Objective To compare cost-effectiveness between endoscopical esophageal variceal ligation (EVL) combined non-selective beta-receptor blocker strategies and covered-stents transjugular intrahepatic portosystemic shunt (cTIPS) in preventing esophageal variceal rebleeding in liver cirrhosis with portal hypertension.And to explore the threshold of cost-effectiveness in stents in China.Methods According to clinical practice and associated guidelines,a six state Markov-based decision analytic model was established with TreeAge Pro Suite 2014 to compare the cost-effectiveness between two interfering strategies after followed up for seven years.The parameters such as costs,life years (LY),quality-adjusted life-years (QALY) and incremental costeffectiveness ratio (ICER) were directed.Results The results of baseline research in the seven-year follow-up period indicated that the cost of endoscopical EVL combined non-selective beta-receptor blocker B was 7 444.25 United States dollar (USD)/each,and yielded 1.98 QALY.The expected cost of cTIPS was 13 151.69 USD/ each and could have 2.34 QALY.In the 7th year,ICER was 16 001.74 USD.Based on willingness-to-pay (WTP) threshold of China (19 887.00 USD),cTIPS had better cost-effectiveness than endoscopical EVL combined non-selective beta-receptor blocker B.The price of covered stents less than 5 401.52 USD had cost-effectiveness.The results of single factor sensitivity analysis indicated that rebleeding probability of endoscopical EVL combined non-selective beta-receptor blocker B group was the most influential factor in the result of model.The second important factor was the cost of cTIPS.The probabilistic sensitivity analysis reported cTIPS to be the optimal strategy at WTP of 19 887.00 USD in 83％ of the iterations.Conclusions Seven-year follow-up indicates that cTIPS may be a more cost-effective strategy than endoscopical EVL combined non-selective beta-receptor blocker B in preventing esophageal variceal rebleeding.The price of covered stents less than 5 401.52 USD which have cost-effectiveness in China.

Objective To investigate the correlation between clinicopathological features and lymph node metastasis (LNM) in early gastric cancer (EGC).Methods From January 2006 to June 2009,the clinical data of 473 patients with EGC were collected.The data of patients including gender,age,tumor size,tumor number,general classification,differentiation degree,invasion depth,ulcer in tumor,nerve invasion,and lymphatic tumor cell embolus were analyzed.Chi-square test was performed to analyze the correlation between clinicopathological features and LNM in EGC.Logistic regression analysis was used to analyze the independent risk factor of LNM in EGC.Results Among 473 patients with EGC,77 patients had LNM and the metastasis rate was 16.3％.The metastasis rate of the female patients (24.6％,41/167) was higher than that of the male (11.8 ％,36/306).The metastasis rate of the tumors with maximum diameter over 2 cm (22.0％,39/177) was higher than that of the tumors less than 2 cm (12.8％,38/296).The metastasis rate of the elevated lesions (26.1％,6/23) was higher than that of flat and concave lesions (9.0 ％,15/167;19.8％,56/283).The metastasis rate of poorly differentiated tumors was higher than moderate differentiated and high differentiated tumors (12.7 ％,23/181; 7.1％,3/42).The metastasis rate of tumors invading into submucosa (22.9％,41/179) was higher than that of tumors invading into mucosa (12.2％,36/294).The metastasis rate of tumors with lymphatic embolus (40.7％,11/27) was higher than that of tumors without lymphatic embolus (14.8％,66/446) and the differences were statistically significant (x2 =12.960,6.873,10.704,7.382,9.277 and 12.572,all P＜0.05).The results of multifactor analyzed by Logistic regression analysis revealed that female,maximum diameter over 2 cm,poorly differentiated type and invasion to submucosa were the independent risk factors of LNM in EGC (relative risk (RR)=2.53,2.14,1.63 and 2.39,all P＜0.01).Conclusion Female,maximum diameter over 2 cm,poorly differentiated type and invasion to submucosa are the independent risk factors of LNM in EGC.

Objective To establish human embryonic stem cells (hESCs) feeder-independent and cell factor-free culture system. Methods Effect of high and low clone densities of hESCs culture was compared and impact of the clone densities to hESCs culture media was analyzed. Results HESCs could maintain their undifferentiated states at high clone density (34 clones/cm2) without cell factors. At the same time,the bone morphology protein (BMP)-like induction of N2 and B27 supplements (NB) medium could be modulated by the clone density,and high level of BMP-like induction was accompanied by high clone density. Conclusion High clone density of hESCs can change the environments by themselves to maintain the undifferentiated states,which provides a new clue to explore the mechanism of undifferentiated states of hESCs and simplify the culture medium.

Objective:To analyze the clinicopathological characteristics of patients with unknown etiology of portal hypertension and investigate the efficacy of endoscopic management of gastroesophageal varices in these patients.Methods:Patients with unknown etiology of portal hypertension and gastroesophageal varices who received liver biopsy between January, 2017 and January, 2020 in Zhongshan Hospital were included. The characteristics of pathology, portal computed tomography (CT) angiography, and endoscopy were recorded and follow-up for the occurrence of bleeding after treatment.Results:A total of 31 patients were included and divided into cirrhosis with unknown etiology group ( n=10) and non-cirrhotic portal hypertension group ( n=21). Patients in the non-cirrhotic group were younger [28.0(29.5-49.5) vs 58.5(43.5-65.8), P=0.004] and mostly male (71.4%), and fewer comorbidities including diabetes (4.8% vs 40.0%, P=0.027). The features of pathology finding including vasculopathy, cholestasis, and hepatic sinusoidal dilatation as well as the Sarin classification and bleeding rate of gastroesophageal varices, proportion of patients receiving endoscopic treatment were shown similar between the two groups ( P>0.05). The hepatic venous pressure gradient (HVPG) was significantly lower in the non-cirrhotic group [4.5(2.8-12.8)mmHg vs 12(8-18)mmHg, P=0.018]. Among them, 21 patients received endoscopic treatment, and the bleeding rate had no difference between these two groups after endoscopic treatment ( P=0.751). Conclusions:Non-cirrhotic portal hypertension in a predominantly young male population has similar clinicalpathological characteristics when compared to cirrhotic portal hypertension with unknown etiology. HVPG can not reflect the actual portal pressure in these patients. Endoscopic treatment is the effective treatment option for the prevention of variceal bleeding.

Objective:In this study, a simple and easy diagnostic index of sarcopenia based on computed tomography (CT) images, linear skeletal muscle index (LSMI), was proposed and its diagnostic efficiency was verified.Methods:From April 2013 to September 2017, patients with cirrhotic gastroesophageal varices were selected from the Department of Gastroenterology, Zhongshan Hospital, Fudan University. The SMI of the third lumbar lower than 50 cm 2/m 2 in male and 39 cm 2/m 2 in female was defined as sarcopenia. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index and receiver operating characteristic (ROC) curve were used to evaluate the diagnostic efficacy of LSMI in patients with cirrhotic gastroesophageal varices. Results:A total of 115 patients with cirrhotic gastroesophageal varices were finally recruited. All participants were randomly divided into modeling group ( n=58) and validation group ( n=57). In the modeling group, the area under the ROC curve of LSMI was 0.913(95% CI:0.84-0.986, P<0.001) in total population, 0.895(95% CI:0.793-0.997, P<0.001) in male and 0.917(95% CI:0.782-1.000, P<0.008) in female. The cut-off value of LSMI was 24.114 cm 2/m 2 in male and 22.54 cm 2/m 2 in female. According to the diagnostic cut-off value of the modeling group, the area under the ROC curve of LSMI was 0.846(95% CI:0.737-0.954, P<0.001) in the validation group. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 88.5%, 80.6%, 79.3%, 89.3% and 0.691, respectively. Conclusions:48.7% of patients with cirrhosis of esophageal and gastric varices have sarcopenia. LSMI is a simple and convenient method for diagnosis of sarcopenia in patients with liver cirrhosis.

Objective To explore the prognosis of endoscopic tissue adhesives injection in treating liver cirrhosis patients with esophageal gastric varices (GOV),and to evaluate the effects of various factors on bleeding after treatment.Methods A total of 157 liver cirrhosis patients with GOV treated by endoscopic tissue adhesives injection with or without ligation therapy were retrospectively analyzed.The basic information,liver function and blood biochemical values of patients at enrollment were investigated.The analysis of bleeding after treatment was conducted by Kaplan-Meier.The survival curves comparison was conducted by Log-rank test.Logistic regression model was used for multivariate analysis.The prognosis predictors were evaluated by receiver operating characteristics (ROC) curves and the area under the curve (AUC).Results Rebleeding happened in 26 of 157 patients.The median rebleeding time was 3.4 months.The results of univariate analysis indicated that there were statistical differences in FIB4 scores (Z=-1.282,P=0.100) and the inner diameter of the right portal vein (Z=-1.812,P=0.035) between bleeding group and no bleeding group.The results of multivariate analysis showed that the inner diameter of the right portal vein was independent prognostic factor of rebleeding (OR =1.733,95％ CI:1.045 to 2.874,P =0.033).Optimal diagnostic threshold was 8.5 mm (AUC=0.724,95 ％CI:0.537 to 0.910),sensitivity and specificity was 77.8％ and 66.6％ respectively.Conclusions The inner diameter of the right portal vein was one of the important factors that affected the efficacy of tissue adhesives injection in preventing bleeding and the prognosis.FIB4 score had certain reference value in predicting recurrence or bleeding after treatment.

BACKGROUND/AIMS: Gastroesophageal variceal hemorrhage is a common complication of portal hypertension. Endoscopic therapy is currently recommended for preventing gastroesophageal variceal rebleed. However, the rate of variceal rebleed and its associated mortality remain concerning. This study is aimed at differentiating patient response to endoscopic therapy based on endoscopic ultrasound (EUS) findings. METHODS: One-hundred seventy patients previously treated with repeat endoscopic therapy for secondary prophylaxis were enrolled and classified into two groups based on treatment response. Prior to consolidation therapy, all patients received an EUS examination to observe for extraluminal phenomena. All available follow-up endoscopic examination records were retrieved to validate study results. RESULTS: Of the 170 subjects, 106 were poor responders, while 64 were good responders. The presence of para-gastric, gastric perforating, and esophageal perforating veins was associated with poor patient response (p < 0.001). The odds ratio for para-gastric veins was 5.374. Follow-up endoscopic findings for poor responders with incomplete variceal obliteration was closely correlated with the presence of para-gastric veins (p=0.002). CONCLUSIONS: The presence of para-gastric veins is a characteristic of poor response to endoscopic therapy for treating gastroesophageal varices. Early identification of this subgroup necessitates a change in course of treatment to improve overall patient outcome.
Cyanoacrylates ; Endosonography ; Esophageal and Gastric Varices ; Follow-Up Studies ; Hemorrhage ; Humans ; Hypertension, Portal ; Mortality ; Odds Ratio ; Risk Assessment ; Ultrasonography* ; Varicose Veins* ; Veins

Objective: To analyze and explore the clinical characteristics and prognosis of patients with "double hit" multiple myeloma (MM) . Methods: We retrospectively analyzed 89 MM patients in our department of Shanghai Changzheng Hospital from 2010-2016. All patients were assayed by fluorescence in situ hybridization (FISH) and TP53 gene sequencing, based on Dr. Walker BA proposed the "double hit" MM concept, and then the clinical features and prognosis were evaluated. Results: In the results, 15 (16.85%) cases harbored "double hit" showed the median PFS of 8.4 months and the median OS 22.2 months, which was significantly lower than non-"double hit" patients with median PFS 14.2 months and the median OS 39.2 months, respectively (P<0.05) . Multivariate analysis displayed that the "double hit" was an independent poor prognostic factor on PFS (HR=2.171, 95%CI 1.206-3.907, P=0.010) and OS (HR=4.106, 95%CI 2.116-7.969, P<0.001) . Moreover, "double hit" MM patients had the higher adverse prognosis risk, which showed the shorter median OS and PFS than stage III of R-ISS patients (PFS 8.4 vs 11.8 months; OS 22.2 vs 24.3 months, P<0.05, respectively) . Conclusion Patients with "double hit" MM have a very poor clinical prognosis. Prospective clinical studies are urgently needed to improve these extra high risk patients.

Objective: To predict the efficacy of endoscopic tissue adhesives in the treatment of gastric varices in patients with liver cirrhosis by Nomogram model. Methods: From August 2014 to September 2017, 158 patients with liver cirrhosis caused esophagogastric variceal bleeding and received endoscopic tissue adhesives treatment at Zhongshan Hospital, Fudan University were collected. All patients were followed for 12 months. The primary outcome was rebleeding. The factors of rebleeding after endoscopic treatment of esophagogastric varices were analyzed. Nomogram prognostic model was developed and compared with Child-Pugh grading, computed tomography angiography (CTA) and hepatic venous pressure gradient (HVPG) in prognostic accuracy in rebleeding after endoscopic treatment in liver cirrhosis caused esophagogastric varices. Univariate and multivaricate Cox regression analysis, Kaplan-Meier curve and log-rank test were performed for statistical analysis. Results: During the follow-up, rebleading occurred in 18 cases (11.4%), 37 cases (23.4%) and 49 cases (31.0%) at 2, 6, and 12 months after endoscopic treatment. The results of univariate Cox regression analysis showed the risk factors of rebleeding after endoscopic treatment of gastric varices included gender, alcoholic liver cirrhosis, diabetes mellitus, Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence vs. absence) HVPG (<16 mmHg vs. ≥16 mmHg, 1 mmHg = 0.133 kPa), extensive portal embolism, esophageal varices, type 2 gastric varices, injection points of tissue adhesive (≤3 points vs. > 3 points), injection volume of tissue adhesive (≤ 3 mL vs. > 3 mL) (hazard ratio (HR)=0.575, 2.018, 1.562, 3.433, 2.945, 1.859, 2.743, 0.324, 1.840, 1.477, and 1.716; 95% confidence interval (CI) 0.305 to 1.084, 0.902 to 4.514, 1.753 to 6.724, 1.663 to 5.217, 1.012 to 3.415, 0.852 to 8.830, 0.079 to 1.335, 1.012 to 3.317, 0.839 to 2.602, and 0.935 to 3.152; all P<0.2). The results of multivariate Cox regression analysis indicated that Child-Pugh grade, extraluminal vessels by CTA, and HVPG (HR = 2.095, 95% CI 1.099 to 3.995, P = 0.025) were all independent risk factors of rebleeding after endoscopic treatment of gastric varices (HR=2.665, 2.886, and 2.095; 95% CI 1.339 to 5.300, 1.580 to 5.271, and 1.099 to 3.995; all P<0.05). Kaplan-Meier curves showed that Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence or absent) and HVPG (<16 mmHg vs. ≥16 mmHg) could effectively predict cumulative non-rebleeding rate in one year after endoscopic treatment of gastric varices, and the differences were statistically significant (all P<0.05). Receiver operataring characteristic curve analysis demonstrated that the predictive value of the model combined with Child-Pugh grade, extraluminal vessels on CTA and HVPG was higher than that of Child-Pugh grade and HVPG (AUC=0.746, 0.673 and 0.585; 95% CI 0.662 to 0.829, 0.583 to 0.762, and 0.486 to 0.683; P<0.01, P=0.001 and P=0.089, respectively). Patients were divided into low, medium, and high-risk groups according to the 25th and 75th percentiles of the Nomogram score. The results showed that Nomogram model could effectively distinguish high-risk groups of rebleeding after endoscopic treatment of gastric varices, and the difference was statistically significant (P <0.01). Conclusions Extraluminal vessels on CTA, HVPG and Child-Pugh grade are independent prognostic evaluation indexes of rebleeding after endoscopic treatment of gastric varices. The predictive accuracy of Nomogram model based on these three prognostic factors may be better than Child-Pugh grade and HVPG.

Objective: To analyze the significance of serum free light chain (sFLC) for the prognosis of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 621 NDMM patients in Changzheng Hospital from June 2010 to December 2016 was retrospectively analyzed. The serum free light chain levels were measured and the ratios of κ/λ chains were calculated. The significance of serum free light chain ratio (sFLCR) for the prognosis of NDMM patients was analyzed. Results: Among the 621 NDMM patients, 42 patients (6.8%) were in the normal free light chain ratio group (0.26≤sFLCR≤1.65), 247 patients (39.8%) were in the low free light chain ratio group (0.01＜sFLCR＜0.26 or 1.65＜sFLCR＜100), and 332 patients (53.5%) were in the high free light chain ratio group (sFLCR≤0.01 or sFLCR≥100). Compared with normal sFLCR group, the abnormal sFLCR group showed low level of hemoglobin; elevated levels of bone marrow plasma cells, serum creatinine and β 2 -MG, and more patients were in DS stage Ⅲ and ISS stage Ⅲ with high risks of cytogenetics(all P＜0.05). The overall survival (OS) in the normal sFLCR group was significantly better than the abnormol sFLCR groups (not reached vs 58.7 months, P=0.043). Compared with the patients with both high sFLCR and low risks of cytogenetics, the patients with high sFLCR and high risks of cytogenetics showed shorter overall survival time (median OS time was 41.6 months vs 61.4 months, P=0.015). Conclusion The NDMM patients with significantly abnormal sFLCR may indicate more tumor load and higher aggressive progression. sFLCR should be an independent prognostic indicator for the outcome of multiple myeloma. The patients with high sFLCR and cytogenetic abnormalities, have worse prognosis than the others.