Gut microbiota-drug interactions in cancer pharmacotherapies: implications for efficacy and adverse effects.

INTRODUCTION: The gut microbiota is involved in host physiology and health. Reciprocal microbiota-drug interactions are increasingly recognized as underlying some individual differences in therapy response and adverse events. Cancer pharmacotherapies are characterized by a high degree of interpatient variability in efficacy and side effect profile and recently, the microbiota has emerged as a factor that may underlie these differences. AREAS COVERED: The effects of cancer pharmacotherapy on microbiota composition and function are reviewed with consideration of the relationship between baseline microbiota composition, microbiota modification, antibiotics exposure, and cancer therapy efficacy. We assess the evidence implicating the microbiota in cancer therapy-related adverse events including impaired gut function, cognition, and pain perception. Finally, potential mechanisms underlying microbiota-cancer drug interactions are described, including direct microbial metabolism, and microbial modulation of liver metabolism and immune function. This review focused on preclinical and clinical studies conducted in the last 5 years. EXPERT OPINION: Preclinical and clinical research supports a role for baseline microbiota in cancer therapy efficacy, with emerging evidence that the microbiota modification may assist in side effect management. Future efforts should focus on exploiting this knowledge toward the development of microbiota-targeted therapies. Finally, a focus on specific drug-microbiota-cancer interactions is warranted.

Metastatic lung cancer presenting as gastric outlet obstruction: diagnosis and management with laparoscopic gastric bypass: a novel technique.

Metastatic tumours of the duodenum are relatively rare. Here we present a case of a 64-year-old Caucasian male who presented with a 3-week history of postprandial vomiting, weight-loss and epigastric discomfort. Imaging and biopsy revealed that the patient had a primary lung tumour in his right upper lung lobe as well as a duodenal metastasis leading to gastric outlet obstruction (GOO). The patient was stabilised and subsequently underwent a laparoscopic gastric bypass to palliate the gastric outlet obstruction. Appropriate management of metastatic GOO involves accurate diagnosis and treatment with either enteral stenting or laparoscopic gastric bypass. It is suggested that the decision whether to stent or surgically bypass the obstruction can be based on the patient's life expectancy and performance status. Regardless of the approach, palliating metastatic GOO can improve the quality of life of carefully chosen symptomatic patients. We describe a technique of laparoscopic palliative gastric bypass which has not been reported previously in the literature.

Regional chemotherapy for liver-limited metastatic colorectal cancer.

This review examines the development of hepatic arterial infusion (HAI) of chemotherapy over the past 40 years. Liver metastases are mainly supplied by the hepatic artery, and high levels of intratumoral drug delivery are achievable with the use of HAI. Floxuridine, 5-fluorodeoxyuridine is commonly used, but intra-arterial oxaliplatin and mitomycin- C also have advantages. The dramatic responses observed with HAI plus systemic therapy offer the possibility of resection and cure in select patients. Resectability of liver-limited colorectal cancer metastases should be considered as an endpoint for all patients. Hepatic arterial infusion may be used in palliative, neoadjuvant, and adjuvant settings. Herein, combinations of systemic chemotherapy with HAI are discussed, along with the role of newer cytotoxic and biologic agents. The first-pass extraction of some drugs given by regional perfusion in the liver limits systemic side effects. Toxicity includes catheter-related complications and biliary and gastrointestinal ulcers. The role of HAI therapy for the treatment of unresectable and resectable disease, as well as the use of other regional strategies such as embolization and ablation, are discussed.

Cardiac toxicity in breast cancer survivors: review of potential cardiac problems.

As breast cancer survival is increased by the diagnosis of earlier-stage disease and treatments improve, the side effects of cancer treatments, such as cardiotoxicity, remain clinically important. Although physicians have known for 30 years that anthracyclines cause acute and chronic cardiotoxicity, the cardiotoxic effects of radiation therapy, hormonal therapy (including tamoxifen and the aromatase inhibitors), and chemotherapy with taxanes and trastuzumab treatment have emerged more recently. This review examines the cardiac toxicity of adjuvant therapy, monitoring for early changes and existing guidelines for monitoring cardiac function in patients with breast cancer.