The construction and application of registry and follow-up database in hepatobiliary tumor patients / 中华消化外科杂志

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.

Effect and mechanism of YAP in hepatic ischemia-reperfusion injury / 器官移植

Objective To explore the effect and mechanism of Yes-associated protein (YAP) in hepatic ischemia-reperfusion injury (IRI) of mice. Methods Forty male C57BL/6 mice were randomly divided into the sham operation group (Sham group), lysophosphatidic acid (LPA) + Sham group, IRI group and LPA+IRI group, 10 mice in each group. Liver tissue and serum samples were collected at 6 h after ischemia-reperfusion. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Histopathological changes and macrophage infiltration of liver tissues were detected by hematoxylin-eosin (HE) staining and immunohistochemical staining. The protein expression level of YAP was detected by Western blot. The messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-1 and IL-6 were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Western blot results demonstrated that the protein expression level of YAP in the LPA+IRI group was significantly up-regulated than that in the IRI group. Compared with the Sham group, the ALT and AST were significantly higher in the IRI group (both P < 0.05). The serum levels of ALT and AST in the LPA+IRI group were significantly lower than those in the IRI group (both P < 0.05). HE staining revealed that the morphology of hepatocytes was normal in the Sham group and LPA + Sham group. Pathological changes, such as liver congestion, liver cell swelling and structural abnormalities of hepatic lobule, occurred in the LPA+IRI group and IRI group. Compared with the IRI group, pathological changes were alleviated in the LPA+IRI group. RT-PCR indicated that the mRNA expression levels of TNF-α, iNOS, IL-1 and IL-6 in the LPA+IRI group were lower than those in the IRI group (all P < 0.05). Immunohistochemical demonstrated that LPA partially inhibited macrophage infiltration in ischemic tissues after IRI. Conclusions YAP can significantly mitigate hepatic IRI. The mechanism is associated with the regulation of macrophage recruitment and activation.

Construction and application value of CT-based radiomics model for predicting recurrence of early-stage hepatocellular carcinoma after resection / 中华消化外科杂志

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.

Clinical efficacy and prognostic factors analysis of radical hepatectomy of hepatocellular carcinoma in 760 patients / 中华消化外科杂志

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.

Impact of microwave dealing with the cutting surface on the hepatocellular carcinoma recurrence after hepatectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the impact of microwave dealing with cutting surface on perioperative liver function recovery and recurrence and metastasis after hepatectomy for HCC.</p><p><b>METHODS</b>Clinical data of 133 patients with HCC from March 2009 to November 2010 were retrospectively analyzed. They were divided into the conventional surgery group (66 cases) and microwave treatment group (67 cases). A domestic ECO-100 microwave knife was inserted into the liver cutting surface 0.5 cm from the cutting edge, and repeated multi-point burning with an average time of 25 minutes in the microwave treatment group. Then the perioperative liver function recovery and recurrence and metastasis in the two groups were compared.</p><p><b>RESULTS</b>The operation time of conventional surgery group was (158.0 ± 31.0) minutes, and that of microwave treatment group was significantly longer (181.0 ± 28.0) minutes (P=0.027). There were no significant differences in the liver function recovery between the two groups (P>0.05). There were 6 cases of recurrence and metastasis after 6 months and 9 cases after 12 months in the microwave treatment group, while there were 15 cases of recurrence and metastasis after 6 months and 20 cases after 12 months in the conventional surgery group, showing a significant difference (P=0.034 and 0.022, respectively).</p><p><b>CONCLUSIONS</b>Microwave dealing with the cutting surface has no significant effect on perioperative liver function recovery in hepatectomy. However, microwave treatment can reduce the in situ recurrence in HCC patients within the first year after surgery, indicating a good clinical application value.</p>

Application value of fast-track surgery on liver transplantation / 器官移植

Objective To explore the impact of fast-track surgery (FTS)on prognosis of liver transplant patients.Methods Inclusion criterias:(1 )primary disease was cirrhosis or primary liver cancer meeting Milan criteria;(2)surgical method was modified piggyback orthotopic liver transplantation (OLT);(3)no liver transplantation operation was performed before.Exclusion criterias:(1 )age ≤ 1 6 years old;(2)receiving OLT more than 1 time;(3)transcatheter hepatic arterial chemoembolization or radiofrequency ablation was performed before or during operation.From January 201 1 to December 201 3 in First Affiliated Hospital of Nanjing Medical University,52 patients meeting the criteria above were enrolled into this prospective random single-blinded study (all operations were performed by same team) .According to different peri-operative managements,they were divided into FTS group (n =21 )and non-FTS (NFTS)group (n =31 ).Protocol of FTS included comprehensive pre-operative education,no bowel preparation,no usage of nasogastric tube pre-operation and surgical drainage post-operation,prevention of hypothermic during operation, smaller incision,early exercise and enhanced oral nutrition. Intra-and post-operative parameters were compared between 2 groups.Step-by-step Logistic regression was used to evaluate relationship between FTS and clinical parameters,in order to analyze the impact of FTS on the prognosis of liver transplantation.Results Compared with NFTS group,operation time and anhepatic phase time decreased significantly in FTS group,as well as intra-operative bleeding and transfusion (all in P <0.05).Besides,intensive care unit (ICU)days and total length of stay in FTS group were shorter than those in NFTS group,which indicated a better prognosis of patients in FTS group (both in P <0.05 ).Logistic regression suggested that FTS management was a favorable factor of shortening ICU days (odds ratio:0.301 ,95% confidence interval:0.1 84-0.494,P =0.000)and total length of stay (odds ratio:0.1 48,95% confidence interval:0.085-0.257,P =0.000).Conclusions Application of FTS in perioperative period can improve the prognosis of liver transplant patients.

Risk factors of postoperatively prolonged mechanical ventilation after liver transplantation / 中华器官移植杂志

Objective To analyze the risk factors of postoperatively prolonged mechanical ventilation (PMV) after liver transplantation.Method The clinical data of 117 patients who received liver transplantation were retrospectively reviewed.According to the duration of postoperative mechanical ventilation (＜24 h or ≥24 h),the patients were divided into two groups.Commonly-used clinical and lab indexes before,during and after operations were analyzed by using single variance logistic regression analysis,and the screened indexes were analyzed by stepwise multiple variance logistic regression analysis.Result Forty-two patients (35.9％) were diagnosed with PMV after liver transplantation.The intensive care unit stay in the control group was (1.60 ± 1.17) days,shorter than in PMV proup (9.35 ± 10.61days).Sixty indexes were analyzed by univarite logistic regression,and 49 indexes showed statistically significant differences (P ＜ 0.2).Multiple variance logistic regression analysis revealed that the levels of preoperative blood glucose,model for end-stage liver disease score (MELD),the blood loss volume during the operation and the levels of glutamic oxalacetic transaminase within 24 h after the operation showed significant difference.Conclusion Preoperative hyperglycemia,high MELD score,excessive intraoperative blood loss volume and the high level of glutamic oxalacetic transaminase after the operation are independent risk factors of PMV.

Diagnosis and surgical treatment of hepatic perivascular epithelioid cell carcinoma / 中华消化外科杂志

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.

Status and challenges of liver transplantation in China / 中华消化外科杂志

In recent 20 years,liver transplantation has been rapidly developed in China,and the number of cases and patient outcomes have continued to improve.However,many problems emerged,such as mismatch of donor source and unbalanced distribution system,the research achievements lacking of innovation and core competitiveness,and clinical study level lags behind.In order to solve the problems mentioned above,the First Affiliated Hospital of Nanjing Medical University has carried out a series of work,such as expanding the donor pool,improving clinical technologies,and strengthening basic researches.

Postoperative low platelet counts correlate with delayed liver function recovery after partial hepatectomy in patients with hepatocellular carcinoma / 中华普通外科杂志

Objective To investigate the correlation of postoperative platelet counts with liver function recovery after partial hepatectomy in patients with hepatocellular carcinoma.Methods 212 patients with hepatocellular carcinoma were enrolled in this study.The relation between postoperative platelet counts and serum levels of ALT,AST,TB and PT after operation was analyzed.Results There were 78 patients with a low (＜ 100 × 109/L) immediate postoperative platelet count in this series of 212 patients who underwent partial liver resection for hepatocellular carcinoma,and 134 patients with a normal platelet count (≥ 100 × 109/L).Based on the criteria,27 patients were categorized as having delayed postoperative liver function recovery.There was no perioperative mortality in this study.Postoperative peak levels of ALT,AST and TB were significantly higher in patients with low postoperative platelet counts than those with normal platelet counts (P ＜ 0.05).Statistical analysis showed that low postoperative platelet counts after partial liver resection for hepatocellular carcinoma correlated with increased risk of delayed postoperative recovery (x2 =9.112,P =0.003).Conclusions Low postoperative platelet counts were associated with delayed liver function recovery after partial hepatectomy in patients with hepatocellular carcinoma.

Clinical outcomes of Ex Vivo liver resection and liver autotransplantation for hepatic alveolar echinococcosis / 华中科技大学学报（医学）（英德文版）

The effectiveness of liver autotransplantation for patients with partial hepatic alveolar echinococcosis was analyzed. We retrospectively studied 6 patients with hepatic alveolar echinococcosis who underwent liver autotransplantation in our hospital from 2008 to 2010. We also summarized the surgical indications of liver autotransplantation for hepatic alveolar echinococcosis and our experience in the management of postoperative complications of liver autotransplantation. Of 6 patients, 5 achieved good curative results, and one died of multiple organ failure caused by portal vein thrombosis. Main complications included postoperative bleeding, bile leak and small-for-size liver graft syndrome. Liver autotransplantation offers a new approach to cure hepatic alveolar echinococcosis with non-resectable lesions. It could be the most effective method to cure intractable hepatic alveolar echinococcosis if correct handling in operation and proper prevention of complications are performed. But the long-term outcomes are still needed to be confirmed in longer follow-up.

Expressions of CD90 and hTERT in hepatocellular carcinoma and Their Clinical Significance / 中华肝胆外科杂志

ObjectiveTo study the expressions of CD90 and hTERT in hepatocellular carcinoma (HCC),and their relationships to progression of tumor.MethodsThe expressions of CD90 and hTERT in hepatocellular carcinoma were detected by S-P immunohistochemical staining.Twenty patients with hemangiomas of liver were used as control.ResultsCompared with the control group,the positive rates of CD90 and hTERT in HCC were significantly higher (63.9％ and 47.2％ vs 0％ and 0％).The positive rates of CD90 and hTERT were significantly higher in patients with tumors at UICC Ⅲ-Ⅳ stage than at UICC stage Ⅰ -Ⅱ (79.1％ and 62.5％ vs 33.3％ and 16.6％).The CD90 expression correlated with hTERT positively.There were significant differences in survival between patients with CD90+ and CD90- or hTERT+ and hTERT-.The median postoperative survivals for patients with CD90+ and hTERT+,CD90- and hTERT- were 85 d and 76 d,505 d and 463 d,respectively.ConclusionsCD90 expression correlated positively with progression of HCC.It has the potential to serve as a prognostic marker for HCC.

Antibody-directed lentiviral vector-mediated hepatocarcinoma cells targeting IGF1R- siRNA/P53 genes therapy / 中华肝胆外科杂志

ObjectiveTo investigate the targeting infection of single chain antibody againstAFP (scFv anti-AFP) directed lentivirus and the inhibitory effects of a dual-growth inhibition systemon hepatocarcinoma cells.MethodsPlasmids WtP53-pPRIME-miR30-shRNA-IGF1R,pMD2G-Anti-AFP,and psPAX2 have previously been constructed to cotransfect to the packaging cell line 293Tusing Lipofectamine2000.The infection results were observed through fluorescence microscopy.PCRand Western blotting were used to demonstrate the successful transduction and transcription of theWtP53-pPRIME-miR30-shRNA-IGF1R gene.The effects of reconstructed lentivirus infected liver cellgrowth were assessed by the cell growth curve of CCK8 cells. Apoptosis was evaluated by theTUNEL assay.ResultsRecombined lentivirus was successfully constructed with the functional PFUtiters of recombined lentivirus at 4.58× 109PFU/ml.This positive result was confirmed by PCR andWestern blotting.ConclusionsThe targeted therapy mediated by anti-AFP scFv could significantlyinhibit the proliferation of HEP3B cells and promote the apoptosis.

Clinical outcomes of Ex Vivo liver resection and liver autotransplantation for hepatic alveolar echinococcosis / 华中科技大学学报（医学）（英德文版）

The effectiveness of liver autotransplantation for patients with partial hepatic alveolar echinococcosis was analyzed. We retrospectively studied 6 patients with hepatic alveolar echinococcosis who underwent liver autotransplantation in our hospital from 2008 to 2010. We also summarized the surgical indications of liver autotransplantation for hepatic alveolar echinococcosis and our experience in the management of postoperative complications of liver autotransplantation. Of 6 patients, 5 achieved good curative results, and one died of multiple organ failure caused by portal vein thrombosis. Main complications included postoperative bleeding, bile leak and small-for-size liver graft syndrome. Liver autotransplantation offers a new approach to cure hepatic alveolar echinococcosis with non-resectable lesions. It could be the most effective method to cure intractable hepatic alveolar echinococcosis if correct handling in operation and proper prevention of complications are performed. But the long-term outcomes are still needed to be confirmed in longer follow-up.

The pretreatment of triptolide could prevent the liver ischemia-reperfusion injury by inducing regulatory T cells in mice / 中华肝胆外科杂志

ObjectiveTo investigate the effect and related mechanism of triptolide pretreatment to prevent from ischemia/reperfusion (I/R) injury in mice liver. MethodsSixty male C57BL/6 mouse were randomized into four groups (15/group): A:sham group with saline , B: sham group with triptolide, C: saline I/R group, D: triptolide I/R group. The mice were pretreated with either saline or triptolide (0. 1 mg/kg/d) through intraperitoneal (ip) injection for one week. The mouse partial liver model of I/R injury was established, and samples were collected at 24 h after the I/R injury. ResultsSerum ALT and AST levels were significantly decreased and histological damage was significantly alleviated in the triptolide I/R group as compared with the saline I/R group (P＜0.05), the concentration of MDA in the triptolide groups was significantly decreased, while SOD activity was significantly increased compared with that of the saline I/R group (P＜0.05). The percentages of CD4+ CD25+ regulatory T cells (Tregs) cells among CD4+ T cells in groups A, B, C, and D were(7. 55 ± 1.87)%, (12. 59±3. 87)%,(7. 85±1.07)%, and(12. 02±3. 16)% in liver tissue, respectively. The expression levels of Foxp3 mRNA were significantly higher in the triptolide I/R group than those of saline I/R group (P＜0. 05). ELISA showed that triptolide could significantly inhibit the levels of IL-6, IL-Iβ and TNF-αand promoted the level of IL-10 in the serum (P＜0.05). Conclusion Pretreatment with triptolide could effectively prevent from liver I/R injury, which may be related to the induction of Treg cells by triptolide, the increase in the level of IL-10 in serum, and the inhibition of IL-6, IL-1β and TNF-α production in serum.

Protective mechanism of low dose of triptolide pretreatment against liver ischemia/reperfusion injury in mice / 中华器官移植杂志

Objective To investigate the protective effect of triptolide (TPT) pretreatment against liver ischemia/reperfusion (I/R) injury in mice and the possible mechanism. Methods Sixty male C57BL/6 mice were randomly divided into four groups (15/group): ( 1 ) TPT I/R group: The mouse partial liver model of I/R injury was established by the method of Koba-yashi. The portal triad (hepatic artery, portal vein, and bile duct) was occluded with a microvascular clamp for 90 min and 24 h reperfusion; (2) Sham group with TPT: Mice underwent surgical procedures including isolation of the portal triad without occlusion; (3) Saline I/R group: Surgery was performed as the same in the TPT I/R group, (4): Sham group with saline: Surgery was performed as the same in the TPT sham group, and the mice were pretreated with either saline or TPT (0. 1 mg · kg-1 day-1 ) by intraperitoneal injection for one week. The samples were collected at the 24th h after the I/R injury.The serum ALT and AST levels were determined, the histologic changes were observed by HE staining, the percentage of Th17 cells among mononuclear cells in liver tissue was analyzed by flow cytometry, the expression of IL-17 and ROR-γt mRNA was detected by real-time PCR, and the serum IL-6, IL-17 and TGF-β levels were measured by enzyme-linked immunosorbent assay (ELISA).Results Serum ALT and AST levels were significantly decreased and the histological damage was significantly alleviated in the TPT I/R group as compared with saline I/R group (P＜0. 05). The percentage of Th17 cells among mononuclear cells in TPT I/R group, TPT sham group, saline I/R group, TPT saline group was ( 1.77 ± 0. 53)％, (0. 41± 0. 18)％, (4. 26 ± 0. 82)％ and (0. 72 ± 0. 23) ％ in liver tissue, respectively. The expression levels of the IL-17 and ROR-γt mRNA in the liver tissue, and IL-6, IL-17 and TGF-β levels in the serum were significantly lower in TPT I/R group than in saline I/R group (P＜0. 05). Conclusion Pretreatment with low dose of TPT could effectively protect the liver from I/R injury in mice, which may be related to the inhibition of Th17 cells.

The study on the application of abdominal drainage after liver resection / 中华普通外科杂志

Objective To investigate the application of abdominal drainage after liver resection.Methods From Jan 2008 to June 2009,210 consecutively admitted patients undergoing liver resection by the same surgical team were chronologically allocated into drainage group(120)and non-drainage group (90).Patient's preoperative characteristics,operation-related factors,postoperative complications and hospital stay were compared between the two groups.Results Postoperative complications were comparable between the two groups,which was not significantly different among preoperative characteristics and operation-related factors(P>0.05).Mortality was 0.8% in drainage group and 1.1% in non-drainage group,again,the difference was not significant(X~2=0.042,P>0.05).Snrgical complications were significantly higher in drainage group than in non-drainage group,especially for abdominal infection and ascites occurrence(P<0.05).The hospital stay was significantly longer in the drainage group(13.1 ±5.2)days than the non-drainage group(11.4±5.6)days.Conclusions Postoperative abdominal drainage is not necessary for patients undergoing liver resection,furthermore,abdominal drainage increases postoperative complications.

Protective effect of edaravone against hepatic ischemia-reperfusion injry in small-for-size rat liver grafts / 中华器官移植杂志

Objective To investigate the protective effect of edaravone against ischemiareperfusion injury in small-for-size rat liver grafts and its possible mechanisms. Methods 40 % small-for-size rat liver transplantation model was established by using modified two-cuff technique, adult male SD rats were used as donors and recipients, and 16 recipient rats were randomly divided into two groups (8 cases in each group), saline control group (control group) and edaravone treatment group (ED group). In the ED group, 3 mg/kg edaravone was given intravenously via penile vein 30 min before transplantation in the recipients. The same amount of saline was given in the control group at the same time points. Serum hepatic function (AST and ALT) and histopathological changes were analyzed; the contents of MDA and SOD, and hepatic myeloperoxidase (MPO) activity in liver grafts after 6 h were determined; and TNF-α levels at 6th h after reperfusion were measured by using enzyme-linked immunosorbent assay (ELISA method). Results As compared with control group,serum AST and ALT levels were significantly reduced at the 6th h after reperfusion in ED group (AST: 825. 50 5±72. 87 vs 1188. 03 ± 124. 04; ALT. 687. 40 5±72. 21 vs 988. 66 ± 91.07, P<0. 01 ).The content of MDA was lower and SOD level was higher in ED group significantly than in control group (P<0. 01). As compared with control group, hepatic TNF-α levels and MPO activity at the 6th h after reperfusion were significantly decreased in ED group (P<0. 01 ). Histopathological analysis revealed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focal necrosis, significant edema, congestion and inflammatory cell infiltration in periportal area at the 6th h after reperfusion in control group, but minimal liver damage was observed in ED group. Conclusion Edaravone could ameliorate early ischemia-reperfusion injury in small-for-size liver grafts significantly.The protective mechanisms were mediated in part by increasing antioxidant ability, inhibiting lipid peroxidation, and down-regulating inflammatory reaction.

Initial study of CD133 as one of the surface markers in liver cancer stem cells / 中华消化外科杂志

Objective To detect the expression of CD133 in hepatic cell lines SMMC7721 and bcl-7402, and to investigate the possibility of CD133 as the surface marker of liver cancer stem cells. Methods The cell cycle and expression of CD133 in hepatic cell lines SMMC7721 and bcl-7402 were detected by flow eytometry. Magnetic cell sorting was used to isolate CD133-positive and CD133-negative cells. The differences in morphology, proliferation and differentiation between CD133-positive and CD133-negative cells were observed and analyzed by one-way ANOVA and u test. Results The percentages of CD133-positive cells in SMMC7721 and bcl-7402 cell lines were 0.7% -1.0% and 1.7% -8.9%, respectively. The percentages of CD133-positive cells in G0>/G1> phase in the 2 cell lines were 85.3% and 89.4%, which were significantly higher than CD133-negative cells and unsorted cells (F = 14.49, 38.84, P <0.05). The in vitro proliferation capability of CD133-positive cells was greater than that of CD133-negative cells and unsorted cells, especially during day 1-3 and day 5-7 (F =49.32,784.04, 89.91, 152.83, P < 0. 05). During the cultivation, the proportion of the CD133-positive cells decreased as time passed by, and the proportion of CD133-positive cells was nearly the same as unsorted cells on day 15 (u =O. 271, P <0.05). Conclusions CD133-positive ceils have strong capability of proliferation and differentiation in SMMC7721 and bcl-7402 cell lines in vitro. CD133 is one of the surface markers of liver cancer stem cells.