Citations

Objective (1) To characterize long‐term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium‐sized vestibular schwannoma (VS) using a validated self‐assessment inventory; and (2) to identify clinical variables associated with long‐term dizziness handicap. Study Design Cross‐sectional observational study. Setting Two independent tertiary academic referral centers: one located in the United States and one in Norway. Subjects and Methods All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. Results The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long‐term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long‐term dizziness handicap. Conclusion At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long‐term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship.

Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high‐volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19‐9 independently indicated surgical response in pancreatic cancer. Patients with CA19‐9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19‐9 levels decreased postoperatively. CEA and CA125 in the presence of CA19‐9 ≥1000 U/mL could independently predict the non‐decrease of CA19‐9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA+/CA125+/CA19‐9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy.

Purpose: To determine whether on-clamp partial nephrectomy (ON-PN) has any significant impact on long-term renal function in a two kidney model. Patients and Methods: From November 1999 to July 2013, 607 patients underwent PN at our institution. After excluding patients with solitary kidneys, multiple renal masses, and follow-up less than 90 days, 331 remained. Patient demographics were assessed, as was renal function based on pre- and postoperative mercaptoacetyltriglycine (MAG-3) renal scans and change in estimated glomerular filtration rate (eGFR) using the preoperative and most recent recorded creatinine levels. Results: There were a total of 236 patients who underwent ON-PN and 95 who underwent off-clamp PN (OFF-PN) during the study period. The longest follow-up was 12.6 years with mean follow-up of 3 years. Mean ischemia time of patients undergoing ON-PN was 25 minutes (range 8–63 min). No differences were noted between the ON-PN and OFF-PN cohorts with respect to estimated change in eGFR (ON-PN: −6.07 mL/min/1.73 m 2 vs OFF-PN: −6.00 mL/min/1.73 m 2 , P =0.69). No differences were noted in the % change in the MAG-3 renal scans (ON-PN: −0.77% vs OFF-PN: −1.1%, P =0.94). A post hoc sensitivity analysis of the same two variables stratified by age revealed no differences in change in estimated GFR or % change in differential function on renal scan. Conclusions: In the two kidney model, ischemia does not appear to affect long-term renal function outcomes after PN. These data provide evidence that ON-PN is perfectly acceptable in the appropriately selected patient with two kidneys.

The value of pelvic examination for healthy asymptomatic women has been called into question given the lack of benefit for ovarian and endometrial cancer screening, the ability to screen for sexually transmitted infections without a pelvic examination, and the uncoupling of the procurement of contraception with a pelvic examination. Still, there are indications for performing pelvic examinations in symptomatic women and in some high risk women. How do we as clinicians apply current evidence and expert opinion to our medical practice? Our recommendation to consider a pelvic examination at 3-5-year intervals with cervical cancer screening to elicit gynecologic and sexual health concerns offers a compromise between continuation of unnecessary annual pelvic examinations and complete elimination of these examinations.

BackgroundDevice infection is associated with increased mortality in patients receiving cardiovascular implantable electronic device (CIED) therapy. However, long‐term mortality associated with CIED infections has not been systematically analyzed in larger studies. This study sought to determine the long‐term mortality associated with CIED infection in a large cohort of Medicare beneficiaries.MethodsWe used a retrospective study design to analyze 3‐year mortality in 200,219 Medicare fee‐for‐service patients admitted for CIED generator implantation, replacement, or revision between January 1, 2007 and December 31, 2007. Multivariate analysis adjusting for age, sex, race, and 28 comorbidities was performed to determine the relative risk (RR) of death in the 12 quarters following CIED infection.ResultsPatients with CIED infection, compared to device recipients without infection, had increased mortality that persisted for at least 3 years after the admission quarter for all device types: pacemakers (PMs: 53.8% vs 33%; P < 0.001), implantable cardioverter defibrillator (ICD: 47.7% vs 31.6%; P < 0.001), and cardiac resynchronization therapy‐defibrillator (CRT‐D: 50.8% vs 36.5%; P < 0.001). After adjusting for patient demographics and comorbidities, significantly increased RR of death following CIED infection persisted for at least 3 years following PM infection, and for at least 2 years with single‐ and dual‐chamber ICD infection.ConclusionsCIED recipients who develop device infection have increased, device‐dependent, long‐term mortality even after successful treatment of infection. The etiology of this persistent increased risk of death associated with CIED infection is unknown and merits further investigation.

Context.— Both the regulations in the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and the checklists of the College of American Pathologists (CAP) Laboratory Accreditation Program require clinical laboratories to verify performance characteristics of quantitative test systems. Laboratories must verify performance claims when introducing an unmodified, US Food and Drug Administration–cleared or approved test system, and they must comply with requirements for periodic calibration and calibration verification for existing test systems. They must also periodically verify the analytical measurement range of many quantitative test systems. Objective.— To provide definitions for many of the terms used in these regulations, to describe a set of basic analyses that laboratories may adapt to demonstrate compliance with both CLIA and the CAP Laboratory Accreditation Program checklists for performing calibration verification and for verifying the analytical measurement range of test systems, to review some of the recommended procedures for establishing performance goals, and to provide data illustrating the performance goals used in some of the CAP's calibration verification and linearity surveys. Data Sources.— The CAP's calibration verification and linearity survey programs, the CLIA regulations, the Laboratory Accreditation Program requirements, and published literature were used to meet these objectives. Conclusions.— Calibration verification and linearity and analytical measurement range verification should be performed using suitable materials with assessment of results using well-defined evaluation protocols. We describe the CAP's calibration verification and linearity programs that may be used for these purposes.

Abstract Since most GWAS hits fall in non-coding regions of the genome and long non-coding RNAs (lncRNAs) are emerging as drivers of carcinogenesis, we hypothesized that SNPs in lncRNAs influence epithelial ovarian cancer (EOC) risk. A comprehensive lncRNA database (lncRNA db) that contained 104 human lncRNAs when downloaded in November 2011 was used to identify 1,737 variants in 63 unique lncRNAs that were represented in three genome-wide association studies from North America, the United Kingdom, and Poland (3,995 EOC cases and 3,277 controls of European background). SNPs with MAF &lt;5% were excluded, and missing genotypes were inferred with Mach using the HapMap CEU population. Unconditional logistic regression treating alternate alleles as an ordinal variable was used to evaluate individual SNP-EOC risk associations. Subgroup analysis was conducted for serous adenocarcinomas (N= 2,066), the main histologic subtype of EOC. Models were adjusted for study and European ancestry using the first two principal components (PCs). We reduced correlated signals (r2 ≥ 0.8) within each lncRNA and kept the most statistically significant variants based on Wald tests, resulting in 651 SNPs for further analyses. Fisher's product method was used to aggregate evidence of multiple variants within each lncRNA using 10,000 permutations. To adjust for multiple comparisons, a false discovery rate (FDR) of 10% was used. A replication phase was carried out for top-ranked SNPs from an additional 9,854 EOC cases (5,802 serous) and 17,633 controls genotyped through an international effort known as the Collaborative Oncological Gene-Environment study (COGS). Four lncRNAs, WT1-AS (p = 0.005, n = 2 SNPs), Hoxa11as (p = 0.013, n = 2), AK082072 (p = 0.016, n = 4) and H19 (p = 0.020, n = 2), were significantly associated with EOC risk among all histologies (FDR ≤ 10%). The SNP in WT1-AS most significantly associated with EOC risk was rs3809061 (T&gt;C) (minor allele frequency= 36%, odds ratio (OR) = 0.91, CI: 0.84-0.97, p = 0.008). Among serous cases, rs3809061 was also protective (OR = 0.92, p = 0.04). These findings were replicated by a correlated SNP rs2301250 (r2 = 0.84) evaluated in COGS among serous cases (OR = 0.94, CI: 0.90-0.99, p = 0.009) and less significant among all histologies (OR = 0.96, CI: 0.93-1.00, p = 0.054). We further interrogated its functional role by performing an expression quantitative trait locus analysis on WTI-AS mRNA expression using the Cancer Genome Atlas (TCGA) data (N = 462 serous cases). WT1-AS expression was significantly higher among carriers of the variant allele (compared to TT homozygotes) using the Mann-Whitney U test (p = 0.001). WT1-AS is the antisense and possible regulator of WT1, a tumor suppressor gene reported to be prognostic in advanced EOC. These findings implicate germline lncRNA variants associated with EOC risk that merit further investigation. Citation Format: Yian Ann Chen, Zhihua Chen, Jennifer Permuth-Wey, Ya-Yu Tsai, Hui-Yi Lin, Xiaotao Qu, Kate Lawrenson, David Fenstermacher, Catherine M. Phelan, Alvaro Monteiro, Simon A. Gayther, Steven A. Narod, Rebecca Sutphen, Michael J. Birrer, Nicolas Wentzensen, Joellen M. Schildkraut, Ellen L. Goode, Paul Pharoah, Thomas Sellers. Variants in long non-coding RNAs are associated with epithelial ovarian cancer risk in a pooled analysis of three genome-wide association studies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4579. doi:10.1158/1538-7445.AM2013-4579