Comprehensive treatment strategy for hepatocellular carcinoma based on surgical treatment in the era of targeted therapy and immunotherapy / 中华消化外科杂志

Hepatocellular carcinoma is still a severe threat to people′s health of China. Most patients have advanced disease at the time of first diagnosis and lose the opportunity of radical surgery. In the past, the traditional medical drug treatment and radiotherapy are ineffective, which make the treatment of hepatocellular carcinoma into a bottleneck. With the emergence of target therapy represented as tyrosine kinase inhibitors and immunotherapy represented by programmed death-1 antibody and programmed death-ligand 1 antibody, the treatment of hepatocellular carcinoma has entered a new era and patients with advanced hepatocellular carcinoma have seen a new hope. The systemic therapy represented by target therapy and immunotherapy has not only greatly improved the survival of patients with advanced hepatocellular carcinoma, but also changed the treatment concept of hepatocellular carcinoma from single-drug therapy to combined therapy with multiple means. The treatment of hepatocellular carcinoma has changed from the era of surgery as the king to the era of surgery as the mainstay of whole-process management and comprehensive treatment. The authors review previous studies and their own experience to elaborate on the comprehensive treat-ment strategy for hepatocellular carcinoma based on surgical treatment in the era of targeted therapy and immunotherapy.

Application value of machine learning algorithms and COX nomogram in the survival prediction of hepatocellular carcinoma after resection / 中华消化外科杂志

Objective:To investigate the application value of machine learning algorithms and COX nomogram in the survival prediction of hepatocellular carcinoma (HCC) after resection.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 375 patients with HCC who underwent radical resection in the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from January 2012 to January 2017 were collected. There were 304 males and 71 females, aged from 21 to 79 years, with a median age of 57 years. According to the random numbers showed in the computer, 375 patients were divided into training dataset consisting of 300 patients and validation dataset consisting of 75 patients, with a ratio of 8∶2. Machine learning algorithms including logistic regression (LR), supporting vector machine (SVM), decision tree (DT), random forest (RF), and artificial neural network (ANN) were used to construct survival prediction models for HCC after resection, so as to identify the optimal machine learning algorithm prediction model. A COX nomogram prediction model for predicting postoperative survival in patients with HCC was also constructed. Comparison of performance for predicting postoperative survival of HCC patients was conducted between the optimal machine learning algorithm prediction model and the COX nomogram prediction model. Observation indicators: (1) analysis of clinicopathological data of patients in the training dataset and validation dataset; (2) follow-up and survival of patients in the training dataset and validation dataset; (3) construction and evaluation of machine learning algorithm prediction models; (4) construction and evaluation of COX nomogram prediction model; (5) evaluation of prediction performance between RF machine learning algorithm prediction model and COX nomogram prediction model. Follow-up was performed using outpatient examination or telephone interview to detect survival of patients up to December 2019 or death. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the paired t test. Measurement data with skewed distribution were expressed as M ( P25, P75) or M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were represented as absolute numbers. Comparison between groups was performed using the chi-square test when Tmin ≥5 and N ≥40, using the calibration chi-square test when 1≤ Tmin ≤5 and N ≥40, and using Fisher exact probability when Tmin <1 or N <40. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The COX proportional hazard model was used for univariate analysis, and variables with P<0.2 were included for the Lasso regression analysis. According to the lambda value, variables affecting prognosis were screened for COX proportional hazard model to perform multivariate analysis. Results:(1) Analysis of clinicopathological data of patients in the training dataset and validation dataset: cases without microvascular invasion or with microvascular invasion, cases without liver cirrhosis or with liver cirrhosis of the training dataset were 292, 8, 105, 195, respectively, versus 69, 6, 37, 38 of the validation dataset, showing significant differences between the two groups ( χ2=4.749, 5.239, P<0.05). (2) Follow-up and survival of patients in the training dataset and validation dataset: all the 375 patients received follow-up. The 300 patients in the training dataset were followed up for 1.1-85.5 months, with a median follow-up time of 50.3 months. Seventy-five patients in the validation dataset were followed up for 1.0-85.7 months, with a median follow-up time of 46.7 months. The postoperative 1-, 3-year overall survival rates of the 375 patients were 91.7%, 79.5%. The postoperative 1-, 3-year overall survival rates of the training dataset were 92.0%, 79.7%, versus 90.7%, 81.9% of the validation dataset, showing no significant difference in postoperative survival between the two groups ( χ2=0.113, P>0.05). (3) Construction and evaluation of machine learning algorithm prediction models. ① Selection of the optimal machine learning algorithm prediction model: according to information divergence of variables for prediction of 3 years postoperative survival of HCC, five machine learning algorithms were used to comprehensively rank the variables of clinicopathological factors of HCC, including LR, SVM, DT, RF, and ANN. The main predictive factors were screened out, as hepatitis B e antigen (HBeAg), surgical procedure, maximum tumor diameter, perioperative blood transfusion, liver capsule invasion, and liver segment Ⅳ invasion. The rank sequence 3, 6, 9, 12, 15, 18, 21, 24, 27, 29 variables of predictive factors were introduced into 5 machine learning algorithms in turn. The results showed that the area under curve (AUC) of the receiver operating charateristic curve of LR, SVM, DT, and RF machine learning algorithm prediction models tended to be stable when 9 variables are introduced. When more than 12 variables were introduced, the AUC of ANN machine learning algorithm prediction model fluctuated significantly, the stability of AUC of LR and SVM machine learning algorithm prediction models continued to improve, and the AUC of RF machine learning algorithm prediction model was nearly 0.990, suggesting RF machine learning algorithm prediction model as the optimal machine learning algorithm prediction model. ② Optimization and evaluation of RF machine learning algorithm prediction model: 29 variables of predictive factors were sequentially introduced into the RF machine learning algorithm to construct the optimal RF machine learning algorithm prediction model in the training dataset. The results showed that when 10 variables were introduced, results of grid search method showed 4 as the optimal number of nodes in DT, and 1 000 as the optimal number of DT. When the number of introduced variables were not less than 10, the AUC of RF machine learning algorithm prediction model was about 0.990. When 10 variables were introduced, the RF machine learning algorithm prediction model had an AUC of 0.992 for postoperative overall survival of 3 years, a sensitivity of 0.629, a specificity of 0.996 in the training dataset, an AUC of 0.723 for postoperative overall survival of 3 years, a sensitivity of 0.177, a specificity of 0.948 in the validation dataset. (4) Construction and evaluation of COX nomogram prediction model. ① Analysis of postoperative survival factors of HCC patients in the training dataset. Results of univariate analysis showed that HBeAg, alpha fetoprotein (AFP), preoperative blood transfusion, maximum tumor diameter, liver capsule invasion, and degree of tumor differentiation were related factors for postoperative survival of HCC patients [ hazard ratio ( HR)=1.958, 1.878, 2.170, 1.188, 2.052, 0.222, 95% confidence interval ( CI): 1.185-3.235, 1.147-3.076, 1.389-3.393, 1.092-1.291, 1.240-3.395, 0.070-0.703, P<0.05]. Clinico-pathological data with P<0.2 were included for Lasso regression analysis, and the results showed that age, HBeAg, AFP, surgical procedure, perioperative blood transfusion, maximum tumor diameter, tumor located at liver segment Ⅴ or Ⅷ, liver capsule invasion, and degree of tumor differentiation as high differentiation, moderate-high differentiation, moderate differentiation, moderate-low differentiation were related factors for postoperative survival of HCC patients. The above factors were included for further multivariate COX analysis, and the results showed that HBeAg, surgical procedure, maximum tumor diameter were independent factors affecting postoperative survival of HCC patients ( HR=1.770, 8.799, 1.142, 95% CI: 1.049- 2.987, 1.203-64.342, 1.051-1.242, P<0.05). ② Construction and evaluation of COX nomogram prediction model: the clinicopathological factors of P≤0.1 in the COX multivariate analysis were induced to Rstudio software and rms software package to construct COX nomogram prediction model in the training dataset. The COX nomogram prediction model for predicting postoperative overall survival had an consistency index of 0.723 (se=0.028), an AUC of 0.760 for postoperative overall survival of 3 years in the training dataset, an AUC of 0.795 for postoperative overall survival of 3 years in the validation dataset. The verification of the calibration plot in the training dataset showed that the COX nomogram prediction model had a good prediction performance for postoperative survival. COX nomogram score=0.627 06×HBeAg (normal=0, abnormal=1)+ 0.134 34×maximum tumor diameter (cm)+ 2.107 58×surgical procedure (laparoscopy=0, laparotomy=1)+ 0.545 58×perioperative blood transfusion (without blood transfusion=0, with blood transfusion=1)-1.421 33×high differentiation (non-high differentiation=0, high differentiation=1). The COX nomogram risk scores of all patients were calculated. Xtile software was used to find the optimal threshold of COX nomogram risk scores. Patients with risk scores ≥2.9 were assigned into high risk group, and patients with risk scores <2.9 were assigned into low risk group. Results of Kaplan-Meier overall survival curve showed a significant difference in the postoperative overall survival between low risk group and high risk group of the training dataset ( χ2=33.065, P<0.05). There was a significant difference in the postoperative overall survival between low risk group and high risk group of the validation dataset ( χ2=6.585, P<0.05). Results of further analysis by the decision-making curve showed that COX nomogram prediction model based on the combination of HBeAg, surgical procedure, perioperative blood transfusion, maximum tumor diameter, and degree of tumor differentiation was superior to any of the above individual factors in prediction performance. (5) Evaluation of prediction performance between RF machine learning algorithm prediction model and COX nomogram prediction model: prediction difference between two models was investigated by analyzing maximun tumor diameter (the important variable shared in both models), and by comparing the predictive error curve of both models. The results showed that the postoperative 3-year survival rates predicted by RF machine learning algorithm prediction model and COX nomogram prediction model were 77.17% and 74.77% respectively for tumor with maximum diameter of 2.2 cm ( χ2=0.182, P>0.05), 57.51% and 61.65% for tumor with maximum diameter of 6.3 cm ( χ2=0.394, P>0.05), 51.03% and 27.52% for tumor with maximum diameter of 14.2 cm ( χ2=12.762, P<0.05). With the increase of the maximum tumor diameter, the difference in survival rates predicted between the two models turned larger. In the validation dataset, the AUC for postoperative overall survival of 3 years of RF machine learning algorithm prediction model and COX nomogram prediction model was 0.723 and 0.795, showing a significant difference between the two models ( t=3.353, P<0.05). Resluts of Bootstrap cross-validation for prediction error showed that the integrated Brier scores of RF machine learning algorithm prediction model and COX nomogram prediction model for predicting 3-year survival were 0.139 and 0.134, respectively. The prediction error of COX nomogram prediction model was lower than that of RF machine learning algorithm prediction model. Conclusion:Compared with machine learning algorithm prediction models, the COX nomogram prediction model performs better in predicting 3 years postoperative survival of HCC, with fewer variables, which is easy for clinical use.

Influencing factors for the early recurrence of synchronous colorectal cancer liver metastases / 中华肝胆外科杂志

Objective:To investigate the definition and influencing factors of early recurrence after resection for synchronous colorectal cancer liver metastases (sCRLM).Methods:Patients with sCRLM in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from December 2008 to December 2016 were included. Restricted cubic spline was used to determine the correlations between the time of recurrence and the long-term prognosis. The univariable and multivariable Cox was performed to measure the feasibility of recurrence within 6 months as the early recurrence. Then apply logistic regression, support vector machine, decision tree, random forest, artificial neural network and XGBoost, these machine learning algorithm to comprehensively rank the importance of every clinicopathological variable to early recurrence, and according to the comprehensively ranks, we introduced variables into the multivariable logistic regression model and observed the receiver operating characteristic curve (ROC) of the logistic regression model, based on the ROC area under curve, Akaike information criterion, and Bayesian information criterion, we identified the best performed variable combination and introduced them into the multivariate logistic regression analysis to confirm the independent risk factors for early recurrence. Subsequently, inverse probability weighting (IPTW) was performed on the therapy-associated independent risk factor to evaluate and validate its influence on the early recurrence of sCRLM patients after reducing the standardized mean difference of all covariates.Results:A total of 228 sCRLM patients who received resection were enrolled and followed up from 2.10 to 108.57 months. There were 142 males and 86 females, aged (55.89±0.67) years old. In 170 (74.6%) patients with recurrence, restricted cube analysis determined that the hazard ratio (HR) of disease free survival (DFS) and overall survival (OS) satisfies a linear relationship ( P<0.05), and Cox analysis indicated that 6 months as the time cutoff for defining early recurrence was feasible ( HR=3.405, 95% CI: 2.098-5.526, P<0.05). Early recurrence was occurred in 93 (40.79%) patients. The survival rate of patients in early recurrence group was significantly lower than that in the late recurrence group ( HR=3.405, 95% CI: 2.098-5.526, P<0.05, and the 5-year survival rate was 14.0% vs 52.0%). Comprehensive analysis of 6 machine learning algorithms identified that the total number of lymph node dissection >22 ( OR=0.258, 95% CI: 0.132-0.506, P<0.05) is an independent protective factor for early recurrence, while the number of liver metastases>3 ( OR=4.715, 95% CI: 2.467-9.011, P<0.05) and postoperative complications ( OR=2.334, 95% CI: 1.269-4.291, P<0.05) are independent risk factors. Finally, the IPTW analysis fully reduced the influence of covariate confounding influence via causal inference to prove lymph node dissection associated with early recurrence (IPTW OR=0.29, P<0.05), benefiting the DFS (IPTW HR=0.4887, P<0.05), but without influence on OS (IPTW HR=0.6951, P>0.05). Conclusion:Six months after sCRLM as the definition of early recurrence, it has significant feasibility. The long-term survival of patients with early recurrence is poor. The independent influencing factors of early recurrence after sCRLM are the total number of lymph node dissection, the number of liver metastases and postoperative complications disease.

Current status of surgical treatment of colorectal cancer liver metastases / 中华肝胆外科杂志

Surgical resection is the gold standard for the better survival of patients with colorectal cancer liver metastases (CRLM). With the progress of systematic therapy, the concept of surgical treatment for CRLM is continually being updated. This article discussed the current status of surgical treatment of CRLM based on the authors’ clinical experience.

Trend analysis of age of diagnosis for liver cancer in cancer registry areas of China, 2000-2014 / 中华预防医学杂志

Objective@#To investigate trends of mean age of diagnosis for liver cancer during 2000 to 2014, which may provide basic information for making feasible cancer prevention strategies.@*Methods@#Based on the continuous cancer incidence data from 22 cancer registries of China between 1 January 2000 and 31 December 2014, the incidence by birth-cohort (year of birth between 1925 and 1994) and age specific incidence rates were calculated. The incidence of different age groups were also calculated. World Segi's population was used for age standardization. The liner regression model was applied to analyze the changing trend of mean age of diagnosis.@*Results@#In 2014, the incidence rate for population with 80 years older and above was 108.21 per 100 000, whereas the rate for population at 30-39 years old was 5.09 per 100 000. But the mean age of diagnosis for liver cancer showed an increasing trend from 2000 to 2014. For male, it had increased from 58.80 to 62.35 (t=18.70, P<0.001) . For female, it had increased from 64.02 to 68.99 (t=20.50, P<0.001) . After age standardization, the mean age of diagnosis still showed increasing trend. Meanwhile, the proportion of liver cancer in people above 70 years old was 25.05% in 2014, which was higher than that in 2000 (22.49%).@*Conclusion@#The mean age of liver cancer incidence was increasing during 2000-2014.

Correlation between postoperative neutrophil to lymphocyte ratio and recurrence and prognosis of hepatocellular carcinoma after radical liver resection / 中华肿瘤杂志

Objective@#To investigate the correlation between postoperative peripheral blood neutrophil to lymphocyte ratio (NLR) and recurrence and prognosis of patients with hepatocellular carcinoma (HCC).@*Methods@#The clinicopathological and follow-up data of 344 patients with HCC who underwent radical liver resection from May 2010 to April 2014 were analyzed retrospectively.@*Results@#Of the 344 patients, 104 had early recurrence and 84 had late recurrence. Receiver operating characteristic (ROC) curve analysis showed that the NLR predicted area under the curve (AUC) of early recurrence was 0.622 (P<0.001), the optimal cut-off value was 2.41. The AUC of late recurrence was 0.634 (P=0.001), the optimal cut-off value was 2.15. Cox multivariate analysis showed the serum concentration of hepatitis B surface antigen (HR=2.508, 95% CI: 1.311-4.798), microvascular invasion (HR=2.422, 95% CI: 1.239-4.734), Milan criteria (HR=2.373, 95% CI: 1.427-3.948) and postoperative NLR (HR=2.285, 95% CI: 1.379-3.788) were independent risk factors of early recurrence after HCC resection. Postoperative NLR (HR=2.927, 95% CI: 1.630-5.255), liver cirrhosis (HR=2.531, 95% CI: 1.291-4.962) and serum concentration of albumin (HR=2.257, 95% CI: 1.251-4.073) were independent risk factors of late recurrence after HCC resection. The median recurrence-free survival (RFS) of the 344 patients was 45.0 months, and the median overall survival (OS) was 63.2 months. ROC curve analysis showed that the postoperative NLR predicted 5-year survival AUC was 0.689 (P<0.05), with an optimal cutoff of 2.29. Cox multivariate analysis showed microvascular invasion (HR=2.247, 95% CI: 1.534-3.291), postoperative NLR (HR=2.217, 95% CI: 1.653-2.974), and liver cirrhosis (HR=1.685, 95% CI: 1.168-2.431), Milan criteria (HR=1.679, 95% CI: 1.238-2.277), serum concentration of hepatitis B surface antigen (HR=1.623, 95% CI: 1.102-2.392), serum concentration of albumin (HR=1.43, 95% CI: 1.066-1.918) were independent factors of RFS after HCC resection, while microvascular invasion (HR=3.862, 95% CI: 2.407-6.197), Barcelona staging (HR=2.864, 95% CI: 1.600-5.125), postoperative NLR (HR=2.688, 95% CI: 1.782-4.055), liver cirrhosis (HR=2.039, 95% CI: 1.184-3.514), serum concentration of albumin (HR=1.81, 95% CI: 1.204-2.720) were independent factors of OS.@*Conclusions@#For HCC patients who receive radical liver resection, postoperative NLR ≥2.29 implicates poor prognosis. Moreover, postoperative NLR ≥2.41 suggests early recurrence, while NLR ≥2.15 suggests late recurrence.

Clinical features of and treatment strategies for primary retroperitoneal neurofibromas: clinical analysis of 7 cases / 中华普通外科杂志

Objective To investigate the clinical features,diagnosis and treatment strategies for primary retroperitoneal neurofibromas.Methods The clinical data of 7 patients with primary retroperitoneal neurofibromas admitted to Cancer Institute & Hospital,Chinese Academy of Medical Sciences,from Jan 2000 to Jul 2017,were retrospectively analyzed.Results The average age was (42 ± 11) years and six were female.6 cases were with solitary tumor and 1 case was with multiple tumors.Clinical symptoms and imaging were of no help in determining tumor type.All patients underwent surgical resection.Postoperative pathology confirmed retroperitoneal neurofibroma in all seven patients,including 1 case with neurofibromatosis type Ⅰ and retroperitoneal malignant peripheral nerve sheath tumor.On immunohistochemistry all of the tumors were S-100 protein positive.At the end of the follow-up period ranging from 14 months to 166 months,sevent patients were alive and two patients experienced tumor recurrence.The longest disease-free survival time was 166 months.Conclusion Primary retroperitoneal neurofibromas are a rare type of primary retroperitoneal tumors that require diagnosis at pathology.Clinical symptoms and imaging of primary retroperitoneal neurofibromas patients were found to be ineffective at determining tumor type.Patients had a good prognosis after tumor resection.

A new prognostic score system of hepatocellular carcinoma following hepatectomy / 中华肿瘤杂志

Objective@#To establish a new scoring system based on the clinicopathological features of hepatocellular carcinoma (HCC) to predict prognosis of patients who received hepatectomy.@*Methods@#A total of 845 HCC patients who underwent hepatectomy from 1999 to 2010 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. 21 common clinical factors were selected in this analysis. Among these factors, the cut-off values of alpha-fetoprotein (AFP), alkaline phosphatase (ALP) and intraoperative blood loss were evaluated by using a receiver operating characteristic (ROC) curve analysis.The Kaplan-Meier method and Cox regression model were used to evaluate the independent risk factors associated with the prognosis of HCC patients after hepatectomy. HCC postoperatively prognostic scoring system was established according to the minimum weighted method of these independent risk factors, and divided the patients into 3 risk groups, including low-risk, intermediate-risk and high-risk group. The relapse-free survival (RFS) and overall survival (OS) were compared among these groups.@*Results@#The univariate analysis showed that clinical symptoms, preoperative α-fetoprotein (AFP) level, serum alkaline phosphatase (ALP) level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with median RFS of these HCC patients (P<0.05). Alternatively, clinical symptoms, preoperative AFP level, serum ALP level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological lymphocyte invasion, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with the median OS of these HCC patients (P<0.05). The multivariate analysis showed that AFP ≥20 ng/ml, clinical symptoms, tumor diameter ≥5 cm, multiple tumors, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, moderate and severe liver cirrhosis, non- anatomic resection were the independent risk factors of RFS and OS (P<0.05). The independent risk factor of RFS was intraoperative bleeding loss ≥325 ml (P<0.05); The independent risk factors of OS were abdominal lymph node metastasis and pathological tumors thrombus (P<0.05). The respective weight of 11 independent factors was used to establish the scoring system (scores range from 0 to 26). In the score system, 0 to 5 points were defined as the low-risk group (286 cases), 6 to 12 points were determined as the intermediate-risk group (503 cases), more than 13 points were classified as the high-risk group (56 cases). The median RFS of the low-risk, intermediate-risk and high-risk group were 80, 27 and 6 months, respectively. The differences were statistically significant (P<0.001). The median OS of the three groups were 134, 51 and 15 months, respectively, and the differences were statistically significant (P<0.001).@*Conclusion@#This new score system provides effective prediction of postoperative prognosis for HCC patients.

Prognostic analysis of colorectal liver metastases treated by surgery combined with intraoperative radiofrequency ablation / 中华外科杂志

Objective@#To investigate the clinical value of intraoperative radiofrequency ablation (RFA) in the treatment of colorectal liver metastasis (CLM).@*Methods@#A retrospectively analysis of 187 patients with CLM who underwent liver resection with or without RFA from January 2009 to August 2016 in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences was performed. According to whether RFA was used intraoperatively, patients were divided into resection only group and combined treatment group. The clinical and pathological characteristics of the two groups were compared to explore factors influencing survival and recurrence. Imbalance of background characteristics between the two groups was further overcome by propensity score matching method (PSM).@*Results@#The number of liver metastases (267), simultaneous liver metastases (100%), bilobar involvement (73.3%) and preoperative chemotherapy (93.3%) rates were significantly higher in the combined treatment group than those in the resection only group(471, 74.7%, 42.0% and 63.1%)(all P<0.05). In the combined treatment group, median overall survival (OS) was 25.7 months; and 3-year and 5-year OS were 47.9% and 28.8%, respectively. In the resection only group, the median survival time was 46.9 months; and 3-year and 5-year OS rate was 59.1% and 42.4%, respectively (χ2=4.579, P=0.034). Median disease-free survival (DFS) was 5.4 months in the combined treatment group, and 10.1 months in the resection only group (χ2=5.399, P=0.023). In multivariate analysis, intraoperative RFA was not an independent prognostic factor for OS and DFS (HR=0.98, 95%CI: 0.47-2.08, P=0.965; HR=1.21, 95%CI: 0.71-2.07, P=0.465). After PSM, the median OS of the resection only and the combined treatment groups were 30.2 and 25.7 months (χ2=0.876, P=0.350). The median DFS in the two groups was 5.3 and 4.2 months, respectively (χ2=0.199, P=0.650).@*Conclusion@#In patients with similar tumor burden, liver resection combined with intraoperative RFA for unresectable CLM can achieve long-term outcomes similar to hepatectomy alone for resectable CLM.

Basic characteristics and survival analysis of patients with hepatocellular carcinoma / 中华肿瘤杂志

Objective@#To analyze the basic characteristics of patients with hepatocellular carcinoma (HCC), and further explore the major factors affecting the prognosis of HCC patients.@*Methods@#A total of 800 HCC patients were randomly selected from the Cancer Hospital, Chinese Academy of Medical Sciences. Their clinical and follow-up information was obtained from medical record. Univariate analysis of variance, Kaplan-Meier method and Cox regression analysis were used to analyze the patients′ age at diagnosis and survival time, etc.@*Results@#The average age of diagnosis was 55.04 years among all the 800 HCC patients, and the sex ratio of male to female was 4.48. The infection rates of HBV and HCV were 78.6% (629/800) and 5.8% (46/800), respectively. The smoking rate was 41.0% (328/800) and the alcohol consumption rate was 38.5% (328/800). 259 (32.4%) patients underwent radical treatments with liver resection as major therapy, and 541 (67.6%) patients adopted non-radical treatments with transcatheter arterial chemoembolization (TACE) as major therapy. The 1-, 3- and 5-year survival rates of the HCC patients were 73.2%, 53.7% and 42.4%, respectively. The risk factors for prognosis included alcohol abuse and treatment methods. The HR of alcohol abuse was 1.326 (95%CI: 1.058 to 1.661) and HR of treatment methods was 3.301 (95% CI: 2.483 to 4.387).@*Conclusions@#Men account for the majority of HCC patients, and most patients have a lower age at diagnosis and adopt non-radical treatments. The exposure rates of HBV infection and alcohol abuse of HCC patients are significantly higher than those of general population. The major risk factors affecting prognosis and survival are treatments and alcohol abuse. Alcohol abuse and HBV may have synergistic effects on the survival of HCC patients.

Imaging features of hepatic epithelioid hemangioendothelioma / 中华消化外科杂志

Objective To analyze and summarize the imaging features of hepatic epithelioid hemangioendothelioma (EHE).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 9 patients with EHE who were admitted to the Cancer Hospital of Chinese Academy of Medical Sciences between June 2012 and June 2016 were collected.Patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations.Number,size,location,shape,density or signal and enhancement method of lesions,with or without lesions fusion and relationship between lesions and vessels were analyzed by 2 imaging doctors.Lesions in left lobe of liver,right lobe of liver and caudate lobe of liver were respectively counted.Real number was a standard as less than 5 lesions and more than or equal to 5 lesions was represented as ≥ 5.Observation indicators:(1) overall imaging features of EHE;(2) MRI findings of EHE;(3) CT findings of EHE;(4) treatment and pathological features of EHE and results of follow-up.Patients received the corresponding treatment after imaging examinations.Follow-up using outpatient imaging examinations was performed to detect tumor recurrence and stable condition of patients up to December 2016.Results (1) Overall imaging features of EHE:of 9 patients with EHE,6 received plain and enhanced scans of MRI,3 received plain and enhanced scans of CT (1 combined with MRI),1 received enhanced scan of CT.Lesions in right lobe of liver were more than that in left lobe of liver,and there were fewest lesions in caudate lobe of liver.Lesions were round or similar-round shape,with a maximum diameter of 2.5-6.1 cm and an average diameter of 3.6 cm.Four patients had total 2-5 lesions and less than 5 lesions in each lobe of liver,without lesions fusion,including 1 with halo sign and capsule retraction sign and 1 with halo sign.Of other 5 patients,2 had more than or equal to 5 lesions in each lobe of liver and 3 had more than or equal to 5 lesions in 2 lobes of liver;4 had halo sign,lollipop sign,capsule retraction sign and a tendency of lesions fusion,1 had halo sign and capsule retraction sign.The halo sign,lollipop sign,capsule retraction sign and a tendency of lesions fusion were 7/9,4/9,6/9 and 4/9 in 9 patients,respectively.(2) MRI findings of EHE:6 patients received plain and enhanced scans of MRI.① Four patients had clearhalo sign on T2 weighted imaging (T2WI),in portal vein phase and hepatobiliary phase.Three patients had slightly central hyperintensity and thick ring of slightly peripheral hyperintensity on T2WI.There were slightly central hyperintensity and thin ring of slightly peripheral hypointensity in 1 patient,and the halo sign was seen by enhanced scan.There were central hyperintensity and peripheral hypointensity in 2 patients,and the halo signs were clearly seen in hepatobiliary phase.Some patients were combined with multiple manifestations.② There were no obvious halo sign on T2WI,annular enhancement in arterial phase by enhanced scan,no obvious halo sign in portal vein phase and hepatobiliary phase in 2 patients.There were hypointensity on T1WI and isointensity-hyperintensity on DWI in 6 patients.(3) CT findings of EHE:plain scan of CT in 4 patients showed slightly hypodense shadow,without calcification.Enhanced scan of CT in 3 patients showed that obvious halo-like enhancement was seen in portal vein phase and halo rings were less obvious than that by MRI examination.(4) Treatment and pathological features of EHE and results of follow-up:of 9 patients with EHE,4 underwent surgical resection based on lesions ≤5 and surgical specimens were detected by pathological examination,5 underwent interventional treatment and pathologic examination with biopsy.Gross specimen examination showed that lesions were solid and stiff,with greyish white section plane and infiltrative margin.Tumor cells consisted of epithelioid cells under the microscopy,without atypia and with rare mitotic figures,and vacuoles were seen in cytoplasm.Immunohistochemistry showed CD31 and CD34 were positive.Nine patients were followed up for 6-54 months.During the follow-up,4 patients with surgery had no recurrence and 5 patients with interventional therapy remained stable condition.Conclusions Imaging manifestations of hepatic EHE are the more typical when lesions of EHE became more.Hepatic EHE has a tendency of lesion fusion,halo sign,capsule retraction sign and lollipop sign.Imaging manifestations on T2WI with fat suppression,in portal vein phase and hepatobiliary phase are helpful to improve the diagnosis of hepatic EHE.

Exploration on the purchasing mode of hospital equipment / 中国医学装备

Objective:Through the discussion on the purchasing mode of hospital equipment in China, fully understand the advantages and disadvantages of various procurement ways, choose reasonable acquisition method, optimize acquisition method, standardize the procurement management objective.Methods: By using the method of analogy, comparison of the four main acquisition methods. By the comparative analysis, the scope of each purchase way was confirmed. Results: Public bidding was better for more than 500000 yuan or the treasury payment items, competitive negotiation approach applies to 50000 yuan-500000 yuan purchase project. Consultation approach can be applied to 50000 yuan purchase project. Information project procurement preferred to methods of government procurement.Conclusion: Reasonable choices of purchasing and proper optimization has significant meaning for equipment purchasing and management in hospital.

Correlation of carcinoembryonic antigen with prognosis of hepatocellular carcinoma after hepatectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation between carcinoembryonic antigen (CEA) and prognosis of hepatocellular carcinoma after hepatectomy.</p><p><b>METHODS</b>This study retrospectively analyzed the surgical outcomes of hepatocellular carcinoma (HCC) in 562 patients who underwent hepatectomy between January 2002 and December 2009 in the Cancer Hospital, Chinese Academy of Medical Sciences. Postoperative prognostic factors were analyzed using univariate Kaplan-Meier analysis and multivariate Cox proportional hazards model.</p><p><b>RESULTS</b>The sensibility of serum CEA and CEA-AFP combined in the detection of HCC was 7.1% (40/562) and 55.3% (311/562), respectively. The 1-, 3- and 5-year overall survival rates and disease free survival rates of CEA-negative group (CEA<5 ng/ml) were 93.8%, 75.6%, 59.4%, and 75.0%, 55.9%, 44.5%, respectively (P = 0.003); and the 1-, 3- and 5-year overall survival rates and disease free survival rates of CEA-positive group (CEA ≥ 5 ng/ml) were 87.5%, 60.5%, 46.6% and 52.6%, 36.2%, and 25.4%, respectively (P = 0.045). In the univariate analysis, better prognosis for overall survival (OS) was associated with small tumor ( ≤ 5 cm), single lesion, high-grade histological differentiation, no vascular tumor embolus, negative serum AFP expression, negative serum CEA expression, no/mild cirrhosis, no regional lymph node metastasis, no major vascular invasion, no direct invasion of adjacent organs or with perforation of visceral peritoneum, no transfusion as well as earlier BCLC staging (P < 0.05 for all). In the Cox multivariate analysis, serum AFP-negative expression, serum CEA-negative expression, no/mild cirrhosis, no direct invasion of adjacent organs or with perforation of visceral peritoneum, no transfusion and earlier BCLC staging were independent factors for longer disease free survival (P < 0.05 for all).</p><p><b>CONCLUSIONS</b>Serum CEA-positive expression is correlated to alcoholism and HCC multiple occurrences. Although serum CEA detection has limited value for HCC diagnosis, its positive expression does affect poor prognosis. Higher serum CEA level is an independent prognostic factor for poorer disease free survival.</p>

Jaundice as a prognostic factor in patients undergoing radical treatment for carcinomas of the ampulla of Vater / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Carcinomas of the ampulla of Vater (CAV) is a relatively rare malignant gastrointestinal tumor, and its postoperative prognostic factors have been well studied. However, as its first symptom, the impact of jaundice on the prognosis of CAV is not so clear. This study aims to explore the role of jaundice as a prognostic factor in patients undergoing radical treatment for CAV.</p><p><b>METHODS</b>The clinical data of 195 patients with CAV who were treated in the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 1989 to January 2013 were retrospectively analyzed. Among them, 170 patients with pathologically confirmed CAV entered the statistical analysis. Jaundice was defined as a total bilirubin serum concentration of ≥ 3 mg/dl. Result Of these 170 patients, 99 (58.20%) had jaundice at presentation. Jaundice showed significant correlations with tumor differentiation (P = 0.002), lymph node metastasis (P = 0.016), pancreatic invasion (P = 0.000), elevated preoperative CA199 (P = 0.000), depth of invasion (P = 0.000), and tumor stage (P = 0.000). There were more patients with pancreatic invasion in the jaundice group than in the non-jaundice group. Also, lymph node metastasis was more common in the jaundice group (n = 26) than in the non-jaundice group (n = 8). The non-jaundice group had significant better overall 5-year disease-free survival (72.6%) than the jaundice group (41.2%, P = 0.013). Jaundice was not significantly correlated with the postoperative bleeding (P = 0.050).</p><p><b>CONCLUSIONS</b>Jaundice in patients with CAV often predicts more advanced stages and poorer prognoses. Pancreatic invasion and lymph node metastasis are more common in CAV patients with jaundice. Jaundice is not a risk factor for postoperative bleeding and preoperative biliary drainage cannot reduce the incidence of postoperative complications.</p>

A clinicopathological and prognostic study of rare pathological subtype cases of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features and prognosis of clear cell carcinoma (CCC), giant cell carcinoma (GCC) and sarcomatoid carcinoma (SC), the 3 rare cellular morphological subtypes of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The clinic data of 78 rare pathological subtype HCC cases, which were diagnosed by postoperative pathological examination during October 1998 and June 2013 was analyzed retrospectively. CCC group involved 43 patients (33 male and 10 female), with a median age of 56 years (ranging from 25 to 80 years). GCC group involved 19 patients (16 male and 3 female), with a median age of 59 years (ranging from 38 to 66 years). SC group involved 16 patients (14 male and 2 female), with a median age of 57 years (ranging from 46 to 70 years). Characteristic differences were analyzed by χ(2) test and Fisher exact test. Survival analysis was estimated by Kaplan-Meier method. Cox proportional hazards model was used in survival multivariate analysis.</p><p><b>RESULTS</b>The proportion of multiple lesions in CCC group (4.7%) was significantly lower than those in GCC group (21%) or SC group (25%) (P = 0.034). The histologic grade of CCC group was the best, whereas SC group was the worst (P = 0.000). The survival analysis revealed that median survival time and the 1-, 3-, 5-year survival rates for the 3 groups are CCC group (45 months, 92%, 65%, 45%) > GCC group (13 months, 55%, 30%, 0) > SC group (8 months, 31%, 0, 0), respectively (χ(2) = 4.473 to 26.981, P < 0.05, between each 2 groups). Two cases in CCC group underwent abdominal metastasectomy 18 and 32 months after hepatectomy, and they still achieved long-term survival time. The histologic grade of tumor cell and the TNM staging were 2 independent unfavorable prognostic factors (regression coefficient: 4.038 and 1.354, P < 0.05).</p><p><b>CONCLUSION</b>CCC is a rare low degree malignancy pathological subtype of HCC and may achieve a relatively optimistic prognosis. However, the GCC, especially SC are 2 rare high degree malignancy pathological subtypes of HCC with highly aggressive and poor prognosis.</p>

Clinical characteristics and prognosis of three rare and poor-prognostic subtypes of primary liver carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological features and prognostic factors of three rare and poor-prognostic pathological subtypes of primary liver carcinoma, and improve the clinical diagnosis and surgical treatment.</p><p><b>METHODS</b>A retrospective analysis of clinicopathological data of 69 patients with rare pathological subtypes of primary liver carcinoma, diagnosed by postoperative pathology in our hospital from October 1998 to June 2013 was carried out. The data of 80 cases of common poorly differentiated hepatocellular carcinoma treated in the same period were collected as control group. Kaplan-Meier method was used to analyze the survival rate, and Cox proportional hazards model was used for prognostic analysis in the patients.</p><p><b>RESULTS</b>Thirty-four cases were combined hepatocellular carcinoma and cholangiocarcinoma (CCC, 28 males, 6 females), with a median age of 52 years (range, 33 to 73). Ninteen cases were giant cell carcinoma (GCC, 16 males and 3 females), with a median age of 59 years (range, 38 to 66). Sixteen cases were sarcomatoid carcinoma (SC, 14 males and 2 females), with a median age of 57 years (range, 46 to 70). The survival analysis revealed that median survival time and the 1-, 3-, 5-year survival rates for these 3 groups were 20 months, 61.8%, 29.4%, and 20.6% in the CCC patients, 13 months, 52.6%, 31.6%, and 0% in the GCC patients, and 8 months, 31.3%, 0%, 0% in the SC patients, respectively. The median survival time and survival rate of the SC group were significantly lower than those of the other three groups (P < 0.05). However, in the SC group, the incidences of hilar lymph nodes metastasis, vascular tumor emboli and invasion of adjacent organs were significantly higher than those in the other three groups (P < 0.05). There were no statistically significant differences among the other three groups (P > 0.05). The levels of carcino-embryonic antigen were higher in the three rare subtype groups than that of the control group. The incidences of multiple tumors of the three rare subtype groups were higher than that of the control group (P < 0.05). Positive surgical margin was an independent unfavorable prognostic factor.</p><p><b>CONCLUSIONS</b>The combined hepatocellular carcinoma and cholangiocarcinoma, giant cell carcinoma and sarcomatoid carcinoma have a poor prognosis. Among them sarcomatoid carcinoma is the most malignant and poor prognostic one. Radical resection is recommended.</p>

Detection of circulating tumor cells in patients with hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the detection efficiency of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Immunomagnetic negative enrichment by nanometer magnetic beads and label-free capture with Captor(TM) system were used to isolate and enrich CTCs from peripheral blood of HCC patients, and epithelial and HCC markers were applied to identify CTCs by immunofluorescence staining. CTCs were detected in 50 HCC patients before and after hepatectomy to test the method for isolation, enrichment and identification. The dynamic changes of pre- and post-operative CTCs' numbers were compared. The clinical data were analyzed using SPSS 19.0 software.</p><p><b>RESULTS</b>Negative enrichment methods by nanometer magnetic beads and label-free capture using Captor(TM) system were both suitable for CTCs isolation and enrichment in HCC patients. The positive detection rate of CTCs in HCC patients via negative enrichment was 96.0% (48/50), the preoperative median number of CTCs was 16 per 7.5 ml blood, and the postoperative median number was 17 per 7.5 ml blood.</p><p><b>CONCLUSIONS</b>Both negative enrichment and Captor(TM) system are suitable for isolation and enrichment of CTCs in HCC patients. There is a significant difference in the numbers of CTCs before and after operation, and dynamic detection of CTCs will provide helpful prognostic information for HCC patients in clinics.</p>

Safety of intraoperative electron radiation therapy for primary hepatocellular carcinoma: a cohort study / 中华放射肿瘤学杂志

Objective To investigate the safety of intraoperative electron radiation therapy (IOERT) for stage Ⅰ hepatocellular carcinoma (HCC) by a cohort study.Methods From November 2010 to May 2012,16 patients who were pathologically diagnosed with stage Ⅰ HCC underwent IOERT after radical resection.With a cohort study,87 patients with stage Ⅰ HCC who underwent radical resection alone during the same period were qualified,and according to tumor size (＞ 5 cm and ≤ 5 cm) and resection margin (close margin and negative margin),32 of 87 patients made up the control group.The intraoperative and postoperative adverse events,liver function parameters,coagulogram,and routine blood parameters,as well as IOERT-related adverse reactions,were evaluated.Independent-samples t test was used for analyzing the differences between groups.Results Compared with the control group,the IOERT group had a significantly longer operative time ((275.4 ± 71.55) min vs.(184.7 ± 64.74) min,P =0.000),a slightly higher incidence of intraoperative adverse events (18.75％ vs.6.25％,P=1.000),a slightly lower incidence of operative complications (12.50％ vs.28.12％,P =0.460),and a lower perioperative mortality (0 vs.6％,P =0.440).Liver function parameters showed no significant differences between the two groups (P ＞ 0.05).There were no significant differences between the two groups in postoperative time to grade 1 or normal liver function parameters,median length of postoperative hospital stay,length of hospital stay in the surgical department,time to incision healing,and level of incision healing (P ＞ 0.05).During follow-up,no radiation hepatitis was found in the IOERT group.Conclusions As an adjuvant therapy after radical resection for early HCC,IOERT has no significant side effects on postoperative recovery and liver function,and an intraoperative dose of 15-16 Gy is safe.

Neutrophil-lymphocyte ratio as a prognostic factor for carcinoma of ampulla of Vatar / 中华全科医师杂志

The clinical data of 147 patients with carcinoma of ampulla of Vatar at our hospital from January 1998 to December 2012 were retrospectively analyzed.The neutrophil-to-lymphocyte ratio ( NLR) was calculated from pre-operative complete blood count.They were divided into low NLR group (NLR<5,n=121) and high NLR group (NLR≥5,n=26).The 5-year survival rates of two groups were compared and the prognostic risk factors examined by univariate analysis and Cox model.The 5-year free survival rates of low and high NLR groups were 57.9%and 27.6%respectively ( P=0.005 ).Univariate analysis revealed that depth of invasion (P=0.006),pancreatic invasion (P=0.002),lymph nodal metastasis (P=0.008), poor differentiation ( P =0.008 ) , tumor stage ( P =0.003 ) and per-operative NLR ( P =0.005 ) were significant prognostic factors.Multivariate analysis showed that per-operative NLR significantly increased the risk of recurrence (P<0.05).Pre-operative NLR represents a significant independent prognostic indicator for patients with carcinoma of ampulla of Vatar.

Diagnosis and treatment for duodenal neuroendocrine tumors / 中华普通外科杂志

Objective To evaluate the diagnosis and treatment of duodenal neuroendocrine tumors.Method We retrospectively analyzed data of 15 patients with duodenal neuroendocrine tumors admitted between August 1999 and July 2012.Result In all the 15 cases accurate and definitive diagnosis were achieved via pathological examination and immunohistochemistry.Clinical diagnostic methods included ultrasound,endoscopy,upper gastrointestinal imaging,abdominal CT,MRI,etc.7 cases underwent pancreaticoduodenectomy,2 cases were treated by local excision,4 cases by endoscopic excision,and total gastrectomy and distal gastrectomy was performed in one each case.Conclusions The diagnosis of duodenal neuroendocrine tumors is established mainly by endoscopy and diagnostic imaging.Surgical resection is the treatment of choice.Pancreatoduodenectomy and local excision is applicable for G2 and G3 patients while endoscopic excision can be used for G1 patients.