suffering from gallbladder carcinoma including tissue sampling, placement of intra-arterial infusion pumps, preoperative portal vein embolization (PVE), biliary drainage, management of post-operative complications such as bile leaks or biliary obstruction, and management of chronic pain.

A Systematic Review and Meta-analysis of Intraluminal Brachytherapy Versus Stent Alone in the Treatment of Malignant Obstructive Jaundice.

OBJECTIVES: To evaluate therapeutic outcomes of intraluminal brachytherapy (ILBT) for malignant obstructive jaundice (MOJ) against stent alone. METHODS: The PubMed, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP and ClinicalTrials.gov databases were searched for all relevant comparative studies from the earliest available date up to 1 May 2017. Subgroup analyses were performed according to the type of study design and type of stent. RESULTS: Twelve studies that compared ILBT versus stent alone were eligible. A total of 641 participants with MOJ were included in our meta-analysis. A total of 340 participants were treated with intraluminal brachytherapy (ILBT); the other 301 participants were treated with biliary stent alone (stent group). ILBT was associated with lower risk of stent occlusion (OR 0.19; 95% CI 0.13-0.28; P < 0.00001) and better mean survival (MD = 3.15; 95% CI 2.64-3.66; P < 0.00001) compared with stent alone. However, the two groups were similar in number of complications (OR 0.84; 95% CI 0.45-1.56; P = 0.578), post-treatment reduced level of total bilirubin (TBIL) (MD = 22.71; 95% CI - 7.24-52.65; P = 0.14), post-treatment reduced level of direct bilirubin (DBIL) (MD = - 3.67; 95% CI - 14.09-6.75; P = 0.49), post-treatment reduced level of alanine aminotransferase (ALT) (MD = 21.09; 95% CI - 5.09-47.28; P = 0.11) and post-treatment reduced level of aspartate aminotransferase (AST) (MD = 20.86; 95% CI - 45.86-87.58; P = 0.54). CONCLUSIONS: ILBT was significantly superior to stent alone in terms of stent occlusion and mean survival. Meanwhile, ILBT had comparable outcomes to stent alone in terms of complications and post-treatment reduced levels of TBIL, DBIL, ALT and AST. Therefore, ILBT may be considered a preferable technique for MOJ.

Primary Non-Hodgkin's Lymphoma of the Gallbladder: A Population-based Analysis.

BACKGROUND/AIM: Primary Non-Hodgkin's lymphoma of the gallbladder (PNHL-GB) is extremely rare and data on clinical characteristics, optimal management and outcomes of these patients are limited to anecdotal reporting. We, therefore, sought to examine these patients using a population-based database. MATERIALS AND METHODS: Surveillance, epidemiology, and end results (SEER) database was queried between 1973 and 2013. RESULTS: One hundred and six cases with PNHL-GB were identified (mean age=70.5 ±15 years, whites 92%, male: female 1.03:1). The majority of patients had loco-regional disease (61%) and DLBCL histology (33%). Ninenty cases (85%) had undergone surgical resection, 6 (5.6%) received radiotherapy. Median overall survival (OS) of the entire cohort was 41 months with a 5-year survival rate of 40%. Patients receiving adjuvant RT had superior OS compared to surgery alone (140 ±27 vs. 86 ±16 months, respectively) and patients with DLBCL demonstrated lower survival compared to other histologies (13 vs. 53 months, respectively, p=0.034). CONCLUSION: Our study presents the largest dataset of PNHL-GB describing clinical features and outcomes of these patients in addition to summarizing the literature.

Limited Use of Adjuvant Therapy in Patients With Resected Gallbladder Cancer Despite a Strong Association With Survival.

Background: There are no randomized data to guide clinicians treating patients with gallbladder cancer (GBC). Several retrospective studies reported the survival benefits of adjuvant radiotherapy (RT) and chemoradiation (CRT). In this paper, we examine whether these publications have impacted the utilization of adjuvant therapies and whether their survival benefits are evident in a contemporary cohort of patients. Methods: Using the National Cancer Data Base, we identified 5029 patients diagnosed with T1-3N0-1 GBC and treated with surgical resection from 2005 to 2013. We described trends in receipt of adjuvant treatments for three time periods (2005-2007, 2008-2010, 2011-2013) and calculated three-year overall survival (OS) probabilities for 2989 patients treated in 2005-2010. All statistical tests were two-sided. Results: The percentage of patients who received no adjuvant treatments was unchanged from 2005 to 2013. Adjuvant RT decreased from 4.2% to 1.7% ( P < .001), adjuvant chemotherapy increased from 8.3% to 13.8% ( P < .001), and adjuvant CRT remained stable at 15.9% ( P = .98). Adjuvant treatments were associated with improved three-year OS, with adjusted hazard ratio of 0.47 (95% confidence interval [CI] = 0.39 to 0.58) for CRT, 0.77 (95% CI = 0.61 to 0.97) for chemotherapy, and 0.63 (95% CI = 0.44 to 0.92) for RT. Adjuvant CRT was associated with improved survival in all categories, except T1N0, and in patients with negative and positive margins. Conclusion: Over the past decade there was no increase in the utilization of adjuvant therapies in the United States for patients with resected GBC. Adjuvant therapy is associated with statistically significantly improved three-year OS. This analysis should form the basis for current clinical recommendations and support future prospective trials.

Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients

Background. The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. Methods. 98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated. Results. Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis. Conclusions. The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC (AU)

No disponible

A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer.

PURPOSE: Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer. METHODS: Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography. RESULTS: Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively. CONCLUSIONS: This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.

Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature.

BACKGROUND: Gall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature. METHODS: This report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis. CASE REPORT: A 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2×2cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired. CONCLUSION: There are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer.

Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling.

Biliary tract cancer, or cholangiocarcinoma, arises from the biliary epithelium of the small ducts in the periphery of the liver (intrahepatic) and the main ducts of the hilum (extrahepatic), extending into the gallbladder. The incidence and epidemiology of biliary tract cancer are fluid and complex. It is shown that intrahepatic cholangiocarcinoma is on the rise in the Western world, and gallbladder cancer is on the decline. Radiation therapy has emerged as an important component of adjuvant therapy for resected disease and definitive therapy for locally advanced disease. The emerging sophisticated techniques of imaging tumors and conformal dose delivery are expanding the indications for radiotherapy in the management of bile duct tumors. As we understand more about the molecular pathways driving biliary tract cancers, targeted therapies are at the forefront of new therapeutic combinations. Understanding the gene expression profile and mutational burden in biliary tract cancer allows us to better discern the pathogenesis and identify promising new developmental therapeutic targets.