Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.     

A new acylglycosyl sterol from quisqualis fructus

A new acylglycosyl sterol (4) was isolated from the MeOH extract of Quisqualis Fructus together with four known compounds. On the basis of spectroscopic data, their structures were elucidated as clerosterol (1), betulinic acid (2), methylursolate (3), 3-O-[6'-O-(8Z-octadecenoyl)-beta-D-glucopyranosyl]-clerosterol (4) and alpha-xylofuranosyluracil (5).     

Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice

Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.     

Influencing factors of pressure pain hypersensitivity of the upper trapezius in food service workers with nonspecific neck/shoulder myofascial pain: A cross-sectional study

It is unclear which factors contribute to the developing pressure pain hypersensitivity of the upper trapezius, a type of neurophysiological hyperexcitability. The present study investigated the relationship between physical and psychological factors and pressure pain hypersensitivity of the upper trapezius for each sex. In total, 154 individuals with neck/shoulder myofascial pain participated, among 372 food service workers. Participants completed a questionnaire (Beck Depression Inventory, and Borg Rating of Perceived Exertion scale) and were photographed to measure posture. Pressure pain sensitivity, 2 range of motions (cervical lateral bending and rotation), and 4 muscle strengths (serratus anterior, lower trapezius [LT], biceps, and glenohumeral external rotator) were measured by a pressure algometer, iPhone application, and handheld dynamometer, respectively. For each sex, forward multivariate logistic regression was used to test our a priori hypothesis among selected variables that a combination of psychosocial and physical factors contributed to the risk for pressure pain hypersensitivity. In multivariate analyses, LT strength (odds ratio = 0.94, 95% confidence interval = 0.91–0.97, P = .001) was the only significant influencing factor for pressure pain hypersensitivity in men. Dominant painful ipsilateral cervical rotation range of motion (odds ratio = 0.96, 95% confidence interval = 0.92–0.99, P = .037) was the only influencing factor for pressure pain hypersensitivity in women. LT strength and dominant painful ipsilateral cervical rotation range of motion could serve as guidelines for preventing and managing pressure pain hypersensitivity of the upper trapezius in food service workers with nonspecific neck/shoulder myofascial pain.     

Solid cancer incidence among Chinese medical diagnostic x‐ray workers, 1950–1995: Estimation of radiation‐related risks

The objective of this study was to estimate solid cancer risk attributable to long‐term, fractionated occupational exposure to low doses of ionizing radiation. Based on cancer incidence for the period 1950–1995 in a cohort of 27,011 Chinese medical diagnostic X‐ray workers and a comparison cohort of 25,782 Chinese physicians who did not use X‐ray equipment in their work, we used Poisson regression to fit excess relative risk (ERR) and excess absolute risk (EAR) dose–response models for incidence of all solid cancers combined. Radiation dose reconstruction was based on a previously published method that relied on simulating measurements for multiple X‐ray machines, workplaces and working conditions, information about protective measures, including use of lead aprons, and work histories. The resulting model was used to estimate calendar year‐specific badge dose calibrated as personal dose equivalent (Sv). To obtain calendar year‐specific colon doses (Gy), we applied a standard organ conversion factor. A total of 1,643 cases of solid cancer were identified in 1.45 million person‐years of follow‐up. In both ERR and EAR models, a statistically significant radiation dose–response relationship was observed for solid cancers as a group. Averaged over both sexes, and using colon dose as the dose metric, the estimated ERR/Gy was 0.87 (95% CI: 0.48, 1.45), and the EAR was 22 per 10⁴PY‐Gy (95% CI: 14, 32) at age 50. We obtained estimates of the ERR and EAR of solid cancers per unit dose that are compatible with those derived from other populations chronically exposed to low dose‐rate occupational or environmental radiation.     

Cost-effectiveness analysis of endometrial cancer prevention strategies for obese women

OBJECTIVE: It is unknown whether obese women would benefit from oral contraceptives or screening as endometrial cancer prevention strategies. We estimated the net health benefits and cost-effectiveness of these strategies in a hypothetical cohort of obese women. METHODS: A Markov decision-analytic model evaluated 4 strategies: 1) no prevention (reference strategy); 2) oral contraceptive pills (OCPs) for 5 years; 3) annual screening with endometrial biopsy from age 30; 4) biennial screening from age 30. Net health benefit was life expectancy and primary outcome was the incremental cost-effectiveness ratio. Baseline and transition probabilities were obtained from published literature and the Surveillance Epidemiology and End Results database, and costs were from the U.S. Department of Health and Human Services and Agency for Healthcare Research and Quality. Sensitivity analyses were performed for uncertainty around various measures. RESULTS: Average life expectancy for all strategies ranged from 74.52 to 74.60 years. None of the strategies had an incremental cost-effectiveness ratio less than $50,000 per year of life saved relative to the next best strategy. Endometrial cancer risk in obese women had to be 13 times greater than the general population risk before OCPs were a cost-effective intervention. CONCLUSION: Oral contraceptives and current screening methods are not cost-effective endometrial cancer prevention strategies for obese women. Risk factors such as morbid obesity and longstanding anovulation may define a subgroup at highest risk of endometrial cancer for whom OCPs may be a cost-effective strategy. Interventions that reduce endometrial cancer risk further or those with additional health benefits are needed in this population. LEVEL OF EVIDENCE: III.     

When is a pathology review indicated in endometrial cancer?

OBJECTIVE: Discrepancies may exist between an original pathology report and formal pathology review, with subsequent implications for treatment. We conducted a study of pathology review in endometrial cancer from a population-based study to identify areas of discrepancy and effect on treatment. METHODS: This was a retrospective cohort study in Ontario, Canada from 1996 to 2000. We identified hysterectomy cases from patients with endometrial cancer that were subject to formal pathology review by a gynecologic pathologist at one of six tertiary care centers. Sarcomas and other rare histologic subtypes with fewer than five cases were excluded. We evaluated discrepancy between original pathology and review by demographics, stage, grade, and risk group. Four risk groups were defined: 1) low (stage I), 2) intermediate (stage I and II), 3) high-risk (stage I and II), and 4) advanced stage (all stage III and IV). Reclassification from one risk group to another upon pathology review represented a potential change in treatment. Factors associated with significant discrepancy were identified by a multivariable logistic regression model. RESULTS: Formal pathology review was available on 450 cases. There were no differences by age, year, or hospital type. The overall discrepancy rate was 42.7% (95% confidence interval 38.2-47.3%). The intermediate-risk group had the highest rate of reclassification into another group (33.1%). The most significant rates of discrepancy were associated with endometrioid grades 2 and 3 tumors and stage IIA disease (39.8%, 50.9%, and 79.6%, respectively). CONCLUSION: There was significant discrepancy between original pathology and formal review in endometrial cancer, with implications for guidelines on pathology review at a population level. LEVEL OF EVIDENCE: III     

Effects of Interleukin-17A on the Early Stages of Arterial Thrombosis in Mice

PurposeInterleukin (IL)-17A has been suggested to play a role in the growth and organization of thrombi. We examined whether IL-17A plays a role in the early stages of thrombosis and whether there are sex differences in the effects of IL-17A.Materials and MethodsWe performed a blinded, randomized, placebo-controlled study to compare time to thrombotic occlusion and sex differences therein between mice treated with IL-17A and those treated with saline using a ferric chloride-induced model. We also assessed thrombus histology, blood coagulation, and plasma levels of coagulation factors.ResultsTime to occlusion values did not differ between the IL-17A group and the control group (94.6±86.9 sec vs. 121.0±84.4 sec, p=0.238). However, it was significantly shorter in the IL-17A group of female mice (74.6±57.2 sec vs. 130.0±76.2 sec, p=0.032). In rotational thromboelastometry, the IL-17A group exhibited increased maximum clot firmness (71.3±4.5 mm vs. 66.7±4.7 mm, p=0.038) and greater amplitude at 30 min (69.7±5.2 mm vs. 64.5±5.3 mm, p=0.040) than the control group. In Western blotting, the IL-17A group showed higher levels of coagulation factor XIII (2.2±1.5 vs. 1.0±0.9, p=0.008), monocyte chemoattractant protein-1 (1.6±0.6 vs. 1.0±0.4, p=0.023), and tissue factor (1.5±0.6 vs. 1.0±0.5, p=0.003).ConclusionIL-17A plays a role in the initial st ages of arterial thrombosis in mice. Coagulation factors and monocyte chemoattractant protein-1 may be associated with IL-17A-mediated thrombosis.