Dynamic Changes of Circulating Tumor DNA in Peripheral Blood Predict the Efficacy of TKI in the Treatment of Lung Adenocarcinoma with EGFR Mutation / 中国肺癌杂志

BACKGROUND@#The tyrosine kinase inhibitors (TKI) treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation may have a positive effect, but most patients may develop drug resistance, therefore, the detection of the developing time in drug resistance and the research of the mechanism of drug resistance are need to be solved. While the emerge of next generation sequencing (NGS) have make it possible. The aim of this study is to monitor the efficacy of targeted therapy by studying the variation of circulating tumor DNA (ctDNA) mutation frequency and gene mutation spectrum through the targeted therapy.@*METHODS@#Our center enrolled 22 patients with EGFR mutation detected by tissue or peripheral blood, and collect 8 mL of peripheral blood of the patients for ctDNA sequencing in different phases, before systematic prior treatment, followed-up by 2 months and disease progression after TKI administration.@*RESULTS@#Patients with EGFR gene mutation may acquire a longer median survival time after receiving targeted drug therapy, due to the drop of mutation abundances, while the therapy may have a minor effect in patients which their mutation abundances have slightly decreased compared to the statistics before the cession (P=0.015,3). The significantly reduced group median progression was associated with a longer survival [progression free survival (PFS)=390 d]. At the same time, we found out that when related to TP-53 gene mutation, the effect of targeted drug therapy for EGFR-sensitive mutation was unsatisfactory (the median PFS was 120 d compared with 630 d, P=0.000,2).@*CONCLUSIONS@#Patients who has lower mutation abundance with EGFR sensitive mutations after TKI treatment may have a longer survival period (P<0.05), and the mutation abundance were not significantly dropping or accompanied by other mutations may indicating TKI resistance.

Profile and clinical significance of long non-coding RNA GAS8-AS1 in papillary thyroid microcarcinoma / 中华内分泌代谢杂志

Objective To investigate the expression level and clinical significance of long non-coding RNA(LncRNA) growth arrest specific gene-antisense 1(GAS8-AS1) in papillary thyroid microcarcinoma(PTMC) patients. Methods We investigated the expression profile of GAS8-AS1 in tissue samples of patients with PTMC as well as nodular goiter(NG) by quantitative real-time polymerase chain reaction(RT-qPCR). Results GAS8-AS1 in cancer tissue was down-regulated in PTMC patients compared with adjacent thyroid tissue and NG samples(P<0.05). Lower level of GAS8-AS1 was also correlated with central cervical lymph node metastasis(CLNM, P<0.05). The area under the ROC curve for GAS8-AS1 was up to 0.717 3 in CLNM prediction(P<0.05). Conclusion GAS8-AS1 may act as a potential biomarker for PTC diagnosis and CLNM prediction.

Safety and effectiveness of total splenic vessel ligations in paediatric patients with splenomegaly.

BACKGROUNDS: Splenomegaly may contribute to hypersplenism and can result in thrombocytopenia. Many approaches are used to treat splenomegaly; however, the current management of splenomegaly has intrinsic limitations or disadvantages. Now, we initiate a new approach, that of total splenic vessel (artery and vein) ligations (TSVLs) in paediatric patients with splenomegaly. The purpose of our study is to evaluate the results obtained with TVSLs procedure for paediatric patients. PATIENTS AND METHODS: Seventeen paediatric patients with splenomegaly were screened for enrolment into this retrospective analysis. PROCEDURE: We identified and dissociated the splenic vessel. Next, we ligated the splenic artery and we used clips to ligate the vein distally and proximally. RESULT: The mean [standard deviation (SD)] splenic infarction rate of a total of 17 patients was 77.5 (5.1)% in 6 months after operation. After TSVL, the mean count of platelet (PLT) and white blood cell (WBC) increased significantly and reached a steady state in the third month. Both the PLT and WBC had a significance higher than pre-TSVL in a 1-year follow-up. CONCLUSION: Based on the evidence, we make cautious conclusions that TSVLs are a safe and effective method in the treatment of paediatric patients with splenomegaly, achieving a satisfactory long-term haematological response and benefit.

Design and validation of an early scoring system for predicting early outcomes of type III biliary atresia after Kasai's operation.

BACKGROUND/PURPOSE: The purpose of this study was to determine reliable predictors of outcome of biliary atresia (BA) after Kasai's operation. PATIENTS AND METHODS: This study included two consecutive stages of infants with biliary atresia. First stage, 200 BA cases who underwent Kasai's operation at our institution between May 2006 and May 2010 were retrospectively reviewed. In the first stage, we wanted to calculate a clinical scoring system by logistic regression. For cut-off determination, receiver operating characteristic (ROC) analysis was employed. Second stage (validation of scoring system), we used our scoring system to prospectively predict the outcomes of patients underwent a Kasai operation from inspecting the accuracy of our system. RESULTS: Early cholangitis, age at operation, JC time, post-operative TB, DB, AST, ALT and surgical method entered into our scoring system. The most reliable cut-offs determined by ROC analysis were 7.71 (sensitivity: 86.0%, specificity: 98.0%). We used our scoring system to predict the prognosis of the 15 BA patients and found that 13 of 15 patients were correctly predicted at the cut-off value of 7.71. CONCLUSION: Our scoring system is considered to be a reliable and useful predictor of the prognosis of biliary atresia.

Laparoscopic portoenterostomy versus open portoenterostomy for the treatment of biliary atresia: a systematic review and meta-analysis of comparative studies.

BACKGROUND: Open portoenterostomy (OPE) remains the mainstay in treatment of biliary atresia, while during the past several years, the laparoscopic portoenterostomy (LPE) has been widely introduced. However, safety of LPE remains a major concern. Thus, we conducted a systematic review and meta-analysis to review the currently available data comparing LPE and OPE. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Ovid, Elsevier, Google Scholar Embase, Cohrane library. STUDY SELECTION: Comparative cohort studies. DATA EXTRACTION: Two investigators independently assessed selected studies and extracted the following information: study characteristics, quality, outcomes data, etc. RESULTS: Eleven studies about the effectiveness of LPE compared with OPE were performed by meta-analysis. Meta-analysis found no significant difference between the two groups in operative time, hospital stay, intraoperative blood loss, early clearance of jaundice, cholangitis and variceal bleeding. In addition, the rate of 2-year survival with native liver was significantly high in OPE group than in LPE group. CONCLUSION: Laparoscopic portoenterostomy could not replace open portoenterostomy and open Kasai portoenterostomy remains the gold standard in the treatment of biliary atresia.

Risk factors and surgical outcomes for spontaneous rupture of BCLC stage A and stage B hepatocellular carcinoma / 中华肝胆外科杂志

Objective To investigate the risk factors of spontaneous rupture of BCLC stage A and stage B hepatocellular carcinoma (HCC),and to review the surgical outcomes.Methods From April 2002 to November 2006,89 patients who suffered from spontaneous rupture of HCC of BCLC stage A and stage B were included into this study.A control group of 171 patients was selected by matching the sex,age and BCLC stage.Clinical data and survivals were collected and analysed.Results On multivariate analysis,hypertension (HR 7.38,95％CI:1.91 ～28.58,P＜0.05),cirrhosis (HR6.04,95％ CI:2.83 ～12.88,P ＜ 0.05) and tumor location in segments Ⅱ,Ⅲ,Ⅵ (HR 5.03,95％ CI:2.70 ～ 6.37,P ＜ 0.05) were predictive factors of spontaneous rupture of HCC.In the study group,the median survival and median disease-free survival were 12 months (range,1 ～ 78 months) and 4 months (range,0 ～ 78 months) respectively.The overall survival rates and disease-free survival rates at 1-,3-and 5-year were 66.3％,23.4％,10.1％ and 57.0％,16.8％,4.5％,respectively.Only radical resection remained predictive of overall survival (HR 0.32,95％ CI:0.08 ～ 0.61,P ＜ 0.05) and disease-free survival (HR 0.12,95％ CI:0.01 ～ 0.73,P ＜ 0.05).Conclusions Tumor location,as well as hypertension and cirrhosis were associated with spontaneous rupture of HCC.One-stage hepatic resection should be recommended to patients with ruptured HCC of BCLC stage A and stage B.

New perspectives on the natural history and growth pattern of hepatic hemangioma in adults: a cohort study / 中华肝胆外科杂志

Objective To investigate the natural history and growth pattern of hepatic hemangioma in adults.Methods From April 2010 to March 2013, adult patients with hepatic hemangioma who had no prior treatment were enrolled.A routine follow-up was performed to observe the natural history and complications of these lesions.Results 236 patients were enrolled in the study.The median size of the hemangiomas was 4.5 cm (range 0.6 ～ 19.2 cm).During a median follow-up of 48 months (range 3 ～ 266 months), the hemangiomas increased in size in 61.0％ of patients, remained stable in size in 23.7％, decreased in size in 8.5％.The peak growth period was in patients ＜ 30 years age (0.46 ± 0.41 cm/year) and the growth rate decreased significantly after 50 years of age (0.21 ±0.40 cm/year).Hemangiomas with a size ＜2.0 cm had the lowest growth rate (0.16 ± 0.42 cm/year).The peak growth rate was in hemangiomas 8.0 ～ 10.0 cm (0.80 ± 0.62 cm/year) , but for hemangiomas ＞ 10.0 cm, the growth rate was only (0.47 ±0.91)cm per year.Only 9 patients had severe symptoms caused by the hemangioma.No patients presented with hemangioma-related complications.Conclusions The majority of hepatic hemangiomas have the tendency to increase in size but they rarely caused complications.All the hemangiomas could be safely managed by observation, and surgery should only be considered in patients with complications.

Injection of ethanol into the common bile duct to establish a rat model of biliary atresia / 中国实验动物学报

Objective To establish a new rat model of biliary atresia by pure ethanol injection into the common bile duct.Methods A catheter was inserted and fixed in the common bile duct in male SD rats .Saline (8 rats) or pure ethanol (16 rats) was injected through the catheter ,respectively, and the biochemical and pathological changes in the rats were examined .Results SD rats in the experimental group were divided into a persistent injury and a restoration of liver dysfunction groups according to pathological and biochemical detection .In the persistent injury group , biochemical impair-ments were significantly higher at 8 weeks after ethanol injection than those in the control group and restoration group .Dis-tinct pathological changes in the liver were observed using HE , SMA, and Masson staining .Conclusions It is a reliable animal model of biliary atresia induced by injection of pure ethanol into the common bile duct in the rat .It will provide a useful tool in future studies of biliary atresia .

Prognostic factors of survival in patients with resectable hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective To investigate the appropriate cutoff point of CA19-9 in prognosis and to determine other potential prognostic factors which may affect survival of patients with hilar cholangiocarcinoma (HC) after radical surgery.Methods 168 patients who had undergone radical surgery for hilar cholangiocarcinoma with R0 and R1 resection were selected for the study.Categorized versions were used in univariate model to determine the appropriate cutoff point of CA19-9.CA19-9 and other clinicopathologic factors were analyzed for their influence on survival using multivariate methods.Results The strongest univariate predictor among the categorized preoperative CA19-9 measures was CA19-9 of less than 150 IU/L (P ＜0.001).On univariate analysis,age,differentiation,tumor size,Bismuth-Corlette classification,portal vein invasion,lymph node metastasis,hepatic artery invasion,liver invasion,preoperative biliary drainage,resection margin and preoperative CA19-9 levels were identified as significant prognostic factors.On multivariable analysis,lymph node metastasis,resection margin and preoperative CA19-9 levels were independent prognostic factors of survival.Conclusions A raised preoperative CA19-9 level was an independent prognostic factor of survival for hilar cholangiocarcinoma.The most discriminative cutoff point of CA19-9 for prognosis was at 150 kU/L.

Prognosis after resection of early hepatocellular carcinoma in HBV-related cirrhotic patients / 中华肝胆外科杂志

Objective To identify clinicopathologic factors which predict survival following hepatectomy in HBV-related cirrhotic patients with early hepatocellular carcinoma (HCC).Methods A database was used to identify patients with histologically confirmed early HCC (≤5 cm,no nodal involvement,metastases,or major vascular invasion) who underwent surgical resection (excluding ablation or transplantation).Among 20 700 patients with HCC who were diagnosed at the Eastern Hepatobiliary Surgery Hospital from April 2005 to November 2010,537 (2.6％) patients with early HCC were studied retrospectively.Prognostic factors were evaluated using the Kaplan-Meier curves,Cox proportional hazards models and the receiver operating characteristic (ROC) curves.Results The study included 537 patients.The median tumor size was 2.9 cm,and 33％ of patients had tumors ≤2 cm.Most HCC lesions were solitary (63％) and had no evidence of vascular invasion (64％).Following surgery,the overall median and 5-year survival were 45 months and 33％ respectively.After adjusting for demographic factors and histological grade,tumor size ＞2 cm (hazard ratio [HR]:1.56),multifocal tumors (HR:1.34),and vascular invasion (HR:2.03) remained independent predictors of poor survival (all P ＜ 0.05).Based on these findings,a prognostic scoring system was developed that allotted 1 point each for these factors.Patients with early HCC could be stratified into 4 distinct prognostic groups (median and 5-year survival,respectively):0 points (97 months,96％),1 point (85 months,76％),2 points (76 months,54％),3 points (56 months,39％) (P ＜0.01).Conclusions The present study emphasized the importance of pathologic staging even in patients with small HCC.Anatomical resection of HCC should be the preferred surgical procedure in cirrhotic patients.