IMPORTANCE A reduced incidence of microvascular invasion (MVI) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) may be associated with a decreased risk of early tumor recurrence and better survival after partial hepatectomy. OBJECTIVE To examine the association of preoperative antiviral treatment (AVT) with the incidences of MVI and posthepatectomy early tumor recurrence in HBV-related HCC. DESIGN, SETTING, AND PARTICIPANTS Data on a cohort of 2362 patients who underwent RO resection for HBV-related HCC between January 2008 and April 2010 at the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, were reviewed. The median (interquartile range) postoperative follow-up was 44.8 (22.8-59.3) months. Data were analyzed from June 2016 to October 2017. INTERVENTIONS Preoperative AVT and partial hepatectomy. MAIN OUTCOMES AND MEASURES Overall survival and time to recurrence after surgery were calculated and compared using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Independent risk factors of MVI presence were assessed by logistic regression analysis. RESULTS Among 2362 included patients, 1999 (84.6%) were men, and the median (interquartile range) age was 50.6 (43.1-57.3) years. A total of 2036 patients (86.2%) did not receive any preoperative AVT, while 326 (13.8%) received ongoing AVT more than 90 days before surgery. In the non-AVT group, compared with a preoperative HBV DNA level of less than 2000 IU/mL, a preoperative HBV DNA level of 2000 IU/mL or greater was associated with an increased risk of MVI (odds ratio [OR], 1.399; 95% CI, 1.151-1.701). Compared with the non-AVT group, patients receiving AVT had a lower incidence of MVI (38.7% [126 of 326] vs 48.6% [989 of 2036]; P = .001) and reduced risk of MVI (OR, 0.758; 95% CI, 0.575-0.998). A complete response to AVT was an independent protective factor of MVI (OR, 0.690; 95% CI, 0.500-0.952). Accordingly, preoperative AVT was associated with decreased 6-month, 1-year, and 2-year recurrences vs non-AVT (14.2%, 24.6%, and 38.5%, respectively, vs 23.4%. 37.1%, and 52.3%; P < .001); AVT was protective of early tumor recurrence (hazard ratio, 0.732; 95% CI, 0.605-0.886). In addition, patients in the non-AVT group were more likely to have multiple intrahepatic recurrences (49.1% [549 of 1119] vs 36.2% [54 of 149]; P = .003) and recurrences involving multiple hepatic segments compared with patients receiving AVT. CONCLUSIONS AND RELEVANCE A high preoperative HBV DNA level was an independent risk factor of MVI. Antiviral treatment administered more than 90 days before surgery was associated with reduced incidences of MVI and early tumor recurrence after partial hepatectomy for HBV-related HCC.
IMPORTANCE Loss of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression has been reported in several malignant tumors and predicts dismal survival outcomes. In gastric cancer, existing studies on this topic are limited and the association between MGMT and fluorouracil-based adjuvant chemotherapy remains obscure. OBJECTIVE To investigate the postoperative prognostic significance of MGMT in patients with resectable gastric cancer and its responsiveness to fluorouracil-based adjuvant chemotherapy. DESIGN, SETTING, AND PARTICIPANTS This study recruited 445 consecutive patients with resectable gastric cancer who underwent radical gastrectomy between August 1, 2007, and December 30, 2008, at Zhongshan Hospital at Fudan University in Shanghai, China. Patients were randomly divided into a discovery data set (n = 200) and a validation data set (n = 245), and the range of follow-up time was from 2 to 76 months for the discovery group and 2 to 79 months for the validation group. The immunoreactivity for MGMT in cancer cells was reviewed under a light microscope by 2 pathologists who were blinded to the clinicopathological data. The association of MGMT expression with clinicopathological characteristics and measures and prognosis was inspected. Data and specimens were collected from patients from the date of surgery to April 25, 2014. Data analysis took place from May 9, 2016, to July 15, 2016. MAIN OUTCOMES AND MEASURES Estimates of overall survival on the basis of MGMT expression and hazard ratio (HR) for estimates of overall mortality risk. RESULTS Of the 445 patients included in the study, 315 (70.8%) were men, and the mean (SD) age of all patients was 60 (12) years. Positive expression of MGMT indicated better overall survival for patients with stage II or III gastric cancer in both the discovery data set (HR, 0.52; 95% CI, 0.32-0.84; P =.003) and the validation data set (HR, 0.63; 95% CI, 0.43-0.93; P =.01). Multivariate analysis identified MGMT expression and TNM stage as 2 independent prognostic factors for overall survival. In stage II disease, the benefit from fluorouracil-based adjuvant chemotherapy was superior among MGMT-positive patients (HR, 0.35; 95% CI, 0.13-0.95; P =.007 for interaction) compared with MGMT-negative patients. CONCLUSIONS AND RELEVANCE Positive expression of MGMT in gastric cancer was identified as an independent, favorable prognostic factor. Incorporating MGMT expression into the current TNM staging system could lead to better prognostic accuracy. These findings should be confirmed within the framework of randomized clinical trials associated with genomic DNA sequencing studies.
IMPORTANCE Secondary triage from nontertiary centers is vital to trauma system success. It remains unclear what factors are associated with nontransfer among patients who should be considered for transfer to facilities providing higher-level care. OBJECTIVE To identify factors associated with nontransfer among patients meeting American College of Surgeons (ACS) guideline criteria for transfer from nontertiary centers. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was performed using multilevel logistic regression to ascertain factors associated with nontransfer from nontertiary centers, including demographics, injury characteristics, and center resources. With information obtained from the National Trauma Data Bank (January 1, 2007, to December 31, 2012), relative proportion of variance in outcome across centers was determined for patient-level and center-level attributes. In all, 96 528 patients taken to nontertiary centers (levels III, IV, V, and nontrauma centers) that met ACS guideline transfer criteria were eligible for inclusion. Data analysis was performed from March 17, 2016, to May 20, 2016. MAIN OUTCOMES AND MEASURES The primary outcome was nontransfer from a nontertiary center. RESULTS Among 96 528 patients meeting ACS guideline criteria for transfer taken initially to nontertiary centers, 55 611 (57.6%) were male and the median age was 52 years (interquartile range, 28-77 years). Only 19 396 patients (20.1%) underwent transfer. Patient-level factors associated with nontransfer included age older than 65 years (adjusted odds ratio [AOR], 1.70; 95% CI, 1.46-1.98; P < .001), severe chest injury (AOR, 1.63; 95% CI, 1.42-1.89; P < .001), and commercial insurance (vs self-pay: AOR, 1.39; 95% CI, 1.15-1.67; P < .001). Center-level factors associated with nontransfer included larger bed size (>600 vs <200 beds: AOR, 9.22; 95% CI, 7.70-11.05; P < .001), nontrauma center (vs level III centers: AOR, 2.71; 95% CI, 2.44-3.01; P < .001), university affiliation (vs community: AOR, 9.68; 95% CI, 8.03-11.66; P < .001), more trauma surgeons (per surgeon: AOR, 1.08; 95% CI, 1.06-1.09; P < .001), and more neurosurgeons (per surgeon: AOR, 1.25; 95% CI, 1.23-1.28; P < .001). For-profit status was associated with nontransfer at nontrauma centers (AOR, 1.55; 95% CI, 1.39-1.74; P < .001), but not at level III, IV, and V trauma centers. Overall, patient-level factors accounted for 36% and center-level factors accounted for 58% of the variation in transfer practices. Patient-level factors accounted for more variation at level III, IV, and V trauma centers (44%), but less variation at nontrauma centers (13%). CONCLUSIONS AND RELEVANCE Only 1 in 5 patients meeting ACS transfer criteria underwent transfer. Factors associated with nontransfer may be useful for trauma system stakeholders to target education and outreach to guide development of more inclusive trauma systems. Further study is necessary to critically evaluate whether these ACS criteria identify patients who require transfer.
IMPORTANCE The current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy. OBJECTIVE To construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. DESIGN, SETTING, AND PARTICIPANTS In this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study's inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016. MAIN OUTCOMES AND MEASURES Concordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival. RESULTS Of the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P<.05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual's net survival gain attributable to adjuvant chemotherapy. CONCLUSIONS AND RELEVANCE The survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. (C) 2017 American Medical Association. All rights reserved.