Citations

Abstract Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13–1.63; P = 9.29 × 10−4; 7p13, rs17688601: OR = 0.76; 95% CI, 0.63–0.93; P = 6.59 × 10−3). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10−5) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185–91. ©2016 AACR.

Background. Malignant melanoma of the nail apparatus is exceedingly rare. Increasingly, genetic studies have been employed to aid in distinguishing between malignant melanoma and benign melanocytic nevi. Methods. Archived nail apparatus melanomas were analyzed by fluorescence in situ hybridization (FISH) using probes targeting the genes at 6p25 (RREB1), 11q13 (CCND1), 8q24.1 (MYC), 6q23 (MYB), 9p21 (CDKN2A) and the centromeres of chromosomes 8 (D8Z2) and 6 (D6Z1). The results were correlated with clinical and demographic information. Results. Mean patient age was 57.8 years (range 23-92 years). In all, 5 of 7 (71%) cases involved the upper extremity digits. RREB1 gain was seen in all cases. CCND1 gain was seen in 6 of 7 (86%) cases, 3 of which were amplified. MYB loss and MYC gain were both seen in 5 of 7 (71%) cases. Homozygous loss of CDKN2A was not observed in any case. Two of 7 (28.6%) patients had lymph node metastasis and died of widely metastatic disease. These 2 patients harbored the most genetic aberrations: gains of RREB1, CCND1, and MYC, and MYB loss. Both benign melanocytic nevi controls showed normal FISH results. Conclusions. RREB1 and CCND1 gains are common in nail apparatus melanoma as in most melanomas, and an increased number of genetic aberrations may be associated with a poorer prognosis, though the limited number of cases precludes definitive correlation. FISH appears to be a useful adjunct in the diagnosis of nail apparatus melanomas and improves diagnostic confidence even in the setting of unambiguous histomorphology.

BACKGROUNDPrior studies have shown that a higher hospital volume or physician caseload is associated with better outcomes for complex and uncommon surgical procedures. Similar studies in the medical management of rare diseases such as hematologic cancers are limited. This retrospective, observational study using the US National Cancer Data Base determined the extent to which the number of new non‐Hodgkin lymphoma (NHL) patients treated annually at a treatment facility affected overall survival (OS).METHODSThere were 278,985 patients treated at 1151 facilities from 1998 to 2006. Treatment facilities were classified by quartiles based on the average number of new NHL patients seen annually: quartile 1 (Q1), 2 to 13 patients; quartile 2 (Q2), 14 to 20 patients; quartile 3 (Q3), 21 to 32 patients; and quartile 4 (Q4), 33 or more patients. The outcome of interest was OS according to facility volume.RESULTSThe unadjusted median OS was 61.8 months for Q1, 65.9 months for Q2, 71.4 months for Q3, and 83.6 months for Q4. A multivariate analysis that was adjusted for demographic (sex, age, race, and ethnicity), socioeconomic (income and insurance type), geographic (area of residence), disease‐specific (NHL subtype and stage), and facility‐specific factors (type and location) showed that the facility volume was associated with OS. Compared with patients at Q4 facilities, patients at lower quartile facilities had higher mortality (hazard ratio for Q3, 1.05 [95% confidence interval, 1.04‐1.06]; hazard ratio for Q2, 1.08 [95% confidence interval, 1.07‐1.10]; hazard ratio for Q1, 1.14 [95% confidence interval, 1.11‐1.17]).CONCLUSIONSNHL patients treated at higher volume facilities may survive longer than those treated at lower volume facilities. Further work is needed to understand the mechanisms of these differences and whether volume should be considered in the determination of referrals for NHL patients. Cancer 2016;122:2552–9. © 2016 American Cancer Society.

Objective Cardiovascular disease is a global epidemic, which is largely preventable. Cardiac rehabilitation (CR) is demonstrated to be cost-effective and efficacious in high-income countries. CR could represent an important approach to mitigate the epidemic of cardiovascular disease in lower-resource settings. The purpose of this consensus statement was to review low-cost approaches to delivering the core components of CR, to propose a testable model of CR which could feasibly be delivered in middle-income countries. Methods A literature review regarding delivery of each core CR component, namely: (1) lifestyle risk factor management (ie, physical activity, diet, tobacco and mental health), (2) medical risk factor management (eg, lipid control, blood pressure control), (3) education for self-management and (4) return to work, in low-resource settings was undertaken. Recommendations were developed based on identified articles, using a modified GRADE approach where evidence in a low-resource setting was available, or consensus where evidence was not. Results Available data on cost of CR delivery in low-resource settings suggests it is not feasible to deliver CR in low-resource settings as is delivered in high-resource ones. Strategies which can be implemented to deliver all of the core CR components in low-resource settings were summarised in practice recommendations, and approaches to patient assessment proffered. It is suggested that CR be adapted by delivery by non-physician healthcare workers, in non-clinical settings. Conclusions Advocacy to achieve political commitment for broad delivery of adapted CR services in low-resource settings is needed.

Placebo controlled trials have demonstrated that a tapering course of corticosteroids is an effective therapy for active Crohn’s disease. A populationbased study of 109 patients with Crohn’s disease undergoing their first course of corticosteroids showed that, at the end of one year, 44% of patients were steroid responsive, 36% were steroid dependent and 20% were steroid refractory. Side effects occur frequently during a four-month tapering course of corticosteroids, including moon face, acne, infection, ecchymoses, hypertension, hirsutism, petechial bleeding and striae. More serious side effects occur with long term use, including hypertension, diabetes, infection, osteonecrosis, osteoporosis, myopathy, cataracts, glaucoma and psychosis. Low dose corticosteroids, alternate-day corticosteroids and mesalamine (5-aminosalicylate) are not effective steroid-sparing agents in patients with Crohn’s disease. Controlled ileal release budesonide, 6 mg/day, is an effective steroid-sparing agent, but it does result in some decrease in adrenal function. Azathioprine, 6-mercaptopurine and methotrexate are all effective steroidsparing agents, as is the humanized, anti-tumour necrosis factor monoclonal antibody, CDP571. A preliminary, uncontrolled study has suggested that the mouse/human chimeric monoclonal antibody infliximab may also be steroid sparing. Surgical resection is an effective strategy to reduce steroid use in the short to intermediate term, but postoperative reoccurrence of Crohn’s disease occurs frequently. Given the morbidity associated with prolonged corticosteroid use, medical and surgical treatment strategies to reduce steroid use should be employed routinely.