Nobukazu Kuroda

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.

Fascin, a novel marker of human hepatic stellate cells, may regulate their proliferation, migration, and collagen gene expression through the FAK-PI3K-Akt pathway

Fascin is a component of actin bundles and may regulate various cellular events. The expression and function of fascin in human hepatic stellate cells (HSCs) has remained largely uncharacterized. Fascin expression in human liver tissue was studied using immunohistochemistry. To identify cells expressing fascin, double immunofluorescent staining with vimentin, α-smooth muscle actin (α-SMA), or fibulin-2 was performed and analyzed with confocal microscopy. In culture experiments, fascin expression and the phosphorylation of focal adhesion kinase (FAK) and Akt in LX-2 cells, a cell line of human HSCs, were investigated using western blot. Specific siRNAs were used to reduce the expression of fascin in LX-2 cells. Proliferation and migration were assayed with a CyQuant assay kit and a Matrigel-coated culture insert system, respectively. Levels of matrix metalloproteinase (MMP)-2 and collagen mRNAs were examined using quantitative RT-PCR. Immunohistochemistry revealed the expression of fascin along sinusoids and overlapping with vimentin and α-SMA in both non-fibrotic and fibrotic liver tissue, but it was almost absent in periportal myofibroblastic cells and did not colocalize with fibulin-2, a marker of portal myofibroblasts. In addition, fascin immunoreactivity was almost undetectable in septa of fibrotic human liver tissue. The expression of fascin in LX-2 cells was confirmed using western blot. Two different specific siRNAs against fascin significantly reduced the number of viable LX-2 cells to 65% compared with control cultures and downregulated the mRNAs levels of types I and III collagen and MMP-2 to 62%, 65%, and 70% of control levels, respectively. This condition also reduced the migration activity of LX-2 cells to 46% of control cells and the phosphorylation level of both FAK and Akt. Fascin may be an excellent novel marker of human HSCs that distinguishes HSCs from periportal myofibroblasts. Fascin may regulate functions of human HSCs through the FAK-phosphoinositide 3-kinase-Akt pathway.

Multivariate logistic regression analysis for prediction of clinically relevant pancreatic fistula in the early phase after pancreaticoduodenectomy

Postoperative pancreatic fistula (PF) remains a major complication after pancreaticoduodenectomy (PD). We aimed to investigate the predictors of clinically relevant PF after PD.

Multivariate analysis of liver regenerative capacity after hepatectomy in humans

Many factors affect liver regeneration after partial hepatectomy; however, those factors that are essential for regulation of liver regeneration in humans are not known. Using multiple regression analysis we conducted a study to determine essential factors involved in the speed of liver regeneration after hepatectomy. The subjects were 59 patients who underwent hepatic resection between January 1980 and December 1991. A regression equation for predicting regeneration speed (Y; cm3/day) during the 1st postoperative month was obtained by stepwise forward multiple regression analysis, using 11 explanatory parameters (Xi). The regeneration speed and the resection ratio (%; indicating the magnitude of resection) were calculated based on a computed tomography (CT) scan volumetric study. The degree of liver fibrosis, expressed as the fibrotic index (%), was morphometrically determined in Azan-Mallory stained sections. Of the 11 explanatory parameters, the resection ratio and the fibrotic index had a significant simple correlation with Y. The following regression equation was obtained: Y (cm3/day)=−1.1+3.7 × resection ratio −5.4 × alkaline phosphatase −3.7 × fibrotic index +1.2× total bilirubin −2.6 × glutamic pyruvic transaminase (multiple correlation coefficient, 0.82). We found that the extent of resection and the degree of fibrosis, as well as alkaline phosphatase, total bilirubin, and glutamic pyruvic transaminase, contributed to the speed of regeneration after partial hepatectomy.

Comparison between mucinous cystic neoplasm and intraductal papillary mucinous neoplasm of the branch duct type of the pancreas with respect to expression of CD10 and cytokeratin 20.

Objective: Mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the branch duct type (IPMN-BD) differ in biological and clinical behaviors, but MCN is often misdiagnosed as IPMN-BD. The purpose of this study was to find useful markers for the differential diagnosis of MCN and IPMN-BD. Methods: Immunohistochemically, the expression of the 2 types of mucin (MUC) 1 (MUC1/DF3 and MUC1/CORE), MUC2, MUC5AC, MUC6, human gastric mucin (HGM), caudal-related homeobox transcription factor 2 (CDX2), CD10, cytokeratin (CK) 7, and CK20 was examined in 7 cases of MCN and 16 cases of IPMN-BD. Results: Expression frequencies in MCN and IPMN-BD were 100% versus 44% for MUC1/DF3, 86% versus 31% for MUC1/CORE, 57% versus 19% for MUC2, 86% versus 100% for MUC5AC, 57% versus 88% for MUC6, 86% versus 100% for HGM, 57% versus 0% for CDX2, 71% versus 0% for CD10, 100% versus 69% for CK7, and 86% versus 6% for CK20. Conclusions: Mucin 1/DF3, MUC1/CORE, CDX2, CD10, and CK20 were expressed significantly more frequently in MCN than in IPMN-BD. In particular, CD10 and CK20 showed marked differences in immunohistochemical sensitivity and specificity between MCN and IPMN-BD. It is therefore proposed that CD10 and CK20 may be used for the differential diagnosis of MCN and IPMN-BD.

Does Topical Cooling Alleviate Ischemia/Reperfusion Injury During Inflow Occlusion in Hepatectomy? Results of an Experimental and Clinical Study

Abstract This study was undertaken to evaluate whether topical cooling can alleviate ischemia/reperfusion injury, after continuous inflow occlusion during hepatectomy. Using a canine model of 70% partial liver ischemia (60 min), alteration in the subcellular (cytoplasm, mitochondria, nucleus) elements calcium, sodium, potassium, and chloride, and liver functions following reperfusion were compared between control livers and livers subjected to topical cooling down to 23°± 4.9°C by seeding ice slush over the ischemic lobe. The elements were determined by X-ray microanalysis using liver biopsy specimens. A similar clinical study was undertaken examining ten patients with hepatocellular carcinoma and chronic liver disease who underwent right-sided segmentectomy under continuous right inflow occlusion, five of whom were given topical cooling and five of whom were not. In the experimental study, postreperfusion worsening of liver function tests was significantly suppressed in the cooling group, which was associated with the suppression of subcellular Ca, Na, and Cl increases and K decreases after reperfusion. In the clinical study, the occlusion time was significantly longer in the hypothermic patients than in the normothermic patients, but no significant differences in postoperative liver function or postischemic increases in Ca, Na, or Cl and decreases in K were observed. These experimental and clinical findings suggest that topical cooling alleviates ischemic insult and enhances safe prolonged inflow occlusion.

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.