Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
Summary Background Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the ...benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin. Methods We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18–75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00173615. Findings Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were enrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0·0001) and a better 1-year survival than those who received conventional CPR (log rank p=0·007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio HR 0·51, 95% CI 0·35–0·74, p<0·0001), 30-day survival (HR 0·47, 95% CI 0·28–0·77, p=0·003), and 1-year survival (HR 0·53, 95% CI 0·33–0·83, p=0·006) favouring extracorporeal CPR over conventional CPR. Interpretation Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin. Funding National Science Council, Taiwan.
Abstract Objective Due to the limitations of the small single incision, an ideal preoperative localization technique is essential for surgical resection of small pulmonary nodules by uniportal ...video-assisted thoracoscopic surgery (VATS). The aim of this study is to evaluate the usefulness and safety of preoperative computed tomography (CT)-guided patent blue vital (PBV) dye localization in patients with small indeterminate pulmonary nodules who have undergone uniportal VATS for lung resection. Methods In this retrospective study, 177 consecutive patients (196 pulmonary nodules) who underwent preoperative CT-guided PBV dye localization and uniportal VATS from January 2013 to September 2015 were enrolled. Results The CT-dye localization procedure was performed successfully and correctly for 99.5% (195/196) of the nodules within a mean procedure time of 30 minutes. The mean size of the nodules was 7.8 mm, and their mean depth from the pleural surface was 18.3 mm. Most of the nodules (78.6%, 154/196) were pure ground-glass nodules (GGNs) and part-solid GGN with ground-glass opacity (GGO) of 50% or more. Asymptomatic pneumothorax occurred in 29.4% (52/177) of patients after the localization procedure, but none required invasive treatment. All nodules were successfully resected using uniportal VATS without any conversion to thoracotomy. The postoperative course was smooth, with a short mean hospital stay (3.3 ± 1.2 days) and a low morbidity rate (0.6%, 1/177). Conclusions Preoperative CT-guided PBV dye localization is a feasible, safe, and accurate procedure. It makes uniportal VATS easy for small, poorly located pulmonary nodules with GGO predominance and synchronous multiple nodules.
Objective To assess the independent or comorbid effect of conduct and mood disorders on the risk of suicide. Study design The Taiwan National Health Insurance Research Database was used to derive ...data for 3711 adolescents aged 12-17 years with conduct disorder and 14 844 age- and sex-matched controls between 2001 and 2009. The participants were followed up to the end of 2011, and those who attempted suicide during the follow-up period were identified. Results Adolescents with conduct disorder had a higher incidence of suicide (0.9% vs 0.1%; P < .001) and attempted suicide at a younger age (17.38 ± 2.04 vs 20.52 ± 1.70 years of age) than did the controls. The Cox proportional hazards regression model, after adjustment for demographic data and psychiatric comorbidities, determined that conduct disorder was an independent risk factor for subsequent suicide attempts (hazard ratio, 5.17; 95% CI, 2.29-11.70). The sensitivity after those with other psychiatric comorbidities were excluded revealed a consistent finding (hazard ratio, 10.32; 95% CI, 3.71-28.71). Discussion Adolescents with conduct disorder had an increased risk of suicide attempts over the next decade. Future studies are required to clarify the underlying pathophysiology and elucidate whether prompt intervention for conduct disorder could reduce this risk.
Purpose: Immunotherapy combined with chemotherapy have synergistic effects in multiple malignancies. We aimed to compare the efficacy and safety of toripalimab plus hepatic arterial infusion ...chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib in advanced hepatocellular carcinoma (HCC). Materials and Methods: We conducted this retrospective study at 3 hospitals in China and eligible patients were 18 years or older and had a primary diagnosis of unresectable HCC with macroscopic vascular invasion and/or extrahepatic spread. These patients were treated with toripalimab plus HAIC or lenvatinib monotherapy. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), disease control rate per response evaluation criteria in solid tumors (RECIST) 1.1, and objective response rate (ORR) per RECIST 1.1. The results were compared by Student's test or the chi-square test, and the survival curves were calculated by the Kaplan–Meier method, and propensity-score matching (PSM) was used to reduce bias. Results: A total of 118 patients were recruited for this study: 53 in the TorHAIC group and 65 in the lenvatinib group. We found that the TorHAIC group showed a longer PFS (9.3 95% CI, 7.81-10.8 vs 4.8 months 95% CI, 3.31−6.29; hazard ratio HR = 0.57, 95% CI, 0.38-0.85; p = .006), a longer OS (17.13 95% CI, 13.99−20.27 vs 10.1 months 95% CI, 8.14−12.06; HR = 0.5, 95% CI, 0.31 − 0.81; p = .005), a higher disease control rate (86.8% vs 69.2%, p = .002) and a higher ORR (47.2% vs 9.2%, p < .001) by RECIST criteria than the lenvatinib group. Both toripalimab plus HAIC and lenvatinib had acceptable safety profiles. No treatment-related deaths occurred in this study. In the propensity score-matched cohorts (47 pairs), the outcomes in the TorHAIC group were also better than those in the lenvatinib group (p < .05). Conclusion: Toripalimab plus HAIC was tolerable and effective in advanced HCC and the result needs to be confirmed in the phase III trial.
Background A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the ...longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. Study Design According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. Results The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). Conclusions Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.
Background Massive hemorrhages occur in 6%-10% of patients with advanced cancer. Acute carotid blowout syndrome is the most severe massive hemorrhagic complication in head and neck cancer patients. ...Methods This was a single institute, retrospective, case control study. A total of 45 patients were enrolled in this study. The predisposing factors, management, and prognosis of acute carotid blowout syndrome were evaluated. Results Among the baseline characteristics, the site of the primary tumor ( P = .003), origin of bleeding ( P = .048), method of intervention ( P = .005), and time to intervention ( P = .006) were significantly different factors between survivor and nonsurvivor patients. After 24 hours of onset, a Glasgow Coma Scale score ( P = .000), the use of inotropic agents ( P = .007), and neutrophil-to-lymphocyte ratio ( P = .019) were significantly predicting factors for outcome. Multivariate logistic regression analyses revealed bleeding from common carotid artery was an independent factor for long-term survival (odds ratio, 25.951; 95% confidence interval CI, 1.373-490.441; P < .030). The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively ( P = .092). Conclusions Early and aggressive intervention is important for the successful management of acute carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were predictive factors for patients' outcomes. Bleeding from common carotid artery is an independent prognostic factor in multivariate analysis. Long-term survival can be achieved after successful management.
Background The aim of the present study was to investigate NLRP3 inflammasome expression in human carotid atherosclerotic plaques and its relationship to plaque vulnerability. Methods Carotid ...atherosclerotic plaques collected from 30 patients scheduled for carotid endarterectomy (CEA) were subjected to immunohistochemical, mRNA, and protein expression studies. Ten mesenteric arteries from intestinal cancer patients served as controls for the immunohistochemical studies. Twenty individuals who had no carotid stenosis or coronary artery stenosis served as controls for analyzing atherosclerotic risk factors and for enzyme-linked immunosorbent assay (ELISA) studies. Serum samples were collected from all patients to determine interleukin-1β (IL-1β) and IL-18 levels. Results The NLRP3 inflammasome signaling pathway components NLRP3, ASC, caspase-1, IL-1β, and IL-18 were strongly expressed in carotid atherosclerotic plaques, but not in healthy mesenteric arteries. Immunohistochemical, mRNA, and protein expression studies revealed higher expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in unstable compared to stable plaques. The NLRP3 inflammasome was localized in the cytoplasm of macrophages and foam cells and was associated with cholesterol crystal clefts inside and outside of cells. ELISA showed that the serum levels of the cytokines IL-1β and IL-18 were higher in the CEA group compared to controls. Conclusions These results demonstrated for the first time the close relationship between the expression of NLRP3 signaling pathway and human carotid atherosclerotic plaques. NLRP3, ASC, caspase-1, IL-1β, and IL-18 were associated with plaque vulnerability and atherogenesis. The serum levels of IL-1β and IL-18 may be useful predictors of atherosclerosis.
Background Peroral endoscopic myotomy (POEM) has been developed to provide a less-invasive myotomy for achalasia in adults but seldom has been used in pediatric patients. Objective To evaluate the ...feasibility, safety, and efficacy of POEM for pediatric patients with achalasia. Design Single-center, prospective study. Setting Academic medical center. Patients A total of 27 pediatric patients (mean age 13.8 years, range 6-17 years) with achalasia. Interventions POEM. Main Outcome Measurements The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤3. Secondary outcomes were procedure-related adverse events, clinical reflux adverse events, and lower esophageal sphincter (LES) pressure on manometry before and after POEM. Results A total of 26 cases (96.3%) underwent successful POEM. A submucosal tunnelling attempt failed in 1 case because of serious inflammation and adhesion. No serious adverse events related to POEM were encountered. During a mean follow-up period of 24.6 months (range 15-38 months), treatment success was achieved in all patients (mean score before vs after treatment 8.3 vs 0.7; P < .001). Mean LES pressure also decreased from a mean of 31.6 mm Hg to 12.9 mm Hg after POEM ( P < .001). Five patients developed clinical reflux adverse events (19.2%). Limitations Single center and lack of some objective evaluations. Conclusion This relatively long-term follow-up study adds to the evidence that POEM seems to be a promising new treatment for pediatric patients with achalasia, resulting in long-term symptom relief in all cases and without serious adverse events.
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