Citations

Background: Patients diagnosed with melanoma of the foot have been reported to have a poor prognosis. We reviewed our experience at a tertiary-care medical clinic to determine the disease course in patients diagnosed with melanoma of the foot. Methods: A retrospective review was performed of 38 patients with a diagnosis of primary or locally recurrent melanoma of the foot treated between January, 1988, and July, 2004. The main outcome measures included methods of diagnosis, clinical and histopathologic features, and patterns of recurrence. Results: The mean age at diagnosis was 61 years; most were women (58%) and Caucasian (95%). The average time to diagnosis was 17 months. Initial clinical diagnosis had been considered benign in 12 (32%). The median Breslow thickness was 1.75 mm, T1 lesions were the most common, and acral lentiginous melanoma accounted for 42%. Thirteen patients (34%) had ulcerated lesions. Sentinel lymph node biopsy specimens of 25 patients identified four (16%) with metastatic disease. Surgical complications occurred in 12 patients, usually after skin graft or soft-tissue flap reconstruction. Systemic recurrence developed in six patients, four of whom also had regional recurrence. Conclusions: Most patients were elderly Caucasian women and most presented with early-stage disease, but diagnosis can be difficult and a subgroup presented with thick melanomas. Reconstructive surgical procedures had a high rate of complications; however, overall functional outcomes were good. Stage of cancer at diagnosis was associated with systemic metastases.

658 Background: In patients (pts) with mCRC with an asymptomatic primary tumor, there is limited evidence regarding the indication for primary tumor resection. The primary objective was to evaluate the prognostic value of primary tumor resection in synchronous mCRC pts. Methods: In this IPD analysis, a total of 3,423 pts from 8 first-line randomized trials (RCTs) with systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Five RCTs included targeted (anti-VEGF and/or anti-EGFR) agents. Synchronous mCRC was defined as distant metastases occurring ≤ 6 months of the initial CRC diagnosis. Overall survival (OS) and progression-free survival (PFS) were compared by stratified multivariate Cox models. Results: There were 710 (21%), 1,705 (50%) and 1,008 (29%) pts with non-resected and resected synchronous mCRC and metachronous mCRC, respectively. Compared to the non-resection group, pts in the synchronous resection group were associated with female gender, colon tumor, isolated liver/lung involvement, single metastatic site, and lower LDH (all p<.001). Adjusted for age, gender, performance status and prior chemotherapy, the non-resection group had a significantly worse median OS (16.4m) compared to the resection (22.2m; HR 1.60, 95% CI 1.43-1.78) and metachronous (22.4m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, PFS was significantly worse for the non-resection group (7.9m) compared to the resection (9.7m; HR 1.31, 95% CI 1.19-1.44) and metachronous group (8.9m; HR 1.47, 95% CI 1.30-1.66). Similar trends were observed in pts treated with non-targeted vs targeted agents, and anti-VEGF vs anti-EGFR therapy. In a subset analysis (n= 526), the observed associations remained after additional adjustment for primary tumor location, liver/lung involvement, number of metastatic sites, BMI and LDH. Conclusions: In this largest IPD analysis of mCRC trials to date, primary tumor resection is associated with better OS and PFS in synchronous mCRC pts. These results may be subject to bias since reasons for (non)resection were not available. Prospective RCTs on this topic are ongoing.

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV 1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV 1 , worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

Key Points Significant improvement in outcome is a reality for newly diagnosed AL amyloidosis in the past decade. Six-month mortality among transplant ineligible patients has declined since 2005.

Abstract Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist–hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Methods: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. Results: The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10−17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89–2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44–1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10–1.39; P = 5.3 × 10−4). There was evidence of directional pleiotropy (P = 1.5 × 10−4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P &lt; 4.0 × 10−4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. Conclusions: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. Impact: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503–10. ©2016 AACR.

Abstract Background Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life‐time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a ‘large’ pool of IBS patients across Europe and even the world however, might help identify sub‐populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi‐centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four‐year dialogue amongst experts associated with the European COST action BM1106 GENIEUR ( www.GENIEUR.eu ).

Abstract The histiocytoses are rare disorders characterized by the accumulation of macrophage, dendritic cell, or monocyte-derived cells in various tissues and organs of children and adults. More than 100 different subtypes have been described, with a wide range of clinical manifestations, presentations, and histologies. Since the first classification in 1987, a number of new findings regarding the cellular origins, molecular pathology, and clinical features of histiocytic disorders have been identified. We propose herein a revision of the classification of histiocytoses based on histology, phenotype, molecular alterations, and clinical and imaging characteristics. This revised classification system consists of 5 groups of diseases: (1) Langerhans-related, (2) cutaneous and mucocutaneous, and (3) malignant histiocytoses as well as (4) Rosai-Dorfman disease and (5) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Herein, we provide guidelines and recommendations for diagnoses of these disorders.