Hu Jx

Anatomic resection of segment VIII of liver for hepatocellular carcinoma in cirrhotic patients based on an intrahepatic Glissonian approach

BACKGROUND Isolated segmentectomy VIII is a technically demanding operative procedure and is reported only rarely. To our knowledge, no reports on anatomic segmentectomy based on an intrahepatic approach have been described. For cirrhotic patients with hepatocellular carcinoma (HCC) limited to segment VIII, this is a parenchyma-preserving hepatectomy that can be tolerated. METHODS Eighteen patients with HCC underwent anatomic segment VIII segmentectomy from January 2005 to January 2008 in our institution. The operative techniques, postoperative, and oncologic outcomes were reviewed. RESULTS Anatomic segmentectomy VIII was feasible with the technology described herein in all patients. The perioperative and oncologic outcomes were comparable with those of other similar hepatic resections. The median follow-up time was 28 months. The 3-year survival rate was 65%. CONCLUSION Although complex and technically demanding, an intrahepatic Glissonian approach for anatomic segmentectomy of segment VIII is an oncologically radical but parenchyma-sparing hepatic resection. In terms of preserving greater functioning liver parenchyma, it may be a safe and effective alternative to extensive hepatectomy.

A possible connection between adhesion regulating molecule 1 overexpression and nuclear factor kappa B activity in hepatocarcinogenesis

Adhesion regulating molecule 1 (ADRM1), a 19S proteasome cap-associated protein, and nuclear factor kappa B (NF-κB), a protein transcription factor controlling DNA transcription, may play an important role in tumorigenesis. Overexpression of ADRM1 and activation of NF-κB are well-observed in hepatocellular carcinoma (HCC). However, little is known about whether both are functionally connected during hepatocarcinogenesis, and the mechanisms involved. In this study, using laboratory techniques including short hairpin RNA (shRNA)-mediated knockdown, immunohistochemistry (IHC), both semi-quantitative and real-time RT-PCR, western blotting, MTT assay, transwell assay, flow cytometry and electrophoretic mobility shift assay (EMSA), the expression of ADRM1, the effects of ADRM1 knockdown on NF-κB activity, as well as the biological behavior of HCC cells including proliferation, migration, invasion and apoptosis were investigated in the samples from HCC patients and HCC cell lines. We found that both mRNA and protein levels of ADRM1 were increased in HCC tissues and that this increase in ADRM1 expression was parallel to the metastatic potential of HCC cell lines. After ADRM1 knockdown in MHCC97-H cells, the expression of IκB-α was increased and the NF-κB activity was reduced. Furthermore, ADRM1 knockdown inhibited MHCC97-H cell proliferation and induced cell apoptosis, and the migration and invasion of MHCC97-H cells were significantly repressed. These results indicate that there is a clear functional connection between ADRM1 and NF-κB in hepatocarcinogenesis, despite the precise mechanisms through which the two work together still being unknown.

Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma

Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription-quantitative polymerase chain reaction and immunohistochemical examination; its association with the prognosis of HCC patients was analyzed. In addition, the effects of Numb deletion on proliferation of HCC cells and its relevant molecules were evaluated in Huh7 and HepG2 cells. Numb overexpression was observed in 62% of adjacent non-tumor tissues and 46% of tumor tissues. Overexpression of Numb in HCC was associated with histological grade, portal vein invasion and the number of tumors (P=0.001, 0.022 and 0.034 respectively). Multivariate analysis revealed that Numb expression was an independent prognostic indicator of HCC patients. Methylation of the Numb promoter contributed to hepatocarcinogenesis. In vitro assays demonstrated that Numb silencing resulted in inhibition of cell proliferation, induction of apoptosis, down-regulation of cyclin-dependent protein kinase 4 (CDK4) and S-phase kinase-associated protein 2 (SKP2), and upregulation of Bcl-2 homologous antagonist/killer (BAK) and cyclin-dependent kinase inhibitor 1 (p21). The present study suggests that downregulation of Numb inhibits colony formation and cell proliferation, induces apoptosis of HCC cells and independently predicts the poor prognosis of HCC patients. Thus, Numb has a potential role in the development and progression of HCC.

Null-margin bisegmentectomy VII-VIII for hepatocellular carcinoma in cirrhotic patients.

BACKGROUND/AIMS Preservation of functional liver parenchyma should be a priority in hepatic surgery to avoid postoperative liver failure and enhance the opportunity to perform repeat resection in case of tumor recurrence. METHODOLOGY A tumor localized in segments VII, VIII and adhering to or compressing the middle hepatic vein sometimes indicates a need to perform bisegmentectomy VII-VIII without surgical margin. From June 2006 to June 2011, fourteen patients with such a tumor underwent null-margin bisegmentectomy VII-VIII in our hospital. We retrospectively review our experience with this uncommon and technique-challenging hepatic resection. RESULTS Mean intraoperative blood loss was estimated to be 300 mL and only four patients required blood transfusions less than 4U each person. Mean postoperative hospitalization was 11.2 days. Postoperative complications were encountered in 28.5% of patients and there was no postoperative mortality. Median overall and disease-free survivals were 35 and 23 months, respectively. CONCLUSIONS The lack of ability to obtain an adequate surgical margin should not be considered as a contraindication for hepatectomy of HCC. In patients with impaired liver functional reserve and with right superiorly located tumors, the preservation of the middle hepatic vein should take priority and null-margin bisegmentectomy VII-VIII for HCC should be recommended.

Pharmacological inhibition of TRPV4 channel suppresses malignant biological behavior of hepatocellular carcinoma via modulation of ERK signaling pathway

TRPV4 (transient receptor potential vanilloid 4), a member of the TRP superfamily, has been reported to correlate with several different forms of cancers. However, the role of TRPV4 in human hepatocellular carcinoma (HCC) remains unclear. The present study demonstrated that elevated expression of TRPV4 was shown in HCC tumor tissues when compared with paired non-tumoral livers both in protein and mRNA levels. Furthermore, the enhanced expression of TRPV4 was highly associated with histological grade (P = 0.036) and the number of tumors (P = 0.045). Pharmacological inhibition of TRPV4 channels in HCC cells with the specific antagonist HC-067047 suppressed cell proliferation, induced apoptosis and decreased the migration capability by attenuating the epithelial-mesenchymal transition (EMT) process in vitro. The p-ERK expression was apparently repressed after treatment with the TRPV4 antagonist, further blockade of the ERK pathway with U0126 could significantly aggravate HCC cells apoptosis. In NOD-SCID mouse xenograft models, intraperitoneal injection of HC-067047 could obviously suppress tumor growth and induce apoptosis in vivo. Together, our studies showed that the antitumor effects caused by TRPV4 channel inhibition in HCC cell lines might be attributed to the suppression of EMT process and inactivation of p-ERK which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 channel may be an option for HCC treatment.