Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.

An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50-80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20-70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40-60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.

Sorafenib-induced tuberculosis reactivation.

BACKGROUND: Sorafenib is a multikinase inhibitor with an established role in treating renal cell carcinoma and hepatocellular carcinoma. In vivo studies have demonstrated sorafenib's inhibitory effects on various immune cells and cytokines which are essential to the maintenance of latency of granulomas in patients with latent tuberculosis infection. CASE REPORT: A 74-year-old male with clear cell renal cell carcinoma with pulmonary metastases was treated with sorafenib to good effect. However, he developed productive cough, sweats and weight loss. A computed tomography scan of the thorax demonstrated right lower lobe consolidation and cavitation. Sputum analysis was positive for tuberculous smear and culture. A diagnosis of sorafenib-induced tuberculosis reactivation was made. Sorafenib was held and anti-tuberculous antibiotics were commenced, which led to symptomatic and radiographic improvement. CONCLUSION: The authors postulate that sorafenib could increase the risk of progression from latent to active tuberculosis, and urge vigilance and possible screening for latent tuberculosis in patients who are treated with sorafenib.

Chemotherapy for the conversion of unresectable colorectal cancer liver metastases to resection.

Resection of colorectal liver metastases (CLM) is the ultimate aim of treatment strategies in most patients with liver-confined metastatic colorectal cancer. Long-term survival is possible in selected patients with initially resectable or unresectable CLM. As a majority of patients have unresectable liver disease at the outset, there is a clear role for chemotherapy to downstage liver disease making resection possible. Studies of systemic chemotherapy with or without biologic therapy in patients with unresectable CLM have resulted in increased response rates, liver resection rates and survival. A sound physiologic rationale exists for the use of hepatic arterial infusion (HAI) therapy. Studies have shown that HAI with floxuridine combined with systemic chemotherapy increases response rates and liver resection rates in those patients with initially unresectable CLM. Toxicity from preoperative chemotherapy, biologic therapy and HAI therapy may adversely affect hepatic resection but can be kept minimal with appropriate monitoring. All conversion strategies should be decided by a multidisciplinary team.

The role of floxuridine in metastatic liver disease.

Liver metastases are mainly supplied by the hepatic artery. Sustained high levels of intratumoral drug are achievable with certain drugs given via the hepatic artery. Floxuridine (FUDR) is an ideal drug for hepatic arterial infusion (HAI) due to its short half life, steep dose response curve, high total body clearance, and high hepatic extraction. HAI FUDR has consistently shown higher response rates than systemic chemotherapy alone, and some studies have shown a survival advantage. HAI FUDR in combination with systemic chemotherapy has evolved over the years and may be used in palliative, neoadjuvant, and adjuvant settings. The dramatic responses observed with HAI FUDR plus modern era systemic chemotherapy offer the possibility of resection and cure in selected patients. The high hepatic extraction of FUDR limits systemic side effects. Toxicity includes biliary and gastrointestinal ulcers.

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.