Incidence And Risk Factors Of Contrast Nephropathy After Tace In Patients With Liver Cancer And Chronic Kidney Disease.

PURPOSE: Incidence of contrast induced nephropathy (CIN) and related risk factors in patients with liver cancer and chronic kidney disease after trans-catheter arterial chemoembolization (TACE) is higher. The purpose of this study was to investigate the feasibility and safety of TACE therapy in such patients. METHODS: A retrospective analysis was performed on 103 patients with liver cancer and chronic kidney disease who underwent TACE treatments. TACE was performed according to Seldinger's technique of arterial embolization with minor modifications. Based on CIN diagnostic criteria, patients were divided into non-CIN (n=89) and CIN (n=14) groups. Multiple clinical parameters were assessed for the two groups after TACE. Serum creatinine levels were measured 48-72 h after TACE. RESULTS: Tumor size (>5 cm), TACE frequency, contrast agent dosage, solitary kidney, volume of iodized oil used in the TACE (ml) and urea levels were significantly higher in CIN group in comparison with the non-CIN group, while serum albumin and haemoglobin levels were significantly lower. Multivariate logistic regression analysis confirmed that the volume of iodized oil and TACE frequency were significantly positively correlated, and serum albumin level was negatively correlated in the CIN group. CONCLUSION: Volume of iodized oil, TACE frequency and low serum albumin levels were found to be independent risk factors for CIN after TACE. Thus, it is safe and feasible for hepatocellular carcinoma patients with chronic kidney disease to receive TACE treatment, but adverse events management after TACE needs to be addressed.

Activity of sulfotransferase 1A1 is dramatically upregulated in patients with hepatocellular carcinoma secondary to chronic hepatitis B virus infection.

The phase I metabolizing enzyme and phase II metabolizing enzyme play vital roles in carcinogenesis, but little is known about the changes of their activities in patients with hepatocellular carcinoma (HCC) secondary to chronic hepatitis B virus (HBV) infection. In this study phenacetin, a probe drug (1 g for men and 0.85 g for women orally), was applied for the detection of sulfotransferase 1A1 (SULT1A1) and cytochrome P4501A2 (CYP1A2) activities in 82 healthy participants and 148 HCC, 106 cirrhosis, and 41 chronic hepatitis B patients. In addition, a prospective cohort study for susceptibility to HCC was performed in 205 patients with cirrhosis secondary to chronic HBV infection. Compared with the healthy participants, SLUT1A1 activity increased by 9.7-fold in the HCC patients (P < 0.01). CYP1A2 activity did not significantly differ between the healthy participants and HCC patients. CYP1A2 activity decreased by 91.2% (P < 0.01) and 67.7% (P < 0.05) in the patients with cirrhosis and chronic hepatitis B, respectively; SULT1A1 activity did not increase significantly. During an approximate 2-year follow up, three of the 46 cirrhosis patients with elevated SULT1A1 activity and normal CYP1A2 activity developed HCC, but none of the 159 cirrhosis patients used as parallel controls did (P = 0.012). These results indicate that SLUT1A1 activity is dramatically upregulated in patients with HCC secondary to chronic HBV infection. The upregulation of SULT1A1 activity is not caused by the tumor itself. The interaction between SULT1A1 and CYP1A2 can play an important role in hepatocarcinogenesis in the Chinese population.

Preoperative portal vein embolization for hilar cholangiocarcinoma--a comparative study.

BACKGROUND/AIMS: Preoperative portal vein embolization (PVE) allows potentially curative hepatic resection to be carried out in patients with hepatobiliary malignancies who are otherwise not candidates for resection because of the small size of the future liver remnant (FLR). However, there have only been a few reports on PVE before hepatectomy for hilar cholangiocarcinoma due to the small number of patients who can be treated with radical surgery. METHODOLOGY: Between January 2007 and March 2009, 49 consecutive patients with hilar cholangiocarcinoma who were planned to have hemi-hepatectomy/extended hemi-hepatectomy plus caudate lobe resection in our tertiary referral center were studied. The change in size of the FLR and the operative outcomes were compared between patients with or without PVE. RESULTS: All patients had liver dysfunction as a result of biliary obstruction due to hilar cholangiocarcinoma although they had all received percutaneous transhepatic biliary drainage. PVE was used in 16 patients with an estimated FLR of <50%, while no PVE was carried out in 33 patients with an estimated FLR of >50%. Complications after PVE occurred in 3 patients (18.8%), which included bile leakage (n=1) and coil displacement (n=2). No complication precluded liver resection. The FLR to total liver volume (TLV) ratio at presentation was significantly smaller in patients who underwent PVE than those who did not undergo PVE (40.3 +/- 7.4% vs. 56.6 +/- 5.0%; p < 0.001). After PVE, the FLR to TLV ratio increased significantly (40.3 +/- 7.4% vs. 43.1 +/- 7.0%; p < 0.001) at a mean time of 14.2 +/- 3.5 days. The mean +/- S.D. increase in FLR was 4.6 +/- 3.0 cm3/day. At surgery, the FLR volume was still significantly smaller in the PVE group than the non-PVE (802 +/- 216 cm3 vs. 979 +/- 202 cm3; p = 0.007). In the PVE group, insufficient hypertrophy of the FRL prevented one patient from having surgery, while local tumor progression and peritoneal dissemination precluded hepatectomy in 2 more patients. Finally, 13 patients (81.3%) underwent radical surgery. The PVE group had similar complication and mortality rates compared with the non-PVE group (complication rate, 69.2% vs. 63.6%; mortality rate, 0.0% vs. 9.1%). The 1- and 2-year overall survivals for the PVE group (with intent-to-treat analysis), PVE group (radical surgery only) and the non-PVE group were 57.3% and 43.0%; 71.3% and 53.5%; 70.4% and 54.4%, respectively. There was no significant difference in the survival outcomes. CONCLUSIONS: The results suggested that PVE is a safe and efficacious procedure in inducing adequate hypertrophy of the FLR before major hepatic resection for hilar cholangiocarcinoma with obstructive jaundice which had been relieved by percutaneous transhepatic biliary drainage.

Overexpression of FOXM1 is associated with EMT and is a predictor of poor prognosis in non-small cell lung cancer.

Forkhead box M1 (FOXM1), a member of the Fox family of transcriptional factors, is considered to be an independent predictor of poor survival in many solid cancers. However, the underlying mechanism is not yet clear. The aim of the present study was to investigate the clinical significance of the correlation between FOXM1 and epithelial-mesenchymal transition (EMT) in non-small cell lung carcinoma and the possible mechanism responsible for FOXM1-induced EMT and metastasis. In the present study, expression levels of FOXM1 and EMT indicator proteins were determined by tissue microarray (TMA) and immunohistochemical staining, western blotting and reverse transcription-PCR (RT-PCR). Other cellular and molecular approaches including gene transfection, small interfering RNA (siRNA), and migration and invasion assays were utilized. Our results demonstrated that FOXM1 overexpression was statistically significantly associated with a higher TNM stage (p=0.036), lymph node metastasis (p=0.009) and a positive smoking history of the patients (p=0.044). Additionally, high expression of FOXM1 correlated with loss of E-cadherin expression (p<0.001) and anomalous immunopositivity of Vimentin (p=0.002). Moreover, patient survival analysis demonstrated that high expression of FOXM1 (p=0.043) and the presence of lymph node metastasis (p=0.042) were independent prognostic factors for non-small cell lung cancer (NSCLC). Furthermore, various in vitro experiments indicated that overexpression or knockdown of FOXM1 expression altered EMT through activation or inhibition of the AKT/p70S6K signaling pathway. Collectively, the results suggest that FOXM1 may be used as a prognostic indicator for patients with NSCLC and promotes metastasis by inducing EMT of lung cancer cells through activation of the AKT/p70S6K pathway. Therefore, we suggest that FOXM1 may be a potential target for lung cancer therapy.

In situ detection of tumor infiltrating lymphocytes expressing perforin and fas ligand genes in human HCC.

AIM:To investigate the expression of perforin and fas-ligand (fas-L) of tumor infiltrating lymphocytes (TILs) in human hepatocellular carcinoma (HCC).METHODS:By in situ hybridization and immunohistochemistry, the perforin and fas-L gene expression of TILs was studied in 20 HCC cases.RESULTS: Positive expression of perforin and fas-L genes was detected in 16 HCC cases. One patient had expression of perforin and fas-L genes in the majority of TILs and survived 1.5 years after tumor resection without HCC relapse.This seems that the presence of a large number of activated T cells might be beneficial for the antitumor immunity. In other cases, less than 10% of TILs were able to express perforin and fas-L genes.CONCLUSION:Although there were a number of T cells in HCC, only few of them were immunoactive and able to kill tumor cells. It seems important to promote further proliferation of these activated T cells in vitro or in vivo.