Updates on Gallbladder Cancer Management

Purpose of Review

We will review the current standard of care management for metastatic gallbladder cancer (GBC), recommendations for resection of incidentally or non-incidentally diagnosed GBC, and developments in preoperative risk stratification and adjuvant chemotherapy.

Recent Findings

Gemcitabine-cisplatin is the standard of care therapy for advanced-stage disease. Patients with incidentally diagnosed GBC should undergo re-resection for T1b, T2, or T3 disease. The presence of residual disease is associated with decreased survival. Diagnostic laparoscopy should be used in select patients to avoid unnecessary laparotomy. Major hepatectomy and common bile duct excision should only be performed in select cases. Current standard of care for adjuvant therapy includes 6 months of oral capecitabine.

Summary

Gallbladder cancer continues to carry high mortality rates due to its aggressive course and early spread. Recent developments in preoperative risk stratification, surgical resection, and chemotherapy have greatly shaped management of this malignancy in the current era.

     

Expression Analysis of Survivin and XIAP in Gallbladder Cancer: a Case-control Study in Indo-Gangetic Plain

Purpose

Gallbladder cancer is a highly mortal disease with poor prognosis because of late presentation of disease. Survivin and X-linked inhibitor of apoptosis (XIAP) are one of the two important members of inhibitors of apoptosis. Thus, this study aimed to look at the expression of Survivin and XIAP in gallbladder cancer patients.

Methods

Survivin and XIAP expression were investigated in tissues of gallbladder cancer patients (40 cases) and compared with cholelithiasis as control (40 cases) by using immunohistochemistry. Their expression was correlated with clinicopathological parameters.

Results

Significantly higher (p < 0.05), Survivin protein was expressed in gallbladder cancer (n = 67.5%) than control (n = 35%). But it did not show any significant association with any of the clinicopathological parameter while XIAP was not expressed in the GBC patients (p > 0.05).

Conclusion

Overexpression of Survivin in gallbladder cancer suggests its possible role and association with poor prognosis. But XIAP has not been found to be associated with gallbladder carcinogenesis.

     

Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design

Background and aims

Gallbladder carcinoma is a rare, aggressive malignancy of the biliary tract associated with a poor prognosis. Despite the deployment of targeted therapies that have demonstrated marked survival benefits in many tumor types, traditional cytotoxic chemotherapy has remained the mainstay of treatment for unresectable and metastatic gallbladder cancer.

Methods

Systematic review of ongoing and prior clinical studies shows a paucity of biomarker-driven therapeutic trials using targeted agents in gallbladder cancer. In fact, over the past 6 years, of the 38 therapeutic biliary tract protocols listed on clinicaltrials.gov, only 6 (21 %) utilized targeted therapies based upon tumor biomarkers or genomics. Now that we have entered the era of next-generation sequencing and precision medicine, we are beginning to identify common and specific genetic alterations in gallbladder carcinomas.

Results

A review of the literature reveals alterations in ARID1A, BRAF, CDKN2A/B, EGFR, ERBB2-4, HKN-RAS, PIK3CA, PBRM1, and TP53. Given the widespread use of tumor genomic profiling and the fact that most of the aforementioned alterations are pharmacologically tractable, these observations suggest the potential for new therapeutic strategies in this aggressive malignancy.

Conclusions

Taken together, further understanding of the genomic landscape of gallbladder cancer coupled with biomarker-driven clinical trials that match therapies to targets are urgently needed.

     

A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals,Curcumin, Quercetin,and Allicin,in the Treatment of Gastric Cancer

Objective

Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.

Methods

Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were “curcumin,” “quercetin,” “allicin,” and “gastric cancer” or “cancer.”

Results

Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.

Conclusions

Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents.

Mini-Abstract

Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.

     

Cancers et environnement : explorer les comportements de recherche et les sources d’information des personnes atteintes et non atteintes d’un cancer

Aim

To explore information-seeking behaviors on links between cancers and environment.

Method

Focus groups and individual semi-structured interviews realized, respectively, with individuals without and with personal cancer experience.

Results

The majority of respondents reported informationscanning behaviors. Only half cancer patients searched for information regarding the links between cancers and environment.

Conclusion

Little information is sought on links between cancers and environment.

     

Grundlagen der Kachexie bei Tumorpatienten

Background

The cancer cachexia syndrome is the most common paraneoplastic syndrome affecting approximately half of the patients with a malignant tumor.

Objective

Presentation of the pathophysiological processes in cancer cachexia and the clinical consequences.

Material and methods

Selective literature search in PubMed with inclusion of the current guidelines.

Results

Characteristic of cancer cachexia is a systemic inflammation syndrome. Tumor-specific and proinflammatory mediators lead to loss of appetite, systemic inflammation, metabolic and hormonal changes. Systemic inflammation has effects on protein, carbohydrate and lipid metabolism of the liver and peripheral organs. Frequently, insulin resistance and impaired glucose tolerance are also present. The consequences are a diminished food intake, lower nutrient utilization and loss of muscle tissue, with or without loss of fat mass. In addition, cancer therapy even with newer targeted anticancer agents, may speed up muscle breakdown and promote the development of cancer cachexia.

Conclusion

Cancer cachexia leads to a progressive reduction of performance, to fatigue and a loss of independence. In the multimodal therapy of cancer cachexia syndrome in cancer patients nutritional therapeutic measures represent an important component in order to improve the clinical course of patients.

     

Analysis of gallstone disease after gastric cancer surgery

Background

The incidence rate of newly developed gallstone disease after gastrectomy for gastric cancer is thought to be higher than that in the general population. However, the presentation and management of these gallstones remain under debate, and the role of prophylactic cholecystectomy remains questionable.

Methods

Data on adult patients who were diagnosed with gastric cancer and received gastrectomy between 2000 and 2011 were extracted from the Taiwan National Health Insurance Research Database. A patient was excluded if he or she had gallstone disease or received cholecystectomy before the index date. The incidence of newly developed gallstone disease and its subsequent management were recorded. Data were analyzed to evaluate the factors associated with gallstone development and treatment options.

Results

A total of 17,325 gastric cancer patients who underwent gastrectomy were eligible for analysis. During the follow-up period (mean 4.1 years; median, 2.9 years), 1280 (7.4%) patients developed gallstone disease and 560 (3.2%) patients subsequently underwent cholecystectomy. The in-hospital mortality for cholecystectomy was 1.8% (10/560). Development of gallstone disease was associated with older age, total gastrectomy, duodenal exclusion, diabetes, cirrhosis, and more comorbidities. Factors associated with the use of cholecystectomy to treat gallstone disease included younger age, fewer comorbidities, medical center admission, and presentation as cholecystitis.

Conclusions

Although few patients required further gallbladder removal after gastrectomy for gastric malignancy, the increased mortality rate for subsequent cholecystectomy was worth noting. The decision to undergo prophylactic cholecystectomy might be individualized based upon patient characteristics and the surgeon’s discretion.

     

Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines,platinum, and taxanes

Background

Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan.

Methods

A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes.

Results

Between February 2008 and December 2013, 52 patients received third-line irinotecan monotherapy. Among the 32 patients with measurable lesions, 1 patient achieved a confirmed partial response and 6 patients had stable disease. The overall response rate was 3% and the disease control rate was 22%. Median progression-free survival was 2.3 months [95% confidence interval (CI), 1.8–2.8] and median overall survival was 4.0 months (95% CI, 2.6–5.3). The most common adverse events of grade 3 severity or higher were neutropenia (27%), febrile neutropenia (12%), anorexia (12%), and diarrhea (6%). Although no treatment-related deaths occurred, 2 patients (4%) died of disease progression within 30 days after the last administration of irinotecan.

Conclusion

Irinotecan monotherapy appears to be tolerated but was shown to have modest activity as third-line chemotherapy for advanced gastric cancer.

     

Clinical Factors as a Component of the Personalized Treatment Approach to Advanced Pancreatic Cancer: a Systematic Literature Review

Introduction

Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent.

Discussion

This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection.

Conclusion

Identification and optimization of these clinical factors could make a meaningful impact on the patient’s quality of life.

     

The patients’ experience of a bladder cancer diagnosis: a systematic review of the qualitative evidence

Purpose

Bladder cancer (BC) is a common disease with disparate treatment options and variable outcomes. Despite the disease’s high prevalence, little is known of the lived experience of affected patients. National patient experience surveys suggest that those with BC have poorer experiences than those with other common cancers. The aim of this review is to identify first-hand accounts of the lived experiences of diagnosis through to survivorship.

Method

This is a systematic review of the qualitative evidence reporting first-hand accounts of the experiences of being diagnosed with, treated for and surviving bladder cancer. A thematic analysis and ‘best-fit’ framework synthesis was undertaken to classify these experiences.

Results

The inconsistent nature of symptoms contributes to delays in diagnosis. Post-diagnosis, many patients are not actively engaged in the treatment decision-making process and rely on their doctor’s expertise. This can result in patients not adequately exploring the consequences of these decisions. Learning how to cope with a ‘post-surgery body’, changing sexuality and incontinence are distressing. Much less is known about the quality of life of patients receiving conservative treatments such as Bacillus Calmette-Guerin (BCG).

Conclusions

The review contributes to a greater understanding of the lived experience of bladder cancer. Findings reflect a paucity of relevant literature and a need to develop more sensitive patient-reported outcome measures (PROMs) and incorporate patient-reported outcomes in BC care pathways.

Implications for cancer survivors

Collective knowledge of the patients’ self-reported experience of the cancer care pathway will facilitate understanding of the outcomes following treatment.

     

Communication and comprehensive cancer control coalitions: lessons from two decades of campaigns,outreach, and training

Purpose

Comprehensive cancer control (CCC) coalitions and programs have delivered effective models and approaches to reducing cancer burden across the United States over the last two decades. Communication plays an essential role in diverse coalition activities from prevention to survivorship, including organizational and community capacity-building and as cancer control intervention strategies.

Methods

Based upon a review of published CCC research as well as public health communication best practices, this article describes lessons learned to assist CCC coalitions and programs with systematic implementation of communication efforts as key strategies in cancer control.

Results

Communication-oriented lessons include (1) effective communication work requires listening and ongoing engagement with key stakeholders, (2) communication interventions should target multiple levels from interpersonal to mediated channels, (3) educational outreach can be a valuable opportunity to bolster coalition effectiveness and cancer control outcomes, and (4) dedicated support is necessary to ensure consistent communication efforts.

Conclusions

External and internal communication strategies can optimize coalition efforts and resources to ultimately help produce meaningful improvement in cancer control outcomes.

     

A population-based audit of ethnicity and breast cancer risk in one general practice catchment area in North London,UK: implications for practice

Objectives

To conduct a pilot population-based study within a general practice catchment area to determine whether the incidence of breast cancer was increased in the Ashkenazi population.

Design

Population-based cohort study.

Setting

A single general practice catchment area in North London.

Participants

1947 women over the age of 16 who responded to a questionnaire about ethnicity and breast cancer.

Main outcome measures

Incidence of breast cancer, ethnicity.

Results

This study showed a 1.5-fold (95% CI 0.93–2.39) increase in breast cancer risk in the Ashkenazim compared with the non-Ashkenazi white population. The increased incidence was for both premenopausal and postmenopausal breast cancer (expected incidence pre:post is 1:4 whereas in the Ashkenazim it was 1:1; 51 and 52% of cases respectively). This increase was not shown in the Sephardim. Asians had a reduction in incidence (OR = 0.44; 95% CI 0.10–1.89). Results were adjusted for other risk factors for breast cancer.

Conclusion

This study showed a 1.5-fold increase in breast cancer rates in Ashkenazim compared with the non-Jewish white population when adjusted for age (i.e. corrections were made to allow comparison of age groups) and this is not observed in the Sephardic population. The proportion of premenopausal breast cancer was just over double that of the general population. This is the first general practice population-based study in the UK to address this issue and has implications for general practitioners who care for patients from the Ashkenazi community.

     

Atypical presentation of hepatocellular carcinoma: a mass on the left thoracic wall

Background

Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely.

Case presentation

We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region.

Conclusions

Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified.

     

Diagnostik,Therapie und Nachsorge beim Hodentumor

Background

Testicular cancer is a disease of young adult men, and it is curable in most cases. Even in advanced disease, cure rates reach 80?% nowadays. This was achieved by consistently performing studies concerning the different stages of disease.

Treatment and follow-up care

The concept of treatment is interdisciplinary. After removal of the affected testis, histology and stage determine further therapy, which can be active surveillance, polychemotherapy, radiotherapy, surgery, or a combination of these. Curability also has consequences for the long-term follow-up. We speak about long-term survivorship. Besides looking for recurrences, it is also necessary to observe and treat long-term toxicities caused by the different therapeutic procedures.

Conclusion

Because testicular cancer is rare with about 4500 cases annually, treatment—especially for advanced disease—should be performed at centers. In addition, it is possible to obtain a second opinion using the Interdisciplinary German Testicular Study Group website.

     

Feasibility study of postoperative adjuvant chemotherapy with S-1 in patients with biliary tract cancer

Background

The role of adjuvant chemotherapy has not yet been established for patients with resected biliary tract cancer. S-1 has been shown to exert activity against advanced biliary tract cancer. Therefore, we evaluated the feasibility of adjuvant chemotherapy with S-1 in patients with resected biliary tract cancer.

Methods

Patients with complete macroscopic resection of intrahepatic/extrahepatic bile duct, gall bladder, or ampullary cancer were eligible. S-1 was administered orally twice daily for 4 weeks every 6 weeks, up to 4 cycles. The treatment was continued up to 24 weeks or until recurrence/appearance of unacceptable toxicity. The primary endpoint was the treatment completion rate, which was defined as the percentage of patients who received a relative dose intensity of ≥?75%. This trial was registered as UMIN000004051.

Results

Thirty-three patients were enrolled between June 2010 and March 2011. The relative dose intensity was ≥?75% in 27 patients representing a treatment completion rate of 81.8%. The most common grade 3/4 adverse event was neutropenia (18%). Grade 2 nausea or diarrhea was observed in 12%. The 3-year relapse-free survival rate was 39.4%. The 3-year survival rate was 54.5%.

Conclusion

Adjuvant chemotherapy with S-1 is feasible treatment in patients with resected biliary tract cancer. It is necessary to conduct a phase III study to confirm the efficacy of adjuvant therapy of S-1 in patients with resected BTC.

     

Residential traffic noise and mammographic breast density in the Diet,Cancer, and Health cohort

Objectives

Traffic is the most important source of community noise, and it has been proposed to be associated with a range of disease outcomes, including breast cancer. As mammographic breast density (MD) is one of the strongest risk factors for developing breast cancer, the present study investigated whether there is an association between residential exposure to traffic noise and MD in a Danish cohort.

Methods

We included women with reproductive and lifestyle information available from the Diet, Cancer, and Health cohort, who also participated in the Copenhagen Mammography Screening Programme (n?=?5,260). Present and historical addresses from 1987 to 2011 were found in national registries, and traffic noise was modeled 5 years before mammogram. Analyses between residential traffic noise and MD were performed using logistic regression.

Results

We found no association between residential road and railway noise exposure 5 years before mammogram, and having a mixed/dense versus a fatty mammogram, and no interaction with menopausal status, BMI, HRT use, and railway noise exposure, for analyses on road traffic noise.

Conclusion

The present study does not suggest an association between residential traffic noise exposure and subsequent MD in a cohort of middle-aged Danish women.

     

Physical symptoms in long-term survivors of rare cancer

Purpose

Advances in cancer detection and treatment have resulted in a growing population of long-term survivors, but even years after treatment has concluded, many survivors report physical symptoms that interfere with daily living. While there are studies of late effects following common cancers, less is known about these complications in rare cancers. This study focuses on the physical symptoms reported by long-term survivors enrolled in the NIH-sponsored Rare Cancer Genetics Registry.

Methods

The Rotterdam Symptom Checklist-Modified was administered to evaluate the severity of physical symptoms commonly reported by long-term cancer survivors. Logistic regression was used to assess association between symptoms and demographic and clinical factors.

Results

In 309 subjects with a median time of 7.6 years from a diagnosis of one or more rare cancers, the median number of symptoms present per participant was 7. The most prevalent symptom reported was tiredness/lack of energy, which was present/very bothersome in 70%/25% of registrants. Women, non-whites, current smokers, and upper GI cancer survivors are particularly affected. Overall, symptom prevalence was similar across rare cancer types, time since diagnosis, and type of treatment.

Conclusions

Rare cancer survivors continue to experience troublesome symptoms many years after diagnosis, regardless of cancer type or treatment modality.

Implications for Cancer Survivors

There is a need for continued emphasis on smoking cessation in cancer survivors as well as enhanced monitoring of long-term complications in female, non-white, and upper GI cancer survivors.

     

Nichtkleinzelliges Lungenkarzinom – Pathologie und Biologie

Background

Non-small cell lung cancer (NSCLC) accounts for ca. 75% of malignant epithelial neoplasms of the lungs. In recent years profound insight has been gained regarding the molecular mechanisms of lung carcinogenesis and subsequently new targeted therapies as well as immunotherapies have been developed. These advances have had a significant impact on routine diagnostics in pathology.

Objective

The article aims to give an overview of the most common histological subtypes of NSCLC as well as the morphological, immunohistochemical and molecular characteristics.

Material and methods

Selective search of the PubMed database.

Results and discussion

Adenocarcinomas, squamous cell carcinomas and large cell carcinomas are the most common histological subtypes. With the ancillary methods available in routine pathology even poorly differentiated tumors can be assigned to these entities. The NSCLC show numerous genetic changes of which alterations of EGFR, MET, ALK1 and ROS1 are target structures for personalized therapy.

     

Insights Into the Relationship Between Gut Microbiota and Colorectal Cancer

Purpose of review

There is growing evidence to suggest that gut microbiota plays an important role in colorectal carcinogenesis. Western diet is associated with gut microbial dysbiosis, which leads to inflammation, oxidative stress, and genotoxic effects, all common risk factors for colorectal cancer.

Recent findings

Fusobacterium nucleatum, Helicobacter pylori, Bacteroides fragilis, Escherichia coli, and Streptococcus bovis are the main bacterial species associated with colorectal carcinogenesis. Gut microbiota transforms both diet- (meat, processed meat products, fat) and host (bile acids)-derived precursors into carcinogens and further interferes with anti-cancer drug metabolism, chemotherapy efficacy, and drug-induced toxicity. Nutritional interventions, as well as the administration of beneficial bacteria (probiotics), dietary fiber (including prebiotics) supplements, and synbiotics (probiotic + prebiotic), may reduce the risk of colorectal cancer and side effects of anti-cancer therapy.

Summary

Current evidence suggests gut microbiota may predispose or protect against colorectal cancer. Restoring gut microbial dysbiosis is an emerging nutritional and clinical target in oncology.