[Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study].

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 µg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

[Association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome].

Objective: To investigate the association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome (ACS). Methods: Data of this study were derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a collaborative study of the Chinese Society of Cardiology and the American Heart Association. Since 2014, the CCC-ACS project consecutively enrolled inpatients with ACS, systematically collected their clinical data and evaluated medical quality of these patients from 158 tertiary hospitals and 82 secondary hospitals across China. This study enrolled female patients less than 60 years old with initial ACS, who received coronary angiography in CCC-ACS project. Patients were divided into two groups according to smoking status. A multivariate logistic regression analysis was used to analyze the association between smoking and the severity of coronary lesions among young and middle-aged female patients with ACS. Results: A total of 2 863 female patients younger than 60 years old with initial ACS, who received coronary angiography, were enrolled. Among them, 12% (340 cases) was smokers. Proportion of patients younger than 45 years old was higher (13.2% (45/340) vs. 8.5% (215/2 523), P<0.01) and prevalence of hypertension (59.4% (202/340) vs. 66.7% (1 683/2 523), P<0.01) and diabetes (39.4% (134/340) vs. 44.2% (1 116/2 523), P=0.09) was lower in smoker group than in non-smoker group. However, prevalence of ST-elevation myocardial infarction (66.8% (227/340) vs. 53.7% (1 354/2 523), P<0.01), coronary multi-vessel lesions (39.1% (133/340) vs. 32.6% (822/2 523), P<0.01) and severe stenosis in either single-vessel (56.2% (109/194) vs. 46.1% (706/1 530), P<0.01) or multi-vessel (63.2% (84/133) vs. 58.2% (478/822), P=0.29) was significantly higher in smoker group than in non-smoker group. Multivariate logistic regression analyses showed that after adjusting for age, hypertension, diabetes, elevated low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, elevated triglyceride, renal insufficiency, family history of coronary heart disease and types of ACS, smokers faced a higher risk of coronary multi-vessel lesions, coronary multi-vessel severe lesions and coronary severe lesions with the odds ratios and 95% confidence interval of 1.41 (1.11-1.79), 1.40 (1.10-1.78) and 1.78 (1.11-2.87), compared with non-smokers. Conclusions: Smoking is significantly associated with an increased risk of extensive and severe coronary lesions among young and middle-aged female patients with ACS. This study provides crucial evidence for further understanding the harms of smoking and the need to strengthen the tobacco control education and smoking cessation guidance for young and middle-aged women.

Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies with fluoride.

Fluoride (F-), a known stimulator of G-proteins, was used to examine the relationship between G-proteins and calcium channels (CaC) in rat vascular smooth muscle (VSM). Treatment of isolated rat tail artery helical strips with F- (2.5-20 microM) produced a Ca++-dependent contraction. In the absence of added AlCl3, subthreshold NaF shifted the KCl, as well as the arginine vasopressin and norepinephrine concentration-related tension curves to the left. Nifedipine and verapamil, known CaC blockers, inhibited the NaF-related contraction. AlCl3 (20 microM), which is required for G-protein stimulation by F-, strikingly potentiated the contractile response to F-. The NaF-induced contraction was relaxed by 3-isobutyl-1-methylxanthine as well as by forskolin and by dibutyryladenosine-cyclic AMP, and the effect therefore may be independent of cAMP. 45Ca-uptake was elevated by NaF, and partially blocked by nifedipine and verapamil. NaF also inhibited the basal and forskolin-stimulated cAMP production, suggesting that F- stimulated the putative Gi in the intact VSM cells. NaF stimulated accumulation of IP in a concentration-dependent manner, indicating that F- stimulated the putative G-protein Gp which couples various receptors to hydrolysis of phosphoinositides and mobilization of Ca++. These results indicate that NaF-induced vasoconstriction is related to the opening of the CaC in the plasma membrane and perhaps a subsequent entry of the extracellular Ca++ into the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. II. Studies with guanosine 5'-(gamma)triphosphate.

Our previous studies with fluoride have indicated that G-proteins may mediate the gating of Ca++ channels in vascular smooth muscle (VSM). We now present further studies on the relationship between G-proteins and Ca++ channels in VSM using guanosine-5'-(gamma-thio)triphosphate (GTP gamma S), a hydrolysis-resistant analog of GTP. Rat tail artery helical strips pretreated with GTP gamma S in a cytosol-like solution contracted in a Ca++-dependent manner in the absence of a depolarizing concentration of K+, hormones or any other Ca++ agonists. Contraction was dependent on the concentrations of applied GTP gamma S. The ability of strips pretreated with GTP gamma S to contract in response to Ca++ was not reversed by repeated washing. Incubation with 1 mM GTP applied extracellularly did not induce tension development. Treatment with a subthreshold concentration of GTP gamma S shifted the K+ concentration-related tension curve to the left but did not alter the maximum response. The contractions induced by GTP gamma S pretreatment and by submaximal (60 mM) KCI were additive at all levels of Ca++ tested. Extra tension development could be evoked from tissue maximally contracted with GTP gamma S by adding maximal K+ and norepinephrine. The relaxing sensitivity of the GTP gamma S-related contraction to reversal by nifedipine was between those for K+ depolarization and norepinephrine, and the GTP gamma S-induced rise in tension was partially inhibited by the Ca++ channel blocker nifedipine. Ca++-elicited contraction of the GTP gamma S-pretreated strips was relaxed by forskolin, an adenylate cyclase activator, 3-isobutyl-l-methyl-xanthanine, a cyclic nucleotide phosphodiesterase inhibitor, and dibutyryl cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)