Citations

Objective: To present an unusual case of a temporal bone meningioma with intrafascicular spread throughout the temporal facial nerve from cerebellopontine angle (CPA) to stylomastoid foramen. Patient: Four-year-old female with progressive facial weakness and normal hearing. Main Outcome Measure: Clinical, radiological, and histopathological findings of temporal bone meningiomas. Results: A patient presented with progressive facial weakness and normal hearing. Imaging demonstrated a mass within the left internal auditory canal radiologically consistent with a schwannoma. Asymmetric enlargement with enhancement of the left facial nerve from CPA to the stylomastoid foramen suggested facial schwannoma. At surgery, gross tumor was noted in the internal auditory canal, the fallopian canal seemed expanded and the facial nerve was enlarged and had an irregular contour. Resection of the facial nerve from the CPA to just proximal to its exit at the stylomastoid foramen was necessary to achieve negative margins. Cable grafting was performed. The histopathologic diagnosis was transitional meningioma with intraneural growth throughout the length of the resected facial nerve segment. Conclusion: Meningiomas involving the temporal bone are exceedingly rare. We report a rare case of a child presenting with progressive facial weakness due to a presumed facial schwannoma spreading along the facial nerve throughout its intratemporal course that at surgery was found to be an intrafascicular CN VII meningioma.

AbstractBackground.Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use.Patients and Methods.Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors.Results.Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59–1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65–1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56–1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1–5, 6–10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age.Conclusions.Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use.

AbstractObjectiveThe aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS.MethodsCase–control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex‐ and age‐stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex‐stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity.ResultsOnly 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001).InterpretationHigher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.

Abstract Background: People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive. Methods: 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between alcohol consumption and colorectal cancer. Results: Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (SD) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 g/day and &gt;28 g/day was associated with increased colorectal cancer risk (HR, 1.50; 95% CI, 1.09–2.07 and 1.69; 95% CI, 1.07–2.65, respectively; Ptrend = 0.05), and colon cancer risk (HR, 1.78; 95% CI, 1.27–2.49 and 1.94; 95% CI, 1.19–3.18, respectively; Ptrend = 0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk. Conclusions: Our data suggest that alcohol consumption, particularly more than 28 g/day of ethanol (∼2 standard drinks of alcohol in the United States), is associated with increased colorectal cancer risk for MMR gene mutation carriers. Impact: Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk. Cancer Epidemiol Biomarkers Prev; 26(3); 366–75. ©2016 AACR.

Abstract Background: Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known. Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and MUTYH. We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic component. Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, MSH6 = 1 in 758, PMS2 = 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 3.3 for age &lt;40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively). Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer. Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404–12. ©2016 AACR.

Advances in the field of defibrillation have brought to practice different types of devices that include the transvenous implantable cardioverter-defibrillator (ICD) with or without cardiac resynchronization therapy, the subcutaneous ICD (S-ICD), and the wearable cardioverter-defibrillator. To ensure optimal use of these devices and to achieve best patient outcomes, clinicians need to understand how these devices work, learn the characteristics of patients who qualify them for one type of device versus another, and recognize the remaining gaps in knowledge surrounding these devices. The transvenous ICD has been shown in several randomized clinical trials to improve the survival of patients resuscitated from near-fatal ventricular fibrillation and those with sustained ventricular tachycardia with syncope or systolic heart failure as a result of ischemic or nonischemic cardiomyopathy despite receiving guideline-directed medical therapy. Important gaps in knowledge regarding the transvenous ICD involve the role of the ICD in patient subgroups not included, or not well represented, in clinical trials and the need to refine the selection criteria for the ICD in patients who are indicated for it. S-ICDs were recently introduced into the clinical arena as another option for many patients who have an approved indication for a transvenous ICD. The main advantage of the S-ICD is a lower risk of infection and lead-related complications; however, the S-ICD does not offer bradycardia or antitachycardia pacing. The S-ICD may be ideal for patients with limited vascular access, high infection risk, or some congenital heart diseases. However, more data are needed regarding the efficacy and effectiveness of the S-ICD in comparison to transvenous ICDs, the extent of defibrillation testing required, and the use of the S-ICD with other novel technologies, including leadless pacemakers. Cardiac resynchronization therapy-defibrillators are indicated in patients with a left ventricular ejection fraction ≤35%, QRS width ≥130 ms, and New York Heart Association class II, III, or ambulatory IV symptoms despite treatment with guideline-directed medical therapy. Multiple randomized controlled trials have shown that the cardiac resynchronization therapy-defibrillator improves survival, quality of life, and several echocardiographic measures. One main challenge related to cardiac resynchronization therapy-defibrillators is the 30% nonresponse rate. Many initiatives are underway to address this challenge including improved cardiac resynchronization therapy and imaging technologies and enhanced selection of patients and device programming.