Citations

Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA) genes and tumor necrosis factor (TNF), has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects ofHLAclass I (A, B, and C), class IIDRB1alleles, and the ancestral haplotype (AH) 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A) on overall survival (OS) among patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in a population-based study of non-Hodgkin lymphoma. During a median followup of 89 months, 31% (52 of 166) DLBCL and 28% (46 of 165) FL patients died. Using multivariate Cox regression models, we observed statistically significant associations between genetic variants and survival:HLA-Cw*07:01was associated with poorer OS among DLBCL patients (Hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.01–3.05);HLA-A*01:01was associated with poorer OS (HR = 2.23, 95% CI = 1.24–4.01), andHLA-DRB1*13(HR = 0.12, 95% CI = 0.02–0.90) andHLA-B Bw4(HR = 0.36, 95% CI = 0.20–0.63) with better OS among FL patients. These results support a role forHLAin the prognosis of DLBCL and FL and represent a promising class of prognostic factors that warrants further evaluation.

AbstractBackgroundThe feasibility, safety and outcomes of robotic presacral neurectomy were evaluated.MethodsA retrospective analysis was performed of 33 patients with midline chronic pelvic pain, who underwent robotic presacral neurectomy. Data were collected during the period March 2004–March 2010.ResultsAll patients underwent robotic presacral neurectomy and additional robotic procedures. Mean operating time for robotic presacral neurectomy was 5.8 (range 4.4–6.9) min. Mean blood loss, including concomitant procedures, was 39 (range 15–150) ml. Most patients were discharged the same day (60%) and mean hospital stay was 0.39 (range 0–2) days. There were no conversions or intra‐operative complications. There were two postoperative complications: one pelvic abscess and one Clostridium difficile colitis. Pain improvement was reported by 73% (22/30) of patients.ConclusionRobotic presacral neurectomy is safe and feasible, resulting in improvement of pelvic pain in selected patients. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.

Background Perioperative nerve injury (PNI) is a recognized complication of total hip arthroplasty (THA). Regional anesthesia (RA) techniques may increase the risk of neurologic injury. Using a retrospective cohort study, the authors tested the hypothesis that use of RA increases the risk for PNI after elective THA. Methods All adult patients who underwent elective THA at Mayo Clinic during a 20-yr period were included. The primary outcome was the presence of a new PNI within 3 months of surgery. Multivariable logistic regression was used to evaluate patient, surgical, and anesthetic risk factors for PNI. Results Of 12,998 patients undergoing THA, 93 experienced PNI (incidence = 0.72%; 95% CI 0.58-0.88%). PNI was not associated with type of anesthesia (OR = 0.72 for neuraxial-combined vs. general; 95% CI 0.46-1.14) or peripheral nerve blockade (OR = 0.65; 95% CI 0.34-1.21). The risk for PNI was associated with younger age (OR = 0.79 per 10-yr increase; 95% CI 0.69-0.90), female gender (OR = 1.72; 95% CI 1.12-2.64), longer operations (OR = 1.10 per 30-min increase; 95% CI 1.03-1.18) or posterior surgical approach (OR = 1.91 vs. anterior approach; 95% CI 1.22-2.99). Neurologic recovery was not influenced by the use of RA techniques in patients with PNI. Conclusions The risk for PNI after THA was not increased with the use of neuraxial anesthesia or peripheral nerve blockade. Neurologic recovery in patients who experienced PNI was not affected by the use of RA. These results support the use of RA techniques in patients undergoing elective THA given their known functional and clinical benefits.

Abstract Background Accelerated recovery pathways may reduce length of hospital stay after surgery but there are few data on minimally invasive colorectal operations. Methods An enhanced recovery pathway (ERP) was instituted, including preoperative analgesia, limited intravenous fluids and opiates, and early feeding. Intrathecal analgesia was administered as needed, but epidural analgesia was not used. The first 66 patients subjected to the ERP were case-matched by surgeon, procedure and age (within 5 years) with patients treated previously in a fast-track pathway (FTP). Short-term and postoperative outcomes to 30 days were compared. Results Hospital stay was shorter with the ERP than the FTP: median (interquartile range, i.q.r.) 3 (2–3) versus 3 (3–5) days (P < 0·001). A 2-day hospital stay was achieved in 44 and 8 per cent of patients respectively (P < 0·001). Patients in the ERP had a shorter time to recovery of bowel function: median (i.q.r.) 1 (1–2) versus 2 (2–3) days (P < 0·001). Thirty-day complication rates were similar (32 per cent ERP, 27 per cent FTP; P = 0·570). Readmissions within 30 days were more common with ERP, but the difference was not statistically significant (10 versus 5 patients; P = 0·170). Total hospital stay for those readmitted was shorter in the ERP group (18 versus 23 days). Conclusion ERP decreased the length of hospital stay after minimally invasive colorectal surgery. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Abstract Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Common variants in these evaluated genes do not seem to be strongly associated with EOC risk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered. Cancer Epidemiol Biomarkers Prev; 20(8); 1793–7. ©2011 AACR.

Abstract Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone.

Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow for detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state‐of‐the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory, and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real‐world situations so as to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally, and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.