Junichi Yamanaka

A novel 3D hepatectomy simulation based on liver circulation: Application to liver resection and transplantation

Hepatectomy is a complicated operative procedure because of its anatomical complexity, vascular variability, and impaired hepatic function due to associated hepatitis or cirrhosis. Thus preoperative detailed topography and precise liver resection volume measurements should be obtained for a curative hepatectomy. The aim of this study was to assess the feasibility and accuracy of a novel three‐dimensional (3D) virtual hepatectomy simulation software in patients who underwent liver resection or living donor liver transplantation. We developed the hepatectomy simulation software, which was programmed to analyze detailed 3D vascular structure and to predict liver resection volume and margins. In 72 patients receiving hepatectomy, the predicted liver resection volumes and margins revealed a significant correlation with the actual value with a mean difference of 9.3 mL (P < .0001) and 1.6 mm (P < .01), respectively. The drainage area by hepatic veins was quantified to achieve reconstruction of the corresponding venous branch. In conclusion, this hepatectomy simulation software reliably predicted an accurate liver resection volume, the cancer‐free margin, and the drainage volume of hepatic vein branches. This software may promote curative hepatectomy and may be used for other interventional therapies in the treatment of liver disease. (HEPATOLOGY 2005.)

Correlation of hepatitis virus serologic status with clinicopathologic features in patients undergoing hepatectomy for hepatocellular carcinoma

This study investigated the relationship between clinicopathologic features and various viral serologies in patients who underwent hepatectomy in the treatment of hepatocellular carcinoma (HCC).

Clinicopathologic analysis of stage II–III hepatocellular carcinoma showing early massive recurrence after liver resection

Abstract Background and Aims: Prognosis after hepatectomy for hepatocellular carcinoma (HCC) has been improved by progress in the evaluation of hepatic functional reserve, surgical techniques and perioperative management. However, even when curative resection is performed at a relatively early stage, a considerable number of patients develop early intrahepatic and/or extrahepatic recurrence postoperatively. This study analyzed the clinicopathologic features of HCC with early recurrence.

Left hemihepatectomy with microsurgical reconstruction of the right-sided hepatic vasculature

Abstract. Background: Right hemihepatectomy (RH) for proximal bile duct canceroccasionally results in liver failure. We report the feasibility of left hemihepatectomy (LH) with vascular reconstruction (VR) of the right-sided hilar vessels to preserve hepatic reserve. Methods: Among 110 patients with proximal bile duct cancer (PBC) treated between January 1980 and December 1998, 11 patients underwent LH with VR of eight portal veins and nine hepatic arteries, and 14 underwent RH with VR of four portal veins and one hepatic artery. Microsurgical techniques were used in 80% (8/10) of the hepatic arterial reconstructions. Results: Although operation time was significantly longer in the LH group, hospital mortality, blood loss and incidence of histologically cancer positive margin at the bilioenteric anastomotic site were similar in the two groups. Peak serum liver enzyme concentration was significantly higher in the LH group with longer inflow occlusion time, whereas peak serum total bilirubin concentration was significantly higher in the RH group, which had smaller liver remnant. No liver abscess occurred in any patients who underwent microvascular reconstructions. The cumulative survival of the LH group was worse than that of the RH group, in which the proportion of vascular invasion was lower, but not significantly. Conclusion: LH with right-sided microvascular reconstruction is technically possible and a feasible option when RH is likely to result in postoperative liver failure.

Long-term safety of autotransfusion during hepatectomy for hepatocellular carcinoma.

PurposeTo evaluate the long-term safety of autotransfusion (AT) in hepatectomy for hepatocellular carcinoma (HCC).MethodsBetween 1988 and 1989, 46 patients with HCC underwent hepatectomy with AT (group 1). For a comparison, we matched 50 patients with HCC who underwent hepatectomy, and received homologous but not autologous blood (group 2). The 10-year cumulative survival curves and cancer-free curves of the two groups were examined, and the pattern of recurrence was compared.ResultsGroup 1 had a significantly higher cumulative 10-year survival rate than group 2, at 20% vs 8%, respectively (P < 0.05). Among the patients who underwent curative resection, those in group 1 had significantly better cumulative survival and cancer-free survival rates than those in group 2, at 27% vs 11% (P < 0.05) and 13% vs 0% (P < 0.05), respectively. Among the patients with stage I–II HCC, those in group 1 had significantly better cumulative survival and cancer-free survival rates than those in group 2, at 30% vs 5% (P < 0.01) and 20% vs 5% (P < 0.05), respectively. However, the rates were similar among patients with stage III–IV disease in both groups. The pattern of recurrence in the two groups was similar.ConclusionAutotransfusion promoted survival in patients undergoing hepatectomy for stage I or II HCC.

Optimal route of administration of mixed endothelin receptor antagonist (TAK-044) in liver transplantation

Abstract: It is well known that endothelin-1(ET-1) is a factor involved in the pathogenesis of ischemia-reperfusion injury. This study was undertaken to investigate the optimal route (intravenous vs intraportal) for administering mixed endothelin receptor antagonist (TAK-044) in a liver transplantation. First, in a rat isolated liver cold-perfusion model, the pharmacodynamics of TAK-044 and endothelin-1 (ET) in the liver tissue and the systemic circulation after cold perfusion were compared in the different administration routes. Next, in a rat orthotopic transplantation model, we compared the hepatoprotective effect of TAK-044 among different administration routes. In each model, there were three groups: IV group, intravenous injection of TAK-044 (10 mg/kg) immediately before cold perfusion or an-hepatic phase; IP group, intraportal administration with cold perfusion solution or with reflush solution for the graft; control group, no treatment. In the cold perfusion model, liver tissue ET level increased to a similar extent after reperfusion in the three groups, and the plasma and liver tissue TAK-044 concentrations after reperfusion were highest in the IV group. However, the increase in plasma ET was also greatest, and therefore, the ratio of liver tissue to plasma TAK-044 was lower in the IV group compared with the IP group. In the transplantation model, elevation of plasma ET was significantly higher in the IV group. Leakage of serum alanine aminotransferase (ALT), sinusoidal narrowing, and cell swelling after grafting were significantly suppressed in the IP group. We conclude that intraportal administration before reperfusion offers more efficient accumulation of TAK-044 in the liver tissue, without harmful systemic elevation of ET, and achieves a hepatoprotective effect on the graft compared with intravenous administration.

Minimally invasive laparoscopic liver resection: 3D MDCT simulation for preoperative planning

BACKGROUND/PURPOSE Laparoscopic liver resection has not gained wide acceptance compared with other laparoscopic procedures. We evaluated the impact of simulated surgery using data from multidetector CT scanning on planning for laparoscopic hepatectomy. METHODS The hepatectomy simulation system was programmed to perform three-dimensional reconstruction of the vasculature and to calculate the liver resection volume and surgical margin. In 35 patients undergoing laparoscopic hepatectomy or laparoscopy-assisted hepatectomy, the liver resection volume and margin were estimated by simulation preoperatively. Then, the estimated values were compared with the actual resected liver weight and margin. RESULTS Three-dimensional reconstruction allowed stereoscopic identification of the tumor-bearing portal vein and draining vein. The predicted liver resection volume and margin both showed a significant correlation with the actual values: the mean difference was 21 mL (P < 0.0001) and 1.3 mm (P < 0.01), respectively. Preoperative planning based on simulated resection facilitated laparoscopic mobilization of the liver and mini-laparotomy resection of a large tumor located in the upper right lobe. CONCLUSIONS Three-dimensional simulation of hepatectomy facilitated intraoperative identification of the vascular anatomy, and accurately predicted the resected liver volume and surgical margin. This simulation method should contribute to preoperative planning for safe and curative laparoscopic hepatectomy.

Angiogenesis is crucial for liver regeneration after partial hepatectomy.

BACKGROUND Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. METHODS A sFlt-1-expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti-platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. RESULTS The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1-expressing adenoviral vector-infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1-expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. CONCLUSION The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis.

Viral serostatus and coexisting inflammatory activity affect metachronous carcinogenesis after hepatectomy for hepatocellular carcinoma. A further report.

Abstract: Little data are available regarding the effects of hepatitis virus serostatus and the severity of coexisting chronic inflammation on intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC). We investigated the extent to which these factors modified the prognosis of hepatectomized patients. A total of 274 patients treated in the period January 1981 to December 1996 were divided into three groups: anti-hepatitis C-positive (HCV; n = 144), hepatitis B surface antigen-positive and HCV antibody (Ab)-negative (HBsAg; n = 106), and HBsAg-negative and HCV Ab-negative (NBNC; n = 20). Positivity for HBV-related antibody in the HCV group was 76%. Histologic grading of inflammatory activity from coexisting hepatitis was determined according to Knodels histological activity index (HAI) scoring system. Post-hepatectomy crude survival rates and disease-free survival (DFS) rates were compared, according to tumor characteristics, between the three groups. In the patients overall and also in the patients with a single nodular HCC, the HCV group had significantly higher HAI scores and preoperative serum aspartate aminotransaminase (AST) levels than the other two groups. When the patients were limited to those with a single nodular HCC, the crude survival was similar in the three groups with comparable tumor characteristics; however, the DFS was different (NBNC > HBsAg > HCV). When the patients were further limited to those with a single nodular HCC without microscopic extracapsular spread, in whom removal of the tumor was expected to be microscopically complete, the difference in the DFS became more marked. Irrespective of the viral serostatus, better crude and disease-free survivals were observed in the patients with lower AST levels (≧50 IU/l) than in those with higher AST levels (>50 IU/l). In contrast, there were no differences in survivals and HAI scores according to the presence or absence of HBV-related antibody in the HCV group. From our univariate analysis, we can conclude that the severity of virally induced inflammation, which was well correlated with viral serostatus, may be a factor that affects intrahepatic recurrence, which is more likely to originate from metachronous carcinogenesis. Prior co-infection of HBV in HCV patients may not be an adverse risk factor for intrahepatic recurrence.

Evolution of and obstacles in surgical treatment for hepatocellular carcinoma over the last 25 years: differences over four treatment eras.

Abstract: This study was designed to clarify what differences the last 25 years have made in surgical results for patients with hepatocellular carcinoma (HCC). We examined results for 716 hepatectomized patients in four treatment eras: first era (1973–1980; n = 58), second era (1981–1985; n = 155), third era (1986–1990; n = 243), and fourth era (1991–1997; n = 260). Patient background, tumor characteristics, type of hepatectomy, treatment for intrahepatic recurrences, and surgical results in the four eras were compared by univariate analysis to clarify the factors that have contributed to or impeded progress in the surgical treatment of HCC. Although there were no significant chronological differences in liver pathology and surgical resectability, operative mortality was reduced to 2% in the fourth era, from 29% in the first era. With an increasing proportion of early-stage HCCs (TNM, stages I and II), the cumulative survival rate at 5 years improved in the course of the eras in our overall population of patients (12%, 31%, 38%, and 51%, respectively, for the first, second, third, and fourth eras) and in a subset of the population divided according to tumor stage. Also, we found a chronological improvement in the survival rate at 3 years after intrahepatic recurrence (10%, 28%, 36%, and 44%, respectively in the first second, third, and fourth eras). This improvement was associated with the establishment of an early detection program for intrahepatic recurrences. However, the recurrence rate was similar in any subset of the population through the four eras. Although this univariate study could not determine independent factors that contributed to the chronological progress in results for HCC surgery in the four eras, it is conceivable that the establishment of indication criteria for hepatectomy, an early detection program for primary and recurrent lesions, and the introduction of multimodal treatment for recurrence were contributory factors in this im-provement. A strategy for alleviating the frequent recurrences originating from posthepatectomy metachronous carcinogenesis remains to be established.