Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time. AIM: To explore the prognostic factors and treatments of liver metastases of CRC. METHODS: A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05). CONCLUSION: Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma.

BACKGROUND: Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM: To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS: A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients' wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed. RESULTS: The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION: Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Intermedin promotes hepatocellular carcinoma cell proliferation through the classical Wnt signaling pathway.

The proliferative activity of hepatic carcinoma cells is directly associated with tumorigenesis, tumor development, metastasis and invasion. A variety of cytokines and peptides serve important roles in the development of hepatic carcinoma. The aim of the present study was to examine the effect of intermedin (IMD) on hepatic carcinoma cell proliferation and its mechanism of action. HepG2 hepatic carcinoma cell lines were treated with human recombinant IMD1-53 and its receptor antagonist IMD17-47. Cell proliferation was detected using a Cell Counting kit-8. The activation of the classical Wnt signaling pathway was demonstrated by the ratio of TOPflash:FOPflash luciferase activity. The expression of c-Myc and cyclin D1 downstream of the Wnt signaling pathway were detected using reverse transcription-quantitative polymerase chain reaction analysis. It was demonstrated that IMD may promote the proliferation of HepG2 cells in a time-dependent manner, and that the IMD receptor antagonist IMD17-47 could eliminate this promotion. IMD may activate classical Wnt signaling pathway transcriptional activity and the mRNA levels of certain downstream target genes. Furthermore, blocking of the Wnt signaling pathway may inhibit IMD-induced HepG2 cell proliferation to a certain extent. IMD may promote hepatic carcinoma cell proliferation by binding with receptor antagonist IMD17-47 and activating the Wnt signaling cascade, thus providing a novel avenue for the treatment of hepatic carcinoma.

Intermedin promotes hepatic carcinoma cell proliferation through upregulation of miR-155.

OBJECTIVE: MicroRNAs (miRNAs) plays an important role in the development of malignant carcinoma. The small peptide intermedin (IMD) can promote hepatic carcinoma cell proliferation. The aim of the present study is to examine the effect of miR-155 on IMD-stimulated hepatic carcinoma cell proliferation. METHODS: Proliferation of hepatic carcinoma SMMC7721 cells was detected by CCK-8, expression of proliferating cell nuclear antigen (PCNA) and miR-155 was detected by real-time PCR. RESULTS: We found that IMD promotes the proliferation of SMMC7721 cells in a time and dose-dependent manner. IMD can upregulate the expression of miR-155, and blocking of miR-155 can inhibit the IMD-induced SMMC7721 cell proliferation to some extent. CONCLUSION: This study demonstrated that IMD can promote the proliferation of human hepatic carcinoma cell line SMMC7721 cells through upregulation of miR-155. This study may contribute to hepatic cancer prevention and therapy.