Local Ablative Therapies and Intrahepatic Pressure C. Kawamoto 1 , A. Yamauchi 1 , K. Kaneko 1 , N. Miyagi 1 , K. Kani 1 , T. Aoyama 1 , K. Yakabi 1 1 Saitama Medical Center, Saitama Medical University, Japan Background: Some of the unexpected recurrence observed after radiofrequency ablation (RFA) might be caused by increased intratumoral pressure. The present study examined the relationship between local ablative therapies and intrahepatic pressure. Methods: A. Basic study: Under general anesthesia, laparotomy was performed on 19 pigs. A LeVeen needle and a percutaneous ethanol injection (PEI) needle were inserted into the liver and intrahepatic pressure was monitored using an invasive blood pressure monitor. Ablation was performed as follows: 1. RFA. 1) Single-step method: After fully deploying the electrode, the power was initially applied at 30 W, then increased in increments of 10 W/min until power roll-off. 2) Multi-step method: The array was deployed in 8 steps. At each step, the power was fixed at 30 W until power roll-off. 2. PEI. Injection of ethanol (2 ml). B. Clinical study: We examined the multi-step RFA and PEI for HCC. Under local anesthesia, intratumoral pressure was monitored. 1. RFA. 39 patients with a mean tumor size of 15.3±4.9 mm were studied. 2. PEI. In 10 patients with a mean tumor size of 21.4±8.8 mm, 5 to 10 ml of ethanol was injected per session. Results : A. Basic study: The intrahepatic pressures were: single-step method, 154.5±30.9 mmHg; multi-step method, 24.1±18.2 mmHg; and PEI, 12.0±8.5 mmHg. B. Clinical study: Intratumoral pressure was 39.5±27.9 mmHg for RFA and 12.2±9.0 mmHg for PEI. Conclusion: These results suggest that consideration of intrahepatic pressure is crucial in local ablative therapies. Background: A late evening snack (LES) is recommended for liver cirrhosis. However, no clinical study has evaluated the nutrition status and the effect of LES in cirrhotic patients with hepatocellular carcinoma (HCC). We investigated the effect of LES undergoing hepatic arterial infusion chemotherapy (HAIC) in patients with HCC. Method: Nineteen patients with HCC were enrolled. Ten patients were LES group, and nine were control group. In the LES group, the patients received LES supplementation with a branched-chain amino acid (BCAA)-enriched nutrient mixture. In the control group, the patients received ordinary food. There were no significant differences in relation to age, gender, etiology, Child-Pugh scores, tumor stage, clinical responses to HAIC between two groups. Blood biochemical data, nutrition status using an indirect calorimeter were evaluated at before and at the end of chemotherapy. Results: The non-protein respiratory quotient (npRQ) and molar ratio of branched-chain amino acid to tyrosine (BTR) were significantly improved in the LES group but not in the control group. There were no significant differences in the area under the concentration curve for glucose between before and the end of chemotherapy in two groups. Background & Aims: Hepatocellular carcinomas (HCCs) often show hypoor mixed vascularity, and the prognosis of these relatively hypovascular HCCs is not fully elucidated. Cytokeratin (CK) expression profiles may also be useful prognostic indicators, and specifically CK19 may reflect metastastic potency in HCCs. This study was to assess the prognostic implication of tumor vascularity and its relation to CK19 expression in HCC patients. Methods: A total of 150 patients who underwent surgical resection for HCC were enrolled. Tumor vascularity was evaluated according to arterial enhancement pattern on CT scans and CK19 expression was evaluated using tissue microarray methods. Clinicopathologic data were analyzed using Kaplan-Meier and Cox proportional hazard model. Results: During follow-up period, 91 (60.7%) patients experienced tumor recurrence. Forty-five patients (30%) had hypovascluar tumor at the time of diagnosis, and they showed significantly higher positivity for CK19 expression (p=0.001) and shorter disease-free survival (p=0.023) than patients with hypervascular HCCs. In addition, recurred tumors in these patients showed more frequently hypovascular pattern than in patients with hypervascular HCCs (p=0.001). Hypovascularity at initial diagnosis and microvascualr invasion were independent poor prognostic factors predicting survival. Following treatment of recurred HCCs, hypovascular tumors showed poor response to transarterial chemoembolization (TACE), which resulted in shorter overall survival than hypervascular tumors (P=0.057). Conclusions: These results demonstrate that tumor hypovascularity in HCCs is associated with positive CK19 expression, early tumor recurrence, poor TACE response and poor survival. Therefore, tumor vascularity may also be a prognostic indicator in HCC patients. Background: Hepatic stellate cells (HSCs) transdifferentiate to become extracellular matrix-producing myofibroblasts during liver injury. Myofibroblasts can also promote invasion and metastasis of hepatocellular carcinoma(HCC). In this study, we determine gene expression changes in two different models of HSCs activation and investigate whether induction-activated HSCs(iHSCs) gene expression changes are different from culture-activated HSCs(aHSCs). Methods: HSCs were isolated by density centrifugation and exposed to conditioned medium from rat HCC cell lines C5F. Twenty-seven thousands and one hundred gene expression between quiescent HSCs(qHSCs), aHSCs and iHSCs was analyzed by microarray and confirmed by real-time RT-PCR and Western blot. Results: Sixteen hundreds and seventy-one probe sets were differentially expressed in aHSCs, including genes that encode proinflammatory factors, adhesion molecules, cell surface receptors, signaling transduction and immune factors. Seven hundreds and eleven probe sets were differentially expressed in iHSCs. Induction-activated HSCs showed specific gene expression patterns including Raf1, Rac2, Adam17, Wnt6, MMP-9 and TNF, suggesting that HCC cells can specifically induce HSCs activation. Induction-activated HSCs might play a important role in invasion and metastasis of HCC. Conclusions: Induction-activated HSCs gene expression patterns are different from aHSCs. Culture-activated HSCs does not properly regulate gene expression in HSCs, suggesting that iHSCs may be considered the model for the study of HSCs biology in HCC. 