Elevated CXCL1 increases hepatocellular carcinoma aggressiveness and is inhibited by miRNA-200a.

In this study, we investigated the value of measurement of the chemokine CXCL1 in clinical management of hepatocellular carcinoma (HCC) and its possible role in the molecular pathogenesis of HCC. High CXCL1 expression predicted recurrence in HCC patients and promoted tumor progression in both in vivo and in vitro experimental systems. Overexpression of CXCL1 increased mitochondrial metabolism and activated the epithelial-to-mesenchymal transition (EMT). Using computational analysis we identified the microRNA miR-200a as a putative post-transcriptional regulator of CXCL1. We found that levels of miR-200a were inversely correlated with CXCL1 expression in HCC patient tissue samples by northern blot and qRT-PCR. Furthermore, CXCL1 was identified as a direct target which was bound and inhibited by miR- 200a. These findings provide new insights into the role of CXCL1 in HCC and its post-transcriptional regulation and suggest it may be a prognostic indicator for poor outcomes and a potential target for therapy.

Liver transplantation in adults with portal vein thrombosis: Data from the China Liver Transplant Registry.

OBJECTIVES: Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis. During liver transplantation (LT), PVT may complicate the procedure and lead to a poor prognosis. The aim of this study is to evaluate patients enrolled in the China Liver Transplant Registry, to understand the influence of PVT to the LT recipients. METHODS: We collected data from patients who underwent LT and were entered into the China Liver Transplant Registry. All data of medical records and follow-up were retrospectively reviewed. The preoperative condition, duration of surgery, intraoperative blood loss, postoperative early and late PVT, and survival rates were compared between patients with PVT and those without PVT. Multivariate Cox analysis and survival analysis were used to determine the influence of PVT. RESULTS: A total of 20,524 cases were recruited into the study. In all, 1810 (8.82%) patients were diagnosed with preoperative PVT of various severities. All patients were followed up for an average of 30.25±33.25months (up to a maximum of 171.68months). Patients with PVT had a significantly longer operating time, more intraoperative blood loss and a higher rate of post-LT PVT (P<0.001). Multivariate Cox analysis showed that PVT did not reduce the recipients' survival rate (HR=0.89, 95% CI: 0.774-1.024, P=0.103). There was no significant difference in cumulative survival rate (P=0.059) between patients without PVT, and patients with PVT. CONCLUSIONS: PVT increases the difficulty of LT, but doesn't reduce the survival rate. Therefore, PVT is not an absolute contraindication for LT in experienced transplantation centers.

Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma.

AIM: To investigate the value of chaperonin containing TCP1, subunit 3 (CCT3) to predict the prognosis of patients with hepatocellular carcinoma (HCC) and determine its function in HCC progression. METHODS: CCT3 expression levels were examined in human non-cancerous liver tissues and a variety of HCC cell lines by quantitative real-time PCR and immunoblotting. CCT3 expression was suppressed by small interfering RNA. The effects of reducing CCT3 expression in HCC cells were tested. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay, cell counting experiment, cell cycle assay, apoptosis assay and invasion assay were employed to evaluate cell functions in vitro. Immunohistochemistry was performed on HCC specimens. In addition, CCT3 expression in HCC specimens was also assessed at the protein and mRNA level. Associations between clinicopathological characteristics and prognosis were analyzed, along with the possible mechanisms involved in CCT3's function in HCC progression. RESULTS: The expression levels of CCT3 mRNA and protein were upregulated in HCC cell lines in contrast to adjacent non-cancerous tissues. Reducing CCT3 expression not only suppressed cell proliferation in cell counts, MTT assay, cell cycle assay and induced cell apoptosis (P < 0.05 vs negative control), but also inhibited the tumor cell invasion capacity in vitro (P < 0.01 vs negative control). Overexpression of CCT3 in the nuclei of cancer cells in HCC specimens (58 of 104 patients, 55.8%) was associated with poor prognosis in HCC patients (3-year survival rate, 55.5% vs 84.2%, P = 0.020) after hepatectomy. Mechanistic analyses showed that signal transducer and activator of transcription 3 (STAT3) activation was decreased even when stimulated by interleukin-6 after knocking down CCT3 in the HepG2 cell line. CONCLUSION: Overexpression of CCT3 in the nuclei of cancerous cells is associated with HCC progression. CCT3 may be a target that affects the activation of STAT3 in HCC.

Esophagogastric devascularization without splenectomy in portal hypertension: safe and effective?

BACKGROUND: Esophagogastric variceal hemorrhage is a life-threatening complication of portal hypertension. In this study, we compared the therapeutic effect of a novel surgical procedure, esophagogastric devascularization without splenectomy (EDWS), with the widely used modified esophagogastric devascularization (MED) with splenectomy for the treatment of portal hypertension. METHODS: Fifty-five patients with portal hypertension were included in this retrospective study. Among them, 27 patients underwent EDWS, and the other 28 patients underwent MED. Patients' characteristics, perioperative parameters and long-term follow-up were analyzed. RESULTS: The portal venous pressure was decreased by 20% postoperatively in both groups. The morbidity rate of portal venous system thrombosis in the EDWS group was significantly lower than that in the MED group (P=0.032). The 1- and 3-year recurrence rates of esophagogastric variceal hemorrhage were 0% and 4.5% in the EDWS group, and 0% and 8.7% in the MED group, respectively (P=0.631). CONCLUSIONS: EDWS is a safe and effective treatment for esophagogastric varices secondary to portal hypertension in selected patients. Patients treated with EDWS had a lower complication rate of portal venous system thrombosis compared with those treated with conventional MED.

De novo malignancy after liver transplantation: a single-center experience of 14 cases.

PURPOSE: The aim of this study is to evaluate the incidence of de novo malignancy after liver transplantation (LT) and compare with those among the general Chinese population. METHODS: A total of 466 patients who had a minimum follow-up time of 6 months were enrolled in the study. All data of medical records and follow up were retrospectively reviewed. RESULTS: The incidence rate of de novo malignancy was 3.0% (14 in 466 patients). The median elapsed time from transplant to the diagnosis of de novo malignancy was 42 months (range, 6 to 106 months). The cumulative risk for development of de novo malignancy was 1.6%, 2.7%, and 8.2% at 3, 5 and 10 years after LT, respectively. The patients were all male. The types of de novo tumors included digestive system tumor (8 in 14), lung cancer (2 in 14), urologic neoplasm (2 in 14), and hematologic malignant tumor (2 in 14). Over a mean follow-up of 24 months after diagnosis of de novo malignancy, 7 patients (50.0%) died; the overall 5-year patient survival rate was 54.5%. The relative risk of malignancy following LT was 9.5 folds higher than the general Chinese population. CONCLUSION: The relative risk of malignancy following LT was much higher than the general Chinese population. Digestive system tumor is the most common type of de novo malignancy after LT in China.

Prognostic value of glypican-3 in patients with HBV-associated hepatocellular carcinoma after liver transplantation.

BACKGROUND: Glypican-3 (GPC-3) is frequently overexpressed in hepatocellular carcinoma (HCC). Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy. However, its prognostic value in patients with HBV-associated HCC after liver transplantation (LT) is not clear. The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT. METHODS: A cohort of 104 HCC patients with HBV-associated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohistochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS: GPC-3 was expressed in samples from 74 (71.2%) of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size (P=0.004), encapsulation (P=0.018), pathological stage (P=0.027), portal vein invasion (P=0.043), tumor differentiation (P=0.002) and the Milan criteria (P=0.016). The 5-year survival rate and disease-free survival rate of patients with GPC-3-positive were lower than those (38.2% vs 75.4%, P<0.001; 30.8% vs 69.7%, P=0.001) of patients with GPC-3-negative. Multivariate Cox-regression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate (P=0.031) and disease-free survival rate (P=0.047), together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein. CONCLUSION: GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.

Hepatocellular carcinoma recurrence is an independent risk factor for HB recurrence after liver transplantation.

BACKGROUND/AIMS: To confirm the relationship between hepatitis B recurrence and Hepatocellular carcinoma recurrence. METHODOLOGY: Data from 340 patients undergoing liver transplantation for HBV-related liver disease were retrospectively evaluated. Clinically relevant variables were analyzed using univariate models. Significant variables were subjected to multivariate logistic regression analysis to identify the independent predictors for HBV recurrence. Fifteen samples removed from HCC recurrence patients were stained for HBsAg and HBcAg. RESULTS: The analyzed population included 283 male and 57 female patients. The mean age was 48.5±9.33 years and median follow-up was 47 months. Hepatitis B relapsed in 16 patients (4.7%). Univariate analysis indicated that HCC (P=0.022) and HCC recurrence (P=0.000) were associated to post transplantation HB. Multivariate analysis identified HCC recurrence as an independent risk factor for HB recurrence (hazard ratio: 23.262 (95% CI: 3.752, 144.216); P <0.001). Three of 15 metastatic lesions were positive for HBsAg and 1 lesion was positive for HBcAg. Conclusion: HCC recurrence is an independent risk factor for post transplantation recurrence of hepatitis.

Ileo-colonic intussusception secondary to small-bowel lipomatosis: a case report.

Intestinal lipomatosis is a rare disease with an incidence at autopsy ranging from 0.04% to 4.5%. Because the lipomas are diffusely distributed in the intestine, most patients are symptom-free, and invasive intervention is not advised by most doctors. Here, we describe a case with intussusception due to small-bowel lipomatosis. Partial small bowel resection and anastomosis were performed because the intestinal wall was on the verge of perforation. This case indicates that regular follow-up is necessary and endoscopic treatment should be considered to avoid surgical procedures if the lipoma is large enough to cause intestinal obstruction.

Histological differentiation predicts post-liver transplantation survival time.

OBJECTIVES: Although liver transplantation is the most effective long-term treatment for hepatocellular carcinoma (HCC), the recurrence of HCC remains an issue. Current research examining recurrence after liver transplantation primarily focuses on patients' clinical characteristics. There is no consensus regarding the factors that may relate to predict the survival time and recurrence rates for patients with hepatitis B virus (HBV)-associated HCC transplantation using clinicopathological analysis. METHODS: One hundred and three patients with HCC were enrolled in the study. All data were collected from the China Liver Transplant Registry. The independent variables were as follows: age, gender, etiology, preoperative alpha-fetoprotein (AFP) levels, body mass index (BMI), Model for End-stage Liver Disease (MELD) and Child-Pugh scores, primary tumor, regional nodes, metastasis (TNM) classification, number of tumors, the size for the largest tumor, multifocality, portal vein tumor thrombosis and histological differentiation, and prognostic staging score criteria (Milan criteria). All of the patients had previously undergone liver transplantation. Univariate and multivariate analysis were used to determine the factors related to the survival time and recurrence. RESULTS: After a median follow-up period of 41.05±28.90 months, the 5-year overall survival rate was 46.60%, and the 5-year recurrence rate was 45.63%. Forty-seven patients (45.63%) died due to HCC recurrence during the follow-up period. Patients within Milan criteria exhibited excellent post-transplantation survival times. Univariate analysis suggested that patients with poor tumor differentiation, AFP≥400ng/ml, portal vein tumor thrombosis, and TNM staging of I+II had significantly predicted shorter survival times and higher recurrence than patients displaying good or moderate tumor differentiation, AFP<400ng/ml, no portal vein thrombosis and TNM staging of III+IV for HBV-associated HCC. However, multivariate analysis revealed that poor tumor differentiation and high serum AFP were associated with a shorter survival time. Moreover, poor tumor differentiation suggested high recurrence. In addition, patients' survival time with AFP<400ng/ml was longer than that of patients with AFP≥400ng/ml even in patients with HCC beyond Milan criteria. CONCLUSIONS: Tumor biological characteristics especially histological differentiation and serum AFP level should be considered before performing liver transplantation (LT) for patients with HBV-associated HCC. Furthermore, the AFP level and histological differentiation provide a new method for assessing HCC patient survival time after LT. Histological differentiation independently predicted post-transplantation survival time and recurrence rate for patients with HBV-associated HCC.

Graft versus host disease after liver transplantation: a case report.

In documenting clinical experience in the diagnosis and treatment of graft versus host disease (GVHD), we retrospectively analyzed data of one case that has developed GVHD after liver transplantation. This patient exhibited fever, skin rash, and diarrhea on day 9 after liver transplantation. His liver function was normal. Skin biopsy showed scattered keratinocytes accompanied by satellite-like lymphocyte infiltration and basal cell liquefaction degeneration. After carefully analyzing the complications, we took the strategy of decreasing the dose of tacrolimus. Thereafter, the patient's temperature decreased to normal, his skin rashes subsided, and his diarrhea was relieved. This case suggests that reducing the dosage of immunosuppressive agents can be an effective strategy for GVHD after liver transplantation.

[Management of hepatic artery related complications and its outcome during liver transplantation].

OBJECTIVE: To explore the experience of hepatic arterial reconstruction and management of its complications. METHODS: The clinical data of 570 consecutive orthotopic liver transplantation patients performed from May 2001 to May 2009 in Peking University People's Hospital were analyzed retrospectively in order to summarize the key factors of hepatic arterial reconstruction and the experience of management of its complications. RESULTS: Arterial complications developed in 18 (3.1%) of the 570 patients including 11 cases of hepatic artery thrombosis, 5 cases of hepatic artery stenosis and 2 cases of hepatic artery rupture. Of the 11 cases with early complication (within 4 weeks), 7 patients died, including 2 due to the rupture of hepatic artery and 5 due to acute liver failure and sepsis of hepatic artery thrombosis. Of the 7 cases with late complication, 4 patients died, including 1 due to graft failure and 3 due to ischemic-type biliary complications. CONCLUSION: Good quality of donor artery and proper choice of microsurgical anastomosis technique in hepatic artery reconstruction could significantly reduce the incidence of its complication. Early detection and diagnosis with active early interventional therapy can improve prognosis of the patients.

[Liver transplantation for the patients with end stage liver disease and portal vein thrombosis].

OBJECTIVE: To investigate the outcome of liver transplantation(LT) for end stage liver disease with portal vein thrombosis (PVT) in different processes. METHODS: Data from 308 patients who underwent LT from July 2004 to February 2008 were retrospectively assessed. The processes of varies grades of PVT during LT were analyzed and estimated for whether the outcome of LT was different between patients with or without PVT. RESULTS: There were 46 patients with PVT, including 11 of grade 1, 14 of grade 2, 18 of grade 3 and 3 of grade 4. LT performed in grade 1 and 2 PVT patients without special intervention. LT was performed in 16 patients with grade 3 PVT after simple thrombectomy or thrombus-extraction. The other 2 patients with grade 3 PVT received the donor superior mesenteric vein to act as a bridge between the donor portal vein and host superior mesenteric vein. Two cases with grade 4 PVT received a cavo-portal hemitransposition, and the other one anastomosis between graft portal vein and varicose coronary vein. The postoperative 1-year survival rates of patients without PVT and patients with PVT were 91.6%(240/262), 80.5%(211/262)vs 86.9%(40/46), 76.1%(35/46), respectively. The patients with PVT had a recurrence rate of 4.3%(2/46). CONCLUSION: Most patients suffering from end stage liver disease with PVT can be successfully treated by LT. However, the result of the patients with diffused PVT undergoing LT is relatively poor.

[Analysis of 565 cases of liver transplantation at a single transplantation center].

OBJECTIVE: To determine the preventative and curative strategies after liver transplantation by investigating the risk factors on prognosis. METHODS: The data of 565 consecutive patients who underwent orthotopic liver transplantation were retrospectively analyzed with the survival rate and complication morbidity. RESULTS: The follow-up time ranges from 3 to 104 months of all the 565 patients after liver transplantation. From January 2004 to January 2009, the patient survival rates were 91.2% after 1 month, 84.9% after 1 year, 69.2% after 3 years, and 66.1% after 5 years, while they were 87.8%, 73.2%, 60.2%, and 57.7% from May 2000 to December 2003. The patient survival rates were 83.3% after 1 year, 79.8% after 3 years, and 78.5% after 5 years in non-hepatocellular carcimoma (non-HCC) group, while they were 78.4%, 49.1%, and 45.1% in HCC group. In early stage after surgery, the morbidities of re-operation due to intra-abdominal hemorrage, vascular complication, severe infection, acute renal failure and primary graft dysfunction were 1.1%, 1.6%, 13.6%, 7.4%, and 1.2%, while in late stage, the morbidities of HCC recurrence, biliary complications, HBV recurrence, de novo malignancy, chronic graft dysfunction were 40.3%, 6.7%, 2.1%, 0.9%, 0.9%, and 1.1%, respectively. The HCC recurrent rates were 8.1% versus 62.5% in matching Milan criteria group or exceeding Milan criteria group and the median survival time was 19.6 months of all recurrent patients. CONCLUSION: Liver transplantation has been the effective treatment for end stage liver disease. Due to the shortage of graft,we prefer to do operations for the patients without HCC or the patients with HCC but matching Milan Criteria.