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Biomedical subjects

Kohei Hashizume

Publications and source records attributed to Kohei Hashizume.

17 recordsLinked to original sources

Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma.

For better total survival rate of children with hepatoblastoma, the therapeutic strategy for recurrent or metastatic hepatoblastoma should be improved. From 1991 to 1999, 134 cases of hepatoblastoma were treated by surgery and combination chemotherapy of cisplatin (CDDP) and THP-Adriamycin (THP-ADR) based on the JPLT-1 protocol. In 114 non-metastatic cases, 90 primary liver tumors were resected completely by partial hepatectomy, but 12 recurrences were observed in the liver (4 cases) and the lungs (8 cases). Distant metastases on the diagnosis were observed in 20 cases. The treatment outcome of these 12 recurrent and 20 metastatic tumors was analyzed. In four recurrent liver tumors, surgical resection was performed in all four cases, and all the patients were alive and well. In eight recurrent lung tumors, surgical resection was performed completely in six cases with unilateral lung disease, and five of the six patients were alive and well. In stage IV tumors, the survival rate of the patients having primary tumors within two hepatic sections was significantly higher than that of the patients having primary tumors over three hepatic sections. Active surgical intervention to lung metastases and a more intensive chemotherapy to facilitate complete resection of primary hepatic tumor could improve survival rate of children with refractory hepatoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Experimental study of the embryogenesis of gastrointestinal duplication and enteric cyst.

The theory of gastrointestinal duplication and enteric cyst embryogenesis was verified by examining the developmental process of this experimentally induced anomaly. In Cynopus pyrrhogaster (amphibian) embryos (stage 18), the dorsal midline structures (including the neural plate and notochord) were split regionally to induce partial separation of the notochord and gut anlage endoderm herniation between the split elements of the notochord. Following this procedure, the embryonic development was traced morphologically and histologically. Control embryos were cultured without the procedure. Following the incubation and breeding period, gastrointestinal duplication and enteric cysts were observed with vertebral anomaly, spina bifida, split cord malformation and subcutaneous manifestations in the mature animals. The combination of anomalies that was observed in these experimental animals is consistent with that found in "split notochord syndrome." No abnormal morphology or histology was observed in the control group. The embryogenetic theory of gastrointestinal duplication and enteric cysts was thus verified by simulating the partial separation of the notochord, which induced split notochord syndrome in laboratory animals. The results indicate that gastrointestinal duplication and enteric cysts may arise through a process of herniation of the gut anlage endoderm between split elements of the notochord.

Amphibians↗

Successful repair of the esophagus in type-IV laryngo-tracheo-esophageal cleft using interposed jejunum.

The authors present a female patient of type-IV laryngo-tracheo-esophageal cleft (LTEC) who survived the definitive operation and was discharged from the hospital. Separation of the trachea and the esophagus was very difficult because they formed almost cylindrical common channel and multiple fistulae occurred after the operation. After multiple attempts of closure of the fistulae, one fistula near the carina remained, and the esophagus was reconstructed using interposed jejunum leaving some part of the esophagus connected to the fistula. Now she is practicing oral feeding. This is the fourth long-term survivor of type-IV LTEC in the international literature.

Abnormalities, Multiple↗

Successful transplantation of a 20% partial liver graft in rats: a technical innovation.

BACKGROUND: Graft-size disparity negatively impacts the postoperative outcome in the setting of adult-to-adult living donor liver transplantation. MATERIALS AND METHODS: As a model for partial liver transplantation in rats using a minimized graft volume, we orthotopically transplanted a 20% reduced-size liver with the two-cuff method. Blood chemistry, graft weight restoration, and labeling indices of 5-bromo-2'-deoxyuridine were estimated. RESULTS: We achieved 100% 2-week survival. Hepatic mass was restored rapidly with early normalization of biochemical parameters, although albumin synthesis capacity required more time to recover. CONCLUSION: This technique has great potential for research as well as a therapeutic approach to regeneration and functional recovery of small liver grafts under various posttransplant circumstances.

Animals↗

Congenital extrahepatic portocaval shunt (Abernethy type 2), huge liver mass, and patent ductus arteriosus--a case report of its rare clinical presentation in a young girl.

The authors report a case of congenital extrahepatic portocaval shunt with a hypoplastic portal vein. This type of shunt is called an Abernethy type 2 shunt, where the portal vein and inferior vena cava are connected side to side, and a hypoplastic portal flow exists in the liver parenchyma. This case of a young girl is complicated with a cardiac anomaly and a large hyperplastic nodule in the liver. This phenotype usually is seen in the Abernethy type 1 shunt, which is a side-to-end shunt with the complete absence of a portal vein. In this context, the current case is very unique in its clinical manifestation, and this phenotype has never been reported. Therefore, it is important to speculate the etiology and treatment of this kind of abnormality and its associated hepatic mass.

Abnormalities, Multiple↗

Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors.

Expression of the p16INK4A (p16), p15INK4B (p15), and p14ARF genes, located at 9p21, was examined in pediatric neuroblastoma (NB), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS). p16 expression was absent in 4 of 5 ESs, and 2 of these 4 cases died. p16 expression was reduced or absent in 10 of 12 RMSs, and 4 of these 10 cases died. These results suggested the possibility that p16 expression was associated with the progression of ES and RMS. There has been no previous report on p14ARF in NB. Our investigation might indicate that abnormal expression of the p16 and p14ARF was associated with a poor prognosis in NB, although in some cases of NB normal p16 and abnormal p14ARF expression was seen. These findings suggest an important role of p14ARF gene in the tumorigenesis of NB. The different incidence of expression of the p16, p15, and p14ARF genes in these 3 tumor types may reflect differences of the molecular process through which the 3 tumors develop. Our results suggest that abnormal expression of the p16 and/or p14ARF may be associated with a poor prognosis in these 3 tumors.

Blotting, Southern↗

A potent inhibitor of cytosolic phospholipase A2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injury in mice.

Acute respiratory distress syndrome (ARDS) is an acute lung injury of high mortality rate, and sepsis syndrome is one of the most frequent causes of ARDS. Metabolites of arachidonic acid, including thromboxanes and leukotrienes, are proinflammatory mediators and potentially involved in the development of ARDS. A key enzyme for the production of these inflammatory mediators is cytosolic phospholipase A(2) (cPLA(2)). Recently, it has been reported that arachidonyl trifluoromethyl ketone (ATK) is a potent inhibitor of cPLA(2). In the present study, we hypothesized that pharmacological intervention of cPLA(2) could affect acute lung injury. To test this hypothesis, we examined the effects of ATK in a murine model of acute lung injury induced by septic syndrome. The treatment with ATK significantly attenuated lung injury, polymorphonuclear neutrophil sequestration, and deterioration of gas exchange caused by lipopolysaccharide and zymosan administration. The current observations suggest that pharmacological intervention of cPLA(2) could be a novel therapeutic approach to acute lung injury caused by sepsis syndrome.

Animals↗

Efficacy and safety of immunization for pre- and post- liver transplant children.

BACKGROUND: Infection is a serious complication after liver transplantation. Immunization is one means of controlling infections. The objective of this study was to investigate the efficacy and safety of simultaneous administration of several vaccines before transplantation and the efficacy and safety of administration under immunosuppressive conditions after transplantation. METHODS: Fifty-eight patients who underwent living-related liver transplantation between April 1994 and March 2000 were included in this study. Simultaneous administration of a maximum of six vaccines was performed in a short period of time before transplantation. We also readministered vaccines to 15 patients with waning antibody titers after transplantation from June 1999. We investigated whether patients could seroconvert for measles, rubella, mumps, and varicella after immunization and how long antibody titers could be retained by measuring them several times throughout the period before and after transplantation. We also examined side effects caused by immunization. RESULTS: The rates of seroconversion against measles, rubella, mumps, and varicella after the pretransplantation vaccination were 82%, 100%, 90%, and 95%, respectively. The rates of reseroconversion against measles, rubella, mumps, and varicella after the posttransplantation revaccination were 85%, 100%, 100%, and 71%, respectively. Although antibody titers against these viruses generally waned with time, no patient exhibited any serious illness or side effects. CONCLUSION: Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.

Adolescent↗

Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors.

The hSNF5/INI1 gene, which encodes a subunit of the SWI/SNF family of chromatin-remodeling complexes and is located at 22q11.2, has been reported as a tumor suppressor gene inactivated in malignant rhabdoid tumors (MRTs). We analyzed this gene in varieties of pediatric solid tumors including MRTs, using the reverse transcription-polymerase chain reaction (PCR) and PCR-single strand conformation polymorphism method. We found 5 homozygous deletions, 2 truncated mutations, one missense mutation, and one silent mutation of the hSNF5/INI1 gene in 7 MRT cell lines, and one homozygous deletion, one microdeletion, one splicing acceptor site mutation, and one absence of expression in 7 fresh tumor tissues of MRT and atypical teratoid (AT)/rhabdoid tumors (RTs). Homozygous deletions were also found in one (KYM-1) of 8 rhabdomyosarcoma (RMS) cell lines. To investigate characteristics of the KYM-1 cell line, we have established KYM-1 tumors in nude mice into which KYM-1 cells were transplanted. Notably, we found that MyoD1, known as a marker for RMS, was not expressed in the KYM-1 cell line as well as MRT cell lines and fresh tumors. Histopathologic, cytogenetic, and molecular studies of the KYM-1 cell line and KYM-1 tumors in nude mice have revealed that this RMS cell line should be MRT rather than RMS. RMS-carrying aberrations of the hSNF5/INI1 gene should be reevaluated. No aberrations of this gene were found in the other 34 cell lines or 80 fresh tumor specimens except the single nucleotide polymorphisms in the 3' noncoding region. These results suggest that alterations of the hSNF5/INI1 gene were restricted to MRTs or AT/RTs in pediatric solid tumors.

Adult↗

Immunosuppressive effect of chenodeoxycholic acid on natural killer cell activity in patients with biliary atresia and hepatitis C virus-related liver cirrhosis.

Patients with severe liver diseases, such as liver cirrhosis and biliary atresia, have low natural killer (NK) cell activity. The relations between NK activity and measures of liver function, including serum levels of total bilirubin, total bile acids, bile acid components, aspartate aminotransferase, and alanine aminotransferase, and platelet count were examined in patients with biliary atresia (6 boys and 6 girls; mean age, 4.8+/-5.7 years) and patients with liver cirrhosis due to hepatitis C virus infection (10 men and 2 women; mean age, 54.3+/-13.8 years). Univariate analysis showed that platelet count was positively correlated with NK activity in patients with biliary atresia (r = 0.611, P < 0.05). Serum levels of free chenodeoxycholic acid were negatively correlated with NK activity both in patients with biliary atresia (r = -0.647, P < 0.05) and in patients with hepatitis C virus-related liver cirrhosis (r = -0.876, P < 0.01). None of the other free bile acids or conjugated bile acids or other indicators of liver function were correlated with NK activity. Multiple stepwise regression analysis showed that only levels of free chenodeoxycholic acid were independently correlated with NK activity. All patients with biliary atresia underwent liver transplantation from living related donors. NK activity had increased significantly two months after transplantation (from 24.1+/-20.2% to 49.2+/-12.5%, P < 0.01). In contrast, levels of free chenodeoxycholic acid in transplant recipients had decreased significantly two months after transplantation (from 1.22+/-1.16 to 0.26+/-0.21 micromol/l, P < 0.05). In conclusion, in patients with biliary atresia or liver cirrhosis, NK activity in peripheral blood decreases, mostly because of free chenodeoxycholic acid.

Alanine Transaminase↗

Gastrointestinal bleeding after living-related liver transplantation.

We examined the prevalence of gastrointestinal bleeding in patients undergoing living-related liver transplantation (LRLT). Seventy-seven patients (37 male and 40 female) underwent LRLT at the University of Tokyo Hospital from January 1996 through December 1999. Forty-nine patients were children or adolescents and 28 patients were adults. The mean follow-up period was 21.3 +/- 12.8 months. Nine of the 77 recipients had gastrointestinal bleeding after transplantation. The incidence of posttransplant bleeding was significantly higher in adult recipients than in pediatric recipients (25% vs 4%, P < 0.05). The ratio of graft volume to standard liver volume was significantly lower in adult recipients than in pediatric recipients (41 +/- 6% vs 86 +/- 26%, P < 0.05). Portal vein thrombosis (PVT) developed after LRLT in 8 patients. Variceal bleeding subsequently occurred in all 4 adult patients with PVT but in only 1 of 4 pediatric patients. Small-for-size grafts may cause transient portal hypertension, which increases the risk of gastrointestinal bleeding.

Adolescent↗

Two case reports of childhood liver cell adenomas harboring beta-catenin abnormalities.

The benign epithelial neoplasm liver cell adenoma is rare, especially in childhood. We report 2 such cases, 1 of which was associated with Prader-Willi syndrome. Differential diagnosis of the liver cell adenomas on the basis of histopathologic findings proved difficult and was based on the absence of cellular and nuclear atypia, mitotic activity, and invasive growth. In both cases, immunohistochemical staining demonstrated the nuclear accumulation of beta-catenin, and in 1 case, the tumor cells carried a mutation of the beta-catenin gene. Recently, disregulation of the Wnt/beta-catenin pathway, attributable to abnormalities of the beta-catenin gene, has been reported to be a major event in the development of hepatocellular carcinomas and hepatoblastomas. Our report may be the first to describe the beta-catenin abnormalities in childhood liver cell adenoma. These findings imply that abnormalities of beta-catenin can be an early initiating event in human liver tumorigenesis.

Adenoma, Liver Cell↗

Development of intrahepatic biliary stones after excision of choledochal cysts.

BACKGROUND: The incidence of intrahepatic cholelithiasis and cholangitis has not yet been well studied postoperatively in patients with choledochal cysts. METHODS: One hundred three patients with choledochal cysts had operative cholangiography, underwent standard excision of a choledochal cyst with Roux-en-Y hepatico-jejunal anastomosis, and were at a mean follow-up of 12 1/2 years. The incidence of intrahepatic bile duct stones was analyzed according to the 3 morphologic types of intrahepatic bile duct observed at initial operative cholangiography: type 1, no dilatation of the intrahepatic bile ducts; type 2, dilatation of the intrahepatic bile ducts but without any downstream stenosis; and type 3, dilatation of the intrahepatic bile ducts associated with downstream stenosis. Initially, there was no evidence of intrahepatic bile duct stones in any of the 103 patients. RESULTS: Among 50 type 1 patients, intrahepatic cholelithiasis developed in only 1 patient (2%). Among 43 type 2 patients, 1 patient (2%) had intrahepatic cholelithiasis, and 2 (5%) had postoperative cholangitis. Among 10 type 3 patients, 4 (40%) had intrahepatic cholelithiasis (P <.01), and 3 (30%) had postoperative cholangitis. Time intervals between the initial surgery and the first identification of intrahepatic stones ranged from 3 to 22 years. CONCLUSIONS: One of the major causes of formation of intrahepatic cholelithiasis has been clarified; patients with intrahepatic biliary dilatation with downstream stenosis can get intrahepatic bile duct stones long after excision of a choledochal cyst.

Bile Ducts, Intrahepatic↗

Experimental split cord malformations.

OBJECTIVE: To induce experimental split cord malformations (SCMs) produced through the surgical induction of a dorsal midline fistula. METHODS: In addition, the theory of embryogenesis of SCMs was verified by examining the developmental process of this experimentally induced anomaly. In Cynopus pyrrhogaster (amphibian) embryos (stage 18), the neural plate and notochord were split regionally to construct a fistula that appeared to be the ectopic neurenteric canal. Following this procedure, the embryonic development was traced morphologically and histologically. RESULTS: Following the incubation and breeding period, split cord malformation was observed in some animals. Scoliosis, spina bifida, vertebral anomaly and subcutaneous manifestations were also observed with SCMs. CONCLUSIONS: The observations made in these experimentally induced SCMs are consistent with the findings in human SCMs. We report an experimental animal model of split cord malformation, in which double spinal cords were developed in the spinal canal. In addition, we examined the embryogenesis of SCMs. This study indicates that SCMs may arise through a process of dorsal midline fistula of the neural plate.

Amphibians↗

Impact of graft length on surgical damage after intestinal transplantation in rats.

BACKGROUND: Intestinal grafts greatly affect nutrition and immunology in the host. The growth of the recipient and incidence of graft-versus-host disease depend on graft length. A larger graft may affect the host immune system, but little is known about how the length of the intestinal graft severely affects surgical intervention. We developed a cervical small bowel transplantation (SBT) rat model that minimized technical variations using a cuff method and studied the effects of graft length on surgical damage in SBT. MATERIALS AND METHODS: We transplanted a whole (70 cm) or partial (15 cm) intestine into a syngeneic rat combination of LEW (MHC haplotype: RT1(l)) to LEW and evaluated changes in perioperative hemodynamics and the endogenous endotoxin level. Natural killer (NK) cell activity in the peripheral blood and the immunologic response of the recipient spleen were also studied. RESULTS: In the whole SBT model, body weight loss was more severe than in the segmental SBT model; the rats in the former model often died, while all in the latter survived indefinitely. The systemic blood pressure markedly decreased in the whole SBT group immediately after reperfusion. The proliferative activity of splenic lymphocytes stimulated by concanavalin A was also more severely inhibited in the former model than in the latter postoperatively. NK cell activity in the whole SBT rats declined more severely than the segmental SBT rats 3 days postoperatively. CONCLUSION: The longer graft severely induced surgical intervention; and influenced host immunosuppression, resulting in the higher mortality in rats undergoing whole SBT.

Animals↗

A case of fetal vesicoallantoic cyst in the umbilical cord.

A vesicoallantoic cyst in the umbilical cord was detected by fetal ultrasonography at 16 weeks of gestation. The blood flow through the umbilical vessels was evaluated with periodic color Doppler ultrasonographic examinations because compression by the cyst may cause reduction in blood flow and lead to fetal death. After disappearance of the cyst, the infant was delivered vaginally. Retrograde cystography revealed a narrow channel between the bladder and the navel, confirming patent urachus, which was resected without any complications.

Adult↗