Cachexia in cancer: what is in the definition?

OBJECTIVE: This study aimed to provide evidence-based results on differences in overall survival (OS) rate to guide the diagnosis of cancer cachexia. DESIGN: Data collection and clinical assessment was performed every 3 months (5 visits): baseline data, muscle strength, nutritional and psychosocial status. 2 definitions on cachexia using different diagnostic criteria were applied for the same patient population. Fearon et al's definition is based on weight loss, body mass index (BMI) and sarcopenia. Evans et al nuances the contribution of sarcopenia and attaches additional attention to abnormal biochemistry parameters, fatigue and anorexia. The mean OS rates were compared between patients with and without cachexia for both definitions. RESULTS: Based on the population of 167 patients who enrolled, 70% developed cachexia according to Fearon et al's definition and 40% according to Evans et al's definition. The OS in the cachectic population is 0.97 and 0.55 years, respectively. The difference in OS between patients with and without cachexia is more significant using the diagnostic criteria of Evans et al. The focus of Fearon et al on weight loss and sarcopenia over-rates the assignment of patients to the cachectic group and OS rates have less prognostic value. CONCLUSION: This study presents a correlation with prognosis in favour of Evans et al' definition as a tool for cachexia diagnosis. This means that weight loss and BMI decline are both key factors in patients with cancer leading to cachexia but less decisive as stated by Fearon et al. Instead, extra factors gain importance in order to predict survival, such as chronic inflammation, anaemia, protein depletion, reduced food intake, fatigue, decreased muscle strength and lean tissue depletion. TRIAL REGISTRATION NUMBER: B300201112334.

Lanreotide Autogel in the Treatment of Idiopathic Refractory Diarrhea: Results of an Exploratory, Controlled, Before and After, Open-label, Multicenter, Prospective Clinical Trial.

PURPOSE: Chronic idiopathic diarrhea is the passage of loose stools >3 times daily, or a stool weight >200 g/d, persisting for >4 weeks without clear clinical cause. Patients refractory to standard anti-diarrhetics have limited treatment options. Somatostatin analogues have the ability to reduce gastrointestinal secretions and motility. This study evaluated the efficacy and safety of lanreotide Autogel(*) 120 mg in chronic idiopathic diarrhea. METHODS: Other anti-diarrhetics were not allowed during the study and were stopped at screening. Patients received lanreotide Autogel 120 mg at baseline and day 28. Stool frequency and consistency (Bristol Stool Scale) were recorded; quality of life (QoL) was assessed using the 36-item Short Form Health Survey and irritable bowel syndrome QoL questionnaires; adverse events were monitored. The primary outcome was the proportion of patients with a reduction of ≥50% or normalization to a mean of ≤3 stools/d at day 28. FINDINGS: Thirty-three patients with >3 stools/d at baseline were included; mean (SD) age was 55.2 (16.4) years. Fourteen patients (42.4%) had a response to lanreotide Autogel at day 28 and 17 (51.5%) at day 56. Mean (SD) number of stools decreased significantly from 5.7 (2.2) at baseline to 3.7 (2.2) at day 56 overall (n = 32; P < 0.001). Significant and clinically meaningful improvements in disease-specific QoL were found in the overall populations. No new safety signals emerged. IMPLICATIONS: Lanreotide Autogel 120 mg decreased symptoms in these patients with chronic idiopathic refractory diarrhea, and meaningfully improved QoL. These finding have to be confirmed in further clinical trials. ClinicalTrials.gov IDENTIFICATION: NCT00891371; Eudract CT 2009-009356-20.

Relative adrenal insufficiency in patients with severe acute pancreatitis.

OBJECTIVE: Inadequate cortisol levels and adrenal dysfunction may play a role in the pathophysiology of severe acute pancreatitis. This study aimed to analyse the incidence of relative adrenal insufficiency (RAI) in these patients, to identify factors associated with RAI and to describe how adrenal responsiveness affects outcome. DESIGN: Prospective observational multicenter study. PATIENTS: Twenty-five patients with severe acute pancreatitis. INTERVENTIONS: A short Synacthen test (SST) was performed within 5 days after admission to the hospital. The incidence of RAI, defined as an increment after SST of less than 9 microg/dl was the primary endpoint of the study. Serum cortisol was measured at baseline and at 30 and 60 min after administration of 250 microg adrenocorticotropic hormone. MEASUREMENTS AND RESULTS: Median baseline cortisol level was 26.6 microg/dl, and increased to 43.2 microg/dl and 48.8 microg/dl after 30 min and 60 min respectively. RAI was found in 16% of all patients and in 27% of patients with organ dysfunction. Patients with RAI were more severely ill and had higher SOFA scores from days 4 to 7 after admission. All patients with RAI developed pancreatic necrosis, and all of them needed surgical intervention. Twenty-eight-day mortality was significantly higher in patients with RAI (75% vs. 5%, p =0.007). Patients who died had a lower increment in cortisol levels after the SST than patients who survived. CONCLUSION: RAI is frequent in patients with severe acute pancreatitis and organ dysfunction. It occurs in patients with more severe pancreatitis and is associated with increased mortality.