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Biomedical subjects

Yoshiaki Tsuchida

Publications and source records attributed to Yoshiaki Tsuchida.

At least 19 recordsLinked to original sources
PubMed2006

Irinotecan for children with relapsed solid tumors.

Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen children with relapsed solid tumors received irinotecan 180 mg/m2/day for 3 consecutive days, repeated once after 25 days off. Their original tumors were neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in 1 each. The average age at trials was 6 years. Partial response was achieved in 5 (31.3%) (neuro-blastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2. Irinotecan appears promising, and could become included in the first-line treatment.

Camptothecin↗
PubMed2005

Diversity in neuroblastomas and discrimination of the risk to progress.

The clinical diversity of Neuroblastomas (NBs) was discriminated into three groups with high sensitivity and specificity to patient's outcome. The 'high risk' NB is defined with any of following conditions, MYCN amplification or unfavorable histology of International Neuroblastoma Pathological Classification (INPC) or low Ha-ras/trk A expression. The 'low risk' NB is defined with all following conditions, single copy of MYCN and INPC favorable histology and high Ha-ras/trk A expression and localized tumor. The remaining NBs were classified into 'intermediate risk' ones. According to these criteria, the diversity of the 248 mass-screening NBs was shown with variety progressive risk; 40% were classified in low risk group, 25% were in high risk group and 35% were in intermediate risk group.

Disease Progression↗
PubMed2005

Histologic survey of neuroblastomas after intensive induction chemotherapy.

BACKGROUND: Histology after intensive induction chemotherapy is expected to become a beacon indicating when and how extensively radical surgery and lymph node dissection should be performed in advanced neuroblastoma. A thorough histologic review of surgical specimens was undertaken. PROCEDURE: All specimens from 34 patients who were pretreated intensively (> or =3 cycles) with recent chemotherapy were reviewed. Thirty patients were >12 months of age with stage 3/4 disease, and 4 were <12 months of age but with MYCN-amplified stage 4 diseases. After 3 to 7 cycles (mean, 4.3 cycles) of induction chemotherapy, patients underwent radical surgery of the primary tumor and lymph nodes in all retroperitoneal sections. A single pathologist reviewed all of the specimens, and histologic chemotherapeutic effects were graded as: (+++), <1% viable tumor; (++), 1%-10% viable tumor; (+), 11%-50% viable tumor; (+/-), 51%-90% viable tumor; and (-), >91% viable tumor. RESULTS: Grade (+++) effects were observed in 56% of patients treated with the new regimens, whereas grade (+++) was seen in only 20% treated with regimens before 1991. Operation time and blood loss were 7 hr and 6 min (P = 0.087) and 646 ml (P = 0.064), respectively, in patients with >5 cycles (mean, 5.3 cycles) of chemotherapy, while they were 7 hr and 50 min and 1,168 ml, respectively, in those with approximately 3 cycles (mean, 3.2 cycles). Histologically, metastases were found in the contralateral nodes beyond the aorta in 92% of those whose tumor originated on the left, and in 80% of those with tumors occurring on the right. CONCLUSIONS: Five cycles of induction chemotherapy did not improve histologic chemotherapeutic effects, but helped to facilitate a shorter operation time and less blood loss than 3 cycles of chemotherapy. Surgery after 5 cycles of (98)A(3) also appears to be easier to perform than that after 3 cycles of A(1)/new A(1). Only 14% of the children treated before 1985 with the St. Jude protocols experienced grade (+++) chemotherapeutic effects, and 22% of the patients treated before 1991 with regimen A(1), or new A(1) of the Study Group of Japan showed grade (+++) effects, whereas 56% of the patients treated after 1991 with either regimen A(3) or (98)A(3) exhibited grade (+++) chemotherapeutic effects. Histologic chemotherapeutic effects were roughly parallel with a good prognosis.

Abdominal Neoplasms↗
PubMed2005

Pulmonary metastases after nephrectomy only for small, stage I/favorable-histology Wilms' tumor.

The prognosis for children with Wilms' tumor is reported to be excellent in those who are less than 2 years of age at diagnosis and who have a stage I/favorable-histology tumor with specimen weight less than 550 g. We report on a patient with Wilms' tumor who belonged to this group but who developed pulmonary metastases, and we discuss the diagnostic and therapeutic problems in such patients. The importance of careful evaluation of the renal sinus should be emphasized.

Fatal Outcome↗
PubMed2005

Remission induced by interferon alfa in a patient with massive osteolysis and extension of lymph-hemangiomatosis: a severe case of Gorham-Stout syndrome.

The treatment of massive osteolysis with lymphangioma and/or hemangioma (Gorham-Stout syndrome) has been controversial. The authors report on a patient with multiple massive osteolyses and extensive lymph-hemangiomatosis whose lesions were reduced by interferon alfa therapy. A 2-year-old girl had complained of left chylothorax. Thoracoscopy showed an increase in small lymphatic vessels in the chest wall. The chylothorax was improved by coagulation of the lymphatic vessels. Later, multiple massive osteolyses appeared in the left 11th and 12th ribs, the TH10-L3 vertebrae, and the right femur. There were also hemangiomas in the liver and spleen, a tumor lesion in the left lower chest wall, and hemangiomatous change on the skin surface of the left back. The left lung had only a minimal air content. After OK-432 was injected into the femur and chest wall lesions, the femur lesion disappeared. Then, as right chylothorax appeared, OK-432 was injected into the right pulmonary cavity. The chylothorax disappeared, but pericardial effusion appeared. After steroid pulse therapy, pericardial effusion disappeared. During these treatments, the 7th to 10th ribs disappeared from the x-ray and scoliosis developed. One month later, a cloudy fluid collection in the right lung was found on computed tomography. Interferon alfa and steroid pulse therapy were started. Interferon alfa (1,500,000 units) was subcutaneously administered daily for 2 months and was gradually reduced and maintained at 1,500,000 unit/wk. Steroids were also reduced and maintained at 5 mg/d of predonine. Later, the progress of osteolysis and the extension of lymph-hemangiomatosis stopped. Ten months later, hemangioma in the back disappeared, and the 7th to 10th ribs, which had disappeared, reappeared. The interferon alfa therapy was stopped 14 months after it was administered. The patient's condition has been stable for 10 months since then. At this time, computed tomography shows regression of the hemangiomatous lesion in the back. The authors clinically diagnosed the patient as having Gorham-Stout syndrome with extension of lymph-hemangiomatosis. Interferon alfa with or without steroid therapy should be a choice for patients with extension lesions.

Adrenal Cortex Hormones↗
PubMed2005

Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year-old girl with a unique mutation of PDGFRA.

A 12-year-old girl presented with a large abdominal tumor. At surgery, a huge pedunculated extraluminal tumor was found arising from the greater curvature of the stomach and invading the surrounding structures, and there were also a submucosal tumor measuring 5 x 4 x 4 cm and multiple intramural nodules beside the main tumor. These lesions, which were removed with 1.0-cm surgical margins, were immunohistochemically positive for c-kit (CD117) and CD34. A diagnosis of gastrointestinal stromal tumor (GIST) was made. The huge size of the tumor (3.6 kg in weight and 36 x 25 x 25 cm in diameter), the invasion of the surrounding structures, and the increased mitotic figures indicated the GIST had malignant potential. Sequence analysis of the polymerase chain reaction product of RNAs from the tumor cells revealed a novel platelet-derived growth factor receptor alpha (PDGFRA) mutation, which would exhibit biologic consequences similar to those of the c-kit mutation. The patient underwent a 3-month course of imatinib mesylate as adjuvant chemotherapy because of the possible risk for tumor recurrence. She is now doing well without any evidence of recurrence or metastasis 25 months after the surgery. Only 9 cases of GIST have been reported in children, and a review of those cases revealed GISTs in children would be associated with a better prognosis than in adults and that one third of pediatric GISTs presented with intestinal obstruction in the newborn period.

Antineoplastic Agents↗
PubMed2004

Evidence for segmental bile drainage by hepatic portoenterostomy for biliary atresia: Cholangiographic, hepatic venographic, and histologic evaluation of the liver taken at liver transplantation.

BACKGROUND: The result of hepatic portoenterostomy for biliary atresia (BA) has improved, but there are some patients who experience worsened liver function in the long term after one decrease in jaundice owing to portoenterostomy. However, the cause of the liver dysfunction in the long term has not been clearly ascertained. METHODS: Five patients (5 to 28 years of age) with BA underwent liver transplantation (LT) because of liver dysfunction after successful portoenterostomy. To clarify the cause of liver dysfunction occurring in the long term, the authors performed a cholangiogram, hepatic venogram, and macroscopic/microscopic examination of the liver just after LT. RESULTS: (1) Macroscopically, the liver could be divided into 3 areas, the hypertrophic, atrophic, and intermediate, with findings between those of the hypertrophic and atrophic areas. (2) The divided areas clearly corresponded to the liver segments. Segment IV was the hypertrophic area in all patients, but segments VI and VII were the atrophic areas in 4 of the 5 patients. (3) Based on the cholangiographic and microscopic findings, the hypertrophic area had near-normal structure with bile ducts. The atrophic area had severe fibrosis and contained only a few bile ducts in the intralobular spaces of liver. CONCLUSIONS: It seems that segmental bile drainage must have been established by hepatic portoenterostomy in some patients and that some postoperative patients might have worsened liver function in the long-term follow-up period accompanied with progression of fibrosis and impaired bile drainage. These pathologic changes occur in each liver segment.

Adolescent↗
PubMed2004

An infant with systemic hypertension, renal artery stenosis, and neuroblastoma.

A newborn girl with neuroblastoma presented with hypertension (blood pressure 200/140 mm Hg). The concentration of active renin in the ipsilateral renal vein was exceedingly high compared with those in the other venous systems, and angiography results showed narrowing of the contralateral 2 renal arteries. The tumor regressed in size after chemotherapy, but the blood pressure remained high. Percutaneous transluminal angioplasty (PTA) for the left renal arteries was performed twice, the first one at 5 months of age, which achieved some success in the recovery of impaired kidney function. At 8 months of age, she underwent radical resection of the neuroblastoma and removal of the right kidney, and the blood pressure promptly returned to normal postoperatively. The current patient represents the second youngest, well-documented case of renovascular hypertension with neuroblastoma in early infancy.

Adrenal Gland Neoplasms↗
PubMed2004

Gastrointestinal manometric findings in a patient with total intestinal aganglionosis.

BACKGROUND/PURPOSE: The authors studied gastrointestinal motility in a patient with total intestinal aganglionosis (TIA) and the effect of octreotide (OCT) on ileal motility in this patient. METHODS: The 3200-g girl received ileostomy at 50 cm proximal to the ileocecal site and jejunostomy at 15 cm distal to the ligament of Treitz because of severe ileus owing to TIA. Histology of the intestines, including jejunostomy, showed no ganglion cells. Gastro-duodeno-jejunal and distal ileal manometries were done 8 months after birth. RESULTS: In upper gastrointestinal manometry, sporadic contractions and clusters consisting of 3 to 5 contractions were observed in the duodenum and jejunum, but no typical phase 3 was observed during the 3-hour recording period. In ileal manometry, long-lasting repetitive contractions were recorded at 2 distal sites. In the most proximal ileum, the frequency of contractions was less than in the 2 distal sites. OCT administration induced a decrease in the amplitude of contractions during the first 20 minutes. The amplitude increased thereafter and reached a level higher than that before OCT administration. CONCLUSIONS: In this patient, the predominant manometry finding was the remarkable hypermotility of the ileum. OCT induced a transient decrease in ileal motility and an increase in motility thereafter.

Digestive System Abnormalities↗
PubMed2004

Neonatal ovarian cysts: management with reference to magnetic resonance imaging.

OBJECTIVE: Ultrasound (US) has been used as a tool to determine the indication for surgery for neonatal ovarian cysts. The purpose of this study was to investigate whether magnetic resonance imaging (MRI) contributes to optimal management. METHODS: Between 1993 and 2001, US and MRI studies were simultaneously performed on 13 consecutive infants younger than 2 months of age with ovarian cysts. The US Patterns were classified as complex or simple. Signal intensity (SI) of the cysts on MRI was compared with that of the liver on T1-weighted images (T1WI) and with urine on T2-weighted images (T2WI). We assumed that high SI on T1WI and iso or low SI on T2WI indicated complications. RESULTS: There were 10 complex and three simple cysts on US. Of the 10 complex cysts, two had no complications at surgery or resolved spontaneously. These two cysts showed low SI on T1WI. Eight complex cysts showed high SI on T1WI and all were haemorrhagic. The US diagnosis corresponded to the MRI findings in three simple cysts. The sensitivity of US for haemorrhage was 80%, and that of MRI was 100%. CONCLUSIONS: We found that MRI was a more reliable diagnostic modality than US for diagnosing neonatal ovarian cysts.

Female↗
PubMed2004

Dual signaling and effector pathways mediate human eosinophil activation by platelet-activating factor.

Platelet-activating factor (PAF) induces various cellular functions in eosinophils including chemotaxis, adhesion, superoxide anion (O2-) production, and degranulation. While PAF shares many biological effects with other chemotactic factors such as N-formyl-methionyl-leucyl-phenylalanine, complement fragments, and lipid mediators, PAF is unique in that its action is relatively resistant to pertussis toxin (PTX), and in activating eosinophils more strongly than neutrophils. In this review we consider how PAF might activate human eosinophils in preference to neutrophils, and discuss possible mechanisms of PAF-induced activation of human eosinophils via two distinct signaling and effector pathways. Recently we analyzed O2- production by eosinophils using a sensitive, real-time chemiluminescence method. Our results showed that in human eosinophils PAF activates two distinct signaling and effector pathways coupled to the PAF receptor: one linked to PTX-sensitive G protein(s) and another to PTX-resistant G protein(s), phosphatidylinositol 3-kinase, and cellular adhesion. This activation of two different G proteins by the eosinophil PAF receptor may explain the strong and diverse biological responses of human eosinophils to PAF.

Animals↗
PubMed2003

Intestinal aganglionosis associated with the Waardenburg syndrome: report of two cases and review of the literature.

The authors report two cases of the rare concurrence of intestinal aganglionosis and Waardenburg syndrome in Japanese infants. The patients were a 1-month-old girl and a 3-month-old boy at diagnosis, and both of them had either short segment or ultra-short segment aganglionosis. A review of 48 cases in the literature showed that the extent of the aganglionic segment is quite variable, from nearly total to ultra-short. The clinical features of aganglionosis in Waardenburg syndrome would appear to bear similarity in sex ratio and the extent of aganglionosis with those of Hirschsprung's disease associated with Ondine's curse, another type of neurocristopathy.

Comorbidity↗
PubMed2003

Proinflammatory cytokinemia associated with transient myeloproliferative disorder in down syndrome.

A transient myeloproliferative disorder (TMD) occurs in 10% of the infants with Down syndrome. While most cases resolve within a few months, in 20% of them TMDs are life-threatening or fatal. We encountered 4 patients with TMD, including 1 patient who died of liver failure and disseminated intravascular coagulation. Suspecting involvement of proinflammatory cytokines, we serially assayed them in patients' sera. Cytokines were significantly more abundant in patients than in controls. Interleukins 1 and 2, tumor necrosis factor alpha, interferon gamma, and granulocyte-macrophage colony-stimulating factor were greatly increased, especially in the infant who died. Sustained cytokinemia is likely to participate in TMD pathophysiology, and very high serum concentrations might predict a poor outcome.

Cytokines↗
PubMed2003

Current treatment and future directions in neuroblastoma.

OBJECTIVE: The International Neuroblastoma Staging System (INSS) and Pathology Classification (INPC) were applied to analyze the results of treatment of 644 patients with neuroblastoma treated in Japan during the years from 1995 to 1999, and it was found that the pathology classification (INPC) showed the strongest relevance to prognosis compared to other factors such as stage, MYNC amplification, DNA ploidy and 1p-deletion. Current results of treatment for advanced neuroblastoma are still not satisfactory, so innovative therapeutic methods have been sought during the past 10 years. METHODS: Prospects for irinotecan and recombinant human endostatin (rhEndostatin) were studied expertimentally and clinically. RESULTS: Irinotecan is a water-soluble derivative of camptothecin, which is isolated from a Chinese tree, Camptotheca acuminata; Its effectiveness against neuroblastoma was confirmed by in vivo preclinical studies, and phase I clinical trials in Japan concluded the maximum tolerated dose of this agent is 160-180 mg/m2/day for 3 consecutive days, repeated after 25 days off. Phase II trials with this dose began, and we could obtain some encouraging results with the clinical use of irinotecan. rhEndostatin has been studied in in vivo experimental models. The action of rhEndostatin was quite different from those of other cytotoxic chemotherapeutic agents, and continuous administration of this substance showed a more marked anti-effect than its intermittent use. CONCLUSION: Irinotecan appears to be promising when it is given to the patients neuroblastoma, whereas rhEndostatin needs to have more preclinical studies before it is used in patients.

Angiogenesis Inhibitors↗
PubMed2003

Continuous versus intermittent administration of human endostatin in xenografted human neuroblastoma.

PURPOSE: The authors examined whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against a human neuroblastoma cell line (designated TNB9) using a human neuroblastoma xenograft model and investigated whether continuous infusion is more effective than intermittent administration. METHODS: In the first experiment, when tumors on the back of nude mice reached a weight of 90 to 95 mg, rhEndostatin, 10 mg/kg/d mouse weight, was administered subcutaneously to the mice (n = 5) every day for 10 consecutive days. In the second experiment, the same daily dose of rhEndostatin was administered continuously to the TNB9-bearing mice (n = 6) via subcutaneous infusion pumps for 3 consecutive days with total dose being 30% of that in the first experiment. Nestin and factor VIII expression levels were studied immunohistochemically to elucidate whether histologic evidence of the effects of rhEndostatin was present on day 4 in the second experiment. RESULTS: In the first experiment, relative tumor weight in treated mice (n = 5) was significantly less than that in controls (n = 12) on day 2 only after treatment initiation (P <.05). The maximum inhibition rate (MIR) of TNB9 xenograft growth by rhEndostatin was 46.4%, indicating lack of efficacy. In the second experiment, the effects of rhEndostatin were much more marked than those in the first experiment, with an MIR of 60.7%. The mean relative tumor weight in the treated group (n = 6) in the second experiment was significantly less than that in controls (n = 10) on days 2, 4, and 6 (P <.01) as well as on days 8 and 10 (P <.05). Nestin staining in the endothelium of control tumors (n = 2) was marked, whereas it showed a loss of fibrillar structure in rhEndostatin-treated tumors (n = 2). The number of vessels immunostained with antifactor VIII antibody was markedly reduced in tumors (n = 2) from rhEndostatin-treated mice compared with that in tumors from control animals (n = 2). CONCLUSIONS: Continuous administration of rhEndostatin resulted in more significant tumor regression than intermittent administration of the agent in the same model. This indicates that rhEndostatin, if administered in continuous fashion, could become an effective agent for treating patients with neuroblastoma in the future.

Abdominal Neoplasms↗
PubMed2003

Intrahepatic biliary cysts in biliary atresia in the era of liver transplantation.

OBJECTIVES: The development of intrahepatic biliary cysts (IBC) after Kasai operation in patients with biliary atresia (BA) is recognized as an important problem; however, management strategy for IBC has not been clarified, particularly in the light of the increased use of liver transplantation. METHODS: Forty consecutive BA patients underwent hepatic portoenterostomy during 18 years from 1983 to 2000. We compared the clinical course and prognosis of the patients who developed IBC with those who did not. RESULTS: Seven of the 40 patients developed IBC. Three patients had type A (non-communicating cyst) and three patients had type C (multiple cystic dilation) IBC, and the remaining patients had type B (communicating cyst). Of the 7 patients, one patient underwent successful internal intestinal drainage, and one patient died of complications at the time of internal intestinal drainage. Three patients underwent liver transplantation due to either hepato-pulmonary syndrome (one case) or liver failure (two cases). One patient with IBC with liver failure was judged to require transplant, but was found to have pulmonary hypertension and was thus not a candidate. The remaining patient has survived without jaundice for 21 months postoperatively. Two of 21 patients with good initial bile drainage and without IBC underwent liver transplantation. The percentage of patients undergoing transplant was significantly higher in the group with IBC than in the group without IBC (P < 0.05). CONCLUSIONS: IBC was associated with worsening liver function. Previously, IBC was treated using internal/external drainage, or the patients were observed without treatment, with limited success. We now consider it reasonable to carry out liver transplantation in patients with long-standing IBC.

Adolescent↗