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.

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.

Carcinoma, Hepatocellular ; genetics ; pathology ; Gene Expression Profiling ; Genomics ; Humans ; Liver Neoplasms ; genetics ; pathology ; Neoplasm Metastasis ; genetics ; Neoplasm Recurrence, Local ; genetics

Carcinoma, Hepatocellular ; pathology ; Humans ; Liver Neoplasms ; pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Osteopontin ; Prognosis

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

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

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

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

OBJECTIVETo evaluate the usefulness of serum alpha-fetoprotein (AFP) in clinical diagnosis and screening for hepatocellular carcinoma (HCC).

METHODSTotally 290 HCC patients, 48 liver cirrhosis patients, and 49 healthy subjects were enrolled in this study. Serum AFP analysis was performed to investigate the correlation between the serum AFP level in HCC and the clinical or biochemical parameters of the disease, which included the size and number of tumor and the TNM stage. Sensitivities and specificities of AFP in HCC prediction at different cut-off levels were determined.

RESULTSThe serum AFP level was significantly higher in HCC patients than in liver cirrhosis patients (P = 0.0274) and healthy subjects (P = 0.0001). Among 290 HCC patients, 95 patients (32.8%) were AFP-negative (AFP < 20 microg/L), 195 (67.2%) were AFP-positive (AFP > or =20 microg/L). Sensitivity and specificity of AFP at 20 microg/L cut-off was 67.2% and 29.2%, respectively, and the positive and negative predictive value was 85.2% and 12.8%, respectively. Sensitivity of AFP at 400 microg/L cut-off was only 42.8%. Serum AFP levels were significantly different among HCC with different tumor size (P = 0.0009), tumor number (P = 0.0001), and TNM stage [TNM I vs. TNM III-IV (P = 0.0001); TNM II vs. TNM III-IV (P = 0.0003)].

CONCLUSIONSIncreased serum AFP level is highly suggestive in HCC diagnosis. Combined with other imaging examinations, AFP level can be used for the screening of high risk population and for the follow-up of AFP-positive patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; Diagnostic Techniques and Procedures ; Female ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Male ; Middle Aged ; Sensitivity and Specificity ; Young Adult ; alpha-Fetoproteins ; analysis

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