1. Progress in the molecular mechanism and the prediction of postoperative recurrence of hepatocellular carcinoma
Xin YANG ; Hu-liang JIA ; Lun-xiu QIN
Chinese Journal of Practical Surgery 2019;39(10):1030-1035
The radical resection is the most important treatment for primary liver cancer, but the high recurrence rate is the main obstacle to the survival of postoperative patients.According to the time of tumor recurrence, the postoperative recurrence of liver cancer is divided into the early recurrence and late recurrence. The former is mainly related to the invasion and metastasis of liver cancer, and the latter is mainly caused by multicenter tumor occurrence based on the background of liver disease. The early prediction of postoperative recurrence risk contributes to the timely and effective intervention and improved the prognosis of the patients. In the past ten years, the clinical research on the recurrence of liver cancer has been systematically studied. The molecular mechanism of the metastasis and recurrence has been newly recognized: the metastatic potential of liver cancer begins in the early stage of primary tumor; the imbalance of micro-environmental inflammatory response promotes the metastasis of cancer. At the same time, a variety of molecular markers for predicting the recurrence of liver cancer were identified, and a molecular prediction model for the metastasis of liver cancer was created and optimized. These research results lay the foundation for more accurately understanding of the recurrence and metastasis of liver cancer and developing the more precise prevention and treatment strategies.
2.The progress and challenges of precision oncology
xiu Lun QIN ; 复旦大学肿瘤转移研究所 上海 200040 ; ting Hao SUN ; yu Lu YANG
Fudan University Journal of Medical Sciences 2017;44(6):786-792
Precision oncology is applying established clinic-pathological indexes with molecular profiling to create diagnostic,prognostic,and therapeutic strategies precisely tailor to each patient's requirements.It includes precision prevention (cancer risk detection and prophylactic intervention),precision diagnosis (early detection and diagnosis,molecular classification),and precision treatment (molecular targeted therapies,predicting and monitoring treatment response and precision surgery based on the combination of visual,cytology,pathologic review,as well as molecular profiling assessments).Understanding of cancer and clinical decision making from the molecular level is necessary in era of precision oncology.Many challenges,including the heterogeneity and dynamic evolution of cancer cells,few understanding about cancer biology,pairing the massive genomic data with inaccurate clinical information,limited sensitive drugs and unexplained resistance,insufficient cancer biomarkers for precision diagnosis and treatment,have to be overcome before it can be clinical routines.
5.High expression of thrombin receptor PAR1 in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma in early stage.
Xiao-fei ZHANG ; Qiong-zhu DONG ; Yu-hua XUE ; Hai-jun ZHOU ; Qing-hai YE ; Ning REN ; Hu-liang JIA ; Lun-xiu QIN
Chinese Journal of Hepatology 2011;19(4):266-270
OBJECTIVETo evaluate the relationship between PAR1 (Protease-Activated Receptor 1) expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection.
METHODSReal-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage. Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated.
RESULTSPeritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P < 0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P < 0.05). Kaplan-Meier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival (OS) (P < 0.05) of HCC patients and the time to recurrence (TTR) (P < 0.05). The 1, 3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue.
CONCLUSIONSPeritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.
Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; Receptor, PAR-1 ; metabolism
6.Prognostic analysis of 669 liver metastasis of colorectal cancer cases.
Li REN ; Shi-xu LV ; Yun-shi ZHONG ; Jian-min XU ; Ye WEI ; Jia FAN ; Lun-xiu QIN ; Jian-hua WANG ; Jie-min CHENG ; Sheng QIAN ; Xin-yu QIN
Chinese Journal of Gastrointestinal Surgery 2009;12(4):337-341
OBJECTIVETo evaluate the relation between different therapy and survival rate of liver metastasis of colorectal cancer (LMCC).
METHODSClinical data of 669 LMCC patients,collected from Fudan University Zhongshan Hospital from January 2000 to July 2008, were analyzed retrospectively.
RESULTSOf the 669 cases, 379 cases were synchronous liver metastases(SLM) and 290 cases were metachronous liver metastases(MLM). There were no significant differences in age, gender and position of primary tumor between SLM and MLM groups(P>0.05), but as to liver metastasis characteristics(liver lobe involved, focus number and maximal focus diameter) and CEA, CA19-9 before therapy,there were significant differences(P<0.05). Two hundred and fifty-three cases underwent curative hepatic resection, including 123 cases in SLM and 130 cases in MLM. Until October 31, 2008, all the cases were followed up. The median survival time of SLM was(11+/-1) months and of MLM(23+/-2) months(P<0.01). Five-year survival rate of SLM was 6.4% and of MLM 11.4%(P<0.01). As to different treatments, median survival time and 5-year survival rate of curative hepatic resection group were 37 months and 35.6%, and of non-operation groups(i.e. intervention, chemotherapy, radiofrequency therapy and percutaneous ethanol injection) were 5 to 26 months and 0 to 3.6% respectively(P<0.05).
CONCLUSIONSCurative hepatic resection is the first choice of liver metastasis of colorectal cancer, which can improve the survival rate. Resection rate and survival of MLM are better than those of SLM.
Adult ; Aged ; Colorectal Neoplasms ; pathology ; therapy ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Neoplasms ; secondary ; therapy ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Survival Rate
7.Identification of metastasis-related microRNAs of hepatocellular carcinoma in hepatocellular carcinoma cell lines by quantitative real time PCR.
Yue ZHAO ; Hu-liang JIA ; Hai-jun ZHOU ; Qiong-zhu DONG ; Li-yun FU ; Zhao-wei YAN ; Jian SUN ; Ning REN ; Qing-hai YE ; Lun-xiu QIN
Chinese Journal of Hepatology 2009;17(7):526-530
OBJECTIVETo identify the metastasis-related miRNAs in hepatocellular carcinoma (HCC) cell lines.
METHODSA qRT-PCR method was established and optimized.
RESULTSAll candidate metastasis associated miRNAs except miR-124a were expressed in high metastasis cell line MHCC97H and low metastasis cell line MHCC97L, while some miRNAs were differentially expressed between liver cancer cell line (HepG2) and hepatic cell line (L02) (P less than 0.05), these miRNAs include: miR-148b (1.96+/-0.51 vs 3.76+/-0.28), miR-9 (-4.38+/-0.86 vs -1.10+/-0.53), miR-30c (8.41+/-0.40 vs 6.82+/-0.29), miR-338 (3.14+/-0.29 vs -2.36+/-0.32), miR-34a (0.71+/-0.40 vs -2.95+/-0.26), Let-7g (-4.07+/-0.55 vs -6.98+/-0.56). miR-148b expression was about 4 times higher than miR-148a [5.46 (IQR 4.25-6.67) vs 1.29 (IQR 0.94-1.64)] in all cell line tested (Z=-5.097, P=3x10(-7)).
CONCLUSIONThis study may help to understand the biological significance of miRNAs in HCC metastasis.
Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Cell Line ; Cell Line, Tumor ; DNA, Complementary ; genetics ; Epithelial Cells ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; MicroRNAs ; genetics ; metabolism ; Neoplasm Metastasis ; Polymerase Chain Reaction
8.A clinicopathologic study of hepatic angiomyolipoma.
Tao LI ; Jia FAN ; Lun-xiu QIN ; Jian ZHOU ; Hui-chuan SUN ; Lu WANG ; Qing-hai YE ; Shuang-jian QIU ; Zhao-you TANG
Chinese Journal of Surgery 2009;47(20):1536-1539
OBJECTIVETo investigate the clinicopathologic features, diagnosis and treatment of hepatic angiomyolipoma (HAML).
METHODSThe clinical, histopathological, treatment and prognosis data of 51 patients treated for HAML from October 1998 to October 2007 were retrospectively analyzed.
RESULTSHAML had a female predilection (female/male = 41/10) and the mean age was 44 years old. The main symptoms were abdominal mass (33 cases) and abdominal pain or discomfort (15 cases), the other 2 cases presented as fever. Histopathologically, HAML was composed of a heterogeneous mixture of blood vessels, smooth muscle, and adipose cells. Immunohistochemical staining showed relatively high positive rate of HMB-45 (50/51), SMA (47/49) and S-100 (39/42). All 51 patients underwent partial hepatectomy. The mean hospital stay was 13.8 days and mean intraoperative blood loss was 263 ml. There was no recurrence or metastasis after a mean follow-up of 55.4 months.
CONCLUSIONSHAML is a rare benign mesenchymal tumor of the liver. Definitive diagnosis of HAML depends on the pathohistological findings and HMB-45 positive myoid cell is an important diagnostic marker. Complete surgical resection is the optimal treatment for HAML with favorable prognosis.
Adolescent ; Adult ; Angiomyolipoma ; diagnosis ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; diagnosis ; pathology ; surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult
9.Primary experience of the anatomical laparoscopic left lateral hepatic lobectomy procedure for benign and malignant liver tumors.
Lu WANG ; Jia FAN ; Lun-xiu QIN ; Hui-chuan SUN ; Qing-hai YE ; Jin-cai WU ; Dou-sheng BAI ; Xiao-ying WANG ; Yi-feng HE ; Qi PAN ; Pei CHEN ; Jian ZHOU ; Zhao-you TANG
Chinese Journal of Surgery 2008;46(21):1621-1623
OBJECTIVETo assess the feasibility, safety and outcome of anatomical laparoscopic left lateral hepatic lobectomy for benign and malignant liver tumors.
METHODSFrom April 2005 to May 2008, 11 patients (7 male, 4 female; mean age 51.7 years) underwent anatomical laparoscopic left lateral hepatic lobectomy. Four patients presented with hepatocellular carcinoma and cirrhosis, while 1 patient had metastatic liver tumors from postoperatively colon cancer, five patients had hemangioma (2 cases with gallstones underwent cholecystectomy), 1 patient had a huge symptomatic angiolipoleiomyoma. Mean tumor size was 5.8 cm (range 2.1 to 12.0 cm). All the lesions were localized in the anatomical left lateral lobe (segments II to III).
RESULTSThe mean operative time was 147 min (range 120 to 180 min). There were no intraoperative or postoperative complications, and blood transfusions were not required. The mean postoperative hospital stay was 5.9 days.
CONCLUSIONSAnatomical laparoscopic left lateral hepatic lobectomy are feasible and safety.
Adult ; Aged ; Female ; Hepatectomy ; methods ; Humans ; Laparoscopy ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Treatment Outcome
10.Treatment of postoperative recurrence of hepatocellular carcinoma with radiofrequency ablation comparing with repeated surgical resection.
Zheng-gang REN ; Yu-hong GAN ; Jia FAN ; Yi CHEN ; Zhi-quan WU ; Lun-xiu QIN ; Ning-ling GE ; Jian ZHOU ; Jing-lin XIA ; Yan-hong WANG ; Qing-hai YE ; Lu WANG ; Sheng-long YE
Chinese Journal of Surgery 2008;46(21):1614-1616
OBJECTIVETo evaluate the efficacy of radiofrequency ablation for the treatment of postoperative recurrence of hepatocellular carcinoma and whether radiofrequency ablation can be used as first line treatment for recurrent hepatocellular carcinoma.
METHODSThere were 213 patients with small recurrent hepatocellular carcinoma (tumor size of 3 cm or less and no more than 3 nodules) who treated in Liver Cancer Institute, Fudan University from January 2000 to December 2005. Among these patients 68 were treated with radiofrequency ablation and 145 were treated with repeated surgical resection. Kaplan-Meier method was used to evaluate the overall survival or disease free survival. Log-rank used to determine the survival difference between groups and COX proportional hazard was used for multivariate analysis to evaluate the risk factors for prognosis. The overall survival or disease free survival was calculated from the time treated with radiofrequency or repeated surgical resection.
RESULTSThe 1-, 3-, 5-years overall survival rates were 94.7%, 65.1%, 37.3% and 88.1%, 62.6%, 41.0% in radiofrequency ablation group and surgical repeated resection group, respectively. There was no significant difference between two groups (P = 0.693). However, the disease free survival was better in repeated surgical resection than in radiofrequency ablation, which were 79.4%, 48.1%, 34.4% and 58.0%, 27.8%, 12.4% in repeated surgical resection and radiofrequency ablation, respectively (P = 0.001). The interval between recurrence and initial hepatectomy with more than 2 years was independent factor favor to good prognosis.
CONCLUSIONSRadiofrequency ablation seems to be as effective as repeated surgical resection owing to comparable overall survival and can be considered as alternative therapy for surgical resection treatment of small recurrent hepatocellular carcinoma.
Carcinoma, Hepatocellular ; pathology ; surgery ; Catheter Ablation ; Female ; Follow-Up Studies ; Hepatectomy ; methods ; Humans ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; surgery ; Reoperation ; methods ; Treatment Outcome

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