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T Todoroki

Publications and source records attributed to T Todoroki.

At least 19 recordsLinked to original sources
PubMed2000

Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma.

PURPOSE: The objective of this study was to determine the benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma (Klatskin tumor). METHODS AND MATERIALS: We conducted a retrospective review of 63 patients who underwent surgical resection of Stage IVA Klatskin tumor. Of the 63 patients, 47 had microscopic tumor residue (RT1). Twenty-eight of the 47 patients with RT1 were treated by adjuvant radiotherapy and the remaining 19 patients were treated exclusively by surgical resection. Seventeen of the 28 patients with RT1 were treated by both intraoperative radiotherapy (IORT) and postoperative radiotherapy (PORT); of the remaining 11 patients with RT1, 6 underwent resection and IORT, and 5 underwent resection and PORT. RESULTS: The major complication and 30-day operative death rates were significantly lower in the radiation group (9.5% and 0.0%, respectively) than in the resection alone group (28.5% and 9.5%, respectively). Of the eight 5-year survivors with RT1, 6 had adjuvant radiotherapy and the remaining 2 had resection alone. Adjuvant radiotherapy for patients with RT1 yielded significantly (p = 0.0141) higher 5-year survival rates (33.9%) than in the resection alone group (13.5 %). The best 5-year survival rate (39.2 %) was found in patients who underwent a combination of IORT and PORT after resection. The local-regional control rate was significantly higher in the adjuvant radiation group than in the resection alone group (79.2% vs. 31.2%). CONCLUSION: Our data clearly suggest the improved prognosis of patients with locally advanced Klatskin tumor by integrated adjuvant radiotherapy with IORT and PORT to complete gross tumor resection with acceptable treatment mortality and morbidity.

Adult↗
PubMed2000

Radical resection of hilar bile duct carcinoma and predictors of survival.

BACKGROUND: Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection. METHODS: A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone. RESULTS: The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis. CONCLUSION: This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.

Adult↗
PubMed2000

Enteral vitamin B12 supplements reverse postgastrectomy B12 deficiency.

OBJECTIVE: To examine the development of chemical and clinical vitamin B12 deficiency after total gastrectomy, and to evaluate the efficacy of supplemental oral B12 administration. SUMMARY BACKGROUND DATA: Postgastrectomy anemia is due to deficiencies of iron and vitamin B12, and parenteral B12 administration is the only appropriate treatment. However, no guidelines exist for the prophylactic use of B12 in patients who undergo total gastrectomy, the clinical presentation of B12 deficiency in this context has not been defined, and the question of whether oral B12 administration can be used to prevent and treat B12 deficiency has not been examined. METHODS: Serum B12 concentrations were measured in 31 patients who had undergone total gastrectomy. Symptoms related to B12 deficiency were surveyed in detail. Serum B12 concentrations were measured every 6 months after total gastrectomy in 10 patients. Thirty one patients received supplemental B12: 18 patients orally and 13 by intramuscular injection. RESULTS: The B12 concentration dropped below the lower limit of normal (200 pg/mL) for the first time in two patients at 1 year, in four patients at 2 years, in three patients at 3 years, and in one patient at 4 years. Seventy-eight percent of patients reported some symptoms related to B12 deficiency. The serum B12 concentration in patients who received supplemental B12 orally increased rapidly and all symptoms resolved with oral therapy alone. CONCLUSIONS: B12 deficiency can develop as early as 1 year after total gastrectomy and causes symptoms. Because enteral B12 treatment increases the serum B12 concentration and leads to rapid resolution of symptoms, it should be prescribed routinely to patients undergoing total gastrectomy.

Administration, Oral↗
PubMed2000

Accumulated lipids, aberrant fatty acid composition and defective cholesterol ester hydrolase activity in cholesterol ester storage disease.

We confirmed accumulation of glycogen and lipids, particularly cholesterol esters, in the liver of a patient with cholesterol ester storage disease (CESD). Hepatic cholesterol ester concentration was 100-200 times that found in normal livers. Analysis of the fatty acid composition indicated a higher proportion (41%) of cholesterol linoleate (C18-2), a slightly lower proportion (33%) of cholesterol oleate (C18-1) and normal proportions (14%) of cholesterol palmitate (C16-0) in the CESD patient compared with the control. This fatty acid composition of cholesterol esters and the fatty acid composition of other classes of lipids in the patient's liver resembled that of LDL. We also found that acid cholesterol ester hydrolase activity in the CESD liver was reduced to 5% of that in the control liver, while neutral cholesterol ester hydrolase activity remained at the control level. These results suggest that accumulated cholesterol esters were derived mainly from serum LDL and that the accumulation resulted from lack of acid cholesterol ester hydrolase.

Child, Preschool↗
PubMed2000

Enhanced radiation killing by 5-fluorouracil of biliary tract cancer cell lines.

Despite the frequent clinical use of 5-fluorouracil (5-FU) in combination with radiotherapy for patients with biliary tract cancers, data remain scarce concerning specifically the influence of 5-FU on the sensitivity of these cancer cells to radiation. The present study was carried out to evaluate the effects of concomitant treatment with 5-FU on radiation-induced cell killing in two established human biliary tract cancer cell lines (Mz-ChA-2 and SK-ChA-1 cells). These lines were chosen as we have previously shown that SK-ChA-1 cells are significantly more resistant to both radiation and 5-FU than Mz-ChA-2 cells. Clonogenic survival was employed as the end-point for cell killing. Administration of 5-FU at LD50 doses to each cell line significantly enhanced radiation-induced cell killing. The enhancement ratio (ER) was obtained by dividing the radiation dose required to decrease the cell survival fraction to 37% (D0) by the dose to decrease cell survival to the same level when the cells were also treated with 5-FU. The ER in each of the cell lines was greater when they were incubated with 5-FU after radiation rather than prior to radiation. Longer exposure times with 5-FU resulted in enhanced radiation killing. The ER was significantly higher in the radioresistant cell line than in the radiosensitive line. These findings suggest that therapy with radiation and 5-FU may be of value as components of multidisciplinary treatment for biliary tract cancer. Protracted low dose exposure to 5-FU may prove to be most efficacious in enhancing the effects of radiation therapy.

Biliary Tract Neoplasms↗
PubMed1999

Endothelin antagonist treatment for successful liver transplantation from non-heart-beating donors.

BACKGROUND: With the shortage of cadaveric donors, non-heart-beating donors (NHBDs) are a potential source of liver allografts. However, warm ischemic injury in NHBDs seriously affects the viability of graft liver. Endothelin (ET)-1 has been reported to be involved in the hepatic microcirculatory disturbances after ischemia-reperfusion. METHODS: In a porcine orthotopic liver transplantation model, changes in the serum and liver tissue ET-1 concentration were measured and the effects of an ET receptor antagonist, TAK-044, were evaluated. After cardiac arrest of the donors, liver allografts were subjected to 90 min of warm ischemia, flushed, and preserved for 4 hr at 4 degrees C. The pigs were divided into two groups: a control group (no drug treatment) and a drug-treated group, in which donors and recipients were treated with TAK-044 (10 mg/kg body, drip intravenous injection). Both groups had six donor/recipient pairs. RESULTS: -The ET-1 concentration in the hepatic venous blood increased after reperfusion of the graft in the control group recipients. ET-1 in the graft liver significantly increased during the cold preservation period. TAK-044 treatment significantly increased recipient 7-day survival rate. After reperfusion of the graft, the concentrations of serum liver enzymes and arterial lactate in the drug-treated group were significantly lower than in the control group. The postoperative increase in portal venous pressure was significantly reduced in the drug-treated group. Measurements of liver enzymes in the washed-out preservation fluid at the time of graft rinsing indicated that TAK-044 treatment of the donors significantly suppressed liver enzyme release during ischemia. CONCLUSIONS: These findings indicate TAK-044 treatment has protective effects on postoperative function of hepatic allografts procured from NHBDs.

Alanine Transaminase↗
PubMed1999

Secretory low-molecular-weight phospholipases A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: factors of chronic proliferative cholangitis.

Intrahepatic calculi is characterized by an intractable course and frequent recurrences, requiring multiple operative interventions. Chronic proliferative cholangitis, an active and long-standing inflammation of the stone-containing bile ducts with the hyperplasia of epithelia and the proliferation of the duct-associated mucus glands, may underlie the complex nature of the disease. In terms of the pathophysiology, interest has been focused on the role of secretory low-molecular-weight phospholipases A2 (sPLA2s) as inflammatory mediators or factors modulating cell functions via their specific sPLA2-receptor, and also on the production and secretion of altered mucin molecules from the inflamed bile ducts. In search of factors involving chronic proliferative cholangitis, the sPLA2 isoforms in the bile such as the pancreatic-type sPLA2 (group IB sPLA2) and the arthritic-type sPLA2 (group IIA sPLA2), were assayed to correlate protein masses of the sPLA2s with alterations in biliary composition. Furthermore, the steady-state messenger RNA (mRNA) levels of the sPLA2s, the membrane-bound sPLA2-receptor, cystic fibrosis transmembrane conductance regulator (CFTR), and mucin core polypeptide (MUC) genes in the bile ducts were assayed by reverse- transcriptase polymerase chain reaction (RT-PCR). Immunoreactive sPLA2-IB and sPLA2-IIA levels were significantly higher in the bile from the stone-containing hepatic ducts (2315 +/- 677 for sPLA2-IB; 281 +/- 42 for sPLA2-IIA ng/dL, mean +/- SEM; n = 20) than in the ductal bile from gallbladder stone patients (609 +/- 92, P <.01; 22 +/- 2, P <.01; n = 24). The increased sPLA2 levels were associated with a concomitant increase in lysophosphatidylcholine, prostaglandin E2 (PGE2), and total mucin concentrations. The affected bile ducts showed an increased mRNA level of sPLA2-IB and sPLA2-IIA compared with the ducts from control subjects, in whom the mRNAs of the sPLA2-receptor and other sPLA2 isoforms, such as groups V and X sPLA2s, were coincidently expressed. Reflecting the increased amounts of total biliary mucins, the affected ducts showed an increase in mRNA levels of CFTR as well as MUC2, MUC3, MUC5AC, MUC5B, and MUC6 compared with the ducts from control subjects. In intrahepatic calculi, an enhanced expression of the sPLA2s and their possible cross-talk via sPLA2-receptor may be of pathophysiological significance for the chronic proliferative cholangitis, in association with the enhanced CFTR expression and the alterations in mucin gene expression in the bile ducts, probably through potentiating arachidonate metabolism with associated biliary alterations favoring growth of preexisting stones and even further progressions.

Bile↗
PubMed1999

Prevention of hepatic ischemia-reperfusion injury by SOD-DIVEMA conjugate.

A protective effect of the SOD (superoxide dismutase)-DIVEMA (divinyl ether and maleic anhydride) conjugate on I-R (ischemia-reperfusion) liver injury was demonstrated. Twenty minutes of normothermic hepatic ischemia was induced by clamping the portal triad of Sprague-Dawley rats. Five minutes before the end of ischemia, SOD, SOD-DIVEMA, or NaCl (0.9%) was given intravenously. Using intravital fluorescence microscopy, hepatic microvascular perfusion was analyzed before ischemia and repeatedly during the 120-min reperfusion period. SOD-DIVEMA significantly restored the sinusoidal perfusion rate (control, 98.0 +/- 0.5; NaCl, 65.5 +/- 7. 7; SOD, 81.5 +/- 8.2; SOD-DIVEMA, 95.8 +/- 0.7%) and reduced the number of leukocytes stagnant in acini (control, 4.4 +/- 0.9; NaCl, 36.6 +/- 6.3; SOD, 27.7 +/- 6.8; SOD-DIVEMA, 12.3 +/- 3.3 cells/lobule) and adherent in postsinusoidal venules (control, 55.0 +/- 24; NaCl, 417 +/- 63; SOD, 253 +/- 58; SOD-DIVEMA, 40.0 +/- 14 cells/mm2). In addition, SOD-DIVEMA maintained postischemic hepatocellular integrity. The SOD-DIVEMA-treated group revealed higher serum SOD enzyme activity compared to the SOD group after 120 min of reperfusion (SOD-DIVEMA, 33.0 +/- 5.9; SOD, 8.6 +/- 3.1 U/ml). The beneficial effect of SOD-DIVEMA was most prominent after 120 min of reperfusion, indicating a longer intravascular half-life of SOD-DIVEMA.

Animals↗
PubMed1999

The prevention of postoperative intraperitoneal adhesions by tranilast: N-(3',4'-dimethoxycinnamoyl)anthranilic acid.

The development of postoperative intraperitoneal adhesions continues to be a major concern for surgeons. The purpose of this study was to establish a postoperative adhesion model in rats, and to assess the effectiveness of tranilast (N-(3',4'-dimethoxycinnamoyl)anthranilic acid) in preventing postoperative adhesion formation. The adhesion model was established in 12 male Donryu rats. This involved two essential factors, drying and bleeding. Another 22 male Donryu rats were used to study the prevention of intraperitoneal adhesions. Tranilast was administered orally pre- and postoperatively. Adhesion strength was evaluated by grading, and basic fibroblast growth factor (bFGF) and transforming growth factor-beta-1 (TGF-beta1) concentration were measured. Postoperative intraperitoneal adhesions were seen in all rats, but the adhesions in the tranilast group were significantly less severe than those in the control group. Serum bFGF and TGF-beta1 levels in the tranilast group were lower at the time of surgery than those in the control group, and bFGF levels were lower at the endpoint of this study in the tranilast group than in the control group. The TGF-beta1 levels at the end-point did not differ between the two groups. These findings demonstrated that tranilast significantly reduced postoperative intraperitoneal adhesion formation.

Abdomen↗
PubMed1999

An endothelin receptor antagonist ameliorates injuries of sinusoid lining cells in porcine liver transplantation.

BACKGROUND: TAK-044 is an endothelin receptor antagonist. Whether the agent has protective effects on liver graft injuries from non-heart-beating donors is unknown. METHODS: In donor pigs, cardiac arrest was induced by stopping the respirator. Forty-five minutes after cessation of the respirator, the liver was flushed with University of Wisconsin (UW) solution, preserved for 8 hours at 4 degrees C, and transplanted orthotopically. The pigs were divided into two groups: a control group and a drug-treated group in which TAK-044 was given in the UW solutions (10 mg/L) and was administered to recipients (10 mg/kg body weight). RESULTS: TAK-044 treatment significantly increased recipient survival rate. After reperfusion of the graft, portal venous pressure and 15-minute retention rate of indocyanine green were significantly reduced in the drug-treated group. Electron microscopic findings indicated that TAK-044 attenuated endothelial cell injuries. CONCLUSION: TAK-044 treatment improves the viability of livers harvested from non-heart-beating donors. The main effect of the agent is protection of endothelial cells from ischemia/reperfusion injuries.

Animals↗
PubMed1999

Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1.

Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions.

Angiostatins↗
PubMed1999

Treatment of gallbladder cancer by radical resection.

BACKGROUND: The use of radical resection for gallbladder cancer is controversial. This study evaluated results of resection for gallbladder cancer and analysed prognostic factors. METHODS: A retrospective review of 135 patients who underwent surgical resection for gallbladder cancer between 1976 and 1998 was performed. Of these, 123 patients underwent radical resection and the remaining 12 had palliative resection. The resections included 32 hepatopancreatoduodenectomies and 57 with adjuvant radiotherapy. Twelve prognostic factors were analysed. A subset of 96 patients with stage IV disease was analysed separately with respect to residual tumour level and adjuvant radiotherapy. RESULTS: Surgical resection was associated with a 5-year survival rate of 36 per cent, with a mean follow-up time of 870 days. Twenty-two patients have survived more than 5 years including three with stage IV disease. Overall operative morbidity and mortality rates were 13 and 4 per cent respectively. The 5-year survival rate decreased with disease stage: 100, 78, 69 and 11 per cent for stages I (n = 13), II (n = 19), III (n = 7) and IV (n = 96) respectively. Performance status, jaundice, histopathological type and grade, primary tumour, lymph node, distant metastasis, stage grouping, residual tumour level and adjuvant radiotherapy were significant prognostic factors. CONCLUSION: With careful patient selection, radical resection for gallbladder cancer improves the prognosis with acceptable operative mortality and morbidity rates, even for stage IV disease, provided that complete gross tumour resection is combined with radiotherapy.

Adult↗
PubMed1999

Cytogenetic aberrations detected by flow cytometry and fluorescence in situ hybridization in colorectal cancers: two cytogenetic pathways in colorectal carcinogenesis.

We measured DNA content by flow cytometry and determined the number of chromosomes 7, 17 and 18 by fluorescence in situ hybridization using DNA probes in 38 sporadic colorectal adenocarcinomas including 14 early cancers. Based on DNA ploidy and the copy number of chromosome 18, colorectal cancers were divided into two groups. In early cancers (mucosal and submucosal adenocarcinomas), monosomy 18 with DNA hypotriploidy was detected exclusively in 6 sessile tumors without adenoma portions. Seven of the remaining 8 tumors in which adenoma portions coexisted manifested disomy 18 and DNA diploidy or near diploidy. These tumors were considered to occur along the adenoma-carcinoma sequence. In contrast, monosomy 18 was accompanied by DNA diploidy or near diploidy in advanced cancers penetrating the muscularis propria. In advanced cancers, DNA hypertriploidy was linked with disomy 18 and chromosomes 7 and 17 were trisomic or tetrasomic. Observations indicate at least two different cytogenetic pathways in colorectal carcinogenesis. According to these findings, two thirds of advanced cancers were estimated to originate from adenoma, and the others were not.

Adenoma↗
PubMed1999

Killing effects of 5-fluorouracil on human biliary tract cancer cell lines.

Data concerning the cellular sensitivity of human biliary tract cancer cell lines to 5-FU are scarce. The purpose of the present study was to evaluate the cellular sensitivity of Mz-ChA-2 (derived from gall bladder cancer) and SK-ChA-1 (derived from bile duct cancer) to 5-FU. The clonogenic capacity of these lines after pulse (1 h) or continuous (168 h) administration of various 5-FU concentrations (0.1-100 microg/ml) was evaluated in exponentially growing cells as well as in those that had reached the plateau phase. In both cell lines, exponentially growing cells were 1.8-times more susceptible to 5-FU than those in plateau phase. However, when cells in the same growth phase were compared, Mz-ChA-2 cells were 10 times more sensitive to the drug than SK-ChA-1 cells. Regardless of the growth phase or cell line, increasing the duration of exposure to 5-FU decreased the proportion of surviving cells. Even at a non-cytocidal dosage, exposing the cells for three doubling times markedly decreased the number of viable cells remaining after treatment.

Antimetabolites, Antineoplastic↗
PubMed1999

Conformal irradiation for hepatobiliary malignancies.

The term 'conformal irradiation' is usually used to describe the delivery of sophisticated high dose external beam irradiation (EBRT) with the aid of 3-D treatment planning and the option of both coplanar and non-coplanar beams. Data will be presented from the University of Michigan which suggest that conformal high dose EBRT (48-72.6 Gy) can be used for intrahepatic cancers, both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC), to potentially increase local control and survival over what would be expected with lower dose EBRT. For purpose of this discussion, the term conformal irradiation will be expanded to include other techniques which conform the high dose irradiation boost volume in close proximity to unresected tumor or positive margins of resection. Data will be presented from series which utilize transcatheter iridium and intraoperative electron irradiation (IOERT) supplements to EBRT +/- concomitant chemotherapy. Each method intensifies treatment in an attempt to improve local control and survival.

Bile Duct Neoplasms↗
PubMed1999

Future role of radiotherapy as a component of treatment in biliopancreatic cancers.

For resected and unresectable pancreas cancers, data will be summarized from both adjuvant and locally unresectable pancreas cancer series (EBRT +/- IOERT) to demonstrate the justification of continuing to utilize chemo-irradiation as a component of treatment. The resultant improvements in local control with combined modality treatment, however, achieve only minimal improvements in survival in view of the high incidence of abdominal relapse (liver and peritoneal). Further improvement in survival may necessitate regional approaches for chemotherapy or may await advances in gene therapy. For locally unresectable and resected but residual bile duct malignancies, chemoirradiation appears to enhance tumor control and survival. Dose intensification of both modalities may be useful in improving disease control and survival. After chemoirradiation, the addition of liver transplant, in carefully selected patients who are unresectable with standard resection, may further enhance disease control and survival over what would be expected with either approach in isolation.

Biliary Tract Neoplasms↗
PubMed1999

[Chemoradiation therapy for advanced esophageal cancers--report of 3 cases].

Three cases of prominent-type advanced esophageal cancer were treated with chemoradiation therapy using a 5-FU analog and low dose CDDP. All cases showed a complete response after the treatment. Only mild bone marrow suppression was found in one case. This protocol will be applied for patients with prominent-type advanced esophageal cancers, especially high risk patients.

Aged↗