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Biomedical subjects

Takashi Kanematsu

Publications and source records attributed to Takashi Kanematsu.

At least 19 recordsLinked to original sources
PubMed2007

Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery.

AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepatobiliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arterial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignancies, and the surgical procedures included hepatopancreatoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenectomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful hemostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arterial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic artery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral pathways to the liver created by the primary surgical procedure and a short postoperative interval may lead to an unfavorable outcome.

Aged↗
PubMed2006

HER2-specific T-cell immune responses in patients vaccinated with truncated HER2 protein complexed with nanogels of cholesteryl pullulan.

PURPOSE: We developed a complex of tumor antigen protein with a novel nanoparticle antigen delivery system of cholesteryl pullulan (CHP). To target HER2 antigen, we prepared truncated HER2 protein 1-146 (146HER2) complexed with CHP, the CHP-HER2 vaccine. We designed a clinical study to assess the safety of the vaccine and HER2-specific T-cell immune responses measured by the newly developed enzyme-linked immunospot assay with mRNA-transduced phytohemagglutinin-stimulated CD4(+) T cells in HLA-A2402-positive patients with therapy-refractory HER2-expressing cancers. EXPERIMENTAL DESIGN: Nine patients with various types of solid tumors were enrolled. Each patient was s.c. vaccinated biweekly with 300 microg of CHP-HER2 vaccine for three times followed by booster doses. HER2-specific T-cell responses were evaluated by enzyme-linked immunospot assay by targeting autologous phytohemagglutinin-stimulated CD4(+) T cells transduced with 146HER2-encoding mRNA to cover both identified peptides and unknown epitopes for MHC class I and class II that might exist in the sequence of the vaccine protein. RESULTS: CHP-HER2 vaccine was well tolerated; the only adverse effect was grade 1 transient skin reaction at the sites of vaccination. HER2-specific CD8(+) and/or CD4(+) T-cell immune responses were detected in five patients who received four to eight vaccinations, among whom both T-cell responses were detected in these patients. In four patients with CD8(+) T-cell responses, two patients reacted to previously identified HER2(63-71) peptide and the other two reacted only to 146HER2 mRNA-transduced cells. CONCLUSIONS: CHP-HER2 vaccine was safe and induced HER2-specific CD8(+) and/or CD4(+) T-cell immune responses.

Adult↗
PubMed2006

Comparison between bioartificial and artificial liver for the treatment of acute liver failure in pigs.

AIM: To characterize and evaluate the therapeutic efficacy of bioartificial liver (BAL) as compared to that of continuous hemodiafiltration (CHDF) with plasma exchange (PE), which is the current standard therapy for fulminant hepatic failure (FHF) in Japan. METHODS: Pigs with hepatic devascularization were divided into three groups: (1) a non-treatment group (NT; n = 4); (2) a BAL treatment group (BAL; n = 4), (3) a PE + CHDF treatment group using 1.5 L of normal porcine plasma with CHDF (PE + CHDF, n = 4). Our BAL system consisted of a hollow fiber module with 0.2 mum pores and 1 multiply 10(10) of microcarrier-attached hepatocytes inoculated into the extra-fiber space. Each treatment was initiated 4 h after hepatic devascularization. RESULTS: The pigs in the BAL and the PE + CHDF groups survived longer than those in the NT group. The elimination capacity of blood ammonia by both BAL and PE + CHDF was significantly higher than that in NT. Aromatic amino acids (AAA) were selectively eliminated by BAL, whereas both AAA and branched chain amino acids, which are beneficial for life, were eliminated by PE + CHDF. Electrolytes maintenance and acid-base balance were better in the CPE + CHDF group than that in the BAL group. CONCLUSION: Our results suggest that PE + CHDF eliminate all factors regardless of benefits, whereas BAL selectively metabolizes toxic factors such as AAA. However since PE + CHDF maintain electrolytes and acid-base balance, a combination therapy of BAL plus CPE + CHDF might be more effective for FHF.

Amino Acids, Aromatic↗
PubMed2006

Biliary complications in recipients of living-donor liver transplantation.

The key points of the management of biliary complications in recipients of living-donor liver transplantation are described. The characteristics of these complications are somewhat different from those in deceased-donor liver transplantation, mainly due to the technical difficulties. Appropriate prevention, diagnosis, and treatment are essential for successful transplants, to avoid the development of secondary biliary cirrhosis when complication occurs.

Biliary Tract Diseases↗
PubMed2006

Endoscopic naso-pancreatic stent-guided single-branch resection of the pancreas for multiple intraductal papillary mucinous adenomas.

In benign or low-grade malignant pancreatic tumors, complete removal of the lesion is sufficient for a cure, and thus minimal resection techniques with preservation of the pancreatic functional reserve have advantages over more extended pancreatic resections. However, a high incidence of postoperative pancreatic fistula in such procedures has been reported. Moreover, branch-type intraductal papillary mucinous neoplasms of the pancreas tend to locate in the head of the pancreas, and show less malignant potential. We describe an endoscopic naso-pancreatic stent-guided single-branch resection of the pancreas for branch-type multiple intraductal papillary mucinous adenomas, along with a gastric wall-covering method for the prevention of pancreatic leakage.

Adenoma↗
PubMed2006

Lysosomal turnover of GABARAP-phospholipid conjugate is activated during differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway.

Although conjugation of overexpressed GABARP to phospholipid has been reported during starvation-induced autophagy, it is unclear whether endogenous GABARAP-phospholipid conjugation is also activated under starvation conditions. We observed little accumulation of GABARAP-phospholipid conjugate (GABARAP-PL) in mouse liver and kidney under starvation conditions, whereas endogenous LC3-phospholipid conjugate (LC3-II) accumulated. A small amount of endogenous GABARAP-PL was observed in the heart, independent of starvation. In rapamycin-treated HEK293 cells, there was little accumulation of endogenous GABARAP-PL, even in the presence of lysosomal protease-inhibitors, whereas there was significant accumulation of endogenous LC3-II, together with inactivation of the mTor kinase-signaling pathway. In HeLa and C2C12 cells, GABARAP-PL accumulation in the presence of lysosomal protease inhibitors was independent of starvation-induced autophagy, whereas LC3-II accumulation was significant during starvation-induced autophagy. Interestingly, we observed activation of lysosomal turnover of GABARAP-PL during the differentiation of C2C12 cells to myotubes, along with increased lysosomal turnover of LC3-II. Under these conditions, S6 ribosomal protein was still phosphorylated, suggesting that the mTor kinase-signaling pathway is active during the differentiation of C2C12 cells to myotubes, in contrast to starvation-induced autophagy. These results indicated that lysosomal turnover of GABARAP-PL was activated during the differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway, whereas little lysosomal turnover of GABARAP-PL was activated during starvation-induced autophagy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Evaluation and management of thoracopancreatic fistula.

BACKGROUND: Thoracopancreatic fistula is a rare clinical entity but a serious complication of inflammatory pancreatic diseases, caused by a disruption of the pancreatic ductal system. Its diagnosis is frequently misleading, however, and thus is often delayed. METHODS: Seven patients with thoracopancreatic fistula who presented at our department between March 2002 and July 2005 were investigated, focusing on the diagnostic work-up as well as the treatment strategies, the response to therapy, and the outcome. RESULTS: Thoracopancreatic fistulas developed secondary to alcohol-related chronic pancreatitis in 6 patients and acute severe pancreatitis in 1. The disruption sites of the pancreatic ductal system were the head of the pancreas in 2 patients, the pancreatic body in 2 patients, and the pancreatic tail in 3 patients. All patients, except 1, were complicated with stricture of the main pancreatic duct, with ductal disruptions developing distal to the pancreatic strictures. The precise demonstration of the pancreatic ductal anatomy with ultrasonography, computed tomography (CT), conventional magnetic resonance imaging (MRI), and endoscopic retrograde cholangiopancreatography was limited. In contrast, MR-cholangiopancreatography (MRCP) provided excellent mapping of the pancreatic ductal stricture, disruption, and fistula in 6 patients. Various medical therapies failed to close the fistula in all patients. Subsequent treatments, based on the assessment of pancreatic ductal anatomy with MRCP, included endoscopic transpapillary implantation of a pancreatic stent, a longitudinal pancreaticojejunostomy, distal pancreatectomy, and peritoneal drainage. All patient outcomes were favorable. CONCLUSIONS: MRCP is an essential diagnostic modality in all suspected cases of thoracopancreatic fistula. The goal of treatment should be directed toward a sufficient decompression of the obstructed pancreas. If severe pancreatic stricture is present, then surgical decompression may be required in accordance with the individual pancreatic ductal anatomy.

Adult↗
PubMed2006

A case of mucin producing liver metastases with intrabiliary extension.

A 75-year-old man was admitted to our hospital with a diagnosis of liver metastases from colon cancer. He underwent right hemicolectomy for cecal cancer eight years ago, and had a metastatic liver tumor in segment 8 (S8), which was surgically resected about 4 years after the initial operation. Histopathological examination of the resected specimens from both operations revealed a well-differentiated adenocarcinoma with mucinous carcinoma. Four months after the second operation, computed tomography demonstrated a low-density lesion at the cut surface of the remnant liver. Although it was considered to be a postoperative collection of inflammatory fluid, it formed a cystic configuration and increased in size to approximately 5 cm in diameter. With a tentative diagnosis of a recurrence of metastatic cancer, partial hepatectomy of S8 was performed. Histological examination of the resected specimens also revealed mucinous adenocarcinoma, which had invaded into the biliary ducts, replacing and extending along its epithelium. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 20, but negative for CK7. Therefore, the tumor was diagnosed as a metastatic adenocarcinoma from colonic cancer. Liver metastases of colorectal adenocarcinoma sometimes invade the Glisson's triad and grow along the biliary ducts.

Adenocarcinoma↗
PubMed2006

Bile-reflux into the pancreatic ducts is associated with the development of intraductal papillary carcinoma in hamsters.

BACKGROUND: Reflux of pancreatic juice into the biliary tract is a well-known risk factor for the development of biliary carcinoma. In this study, we investigated the significance of bile-reflux into the pancreatic ducts in pancreatic carcinogenesis, especially in the development of carcinoma in the main pancreatic duct in hamsters. MATERIALS AND METHODS: Syrian hamsters were subjected to three different surgical procedures: cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (Model A); cholecystoduodenostomy along with a dissection of the common bile duct (Model B); or simple laparotomy (Model C). The animals then received weekly subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP), for 9 weeks, and were killed for pathological investigation at 16 weeks after the initial BOP administration. RESULTS: Pancreas carcinomas developed in 95, 88, and 90% of the Model A hamsters (n = 22), B (n = 24), and C (n = 21), respectively. The induced pancreatic tumors were histologically classified into four types: papillary; tubular; cystic adenocarcinoma; or intraductal carcinoma of the main pancreatic duct consisting of intraductal papillary carcinoma (IPC) and intraductal tubular carcinoma (ITC). The number and the incidence of IPCs induced in Model A hamsters were 24 lesions and 77% and were statistically higher than those in Model B (7 lesions and 29%) and C hamsters (7 lesions and 33%) (P < 0.01). Bile-reflux into the pancreatic ducts was clearly demonstrated in only hamsters of Model A by means of Indocyanine green injection via the portal vein. Proliferative cell nuclear antigen labeling indices of the epithelial cells in the main pancreatic duct in hamsters, with no BOP treatment, were 3.8, 0.8, and 1.1% in Models A (n = 10), B (n = 10), and C (n = 10), respectively, and the difference was statistically significant (P < 0.01). CONCLUSIONS: Our findings suggest that bile-reflux into the pancreatic ducts is a significant factor predisposing to the development of IPC of the pancreas through an acceleration of epithelial cell kinetics of the main pancreatic duct.

Adenocarcinoma↗
PubMed2006

Protein phosphatase regulation by PRIP, a PLC-related catalytically inactive protein--implications in the phospho-modulation of the GABAA receptor.

PRIP, phospholipase C related, but catalytically inactive protein was first identified as a novel inositol 1,4,5-trisphosphate binding protein. It has a number of binding partners including protein phosphatase (PP1 and 2A), GABAA receptor associated protein, and the beta subunits of GABAA receptors, in addition to inositol 1,4,5-trisphosphate. The identification of these molecules led us to examine the possible involvement of PRIP in the phospho-regulation of the beta subunits of GABAA receptors using hippocampal neurons prepared from PRIP-1 and 2 double knock-out (DKO) mice. Experiments were performed with special reference to the dephosphorylation processes of the beta subunits. The phosphorylation of beta3 subunits by the activation of protein kinase A in cortical neurons of the control mice continued for up to 5 min, even after washing out of the stimulus, followed by a gradual dephosphorylation. That of DKO mice gradually increased in spite of the lower phosphorylation levels induced by the stimulation. There was little difference in the amount of cellular cyclic AMP and protein kinase A activity between the control and mutant mice, indicating that phosphatases such as PP1 and PP2A are primarily involved in the difference. The time course of PP1 activity changes in the vicinity of the receptors in control mice corresponded to the phosphorylation of PRIP, while that of the mutant mice decreased with the period of the incubation. This is a good agreement with the suggestion that PRIP binds to and inactivates PP1, which is regulated by the phosphorylation of PRIP at threonine 94. These results suggest that PRIP plays an important role in controlling the dynamics of GABAA receptor phosphorylation by through PP1 binding and, therefore, the efficacy of synaptic inhibition mediated by these receptors.

Animals↗
PubMed2006

Modulation of GABA(A) receptor phosphorylation and membrane trafficking by phospholipase C-related inactive protein/protein phosphatase 1 and 2A signaling complex underlying brain-derived neurotrophic factor-dependent regulation of GABAergic inhibition.

Brain-derived neurotrophic factor (BDNF) modulates several distinct aspects of synaptic transmission, including GABAergic transmission. Exposure to BDNF alters properties of GABA(A) receptors and induces changes in the expression level at the cell surface. Although phospholipase C-related inactive protein-1 (PRIP-1) plays an important role in GABA(A) receptor trafficking and function, its role in BDNF-dependent modulation of these receptors, together with the role of PRIP-2, was investigated using neurons cultured from PRIP double knock-out mice. The BDNF-dependent inhibition of whole cell GABA-evoked currents observed in wild type neurons was not detected in neurons cultured from knock-out mice. Instead, a gradual increase in GABA-evoked currents in these neurons correlated with a gradual increase in phosphorylation of GABA(A) receptor beta3 subunit in response to BDNF. To characterize the specific role(s) that PRIP plays as components of underlying molecular machinery, we examined the recruitment of protein phosphatase(s) to GABA(A) receptors. We demonstrate that PRIP associates with phosphatases as well as with beta subunits. PRIP was found to colocalize with GABA(A) receptor clusters in cultured neurons and with recombinant GABA(A) receptors when co-expressed in HEK293 cells. Importantly, a peptide mimicking a domain of PRIP involved in binding to beta subunits disrupted the co-localization of these proteins in HEK293 cells and potently inhibited the BDNF-mediated attenuation of GABA(A) receptor currents in wild type neurons. Together, the results suggest that PRIP plays an important role in BDNF-dependent regulation of GABA(A) receptors by mediating the specific association between beta subunits of these receptors with protein phosphatases.

Animals↗
PubMed2006

A phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and Low-dose consecutive (Cisplatin) CDDP) in advanced biliary tract carcinoma.

BACKGROUND: Unresectable biliary tract carcinoma is known to demonstrate a poor prognosis. We conducted a single arm phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and Low-dose consecutive (Cisplatin) CDDP) for advanced biliary tract malignancies basically on an outpatient basis. METHODS: Between February 1996 and September 2003, 42 patients were enrolled in this trial. LFP THERAPY: By using a total implanted CV-catheter system, 5-FU (160 mg/m2/day) was continuously infused over 24 hours for 7 consecutive days and CDDP (6 mg/m2/day) was infused for 30 minutes twice a week as one cycle. The administration schedule consisted of 4 cycles as one course. RESIST criteria (Response evaluation criteria for solid tumors) and NCI-CTC (National Cancer Institute-Common Toxicity Criteria) (ver.3.0) were used for evaluation of this therapy. The median survival time (MST) and median time to treatment failure (TTF) were calculated by the Kaplan-Meier method. RESULTS: Patients characteristics were: mean age 66.5(47-79): male 24 (54%): BDca (bile duct carcinoma) 27 GBca (Gallbladder carcinoma) 15: locally advanced 26, postoperative recurrence 16. The most common toxicity was anemia (26.2%). Neither any treatment related death nor grade 4 toxicity occurred. The median number of courses of LFP Therapy which patients could receive was two (1-14). All the patients are evaluable for effects with an over all response rates of 42.9% (95% confidence interval C.I.: 27.7-59.0) (0 CR, 18 PR, 13 NC, 11 PD). There was no significant difference regarding the anti tumor effects against both malignant neoplasms. Figure 2 Shows the BDca a longer MST and TTF than did GBca (234 vs 150, 117 vs 85, respectively), but neither difference was statistically significant.The estimated MST and median TTF were 225 and 107 days, respectively. The BDca had a longer MST and TTF than GBca (234 vs 150, 117 vs 85, respectively), but neither difference was statistically significant. CONCLUSION: LFP therapy appears to be useful modality for the clinical management of advanced biliary tract malignancy.

Aged↗
PubMed2006

Remission of primary low-grade gastric lymphomas of the mucosa-associated lymphoid tissue type in immunocompromised pediatric patients.

We report the remission of primary gastric lymphoma of the mucosa-associated lymphoid tissue (MALT) type in two immunocompromised pediatric patients. Patient 1, a 14-year-old boy in an immunocompromised state of unknown cause, complained of repeated abdominal pain. Examinations revealed gastric MALT with local invasion and lymph node involvement. Serum anti-Helicobacter pylori (H pylori) antibody was positive. H pylori eradication was abandoned due to its adverse effects. The MALT lesion spontaneously regressed over the next 24 months without any treatment for lymphoma. Patient 2, a 6-year-old boy, underwent cord blood transplantation for the treatment of adrenoleukodystrophy. He was administered immunosuppressants for graft-versus-host disease after transplantation. Nausea and hematochezia appeared and further examinations revealed gastric MALT with H pylori gastritis. Treatment consisting of medication for the H pylori infection alone eradicated the H pylori and completely resolved the patient's MALT lesion, as well. Patients 1 and 2 were followed up over periods of 10 years and 3 years, respectively, without any signs of relapse. In conclusion, gastric lymphoma of the MALT type can be cured by conservative treatment even in immunocompromised pediatric patients.

Adolescent↗
PubMed2006

Destructive granuloma derived from a liver cyst: a case report.

We herein report the case of an idiopathic liver cystic mass which aggressively infiltrated the thoraco-abdominal wall. A 74-year-old woman who had a huge cystic lesion in her right hepatic lobe was transferred to our hospital for further examinations. Imaging studies revealed a simple liver cyst, and the cytological findings of intracystic fluid were negative. She was followed up periodically by computed tomography (CT) scans. Seven years later, she complained of a prominence and dull pain in her right thoraco-abdominal region. CT revealed an enlargement of the cystic lesion and infiltration into the intercostal subcutaneous tissue. We suspected the development of a malignancy inside the liver cyst such as cystadenocarcinoma, and she therefore underwent surgery. A tumor extirpation was performed, including the chest wall, from the 7th to the 10th rib, as well as a right hepatic lobectomy. Pathologically, the lesion consisted of severe inflammatory change with epithelioid cell granuloma and bone destruction without any malignant neoplasm. No specific pathogens were evident based on further histological and molecular examinations. Therefore the lesion was diagnosed to be a destructive granuloma associated with a long-standing hepatic cyst. Since undergoing surgery, the patient has been doing well without any signs of recurrence.

Abdominal Wall↗
PubMed2006

Intraoperative pancreatography and gastric-wall-covering method for the prevention of pancreatic leakage after enucleation of insulinoma in the pancreas.

Pancreatic leakage is one of the most common complications following pancreatic surgery. Although several surgical techniques and several devices for the management of pancreatic ducts have been advocated to prevent pancreatic leakage, its incidence is still not acceptable. We report our new surgical technique, a gastric-wall-covering method, for the prevention of pancreatic leakage in the enucleation of insulinoma in the pancreas, along with intraoperative pancreatography for navigation surgery of the pancreatic duct. Our novel techniques help to prevent pancreatic leakage following pancreatic surgery, including partial resection of the pancreas.

Digestive System Surgical Procedures↗
PubMed2006

Common fragile genes and digestive tract cancers.

FRA3B and FRA16D are the most sensitive common chromosomal fragile site loci in the human genome. Two tumor suppressor genes, the fragile histidine triad (FHIT) gene and the WW domain-containing oxidoreductase (WWOX), map to the common fragile sites, FRA3B and FRA16D, respectively. Interestingly, FHIT and WWOX have similarities: for example, they are both larger than 1 Mb and encompass fragile sites, they both show frequent allelic loss regions in various human cancers, they both span a region of homozygous deletion in multiple cancers, and they both frequently show aberrant transcripts. The development of human cancers, including digestive tract cancers, is strongly associated with exposure to environmental carcinogens. Common fragile sites are very sensitive to this type of exposure, and the resulting DNA damage leads to the inactivation of genes such as FHIT and WWOX. We present an overview of these two common fragile genes, namely FHIT/FRA3B and WWOX/FRA16D, in digestive tract cancers.

Acid Anhydride Hydrolases↗
PubMed2006

Inferior branch-preserving superior head resection of the pancreas with gastric wall-covering method for intraductal papillary mucinous adenoma.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas showed significantly less aggressive pathologic features compared with common pancreatic cancer. Therefore, several organ-preserving techniques, including duodenum-preserving pancreatic head resection, have been advocated in surgical procedures for IPMN. We describe a surgical technique of superior head resection of the pancreas with inferior branch preservation followed by a gastric wall-covering method for the prevention of pancreatic leakage in patients with IPMN of the pancreas head.

Abdominal Pain↗