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    Yoshihiro Sakamoto

    There has been a pressing need to develop optimal regimen for neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). The safety and efficacy of gemcitabine, S-1, and LV combination (GSL) therapy as NAC for borderline resectable (BR)... more
    There has been a pressing need to develop optimal regimen for neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). The safety and efficacy of gemcitabine, S-1, and LV combination (GSL) therapy as NAC for borderline resectable (BR) and locally advanced (LA) PC was evaluated in this phase II study. Patients with pathologically proven BR or LA PC were enrolled and gemcitabine 1000 mg/m by 30-min infusion on day 1, S-1 40 mg/m orally twice daily, and LV 25 mg orally twice daily on days 1-7 every 2 weeks were provided, and evaluation by CT every 2 courses was performed. The primary end point was R0 resection rate, and the secondary endpoints were resection rate, response rate, adverse events, surgical outcomes, and survival. Twenty-four patients with PC (21 BR and 3 LA) were enrolled. Response rate and disease control rate of NAC were 17.4 and 87.0%. Grade 3 and 4 toxicities involved neutropenia (34.8%), anorexia (17.4%), and mucositis (17.4%). Serum CA19-9 level decreased by 52.2%...
      Recurrent autoimmune hepatitis (AIH) following liver transplantation has been reported in 20-30% of cases, mainly of Western populations. The aim of this study was to review our experience of living-donor liver transplantation (LDLT) in... more
      Recurrent autoimmune hepatitis (AIH) following liver transplantation has been reported in 20-30% of cases, mainly of Western populations. The aim of this study was to review our experience of living-donor liver transplantation (LDLT) in Japanese patients with AIH.   Among 375 adult (age ≥18 years) LDLT performed at our center between 1996 and 2010, 16 (4.2%) were for patients with AIH (n = 12) or AIH-primary biliary cirrhosis overlap syndrome (n = 4). The patient and donor characteristics and post-transplantation course were reviewed.   All recipients were female with a median age of 48 years (range, 21-58). Low-dose methylprednisolone and calcineurin inhibitors were continued in all patients. Acute cellular rejection occurred in 10 (63%), which was more frequent than in our overall series of 28.5% (107/375 cases). Overall survival rate was 81.2% at 5 years. At the end of the follow up (median, 6.0 years [range, 0.1-9.6]), 13 patients were alive with normal liver function tests (aspartate transaminase, 18 ± 5 IU/mL; alanine transaminase, 16 ± 8 IU/mL). None of the survivors exhibited liver function test results suspicious for recurrent AIH, which might indicate liver biopsy.   Survival after LDLT for AIH and overlap syndrome was excellent and there was no evidence of clinical recurrence. The recurrence rate of AIH after liver transplantation may differ among countries, and requires further investigation.
    The prognosis of severe alcoholic hepatitis is poor, and there is no established method for a cure. A 34-year-old man was admitted to Kurume University Hospital because of severe liver dysfunction due to excess alcohol intake. He was... more
    The prognosis of severe alcoholic hepatitis is poor, and there is no established method for a cure. A 34-year-old man was admitted to Kurume University Hospital because of severe liver dysfunction due to excess alcohol intake. He was treated with prednisolone and two sessions of granulocyte and monocyte adsorption apheresis (GCAP) using an Adacolumn, which removes leukocytes--especially granulocytes and monocytes--from the peripheral blood. We evaluated the changes in the serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule-1, as well as the conventional liver tests and peripheral white blood cell count. Prednisolone was effective in the short term but resulted in an increase in C-reactive protein (CRP), peripheral leukocytes, and serum total bilirubin. GCAP performed on the 34th and 41st hospital days produced decreases in the white blood cell count, total bilirubin, and intercellular adhesion molecule-1. The patient survived, despite the expected poor prognosis on admission. GCAP is recommended as a potential therapeutic option for severe alcoholic hepatitis.
    CANGAROO-III is a project to study celestial γ-rays in the 100 GeV region utilizing stereoscopic observations of Cherenkov light with an array of four 10-m imaging atmospheric Cherenkov telescopes (IACTs) (Mori et al., 2000), following... more
    CANGAROO-III is a project to study celestial γ-rays in the 100 GeV region utilizing stereoscopic observations of Cherenkov light with an array of four 10-m imaging atmospheric Cherenkov telescopes (IACTs) (Mori et al., 2000), following the CANGAROO-I 3.8 m ( Hara et al., 1993) and ...
    The standard liver volume (SLV) is widely used in liver surgery, especially for living donor liver transplantation (LDLT). All the reported formulas for SLV use body surface area or body weight, which can be influenced strongly by the... more
    The standard liver volume (SLV) is widely used in liver surgery, especially for living donor liver transplantation (LDLT). All the reported formulas for SLV use body surface area or body weight, which can be influenced strongly by the general condition of the patient. We analyzed the liver volumes of 180 Japanese donor candidates and 160 Swiss patients with normal livers to develop a new formula. The dataset was randomly divided into two subsets, the test and validation sample, stratified by race. The new formula was validated using 50 LDLT recipients. Without using body weight-related variables, age, thoracic width measured using computed tomography, and race independently predicted the total liver volume (TLV). A new formula: 203.3 - (3.61 × age) + (58.7 × thoracic width) - (463.7 × race [1 = Asian, 0 = Caucasian]), most accurately predicted the TLV in the validation dataset as compared with any other formulas. The graft volume for LDLT was correlated with the postoperative prothrombin time, and the graft volume/SLV ratio calculated using the new formula was significantly better correlated with the postoperative prothrombin time than the graft volume/SLV ratio calculated using the other formulas or the graft volume/body weight ratio. The new formula derived using the age, thoracic width and race predicted both the TLV in the healthy patient group and the SLV in LDLT recipients more accurately than any other previously reported formulas.
    Author: Anderson, K. Anjos, JC Ayres, D. Beacom, J. Bediaga, I. de Bellefon, A. Berger, BE Bilenky, S. Blucher, E. Bolton, T. Buck, C. Bugg, W. Busenitz, J. Choubey, S. Conrad, J. Cribier, M. Dadoun, O. Dalnoki-Veress, F. Decowski, M. de... more
    Author: Anderson, K. Anjos, JC Ayres, D. Beacom, J. Bediaga, I. de Bellefon, A. Berger, BE Bilenky, S. Blucher, E. Bolton, T. Buck, C. Bugg, W. Busenitz, J. Choubey, S. Conrad, J. Cribier, M. Dadoun, O. Dalnoki-Veress, F. Decowski, M. de Gouvea, Andre Demutrh, D. ...
    The feasibility of vaccination in liver transplant recipients is highly controversial, and the present study aimed to investigate the efficacy of a 1-year extended, monthly vaccine prophylaxis protocol of a second-generation recombinant... more
    The feasibility of vaccination in liver transplant recipients is highly controversial, and the present study aimed to investigate the efficacy of a 1-year extended, monthly vaccine prophylaxis protocol of a second-generation recombinant vaccine for transplant recipients. The recombinant hepatitis B vaccine (10 µg; Bimmugen, Asteras Pharma Inc., Tokyo, Japan) was administered subcutaneously every month for 12 months as the vaccination protocol to 39 liver transplant recipients in stable condition, including those with hepatitis B-related chronic liver disease (n = 30), those with acute hepatitis B liver failure (HBs-Ab, n = 4), and those with hepatitis B core antibody positive grafts (n = 5). A fixed dose of hepatitis B immune globulin (HBIG) was administered during the study based on the monoprophylaxis approach, and the increase in the hepatitis B surface antibody titer was measured to evaluate the efficacy of the vaccination. The vaccination protocol was initiated 54 (13-124) mont...
    We describe a patch-graft technique using the right ovarian vein for reconstruction of the right hepatic and portal veins after resection in hepatectomy and pancreatoduodenectomy in female patients. After partial resection of the right... more
    We describe a patch-graft technique using the right ovarian vein for reconstruction of the right hepatic and portal veins after resection in hepatectomy and pancreatoduodenectomy in female patients. After partial resection of the right hepatic vein or portal vein for removing either hepatic or pancreatic tumors, the defects were covered by a patch graft from the right ovarian vein. The proximal part of the vein, 5 cm in length, was harvested, divided longitudinally, and then divided into two equal parts, which were sutured together to give a patch measuring 2.5 x 2.0 cm. This technique can be applied for reconstruction after partial resection of the hepatic or portal vein in hepatectomy and pancreatoduodenectomy.
    The scale of high energy physics experiments becomes large. Such a large system makes the data acquisition, DAQ, system bigger and more complex, and the management of the system also becomes more difficult. Therefore, most of the... more
    The scale of high energy physics experiments becomes large. Such a large system makes the data acquisition, DAQ, system bigger and more complex, and the management of the system also becomes more difficult. Therefore, most of the experimenters spend the time to develop the DAQ system for own experiment. However, as the functions required by a DAQ system are almost
    Recently we found that cytokine-induced neutrophil chemoattractant influenced anterior pituitary hormone release in vitro. These observations prompted us to investigate the possibility of the existence of cytokine-induced neutrophil... more
    Recently we found that cytokine-induced neutrophil chemoattractant influenced anterior pituitary hormone release in vitro. These observations prompted us to investigate the possibility of the existence of cytokine-induced neutrophil chemoattractant in the hypothalamus. Immunohistochemistry showed that cytokine-induced neutrophil chemoattractant-like immunoreactivity existed in the paraventricular hypothalamic nucleus, the supraoptic nucleus, both the internal and the external layers of the median eminence and
    Postoperative pancreatic fistula (POPF) is a most striking complication after pancreatic resection. The objective of this study is to reveal the risk factors for POPF defined by the international study group after pancreaticoduodenectomy... more
    Postoperative pancreatic fistula (POPF) is a most striking complication after pancreatic resection. The objective of this study is to reveal the risk factors for POPF defined by the international study group after pancreaticoduodenectomy in a Japanese high-volume center. During the recent 4 years, 220 patients underwent pancreaticoduodenectomies. In patients of obstructive jaundice, preoperative biliary drainage was performed by percutaneous (n = 71) and/or retrograde (n = 38) approach. Pancreaticojejunostomy was performed using either duct-to-mucosa anastomosis (n = 180) or dunking method (n = 40). Risk factors for POPF (grade B or grade C POPF by international definition) were evaluated using univariate and multivariate analyses. POPF was found in 109 (50%) patients; grade A in 45 (21%), grade B in 54 (25%), and grade C in 10 patients (5%). One patient died of intra-abdominal hemorrhage caused by POPF. Univariate and multivariate analyses revealed that independent risk factors for grade B or grade C POPF were the size of the main pancreatic duct (<3 mm; relative risk (RR), 3.3; p = 0.002), body mass index (> or =20, RR 2.5, p = 0.03), and bile juice infection on day 1 (RR, 2.2; p = 0.04). The performance of biliary drainage or method of pancreaticojejunostomy was not a significant risk factor for POPF. Bile juice infection on day 1 was significantly associated with retrograde biliary drainage (p < 0.001). Bile juice infection on day 1 was a significant risk factor for grade B or grade C POPF after pancreaticoduodenectomy. Although the performance or the status of biliary drainage itself was not a risk factor for POPF, percutaneous biliary drainage might be advantageous against retrograde drainage to reduce the risk of biliary infection.
    Surgical resection for pancreatic and hepatic cancer sometimes involves combined resection and reconstruction of the major veins using venous grafts. Autologous venous grafts made from the bilateral gonadal veins (BGVs) have never been... more
    Surgical resection for pancreatic and hepatic cancer sometimes involves combined resection and reconstruction of the major veins using venous grafts. Autologous venous grafts made from the bilateral gonadal veins (BGVs) have never been utilized or discussed. We reconstructed the portal vein (PV), superior mesenteric vein (SMV), and middle hepatic vein (MHV) using cylindrical or patch grafts customized from the BGVs in two female patients and in one male patient. In order to assess the sexual difference in the availability of the cylindrical graft to replace these major veins, we measured the diameters of the BGVs, PV, SMV, and MHV on computed tomography in 50 male and 50 female patients, and estimated the diameter-ratios (DRs) of the cylindrical graft made from BGVs/PV, SMV, and MHV. We assumed that the cutoff value of the DR would be 0.8, for replacing of major veins using cylindrical grafts. The reconstructed PV, SMV, and MHV presented sufficient patency, and the postoperative courses were uneventful. The DRs of BGVs graft/PV, graft/SMV, and graft/MHV were significantly larger in female patients than those in male patients (0.82 vs. 0.54, p < 0.01, 0.96 vs. 0.61, p < 0.01, 1.39 vs. 0.95; p < 0.01) and were larger than 0.8 in 50%, 70%, and 92% in female patients, respectively, and 0%, 8%, and 68% in male patients, respectively. The present newly customized cylindrical and patch grafts made from the BGVs showed sufficient feasibility. A cylindrical graft made from the BGVs would be better utilized in female patients than in male patients.
    The aim of this study was to investigate the clinicopathologic characteristics of sal-like protein 4 (SALL4)-immunopositive hepatocellular carcinoma (HCC). Solitary HCCs that were surgically treated at the University of Tokyo Hospital... more
    The aim of this study was to investigate the clinicopathologic characteristics of sal-like protein 4 (SALL4)-immunopositive hepatocellular carcinoma (HCC). Solitary HCCs that were surgically treated at the University of Tokyo Hospital between 2000 and 2008 were the subject of this study. Diffuse, non-punctate nuclear immunoreactivity to SALL4 was observed in 47 of 337 HCCs (13.9%). Compared to patients with SALL4-negative HCC, patients with SALL4-positive HCC were younger (mean 59.2 years vs. 65.2 years), more frequently female (44.7% vs. 18.3%) and positive for hepatitis B virus angigen (42.6% vs. 18.6%). They had much higher serum levels of alpha-fetoprotein (median 3976.5 ng/ml vs. 14.0 ng/ml) (P < 0.001). Liver function tended to be favourable, as was shown by less indocyanine green retention at 15 minutes (ICG15), in patients with SALL4-positive HCCs (P < 0.001). Histologically, SALL4-positive HCCs exhibited less histological differentiation (P < 0.001) and had a higher frequency of micro- or macrovascular invasion (72.3% vs. 54.1%, P = 0.019) and intrahepatic metastasis (34.0% vs. 19.3%, P = 0.022) than SALL4-negative HCCs. SALL4-positive HCCs were more frequently immunoreactive for cytokeratin 19 (42.6% vs. 11.7%, P < 0.001) and EpCAM (51.1% vs. 8.3%, P < 0.001). The log-rank test indicated short-term disease-free survival (< 1 year) of patients with SALL4-positive HCC was worse than those with SALL4-negative HCC (P = 0.019). Multivariate analyses, however, failed to show the prognostic significance of SALL4 immunoreactivity in HCCs. In conclusion, SALL4-immunopositive HCCs constitute a subset with characteristic patient backgrounds and somewhat aggressive behavior, as was manifested by frequent vascular invasion and intrahepatic metastasis. There was little prognostic significance of SALL4 immunoreactivity in HCCs.
    A 50-year-old woman presented with intermittent diarrhea and upper abdominal pain. Laboratory data showed elevated serum amylase and elastase-I levels. Further image studies revealed a small, well-defined nodular lesion (8 mm in diameter)... more
    A 50-year-old woman presented with intermittent diarrhea and upper abdominal pain. Laboratory data showed elevated serum amylase and elastase-I levels. Further image studies revealed a small, well-defined nodular lesion (8 mm in diameter) without mucin hypersecretion in the main pancreatic duct (MPD) of the pancreatic head and subsequent dilatation of the distal main pancreatic duct. A pylorus-preserving pancreatoduodenectomy with regional lymphadenectomy
    The justification for surgical resection of liver metastases from gastric cancer remains controversial. Twenty-two patients who underwent 26 hepatectomies for liver metastases of gastric cancer between 1985 and 2001 were analyzed. Fifteen... more
    The justification for surgical resection of liver metastases from gastric cancer remains controversial. Twenty-two patients who underwent 26 hepatectomies for liver metastases of gastric cancer between 1985 and 2001 were analyzed. Fifteen clinicopathologic factors were evaluated with univariate and multivariate analyses for survival after hepatic resection. The overall 1-year, 3-year, and 5-year survival rates after hepatectomy for gastric metastases were 73%, 38%, and 38%, respectively. Five patients survived for more than 3 years without recurrence, 3 of whom had synchronous metastases resected at the time of gastrectomy. The best results after surgical resection for liver metastases of gastric cancer were obtained with solitary metastases less than 5 cm in size. The number of liver metastases (solitary or multiple) was the only significant prognostic factor according to both univariate and multivariate analyses. Surgical resection for liver metastases of gastric cancer may be ben...
    Segmental resection of major hepatic veins or the portal vein is sometimes required if one is to secure adequate surgical margins from hepatic or pancreatic malignancies. An external iliac vein is widely sacrificed as a vein graft to... more
    Segmental resection of major hepatic veins or the portal vein is sometimes required if one is to secure adequate surgical margins from hepatic or pancreatic malignancies. An external iliac vein is widely sacrificed as a vein graft to replace the defect, but this is associated with postoperative edema of the lower leg. We developed a new method for constructing the great saphenous vein to interpose the hepatic or portal veins. The great saphenous vein was divided transversely into three sections, which were aligned side-to-side. The three pieces were anastomosed to make a sheet 3 x 2 cm, which was rolled up into a cylindrical form of approximately 1 cm in diameter and 2 cm in length. We applied the finished vein grafts to interpose the major hepatic veins in three patients with metastatic liver tumors and the portal vein in two patients with pancreatic malignancies in cylindrical form and to reconstruct the portal vein in one patient with a pancreas cancer, using a three-row sheet as...
    BACKGROUND: Despite recent advances in surgical techniques, hepatectomies remain one of the most hemorrhagic procedures in abdominal surgery. It is important to identify preoperatively patients who are at high risk of suffering massive... more
    BACKGROUND: Despite recent advances in surgical techniques, hepatectomies remain one of the most hemorrhagic procedures in abdominal surgery. It is important to identify preoperatively patients who are at high risk of suffering massive intraoperative blood loss. METHODS: The clinical records of 251 patients who underwent an elective hepatectomy for liver tumors between September 2007 and December 2009 were reviewed retrospectively. A multivariate logistic regression analysis of preoperative factors potentially influencing intraoperative blood loss was performed. We set the cut-off value of the amount of blood loss for safe hepatectomy as less than 1,500 mL because no patients with blood loss of less than 1,500 mL received blood transfusion in this study. A scoring system to predict blood loss of more than 1,500 mL was constructed and validated in a cohort of 59 subsequent patients. RESULTS: Intraoperative blood loss of more than 1,500 mL was recognized in 35 of 251 patients (13.9%)....
    Pancreas-sparing duodenectomy (PSD) is a promising alternative procedure to pancreaticoduodenectomy for the treatment of duodenal tumors with low-grade malignant behavior. Between March 2003 and September 2012, PSD was performed in 7... more
    Pancreas-sparing duodenectomy (PSD) is a promising alternative procedure to pancreaticoduodenectomy for the treatment of duodenal tumors with low-grade malignant behavior. Between March 2003 and September 2012, PSD was performed in 7 patients with a gastrointestinal stromal tumor (GIST) in the second (n = 5) or third (n = 2) portions of the duodenum. The short- and long-term outcomes of treatment were analyzed in all patients. The median blood loss was 160 mL, and the median operative time was 315 minutes. No pancreatic leakage or perioperative mortality occurred. Surgical margins were negative in all cases. All patients were alive at the median follow-up time of 42 months after PSD. The recurrence-free 5-year survival rate was 53% in all patients. Hepatic metastases developed in 2 of the 5 patients with high- or intermediate-grade risks at the time of diagnosis. Hepatic resection was performed, and imatinib mesylate was administered in the 2 cases. Good short- and long-term outcome...
    It remains unclear whether primary colorectal cancer and synchronous liver metastases (SLMs) should be resected simultaneously or with a staged procedure. We reviewed the short-term outcomes of 127 patients who underwent simultaneous... more
    It remains unclear whether primary colorectal cancer and synchronous liver metastases (SLMs) should be resected simultaneously or with a staged procedure. We reviewed the short-term outcomes of 127 patients who underwent simultaneous resection of primary colorectal cancer and SLM at our institution from January 1993 to December 2011. The proportion of simultaneous resections was 84.7% (127 of 150 patients). There was no postoperative mortality, and the postoperative complication rate was 61.4%. Major complications occurred in 23 (18.2%) patients, and anastomotic failure occurred in 2 (1.6%). The 3-, 5-, and 10-year overall survival rates were 74%, 64%, and 52%, respectively. The median recurrence-free survival period was 7.0 months (95% confidence interval, 4.5-9.5 months) and the 5-year recurrence-free survival rate was 17%. Simultaneous resection can be performed safely in patients with colorectal cancer and SLM.
    Presence of hepatic vein tumor thrombosis (HVTT) in patients with hepatocellular carcinoma (HCC) is regarded as signaling an extremely poor prognosis. However, little is known about the prognostic impact of surgical treatment for HVTT.... more
    Presence of hepatic vein tumor thrombosis (HVTT) in patients with hepatocellular carcinoma (HCC) is regarded as signaling an extremely poor prognosis. However, little is known about the prognostic impact of surgical treatment for HVTT. Our database of surgical resection for HCC between October 1994 and December 2011 in a tertiary care Japanese hospital was retrospectively analysed. We statistically compared the patient characteristics and surgical outcomes in HCC patients with tumor thrombosis in a peripheral hepatic vein, including microscopic invasion (pHVTT), tumor thrombosis in a major hepatic vein (mHVTT), and tumor thrombosis of the inferior vena cava (IVCTT). Among 1525 hepatic resections, 153 cases of pHVTT, 21 cases of mHVTT, and 13 cases of IVCTT were identified. The median survival time (MST) in the pHVTT and mHVTT groups was 5.27 and 3.95 years, respectively (p=0.77), and the median time to recurrence (TTR) was 1.06 and 0.41 years, respectively (p=0.74). On the other han...
    We sought to evaluate whether pancreatic elasticity, measured using acoustic radiation force impulse (ARFI) imaging, can determine the degree of pancreatic fibrosis and risk of pancreatic fistula (PF) in patients undergoing pancreatic... more
    We sought to evaluate whether pancreatic elasticity, measured using acoustic radiation force impulse (ARFI) imaging, can determine the degree of pancreatic fibrosis and risk of pancreatic fistula (PF) in patients undergoing pancreatic resection. Although soft pancreatic texture is a reliable predictor of postoperative PF, noninvasive, quantitative methods of assessing pancreatic hardness have not been established. Shear wave velocity (SWV) of the pancreas was preoperatively measured by ARFI imaging in 62 patients undergoing pancreatic resection. Correlations of SWV with pathologic degree of fibrosis in the resected pancreas, exocrine function of the remnant pancreas, and the incidence of postoperative PF were determined. The SWV was positively correlated with the degree of pancreatic fibrosis (Spearman's rank correlation coefficient [ρ] = 0.660, p < 0.001) and inversely correlated with postoperative amylase concentrations and daily output of pancreatic juice. The incidence of...
    The reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver... more
    The reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival. Recipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted. Early reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The...
    Although radiofrequency ablation (RFA) is an effective local ablative technique for the treatment of hepatocellular carcinoma (HCC), the optimal treatment for recurrence after RFA has not been established. Between September 2002 and... more
    Although radiofrequency ablation (RFA) is an effective local ablative technique for the treatment of hepatocellular carcinoma (HCC), the optimal treatment for recurrence after RFA has not been established. Between September 2002 and December 2011, 46 hepatectomies (salvage group) were performed for intrahepatic (local or multifocal) recurrent HCC after RFA. The difference between the imaging findings before RFA and at the time of salvage resection, especially in the Local recurrent group, and the short-term and long-term outcomes after salvage surgery were analyzed retrospectively by comparing them with those for a matched control group (n = 46) and with those of patients who underwent a second hepatic resection for HCC recurrence after an initial hepatic resection during the same period (n = 155). The tumor-occupying region was more distributed widely before the salvage resection compared with that before RFA, and a more extensive operation would have been required (rather than the...
    Directed differentiation and purification of mesencephalic dopaminergic (mesDA) neurons from stem cells are crucial issues for realizing safe and efficient cell transplantation therapies for... more
    Directed differentiation and purification of mesencephalic dopaminergic (mesDA) neurons from stem cells are crucial issues for realizing safe and efficient cell transplantation therapies for Parkinson's disease. Although recent studies have identified the factors that regulate mesDA neuron development, the mechanisms underlying mesDA neuron specification are not fully understood. Recently, it has been suggested that mesencephalic floor plate (FP) cells acquire neural progenitor characteristics to generate mesDA neurons. Here, we directly examined this in a fate mapping experiment using fluorescence-activated cell sorting (FACS) with an FP cell-specific surface marker, and demonstrate that mesencephalic FP cells have neurogenic activity and generate mesDA neurons in vitro. By contrast, sorted caudal FP cells have no neurogenic potential, as previously thought. Analysis of dreher mutant mice carrying a mutation in the Lmx1a locus and transgenic mice ectopically expressing Otx2 in caudal FP cells demonstrated that Otx2 determines anterior identity that confers neurogenic activity to FP cells and specifies a mesDA fate, at least in part through the induction of Lmx1a. We further show that FACS can isolate mesDA progenitors, a suitable transplantation material, from embryonic stem cell-derived neural cells. Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease.
    The surgical outcome of middle and/or distal bile duct cancer remains unsatisfactory. Although the resectional margin is known to be a predictive factor, the prognostic significance of a positive ductal margin and other radial margin has... more
    The surgical outcome of middle and/or distal bile duct cancer remains unsatisfactory. Although the resectional margin is known to be a predictive factor, the prognostic significance of a positive ductal margin and other radial margin has never been evaluated independently. The clinicopathologic data of 55 patients who had undergone surgical resection for middle and/or distal bile duct cancer between 1987 and 2003 were reviewed retrospectively. The surgical procedures consisted of pancreatoduodenectomy in 42 patients (76%), extrahepatic bile duct resection in 8 patients (15%), major hemihepatectomy (Hx) in 3 patients (5%), and pancreatoduodenectomy plus Hx in 2 patients (4%). In all the patients, intraoperative diagnosis of the ductal margins was performed using frozen sections. Twenty-one clinicopathologic factors, including the status of the ductal margins and of other radial margins, were evaluated using univariate and multivariate analyses. The overall 5-year survival rate and the median survival time were 24% and 38 months, respectively. There were 4 (7%) postoperative deaths. Fifteen of the remaining 51 patients (29%) were determined to have positive hepatic-side ductal margins during operation, and 14 of them underwent additional resection of the bile duct (1.6[range, 1-3] times, on average). As a result, hepatic-side ductal margin (hm) and duodenal-side ductal margin were found to be positive in 6 and 0 patients on the final pathologic analysis, respectively. Two of the 6 patients (33%) with positive hm have developed ductal recurrence so far, but the status of hm was not found to be a significant predictor. The depth of neoplastic invasion into the bile duct wall, pancreatic invasion, radial margin, and blood transfusion were significant prognostic factors by the univariate analysis. Multivariate analysis revealed that the depth of neoplastic invasion and blood transfusion were the independent prognostic factors. In the treatment of middle and distal bile duct cancer, it is of importance to secure a negative radial margin, although it may be less beneficial to obtain a negative hm. Surgeons should make efforts to obtain negative radial margins and to avoid blood transfusion.
    The purpose of this review is to address three important questions concerning hepatic resection for multiple colorectal metastases. (1) Is the number of tumors truly a significant prognostic factor? (2) Are patients with four or more... more
    The purpose of this review is to address three important questions concerning hepatic resection for multiple colorectal metastases. (1) Is the number of tumors truly a significant prognostic factor? (2) Are patients with four or more tumors contraindicated for hepatic resection? (3) Up to how many nodules should we attempt to resect? Although the efficacy of surgical resection for one
    Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular... more
    Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression.
    KEKB is an electron-positron two-ring collider for the leading B meson factory. It consists of an 8 GeV electron ring (HER) and a 3.5 GeV positron ring (LER) and their injector linac. It has been operated since December 1998, and has... more
    KEKB is an electron-positron two-ring collider for the leading B meson factory. It consists of an 8 GeV electron ring (HER) and a 3.5 GeV positron ring (LER) and their injector linac. It has been operated since December 1998, and has recently marked the peak luminosity of 17.12 /nb/s. This peak luminosity is obtained under the crab- ready beam optics
    The paper presents a brief description of the models incorporated in PHITS and the present status of the code, showing some benchmarking tests of the PHITS code for accelerator facilities and space radiation.
    We describe a case in which segmental resection of the third portion of the duodenum was performed for a gastrointestinal stromal tumor (GIST). A 31-year-old woman was found to have a 3.5 cm hypovascular tumor at the posterior inferior... more
    We describe a case in which segmental resection of the third portion of the duodenum was performed for a gastrointestinal stromal tumor (GIST). A 31-year-old woman was found to have a 3.5 cm hypovascular tumor at the posterior inferior aspect of the pancreatic head. Preoperative duodenal biopsy revealed that the tumor was positive for c-kit and vimentin, and was diagnosed as a duodenal GIST. Segmental resection of the third portion of the duodenum with papilloplasty and duodenojejunostomy was carried out and there were no postoperative complications. Pancreatoduodenectomy is not always necessary in the treatment of a duodenal GIST. This duodenectomy procedure can serve as a less extensive resection for a duodenal GIST located in the third portion of the duodenum.
    One of the current most-demanded experiments in neutrino physics is to measure the last mixing angle theta_13. KASKA is an experiment to detect new type of reactor neutrino oscillation and to measure sin^2 2theta_13 accurately using the... more
    One of the current most-demanded experiments in neutrino physics is to measure the last mixing angle theta_13. KASKA is an experiment to detect new type of reactor neutrino oscillation and to measure sin^2 2theta_13 accurately using the world's most powerful nuclear reactor complex; Kashiwazaki-Kariwa nuclear power station. KASKA utilizes near and far detectors of identical structure at nearly optimized baselines
    Results: The serum amylase activity levels of the supe- rior mesenteric artery clamp and nonclamp groups did not differ significantly during the 7 postoperative days. The serum amylase activity levels exceeded 250 U/L in 14 patients... more
    Results: The serum amylase activity levels of the supe- rior mesenteric artery clamp and nonclamp groups did not differ significantly during the 7 postoperative days. The serum amylase activity levels exceeded 250 U/L in 14 patients (group 1) and remained below this level in 26 (group 2). The salivary-type isozyme levels of group 1 increased significantly compared with those of
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