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The treatment of hepatobiliary malignant tumor is characterized by the coexistence of multiple treatment methods and multiple disciplines. In order to evaluate the clinical efficacy of different treatment measures or multiple treatment combinations, and to promote the standardized development of comprehensive treatment patterns for hepatobiliary malignant tumor, the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University constructs the registry and follow-up database in hepatobiliary tumor patients based on the information-based platform of the hospital, which will help guide clinicians to make scientific decisions and improve the level of clinical diagnosis and treatment. This study describes the framework design, function modules, data acquisition process and quality control of the database of hepatobiliary malignant tumor. Based on the observational bidirectional cohort study design, the previous clinical data can be sorted to match the current database, on the other hand, the clinical data can be prospectively collected including basic information, admission evaluation, surgical information and postoperative situation, comprehensive treatment measures, regular reexaminations and long-term follow-up, etc. The data quality control system can be improved by formulating standardized operation procedures, regularly personnel training and full-process data management plans. This database will provide high-quality real-world data for clinicians, researchers, and guideline experts, and then provide high-level medical evidence for the standardized development of comprehensive treatment patterns of hepatobiliary malignancies.
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Objective:To explore the pathogenic characteristics and related risk factors of fungal infection after liver transplantation(LT)from deceased donation and provide rationales for formulating optimal control strategies.Methods:From February 2019 to September 2020, clinical data were retrospectively reviewed for 187 recipients after LT from deceased donation.Univariate and multiple Logistic regression analyses were performed for determining the independent risk factors of postoperative fungal infection.Results:Among 187 LT cases, 26 cases had postoperative fungal infection with a mortality rate of 46.2%(12/26). Lung was the most common fungal infection site, accounting for 80.8%(21/26). The most common pathogenic bacteria of fungal infection were Candida albicans, accounting for 53.3%(16/30). Multiple Logistic regression analysis indicated that operative duration ≥8 h( OR=3.610, 95% CI: 1.079-12.081, P=0.037), re-operation( OR=39.234, 95% CI: 3.512-438.258, P=0.003)and intensive care unit(ICU)retention time ≥7 d( OR=10.070, 95% CI: 3.480-29.140, P=0.002)were independent risk factors of postoperative fungal infection. Conclusions:Postoperative fungal infection is a serious threat to the prognosis of recipients of LT from deceased donation.Minimizing operative duration on the basis of ensuring quality of surgery, strictly grasping the indications for re-operation and transferring out of ICU in early postoperative period may help to lower the risks of fungal infection after LT from deceased donation.
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Hilar cholangiocarcinoma is a highly intractable malignancy, and most patients with this disease were diagnosed as a locally advanced stage at their initial presentation. Surgical resection remains as the only curative treatment for hilar cholangiocarcinoma. Hepatic surgeons focus on how to perform radical resection safely and effectively. For locally advanced hilar cholangio-carcinoma, aggressive surgical approach substantially increases the resectability of tumors which were initially regarded as unresectable. Hemihepatectomy or trisectionectomy combined with caudate lobectomy is the standard operation for radical resection of hilar cholangiocarcinoma, vascular resection and lymphadenectomy can be performed selectively. The safety and success of surgical approach is guaranteed by meticulous preoperative management such as preoperative biliary drainage and portal vein embolization, which prevent fatal postoperative complications. Multidisciplinary approach is required for the treatment of hilar cholangiocarcinoma. The combina-tion of aggressive surgical approach and adjuvant therapy remain a promising approach for further improving the resectability of tumors and the survival of patients.
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Hilar cholangiocarcinoma (HCCA) is the most common biliary malignancy, and surgical operation is the only possible treatment method at present. The nature of surgical margin is an important influencing factor for the long-term survival of patients, and radical resection can bring great survival benefits to patients. The determination of radial margin for HCCA can help to evaluate the nature of surgical margin and predict the prognosis of patients more accurately. This article reviews the latest research advances in the surgical margin of HCCA.
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Cholangiocarcinoma is a rarely malignant tumor with poor overall prognosis. Radical surgery is the only strategy to improve the long-term survival of patients with cholangio-carcinoma of early-stage. For most patients with advanced cholangiocarcinoma, systematic treatment has become the main strategy. But the available first-line drugs for the treatment of cholangiocarcinoma are limited and the curative effect is limited. In recent years, immunotherapy strategies such as immune checkpoint inhibitors have achieved encouraging results in a variety of solid tumors by using the host immune system to carry out effective anti-tumor responses. The authors summarize the research advances of immune checkpoint inhibitors in the treatment of cholangiocarcinoma.
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This article reported a case of malignant insulinoma which recurred as liver metastasis 12 years after the initial pancreatic insulinoma resection. The patient was a 48-year-old woman who was firstly diagnosed as pancreatic insulinoma in 2006 and underwent the surgery involved complete resection of a 1.9 cm×1.3 cm tumor located in pancreas. No signs of either invasion or metastasis was detected according to preoperative imaging examination and intraoperative exploration. The tumor was diagnosed as a benign insulinoma according to histopathological results. The patient had no hypoglycemia and the fasting blood glucose was normal during the subsequent 12 years. The patient underwent a fasting blood glucose of 2.8 mmol/L in 2018, and gradually experienced palpitation and cold sweats, which was relieved by eating. She was hospitalized in May 2018 with blood glucose of 1.73 mmol/L and insulin of 1 128 pmol/L. CT and MRI revealed morphologic changes of postoperative pancreas and abnormal liver signal, the liver tumor was finally identified as insulinoma by modified selective intra-arterial calcium stimulated venous sampling (ASVS). Partial liver resection was performed and the histopathological result was neuroendocrine tumor. Therefore, the disease was diagnosed as liver metastatic malignant insulinoma.
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Objective:To construct a computed tomography (CT)-based radiomics model for predicting tumor recurrence of early-stage hepatocellular carcinoma (HCC) after resection, and explore its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 243 patients with early-stage HCC who underwent hepatectomy in 2 medical centers between January 2009 and December 2016 were collected, including 165 in the First Affiliated Hospital of Nanjing Medical University and 78 in the Wuxi People′s Hospital. There were 182 males and 61 females, aged from 30 to 86 years, with a median age of 57 years. According to the random numbers showed in the computer, 243 patients were randomly assigned into training dataset consisting of 162 patients and test dataset consisting of 81 patients, with a ratio of 2∶1. Using radiomics technique, a total of 3 384 radiomics features were extracted from the tumor and its periphery at arterial-phase and portal-phase images of CT scan. In the training dataset, a radiomics signature was constructed and predicted its performance after dimension reduction of stable features by using aggregated feature selection algorithms [feature ranking via maximal relevance and minimal redundancy (MRMR) combined with random survival forest (RSF) + LASSO-COX regression analysis]. Risk factors for tumor recurrence were selected using the univariate COX regression analysis, and two radiomics models including radiomics 1 (preoperative) and radiomics 2 (postoperative) were constructed and predicted their performance using backward stepwise multivariate COX regression analysis. The two models were validated in the training and test dataset. Observation indicators: (1) follow-up; (2) construction of HCC recurrence-related radiomics signature for early-stage HCC after resection; (3) prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection; (4) construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (5) validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (6) comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems; (7) stratification analysis of postoperative recurrence risk based on radiomics models for early-stage HCC after resection. Patients were followed up using outpatient examination or telephone interview once every 3 months within the first 2 years and once every 6 months after 2 years. The follow-up included collection of medical history, laboratory examination, and abdominal ultrasound examination. Contrast-enhanced CT or magnetic resonance imaging (MRI) examination was performed once every 6 months, and they were performed in advance on patients who had suspected recurrence based on laboratory examination or abdominal ultrasound for further diagnosis. Follow-up was up to January 2019. The endpoint was time to recurrence, which was from the date of surgery to the date of first detected disease recurrence or metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were described as absolute numbesr or percentages, and comparison between groups was analyzed using the chi-square test. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method, and the survival analysis was performed using the Log-rank test. Serum alpha-fetoprotein level was analyzed after the natural logarithm transformation. X-tile software was used to select the optimal cut-point for continuous markers. Results:(1) Follow-up: all the 243 HCC patients received follow-up. Patients in the training dataset were followed up for 4.2-109.2 months, with a median follow-up time of 51.6 months. Patients in the test dataset were followed up for 12.7-107.6 months, with a median follow-up time of 73.2 months. The 2-, 5-year disease-free survival rates were 77.8% and 53.1% of the training dataset respectively, versus 86.4% and 61.7% of the test dataset. There was no significant difference in terms of disease-free survival between two datasets ( χ2=1.773, P>0.05). (2) Construction of HCC recurrence-related radiomics signature for early-stage HCC after resection: of the 3 384 radiomics features, 2 426 radiomics features with high stability were selected for analysis. There were 37 radiomics features identified after combining the top 20 radiomics features ranked by MRMR and RSF algorithms. LASSO-COX regression algorithm further reduced their dimensionality to retain 7 radiomics features and construct a radiomics signature. The indicators including region, scanning phase, and weighting coefficient of above mentioned seven features were Feature 1 (peritumoral, arterial phase, 0.041), Feature 2 (peritumoral, arterial phase, -0.103), Feature 3 (peritumoral, arterial phase, -0.259), Feature 4 (intratumoral, arterial phase, 0.211), Feature 5 (peritumoral, portal venous phase, -0.170), Feature 6 (intratumoral, portal venous phase, 0.130), and Feature 7 (intratumoral, portal venous phase, 0.090), respectively. Radiomics signature score=0.041×Feature 1-0.103×Feature 2-0.259×Feature 3+ 0.211×Feature 4-0.170×Feature 5+ 0.130×Feature 6+ 0.090×Feature 7. (3) Prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection: the radiomics signature showed favorable prediction performance in both training and test datasets, with respective C-index of 0.648 [95% confidence interval ( CI): 0.583-0.713] and 0.669 (95% CI: 0.587-0.750). (4) Construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: results of univariate analysis showed that ln(serum alpha-fetoprotein), liver cirrhosis, tumor margin status, arterial peritumoral enhancement, intratumoral necrosis, radiomics signature, satellite nodules, and microvascular invasion were related factors for tumor recurrence after resection of early-stage HCC ( hazard ratio=1.202, 1.776, 1.889, 2.957, 1.713, 4.237, 4.364, 4.258, 95% CI: 1.083-1.333, 1.068-2.953, 1.181-3.024, 1.462-5.981, 1.076-2.728, 2.593-6.923, 2.468-7.717, 2.427-7.468, P<0.05 ). Results of multivariate analysis showed that the radiomics model 1 (preoperative) consisted of ln(serum alpha-fetoprotein), tumor margin status, and radiomics signature ( hazard ratio=1.145, 1.838, 3.525, 95% CI: 1.029-1.273, 1.143-2.955, 2.172-5.720, P<0.05); the radiomics model 2 (postoperative) consisted of ln(serum alpha-fetoprotein), radiomics signature, microvascular invasion, and satellite nodules ( hazard ratio=1.123, 2.386, 3.456, 3.481, 95% CI: 1.005-1.254, 1.501-3.795, 1.863-6.410, 1.891-6.408, P<0.05). Risk prediction formulas: radiomics model 1 = 0.135×ln(serum alpha-fetoprotein)+ 0.608×tumor margin status (0: smooth; 1: non-smooth)+ 1.260×radiomics signature; radiomics model 2 = 0.116×ln(serum alpha-fetoprotein)+ 0.870×radiomics signature + 1.240×microvascular invasion (0: absent; 1: present)+ 1.247×satellite nodules (0: absent; 1: present). (5) Validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: in both training and test datasets, radiomics model 1 provided good prediction performance, with respective C-index of 0.716 (95% CI: 0.662-0.770) and 0.724 (95% CI: 0.642-0.806), while radiomics model 2 provided better prediction performance, with respective C-index of 0.765 (95% CI: 0.712-0.818) and 0.741 (95% CI: 0.662-0.820). Calibration curves demonstrated good agreement between model-predicted probabilities and observed outcomes. (6) Comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems: in the training dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), Barcelona clinic liver cancer (BCLC) staging, Hong Kong liver cancer (HKLC) staging, and cancer of the liver Italian program (CLIP) classification (C-index=0.562, 0.484, 0.520, 0.622, 95% CI: 0.490-0.634, 0.311-0.658, 0.301-0.740, 0.509-0.736, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.601, 0.523, 0.513, 95% CI: 0.524-0.677, 0.449-0.596, 0.273-0.753, P<0.05). In the test dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), BCLC staging, HKLC staging, CLIP classification (C-index=0.540, 0.473, 0.504, 0.545, 95% CI: 0.442-0.638, 0.252-0.693, 0.252-0.757, 0.361-0.730, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.562, 0.513, 0.521, 95% CI: 0.451-0.672, 0.399-0.626, 0.251-0.791, P<0.05). (7) Stratification analysis of postoperative recurrence risk based on radiomics models for tumor recurrence after resection of early-stage HCC: according to the analysis of X-tile, the score of radiomics model 1 < 1.4 (corresponding to total points < 62.0 in nomogram) was classified into low-risk group while the score of radiomics model 1 ≥ 1.4 (corresponding to total points ≥ 62.0 in nomogram) was classified into high-risk group. The score of radiomics model 2 < 1.7 (corresponding to total points < 88.0 in nomogram) was classified into low-risk group while the score of radiomics model 2 ≥ 1.7 (corresponding to total points ≥ 88.0 in nomogram) was classified into high-risk group. In the training dataset, the 2- and 5-year recurrence rates were 14.1%, 35.3% for low-risk patients and 63.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 70.381, P<0.05). The 2- and 5-year recurrence rates were 12.9%, 38.2% for low-risk patients and 81.8%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 98.613, P<0.05). In the test dataset, the 2- and 5-year recurrence rates were 5.6%, 29.3% for low-risk patients and 70.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 64.453, P<0.05). Ther 2- and 5-year recurrence rates were 5.7%, 28.1% for low-risk patients and 63.6%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 58.032, P<0.05). Conclusions:The 7-feature-based radiomics signature is built by selection of CT radiomics features in this study, and then HCC recurrence-related radiomics prediction model for early-stage HCC after resection is constructed. The proposed radiomics models can complement the existing clinical-radiological-pathological prognostic sources, accurately and individually predict tumor recurrence risk preoperatively and postoperatively, which facilitate clinical decision-support for patients with early-stage HCC.
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Immunotherapy, especially immune checkpoint inhibitors (ICIs), has reformed the situation of cancer management. Encouraging results have been revealed in early stage studies about ICIs in patients with hepatocellular carcinoma.Results of a recent phase Ⅲ study of ICIs combined with anti-angiogenesis therapy in the treatment of hepatocellular carcinoma have achieved a positive result, showing superior advantages in efficacy and safety compared with standard manage-ment. At present, lots of studies in hepatocellular carcinoma patients treated with ICIs combining with traditional therapy like chemotherapy, radiotherapy, antiangiogenetic therapy, locore-gional therapy and another ICIs are held globally. These results will update the strategies of hepatocellular carcinoma.
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Hilar cholangiocarcinoma is one of the most difficult malignant tumors in the biliary system. The best chance of treatment often absent on account of the portal vein and liver lobe are invaded. Although the efficacy of hilar cholangiocarcinoma improved with the development of diagnosis and surgical techniques in recent years, accurate definition, preoperative diagnosis and assessment, operation approach and scope, perioperative management, and the application of liver transplantation still have many disputes. This article aims to reports the advance and controversy in diagnosis and treatment of Hilar cholangiocarcinoma.
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Objective To compare the clinical efficacy of anatomical hepatectomy (AR) and parenchymal-sparing hepatectomy (PSH) for Barcelona clinic liver cancer (BCLC) stage A hepatocellular carcinoma(HCC),and investigate its prognostic factors.Methods The propensity score matching and retrospective cohort study was conducted.The clinicopathological data of 269 patients with BCLC stage A HCC who were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2009 to December 2017 were collected.There were 226 males and 43 females,aged from 23 to 84 years,with a median age of 56 years.All the 269 patients underwent radical resection and were confirmed as HCC using postoperative pathological examination.Of the 226 patients,146 undergoing AR and 123 undergoing PSH were allocated into the AR group and PSH group,respectively.Observation indicators:(1) the propensity score matching conditions and comparison of general data between groups after the propensity score matching;(2) intraoperative and postoperative situations;(3) follow-up and survival situations;(4) prognostic factors analysis.Patients were followed up by outpatient examination and telephone interview to detect survival once every 3 months within 1 year postoperatively,once every 6 months within 2-5 years postoperatively and once a year after 5 years postoperatively up to October 2018.The overall survival time was from surgery data to death or end of follow-up.The tumor-free survival time was from surgery date to time of tumor recurrence detected or end of follow-up without tumor recurrence.The propensity score matching was used to perform 1∶1 matching by nearest neighbor method.Count data were represented as absolute number,comparison between groups was analyzed using the chi-square test and McNemar test after propensity score matching.Measurement data with skewed distribution were represented as M (range),and comparison between groups was done using the Mann-Whitney U test and Wilcoxon signed rank sum test after propensity score matching.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.The COX proportional risk model was used for univariate and multivariate analysis.Results (1) The propensity score matching conditions and comparison of general data between groups after the propensity score matching:180 of 269 patients had successful matching,including 90 in each group.The maximum tumor diameter,cases with vascular embolism,cases of stage Ⅰ and Ⅱ (TNM staging) before matching were 5.0 cm (range,0.8-17.0 cm),42,97,99 in the AR group and 3.0 cm (range,1.0-17.0 cm),16,49,24 in the PSH group,respectively,with statistically significant differences between the two groups (Z =-4.277,x2 =9.803,6.664,P＜ 0.05).The above indices after matching were 4.0 cm (range,0.8-16.0 cm),15,70,68 in the AR group and 3.5 cm (range,1.0-17.0 cm),16,20,22 in the PSH group,with no statistically significant difference between the two groups (Z =-0.241,x2=0.039,0.124,P＞0.05).The confounding bias of maximum tumor diameter,vascular embolism and TNM staging were eliminated.(2) Intraoperative and postoperative situations:the operation time,volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with surgical margin ＜ 1 cm and ≥ 1 cm,cases with postoperative severe complications,duration of hospital stay,cases with postoperative tumor recurrence,cases with tumor recurrence within 2 years postoperatively,cases undergoing surgical treatment due to postoperative tumor recurrence,cases undergoing transcatheter arterial chemoemblization due to postoperative tumor recurrence after matching were 180 minutes (range,60-448 minutes),130 mL (range,30-6 000 mL),9,2,88,8,18 days (range,8-77 days),41,32,15,23 in the AR group,and 150 minutes (range,55-400 minutes),100 mL (range,50-3 000 mL),6,2,88,6,18 days (range,9-37 days),37,29,10,24 in the PSH group,respectively,showing no statistically significant difference between the two groups (Z =-1.987,-0.439,x2 =0.655,0.000,0.310,Z=-0.805,x2=0.362,0.223,0.816,0.624,P＞0.05).(3) Follow-up and survival situations:180 patients were followed up for 4-114 months,with a median time of 43 months.Forty of 180 patients died (21 in the AR group and 19 in the PSH group) and 78 had tumor recurrence (41 in the AR group and 37 in the PSH group).The 1-,3-,5-year overall survival rates and tumor-free survival rates were 92.0％,76.3％,71.8％ and 70.8％,53.0％,47.4％ in the AR group,92.3％,80.6％,62.0％ and 72.3％,56.4％,46.1％ in the PSH group,respectively,showing no statistically significant difference between the two groups (x2 =0.034,0.000,P＞0.05).Stratified analysis:of the AR group,the 1-,3-,5-year overall survival rates and median tumor-free survival rate were 95.3％,82.0％,82.0％ and 54.6％ in the patients with grade Ⅰ of preoperative albumin-bilirubin,100.0％,86.8％,86.8％ and 61.5％ in the patients with maximum tumor diameter ≤≤5 cm,91.3％,75.0％,69.7％ and 43.1％ in the patients with liver cirrhosis,89.9％,73.2％,66.6％ and 54.6％ in the patients with moderate-low differentiated tumor.Of the PSH group,the 1-,3-,5-year overall survival rates and median tumor-free survival rate were 90.9％,74.9％,63.0％ and 43.4％ in the patients with grade Ⅰ of preoperative albumin-bilirubin,98.2％,85.8％,61.7％ and 46.0％ in the patients with maximum tumor diameter ≤≤ 5 cm,98.0％,88.7％,70.0％ and 43.4％ in the patients with liver cirrhosis,90.7％,79.2％,59.0％ and 43.4％ in the patients with moderate-low differentiated tumor.There were no statistically significant difference in the 1-,3-,5-year overall survival rates between the two groups (x2 =1.892,1.320,0.732,0.002,P＞0.05) and a statistically significant difference in the tumor-free survival rate between the two groups (x2 =0.337,0.051,0.551,0.061,P ＞ 0.05).(4) Prognostic factors analysis.Results of univariate analysis showed that preoperative albumin-bilirubin grade,preoperative alpha fetoprotein (AFP),maximum tumor diameter,number of tumors,satellite lesion,vascular embolism,TNM staging,volume of intraoperative blood loss,postoperative severe complications were related factors affecting overall survival after radical resection for HCC (hazard ratio=1.762,1.001,1.139,1.955,2.561,2.495,2.766,1.000,2.599,95％ confidence interval:1.048-2.962,1.000-1.001,1.080-1.201,1.063-3.596,1.254-5.227,1.446-4.304,1.655-4.624,1.000-1.001,1.317-5.128,P＜0.05).Preoperative AST,positive HBsAg,preoperative AFP,maximum tumor diameter,vascular embolism,TNM staging,postoperative severe complications were related factors affecting tumor-free survival after radical resection for HCC (hazard ratio=1.004,1.594,1.000,1.065,2.203,2.132,1.775,95％ confidence interval:1.001-1.007,1.020-2.490,1.000-1.001,1.019-1.113,1.474-3.293,1.462-3.109,1.034-3.047,P＜0.05).Results of multivariate analysis showed that preoperative AFP,maximum tumor diameter,satellite lesion,postoperative severe complications were independent factors affecting overall survival after radical resection for HCC (hazard ratio =1.001,1.114,2.241,2.251,95％ confidence interval:1.000-1.001,1.033-1.202,1.003-5.008,1.100-4.607,P＜0.05).Positive HBsAg was an independent factor affecting tumor-free survival after radical resection for HCC (hazard =1.576,95％ confidence interval:0.987-2.516,P＜ 0.05).Conclusions There was no significant difference in long-term efficacy between AR and PSH in patients with BCLC stage A HCC.Preoperative AFP,maximum tumor diameter,number of tumors,satellite lesion,postoperative severe complications are independent factors affecting long-term survival of BCLC stage A patients after HCC radical resection.
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Completed surgical resection is the only treatment to patients with resectable hilar cholangiocarcinoma (HCCA).R0 resection is considered as a positive factor in long-term survive of patients.However,achieving negative surgical margins often ends in failure as the bile duct bifurcation is very close to the vascular inflow to the liver.Combined resection and reconstruction (CRR) of the portal vein (PV) and/or hepatic artery (HA),is introduced and has been performed widely.This paper focuses on this operation.
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Due to the special location and biological characteristics, the therapy of hilar cholangiocarcinoma is still challenging. Curative resection can offer a better chance for long-term survival than any other therapeutic modalities for hilar cholangiocarcinoma. To meet the demand of precise surgery, the knowledge of anatomy, biological characteristics and liver functional reserve is needed and the technical aspects of pre-surgical intervention, liver resection and reconstruction of vessels are also very important. This review highlights recent improvements in hilar cholangiocarcinoma management, with special attention to the new staging system for hilar cholangiocarcinoma, the perioperative management and the accurate dissection approach to achieve more adequate tumor-free resection margin. Overall, the precise surgical strategy and appropriate surgical techniques may provide an increased chance to cure patients with hilar cholangiocarcinoma.
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China.It has high malignancy,strong invasion and metastasis,and a poor prognosis.It seriously threatens the life and health of people.With the development of modem medical technology,the treatment of HCC has developed into a comprehensive treatment mode based on surgical resection.At present,surgery is still the best cure for liver cancer.The treatment plan should be formulated according to different individuals,such as surgical treatment,ablation,embolization,chemotherapy,molecular targeted therapy,immunotherapy treatment and sequential application of that comprehensive treatment,to improve the overall efficacy of HCC and prolong the survival period and improve the quality of life of patients.The present situation of comprehensive treatment of HCC was discussed in this paper.
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OBJECTIVE:To investigate the compatibility stability of Fat-soluble vitamin (Ⅱ)/Water-soluble vitamin for in-jection with common electrolytes. METHODS:Referring to clinical common dose,Fat-soluble vitamin (Ⅱ) for injection/Wa-ter-soluble vitamin for injection collective packing [containing Fat-soluble vitamin(Ⅱ) for injection 2 ampoules and Water-soluble for injection 1 ampoule] were respectively mixed with Glucose injection,Potassium chloride injection,Concentrated sodium chlo-ride injection,Sodium bicarbonate injection,Potassium aspartate injection,Potassium aspartate and magnesium aspartate injection, Sodium glycerophosphate injection,Multi-trace elements injection (Ⅱ) to obtain mixture A-H. At room temperature (25 ℃),these mixtures were investigated in terms of appearance,pH value,osmotic pressure molar concentration and the number of insolu-ble particles at 0,1,2,3,4 h. The contents of bacterial endotoxin were tested at 0,4 h. RESULTS:Within 4 h after mixing, there was no significant change in appearance of those mixtures;pH value of mixture H changed greatly (RSD=5.13%,n=5), and that of mixture D and G increased significantly. The osmotic pressure molar concentration of those mixtures had no significantly change(RSD<2%,n=5)and lower than 600 mOsmol/kg. The bacterial endotoxin tests of those mixtures were negative. Two and four hours after mixing,the number of insoluble particles ≥10 μm in mixture B was increased significantly;2,3,4 h after mix-ing,the number of insoluble particles ≥10 μm in mixture E,F,H were increased significantly;0 ,1,2,3,4 h after mixing,the number of insoluble particles ≥10 μm in mixture G was increased significantly. There was statistical significance in the number of insoluble particle ≥10 μm in above mixtures compared to mixture A at the same time point(P<0.05),but it was in line with the standard of 2015 pharmacopeia. One,two,three and four hours after mixing,the number of insoluble particle ≥10 μm in mixture D was increased significantly,there was statistical significance compared to mixture A at the same time point(P<0.05);the num-ber of insoluble particle ≥10 μm in mixture D was beyond prescribed scope of pharmacopeia at 2,3,4 h after mixing. Within 4 h after mixing,both the number of insoluble particle ≥10 μm in mixture C and the number of insoluble particle ≥25 μm in edch mixture had no significant change,in accordance with pharmacopeia standard. CONCLUSIONS:Fat-soluble vitamin (Ⅱ)/Wa-ter-soluble vitamin for injection is not suitable for mixing with Multi-trace elements injection(Ⅱ),Sodium glycerophosphate injec-tion or Sodium bicarbonate injection due to great change of pH value and the number of insoluble particles.
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Objective To investigate the clinical efficacy and prognostic factors of radical hepatectomy of hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 760 HCC patients who were admitted to the First Affiliated Hospital of Nanjing Medical University from August 2003 to June 2015 were collected.Surgical procedures were determined according to the location,number and size of tumors and anatomical relations among vessels.Observation indicators included:(1)intra-and post-operative situations:surgical procedures,operation time,volume of intraoperative blood loss,cases of intraoperative blood transfusion,postoperative complications,duration of postoperative hospital stay and pathological examination;(2) follow-up:1-,3-,5-year overall and tumor-free survival situations;(3) prognostic factors analysis of HCC patients.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to January 2016.Measurement data with normal distribution were represented as-x±s.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method.The univariate analysis and multivariate analysis were done using the COX regression model.Results (1) Intra-and post-operative situations:all the 760 patients underwent successful operations,including 419 undergoing anatomical hepatectomy and 341 undergoing non-anatomical hepatectomy.R0 and R1 resections were respectively applied to 742 and 18 patients.Two patients were combined with portal vein resection and reconstruction and 1 was combined with resection and reconstruction of inferior vena cava.Operation time,volume of intraoperative blood loss and cases of intraoperative blood transfusion were (226± 115) minutes,(714±706) mL and 88,respectively.Fifty-five patients had postoperative complications,including 20 with abdominal effusion or abscess,16 with pleural effusion,9 with recurrent fever,8 with incisional infection,7 with intra-abdominal hemorrhage,6 with liver failure,3 with pyloric or intestinal obstruction and 2 with renal failure (some patients with multiple complications).Of the 55 patients with postoperative complications,7 with hemorrhage underwent reoperation or interventional therapy and other patients underwent conventional symptomatic treatment.Of 55 patients,5 patients died and other 50 patients were improved.Duration of postoperative hospital stay was (14±6) days.There were 457 patients with minimum margin of tumors ≤ 1.0 cm and 303 with minimum margin of tumors ＞ 1.0 cm.(2) Followup:all the 760 patients were followed up for 1-139 months,with a median time of 25 months.The overall and tumor-free median survival times were 59 months and 31 months,respectively.The 1-,3-,5-year overall and tumor-free survival rates were 81.7％,63.4％,47.9％ and 68.7％,44.9％,29.6％,respectively.(3) Prognostic factors analysis of HCC patients:results of univariate analysis showed that clinical symptoms,alpha-fetoprotein (AFP),Barcelona clinic liver cancer staging,surgical procedures,intraoperative blood transfusion,minimum margin of tumors,number and diameter of tumors,tumor capsule,tumor differentiation,vascular cancer embolus,macrovascular invasion and tumor staging of American Joint Committee on Cancer (AJCC) were related factors affecting prognosis of HCC patients after radical hepatectomy [HR =1.39,1.50,1.92,0.65,1.45,1.68,1.96,1.66,2.26,1.50,2.68,3.37,2.00,95％ confidence interval (CI):1.08-1.79,1.16-1.94,1.68-2.20,0.50-0.84,1.04-2.02,1.28-2.20,1.54-2.49,1.42-1.94,1.69-3.02,1.22-1.85,1.99-3.60,2.61-4.36,1.77-2.27,P＜0.05].Results of multivariate analysis showed that AFP,number and diameter of tumors,tumor differentiation and tumor staging of AJCC were independent factors affecting prognosis of HCC patients after radical hepatectomy (HR=1.61,1.62,1.31,1.40,1.78,95％CI:1.14-2.26,1.22-2.14,1.06-1.63,1.10-1.79,1.27-2.51,P ＜ 0.05).Conclusions The anatomical and non-anatomical hepatectomies are safe and feasible for optional HCC patients,with a good long-term outcome.AFP,number and diameter of tumors,tumor differentiation and tumor staging of AJCC are independent factors affecting prognosis of HCC patients after radical hepatectomy.
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Hepatobiliary surgery is considered to be technically challenging because of complex intrahepatic and perihilar anatomical structures and variations.Nowadays, three-dimensional imaging technique plays an important role in the time of precise liver surgery.Three-dimensional images depict the spatial location of tumor, and the course, confluence pattern and variation of portal vein, hepatic artery, biliary system and hepatic vein distinctly while showing involved hepatic segments and the relationship with adjacent vessels from omnidirectional view, measuring the length of margin and future remnant liver.With the help of surgical simulation, surgeons can determine the significant vessels preoperatively.The application of three-dimensional imaging technique may improve the resectability and safety of complex hepatobiliary surgery, such as hilar cholangiocarcinoma, centrally located liver tumor, hepatolithiasis and living donor liver transplantation.Meanwhile, three-dimensional visualization facilitates the understanding of two-dimensional images and complicated surgical anatomy for surgeons.
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Although radical resection is the only method to cure cholangiocarcinoma, most patients are in the advanced stage at the time of diagnosis and miss the best time for surgery. The palliative treatment focusing on biliary drainage reconstruction can improve patients′ quality of life and prolong survival time. This article introduces the latest advances in palliative treatment for cholangiocarcinoma in recent years. Patients can benefit from the treatment methods such as biliary stenting and palliative surgery. Local and systemic adjuvant therapies are also indispensible, such as radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, but their therapeutic effects await further investigation. With the continuous development of basic research and medical techniques, the traditional therapeutic methods will be constantly improved. The new therapeutic methods targeting the pathogenesis of cholangiocarcinoma will also play an important role and bring benefits to the patients.
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Objective To study the anatomical variations adjacent to the umbilical portion of the left portal vein (U-point) radiologically and to determine their impact on treatment of hilar cholangiocarcinoma (HCCA).Methods From January 2014 to February 2016,47 consecutive patients who were diagnosed to suffer from Bismuth type Ⅰ,Ⅱ or Ⅲ a HCCA in our institution were retrospectively studied.All these patients underwent enhanced CT examination preoperatively and three-dimensional (3D) models were then reconstructed.Results Any variations of the left biliary system in relation to the U-point were analyzed.The findings showed that:B2 and B3 united above or lateral to the U-point in 31 patients (65.9％);B2 and B3 united medial to the U-point in 4 patients (8.5％);and B4 converged into B3 prior to B2 in 6 patients (12.8％).Rare variations were observed in 6 patients (12.8％).For the confluence patterns of B4:the central type was found in 10 patients (21.3％),the peripheral type in 35 patients (74.5％) and the combined type in 2 patients (4.2％).Analysis of the relationship between B1l and the confluence of B2 and B3 showed the distance to be (31.6 ± 6.2) mm in the above or the lateral patterns and (13.7 ± 4.7) mm in the medial pattern.The difference was significant (P ＜0.05).The distance from B1l to B4 was (7.1 ± 2.0) mm in the central and combined types but (16.4 ±4.0) mm in the peripheral type.The difference was significant (P ＜ 0.05).The left hepatic artery showed variations in the origin and course pattern in 4 (8.5％) and 6 patients (12.8％),respectively.The two-dimensional (2D) and 3D imagings showed excellent consistency in the evaluation of variations of the left biliary system in relation to the U-point and the left hepatic artery.Conclusions It is very important to know the variations of the left biliary and the vascular systems adjacent to the U-point in preoperative evaluating on resectability of HCCA.An accurate assessment could be accomplished using 2D imaging alone.However,3D reconstruction is a useful technique to use in complex case with locally advanced tumors.
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Objective To study the effect of granulocyte-macrophage colony-stimulating factor ( GM-CSF) secreting liver cancer vaccine on killing activity of cytotoxic T lymphocytes ( CTL) of transplanted liver cancer mice and its mechanism.Methods There were three groups:liver cancer vaccine group (A group), liver cancer group (B group) and PBS group (C group).The transplanted liver cancer model was builded with injection of H 22 hepatoma cells, while the GM-CSF secreting liver cancer vaccine group and PBS group was builded.GM-CSF secreting liver cancer vaccine group and PBS group were establised.The levels of CD8 +T cell in peripheral blood were detected by flow cytometry.The killing activity of cytotoxic T lymphocytes ( CTL) of spleen cells was detected by MTT method.The expression levels of tumor necrosis factor-α( TNF-α) and interferon-γ(γ-INF) were detected by Western blot.Results The flow cytometry results showed that, compared with B group, the levels of CD8 +T cell of A group significantly increased (P<0.01).MTT results showed that, compared with B group, the killing activity of cytotoxic T lymphocytes (CTL) in A group significantly increased (P<0.01).Western blot results showed that, compared with B group, the expression levels of tumor necrosis factor-α(TNF-α) and interferon-γ(γ-INF) in A group significantly decreased (P<0.01).Conclusion GM-CSF secreting liver cancer vaccine can significantly inhibit the activity of H22 cell, and its possible mechanism of action may be to activated CD8 +T expression, improve cytotoxic activity of CTL of spleen cells, and reduce TNF-αand γ-INF protein expression.
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Objective To investigate the clinical featurcs of hepatic perivascular epithelioid cell carcinoma (PEComa) and the experiments in the surgical treatment of PEComa.Methods The clinical data of 16 patients with hepatic PEComa who received surgical treatment at the First Affiliated Hospital of Nanjing Medical University from January 2008 to January 2012 were retrospectively analyzed.The incidence,clinical manifestations,imagiong characteristics,surgical outcomes and pathological manifestations of this disease were analyzed.B sonography,hepatic function test,tumor markers test and epigastric computed tomography (CT) were applied to detect tumor recurrence and metastasis.The follow-up was ended in December 2012.Result Middle aged and female patients took large part of the patients.Of the 16 patients,8 had no subjective symptoms,and other patients had discomfort in the right upper quadrant,pain or tenderness of the liver.All the tumors were solitary,and most of them located at the right liver (11 tumors were in the right liver,4 in the left liver,1 in the caudate lobe).No specific features were detected by preoperative B sonography,while inhomogeneous low density in the tumor region was detected on by CT.All the patients received partial liver resection without morbidity and morality.The results of immunohistochemistry showed that thc expressions of HMB-45,Melan-A and vascular smooth muscle actin were positive.The mean time of follow-up was 27.9 months (range,9.0-46.0 months),no tumor recurrence and death was observed during the follow-up.Conclusions Middle aged females are susceptive to hepatic PEComa,and patients have no specific clinical presentations.Preoperative CT examination is helpful for differential diagnosis of PEComa,and partical hepatectomy can achieve satisfactory short-term clinical outcomes.