Citations

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety‐three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

Abstract BACKGROUND Given recent differing findings following 2 randomized clinical trials on degenerative lumbar spondylolisthesis (DLS) surgery, there is a need to better define how subsets of patients fare following surgery. OBJECTIVE To investigate the impact of obesity on patient-reported outcomes (PROs) following DLS surgery. METHODS A total of 12 high-enrolling sites were queried, and we found 797 patients undergoing surgery for grade 1 DLS. For univariate comparisons, patients were stratified by BMI ≥ 30 kg/m 2 (obese) and < 30 kg/m 2 (nonobese). Baseline, 3-mo, and 12-mo follow-up parameters were collected. PROs included the North American Spine Society satisfaction questionnaire, numeric rating scale (NRS) back pain, NRS leg pain, Oswestry Disability Index (ODI), and EuroQoL-5D (EQ-5D) Questionnaire. RESULTS We identified 382 obese (47.9%) and 415 nonobese patients (52.1%). At baseline, obese patients had worse NRS back pain, NRS leg pain, ODI, and EQ-5D scores ( P < .001, P = .01, P < .001, and P = .02, respectively). Both cohorts improved significantly for back and leg pain, ODI, and EQ-5D at 12 mo ( P < .001). At 12 mo, similar proportions of obese and nonobese patients responded that surgery met their expectations (62.6% vs 67.4%, P = .24). In multivariate analyses, BMI was independently associated with worse NRS leg pain and EQ-5D at 12 mo ( P = .01 and P < .01, respectively) despite adjusting for baseline differences. CONCLUSION Obesity is associated with inferior leg pain and quality of life—but similar back pain, disability, and satisfaction—12 mo postoperatively. However, obese patients achieve significant improvements in all PRO metrics at 12 mo.

BACKGROUND: African-Americans (AA) have a higher incidence of hepatocellular carcinoma (HCC) and lower survival. We characterized survival rates and clinical features associated with survival in AA vs. Caucasians with HCC over the past two decades. METHODS: HCC patients from three US medical centers were matched by year of diagnosis (1991–2016): AA ( n = 578)/Caucasian ( n = 578) and placed in one of two groups—HCC diagnosed prior to 2010 or 2010 and after. Data were obtained from chart review and the National Death Index. Multivariate and survival analysis controlling for key predictors were conducted. RESULTS: Prior to 2010, there was no difference in survival between Caucasians and AA ( p = 0.61). After 2010, AA patients had poorer survival compared to Caucasians (35% vs. 44%, respectively, p = 0.044). Over time, survival improved for Caucasians (32% before 2010 vs. 44% after 2010, p = 0.003), but not AA (36% vs. 35%, p = 0.50). AA on presentation (in the after 2010 cohort) were more likely to have BCLC (Barcelona Clinic Liver Cancer) stage C (24% vs. 15%, p = 0.010) and less likely to receive treatment (85% vs. 93%, p = 0.002) compared to matched Caucasians. BCLC beyond stage A (aHR: 1.75, 95% CI: 1.26–2.43, p = 0.001) and child’s class C (aHR 2.05, 95% CI: 1.23–3.41, p = 0.006) were the strongest predictors of mortality, while race was not. CONCLUSIONS: African-Americans presented with more advanced HCC and had poorer survival compared to Caucasians after 2010. Tumor stage was an independent predictor of mortality, but ethnicity was not. Further efforts are needed to improve early HCC diagnosis for AA.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

AbstractGranular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA‐1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), −13q in 4 of 6, and −14 in 4 of 6. Next‐generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB‐1 (P > 0.05). GCA is a variant of IDH‐wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.

Background Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and Results In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial‐dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid‐stimulating hormone ( TSH ) >10.0 mU / mL , n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3< TSH ≤10.0 mU / mL , n=1200. Subjects with a history of hypothyroidism had a significantly lower % Δ CBF Ach (48.26 [80.66] versus 64.58 [128.30]) compared to patients with euthyroidism, while the % Δ CAD Ach did not vary significantly between groups. After adjusting for covariates, females with hypothyroidism still had a significantly lower % Δ CBF Ach (estimated difference in % Δ CBF Ach [ SE ]: −16.79 [8.18]). Conclusions Hypothyroidism in women is associated with microvascular endothelial dysfunction, even after adjusting for confounders, and may explain some of the increased risk of cardiovascular disease in these patients.