Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.

Predictive value of SYNTAX score II for clinical outcomes in octogenarian undergoing percutaneous coronary intervention

Objective To evaluate the predictive value of SYNTAX Score II （SS-II） for percutaneous coronary intervention （PCI） in octogenarian （≥ 80 years old） undergoing PCI. Methods ＆ Results Data from three consecutive years of octogenarian undergoing PCI from Ruijin Hospital （Shanghai, China） was retrospectively collected （n = 308）. Follow up clinical data at one year including all cause mortality, cardiac mortality and main adverse cardiovascular and cerebrovascular events （MACCE） were collected. Patients were stratified according to tertiles of SS-II for PCI： SS-II 〈 26 （n = 104）, SS-II： 27-31 （n = 102）, SS-II 〉 31 （n = 102）. After adjustment for confounding factors, SS-II for PCI was an independent risk factors for all cause mortality （odds ratio： 2.77, 95% CI： 1.13-8.06; P = 0.04）. Kaplan-Meier curves showed higher event rates for all cause mortality and cardiac mortality in higher tertile of SS-II for PCI （Log-Rank test P = 0.002 and P = 0.001, respectively）. SSdl for PCI predicted one year mortality in octogenarian population undergoing PCI. Conclusions In octogenarian, SS-II which incorporated clinical variables with angiographic anatomy variable was suitable in risk stratifying and predicting clinical outcomes at one year.

Clinical Utility of the Ratio Between Circulating Fibrinogen and Fibrin （ogen） Degradation Products for Evaluating Coronary Artery Disease in Type 2 Diabetic Patients

Background:We investigated whether and to what extent the ratio between circulating fibrinogen (Fg) and its degradation products (FDP)reflects the severity of coronary artery disease (CAD) in type 2 diabetic patients.Methods:Plasma levels of Fg and FDP were determined,and Fg/FDP ratio was calculated in 344 consecutive patients with type 2 diabetes and chest pain on exertion undergoing coronary angiography.The severity of CAD was evaluated by the number of significant CAD (＞50％ luminal diameter narrowing) and Gensini score.Results:Plasma Fg was higher,but Fg/FDP ratio was lower in patients with significant CAD (n =255) compared with those without (n =89),due to a disproportionate increase in FDP.Fg and FDP correlated positively,while Fg/FDP ratio negatively,with the number of diseased coronary arteries and the tertile of Gensini score (all P values for trend ＜ 0.01).After adjusting for age,sex,risk factors for CAD,lipid profiles,glycosylated hemoglobin A1c,creatinine,leukocyte count,and high-sensitivity C-reactive protein,Fg/FDP ratio remained an independent determinant for multivessel coronary disease (MVD) (odds ratio [OR],0.869; 95％ confidence interval [CI],0.788-0.958,P =0.005) and high tertile of Gensini score (OR,0.797,95％ CI,0.682-0.930,P =0.004).The area under the curve of Fg/FDP ratio was larger than that of Fg for predicting the presence of MVD (0.647 vs.0.563,P =0.048) and Gensini score ≥ 30 (0.656 vs.0.53 8,P =0.026).Conclusions:Elevated plasma Fg and FDP level and reduced Fg/FDP ratio are associated with presence of CAD,and Fg/FDP ratio is superior to Fg in reflecting severe coronary atherosclerosis for patients with type 2 diabetes.

Effects of atorvastatin on progression of diabetic nephropathy and local RAGE and soluble RAGE expressions in rats

Objective:Advanced glycation end-products (AGEs) exert inflammatory and oxidative stress insults to produce diabetic nephropathy mainly through the receptor for AGEs (RAGE).This study aimed to assess the effect of atorvastatin on diabetic nephropathy via soluble RAGE (sRAGE) and RAGE expressions in the rat kidney.Methods:Thirty-two male Sprague-Dawley rats were divided into four groups based on the presence or absence of streptozotocin-induced diabetes with or without atorvastatin treatment (10 mg/kg for 24 weeks).Serum sRAGE and glycated albumin (GA) levels were measured with enzyme-linked immunosorbent assay (ELISA) and improved bromocresol purple methods.Renal AGEs,RAGE,endogenous secretory RAGE (esRAGE),and sRAGE were determined with reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results:Mesangial expansion and microalbuminuria were aggravated in diabetic rats,and improved with atorvastatin treatment.Serum sRAGE levels were lower in diabetic than in normal rats.After atorvastatin treatment,serum and renal sRAGE levels were up-regulated,while renal RAGE expression was decreased in diabetic rats,associated with a reduction in accumulation of AGEs,though renal esRAGE mRNA expression was not significantly increased.Conclusions:Atorvastatin exerted a beneficial effect on diabetic nephropathy with reduced AGE accumulation,down-regulating RAGE expression and up-regulating sRAGE in the kidney.

Clinical and angiographic features associated with coronary collateralization in stable angina patients with chronic total occlusion

Objective： Coronary collateral circulation is an alternative source of blood supply to myocardium in the presence of advanced coronary artery disease. We sought to determine which clinical and angiographic variables are associated with collateral development in patients with stable angina and chronic total coronary occlusion. Methods： Demographic variables, biochemical measurements, and angiographic findings were collected from 478 patients with stable angina and chronic total coronary occlusion. The presence and extent of collaterals supplying the distal aspect of a total coronary occlusion from the contra-lateral vessel were graded from 0 to 3 according to the Rentrop scoring system. Results： Low （Rentrop score of 0 or 1） and high （Rentrop score of 2 or 3） coronary collateralizations were detected in 186 and 292 patients, respectively. Despite similar age, cigarette smoking, and medical treatment, patients with low collateralization were female in a higher proportion and less hypertensive, and had higher rates of type 2 diabetes and dyslipidemia than those with high coUateralization （for all comparisons, P〈0.05）. In addition, patients with low collateralization exhibited more single-vessel disease, less right coronary artery occlusion, more impaired renal function, and higher serum levels of high-sensitivity C-reactive protein （hsCRP） compared with those with high col- lateralization. Multivariate analysis revealed that age of 〉65 years, female gender, diabetes, no history of hypertension dyslipidemia, moderate to severe renal dysfunction, single-vessel disease, and elevated hsCRP levels were inde- pendently associated with low coronary collateralization. Conclusions： Coronary collateralization was reduced in almost 40% of stable angina patients with chronic total occlusion, which was related to clinical and angiographic factors. The impact of coronary collateralization on outcomes after revascularization needs further investigation.

Valsartan Decreases Platelet Activity and Arterial Thrombotic Events in Elderly Patients with Hypertension

Background：Angiotensin type 1 receptor （AT1R） antagonists are extensively used for blood pressure control in elderly patients with hypertension.This study aimed to investigate the inhibitory effects of AT1R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.Methods：Two-hundred and ten patients with hypertension and aged 〉 60 years were randomized to valsartan （n =140） or amlodipine （n =70） on admission.The primary endpoint was platelet aggregation rate （PAR） induced by arachidonic acid at discharge,and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up.Human aortic endothelial cells （HAECs） were stimulated by angiotensin Ⅱ （Ang Ⅱ,100 nmol/L） with or without pretreatment of valsartan （100 nmol/L）,and relative expression of cyclooxygenase-2 （COX-2） and thromboxane B2 （TXB2） and both p38 mitogen-activated protein kinase （p38MAPK） and nuclear factor-kB （NF-kB） activities were assessed.Statistical analyses were performed by GraphPad Prism 5.0 software （GraphPad Software,Inc.,California,USA）.Results：PAR was lower after treatment with valsartan （1 1.49 ± 0.69% vs.18.71 ± 2.47%,P 〈 0.001）,associated with more reduced plasmalevels of COX-2 （76.94 ± 7.07 U/L vs.116.4 ± 15.89 U/L,P 〈 0.001） and TXB2 （1667 ± 56.50 pg/ml vs.2207 ± 180.20 pg/ml） （all P 〈 0.001）.Plasma COX-2 and TXB2 levels correlated significantly with PAR in overall patients （r =0.109,P 〈 0.001）.During follow-up （median,18 months）,there was a significantly lower thrombotic event rate in patients treated with valsartan （14.3% vs.32.8%,P =0.002）.Relative expression of COX-2 and secretion of TXB2 with concordant phosphorylation ofp38MAPK and NF-kB were increased in HAECs when stimulated by Ang Ⅱ （100 nmol/L） but were significantly decreased by valsartan pretreatment （100 nmol/L）.Conclusions：AT1R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Screening for significant atherosclerotic renal artery stenosis with a regression model in patients undergoing transradial coronary angiography/intervention

Objective:Early detection of atherosclerotic renal artery stenosis (ARAS) is clinically important with respect to blood pressure control, prevention of renal insufficiency, and even improving survival. We investigated whether the presence of significant ARAS (luminal diameter narrowing ≥70%) could be predicted using a logistic regression model before coronary angiography/intervention. Methods:Initially, we developed a logistic regression model for detecting significant ARAS based upon clinical and angiographic features and biochemical measurements in a cohort of 1 813 patients undergoing transfemoral coronary and renal angiography. This model was then prospectively applied to an additional 495 patients who received transradial renal angiography to ascertain its predictive accuracy for the presence of significant ARAS. Results:Multivariate regression analysis revealed that older age (≥65 years), resistant hypertension, type 2 diabetes, creatinine clearance (Ccr) ≤60 ml/min, and multivessel coronary disease were independent predictors for significant ARAS. A logistic regression model for detecting ARAS by incorporating conventional risk factors and multivessel coronary disease was generated as:P/(1 P)=exp( 2.618+1.112[age≥65 years]+1.891[resistant hypertension]+0.453[type 2 diabetes]+0.587[Ccr≤60 ml/min]+2.254[multivessel coronary disease]). When this regression model was prospectively applied to the additional 495 patients undergoing transradial coronary and renal angiography, significant ARAS could be detected with a sensitivity of 81.2%, specificity of 88.9%, and positive and negative predictive accuracies of 53.8% and 96.7%, respectively. Conclusions:The logistic regression model generated in this study may be useful for screening for significant ARAS in patients undergoing transradial coronary angiography/intervention.

Mineral metabolism disturbances are associated with the presence and severity of calcific aortic valve disease

Objective：We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease （CAVD） in patients with normal or mildly impaired renal function. Methods：We measured serum levels of calcium, phosphate, alkaline phosphatase （AKP）, intact parathyroid hormone （iPTH）, 25-hydroxyvitamin D （25-OHD）, and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis （AVSc） （n=164） or stenosis （AVS） （n=96） and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results：Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels （al P〈0.001）. Similarly, osteocalcin, procol agen I N-terminal peptide, andβ-isomerized type I col agen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS （al P〈0.001）. In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding varia-bles, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were in-dependently associated with the presence and severity of CAVD. Conclusions： This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism.

Development of the science of mass casualty incident management: reflection on the medical response to the Wenchuan earthquake and Hangzhou bus fire

Objective： In this paper, we review the previous classic research paradigms of a mass casualty incident （MCI） systematically and reflect the medical response to the Wenchuan earthquake and Hangzhou bus tire, in order to outline and develop an improved research paradigm for MCI management. Methods： We searched PubMed, EMBASE China Wanfang, and China Biology Medicine （CBM） databases for relevant studies. The following key words and medical subject headings were used： ＇mass casualty incident＇, ＇MCI＇, ＇research method＇, ＇Wenchuan＇, ＇earthquake＇, ＇research paradigm＇, ＇science of surge＇, ＇surge＇, ＇surge capacity＇, and ＇vulnerability＇. Searches were performed without year or language restriction. After searching the four literature databases using the above listed key words and medical subject headings, related articles containing research paradigms of MCI, 2008 Wenchuan earthquake, July 5 bus fire, and science of surge and vulnerability were independently included by two authors. Results： The current progresses on MCI management include new golden hour, damage control philosophy, chain of survival, and three links theory. In addition, there are three evaluation methods （medical severity index （MSI）, potential injury creating event （PICE） classification, and disaster severity scale （DSS））, which can dynamically assess the MCI situations and decisions for MCI responses and can be made based on the results of such evaluations. However, the three methods only offer a retrospective evaluation of MCI and thus fail to develop a real-time assessment of MCI responses. Therefore, they cannot be used as practical guidance for decision-making during MCI. Although the theory of surge science has made great improvements, we found that a very important factor has been ignored--vulnerability, based on reflecting on the MCI response to the 2008 Wenchuan earthquake and July 5 bus fire in Hangzhou. Conclusions： This new paradigm breaks through the limitation of traditional research paradigms and will contribute to the development of a methodology for disaster research.

Is right ventricular mid-septal pacing superior to apical pacing in patients with high degree atrio-ventricular block and moderately depressed left ventricular function?

Objective： We are aimed to investigate whether right ventricular mid-septal pacing （RVMSP） is superior to conventional right ventricular apical pacing （RVAP） in improving clinical functional capacity and left ventricular ejection fraction （LVEF） for patients with high-degree atrio-ventricular block and moderately depressed left ventricle （LV） function. Methods： Ninety-two patients with high-degree atrio-ventricular block and moderately reduced LVEF （ranging from 35% to 50%） were randomly allocated to RVMSP （n=45） and RVAP （n=47）. New York Heart Association （NYHA） functional class, echocardiographic LVEF, and distance during a 6-min walk test （6MWT） were determined at 18 months after pacemaker implantation. Serum levels of N-terminal pro-brain natriuretic peptide （NT-proBNP） were measured using an enzyme-linked immunosorbent assay （ELISA） kit. Results： Compared with baseline, NYHA functional class remained unchanged at 18 months, distance during 6MVVT （485 m vs. 517 m） and LVEF （36.7% vs. 41.8%） were increased, but BNP levels were reduced （2352 pg/ml vs. 710 pg/ml） in the RVMSP group compared with those in the RVAP group, especially in patients with LVEF 35%-40% （for all comparisons, P〈0.05）. However, clinical function capacity and LV function measurements were not significantly changed in patients with RVAP, despite the pacing measurements being similar in both groups, such as R-wave amplitude and capture threshold. Conclusions： RVMSP provides a better clinical utility, compared with RVAP, in patients with high-degree atrioventricular block and moderately depressed LV function whose LVEF levels ranged from 35% to 40%.