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Papers by Takatoshi Michigishi

Histopathology, 1990

Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histolog... more Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histologically and immunohistochemically. Nineteen cases were non-Hodgkin's lymphoma (1 5 diffuse and four follicular lymphoma) and one was a plasmacytoma. Immunohistochemical analysis of the lymphomas using paraffin-embedded sections disclosed that 1 7 lymphomas were B-cell type and two were T-cell type. The Keywords: thyroid. lymphoma, immunohistochemistry plasmacytoma was of IgG kappa type. The large majority of the lymphomas were associated with an underlying chronic thyroiditis. The 5-year survival rate of the patients was 70%. An unfavourable diagnosis was more likely when the tumour was diffuse rather than follicular, when it was of diffuse large cell type or of immunoblastic type and when there was cervical lymph node involvement.

Nuclear Medicine Communications, 2005

Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumul... more Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumulation of radiotracers such as 99mTc sestamibi (MIBI). Anti-angiogenic therapy is primarily cytostatic; consequently, its influence on tracer accumulation may differ from that of cytotoxic treatments. Anti-angiogenic therapy employing 2-methoxyestradiol was administered in mice bearing subcutaneous xenografts of LS180 colon cancer cells. The effects of chemotherapy with 5-fluorouracil were examined as a cytotoxic counterpart. Treatments were conducted for 4 days from day 8. Distribution of 99mTc-MIBI and Tc-HL91, a hypoxic marker, was observed on days 8 and 12. Oxygen tension (PO2) in tumours was measured by a microelectrode. Cellular uptake of tracers was examined in vitro in normoxic and hypoxic conditions. 99mTc-MIBI accumulation decreased with increasing tumour weight when no treatment was conducted. Tumour growth was suppressed by anti-angiogenic therapy and chemotherapy. 99mTc-MIBI accumulation in tumours decreased after chemotherapy as compared to pre-therapeutic values, whereas accumulation of 99mTc-HL91 increased. In contrast, accumulation of tracers did not significantly change after anti-angiogenic therapy as compared to that observed pre-therapeutically. Tumour PO2 decreased with increasing tumour volume when no treatment was conducted. Chemotherapy reduced PO2 in tumours. PO2 in tumours treated with anti-angiogenic therapy was as high as that observed before treatment. 2-Methoxyestradiol or 5-fluorouracil did not significantly affect tracer accumulation in cells under both normoxic and hypoxic conditions in vitro. These findings indicate that scintigraphic assessment of therapeutic efficacy of anti-angiogenic therapy should be performed from a perspective distinct from that of cytotoxic treatment.

金沢大学医療技術短期大学部紀要 Memoirs of Kanazawa University School of Paramedicine, 1993

Acta Pathologica Japonica, Sep 1, 1990

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 ... more Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained i n the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion ; the patient i n the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis. Acta Pathol Jpn 40: [676][677][678][679][680][681][682] 1990.

Journal of Nuclear Medicine, Mar 1, 1998

The purpose of the present study was to evaluate the degree of cytological radiation damage to ly... more The purpose of the present study was to evaluate the degree of cytological radiation damage to lymphocytes after1311therapy using the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by 131I Â¡nvivo should result in augmentation of the cells with micronuclei. Methods: We studied 25 patients with differentiated thyroid carcinoma who were treated with 3.7 GBq of 131I.Isolated lymphocytes collected from patients 1 wk after therapy were harvested and treated according to the cytoki nesis-blocked method of Fenech and Morley. The micronucleus number of micronuclei per 500 binucleated cells were scored by visual inspection. As controls, lymphocytes from the same patients before therapy were also studied. In an in vitro study, lymphocytes from three patients at least 3 mo after therapy were exposed to doses varying from 0.25 to 1 Gy and studied with the same method. Results: The mean number (mean Â±s.d.) of micronuclei after treatment was significantly increased (p < 0.05) as compared to control subjects (15.7 Â±2.7 vs. 5.4 Â±1.4). Since there was an interval ranging from 6 to 20 mo (mean 11.8 mo) between the present and the last radioiodine therapy, no significant effect on the frequency of micronucleus with cumulative radiation exposure of 1311to lymphocytes was detected. Internal radiation absorbed doses estimated for 25 patients were 0.33 Â±0.09 Gy in this external irradiation study. Conclusion: The relatively low frequency of lym phocyte micronuclei induced by 131Iin vivo and lack of significant effect on the frequency of lymphocyte micronuclei with cumulative 1311supported the contention that short-term nonstochastic dam age of this therapy with 3.7 GBq of 131Iin thyroid cancer patients is minimal and reversible.

Journal of Nuclear Medicine, Nov 1, 1997

Annals of Nuclear Medicine, 2006

$Research paper thumbnail of 10. Determination of renal plasma flow from the extraction fraction of 99Tcm-DTPA using the Patlak plot method$

Clinical Nuclear Medicine, Sep 1, 1989

European Journal of Nuclear Medecine and Molecular Imaging, 2002

The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the the... more The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tumour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current investigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metastases were established in nude mice by intrasplenic inoculation of LS180 colon cancer cells; following such inoculation, metastases of <1 mm in diameter can be observed at 1 week and these lesions can attain a size of several millimetres at 2 weeks. Daily AT with 2-methoxyoestradiol (2-ME), 75 mg/kg, was initiated at 1 week. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, 131 I-HPMS-1, was implemented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on 131 I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or 131 I-A7 RIT significantly suppressed metastasis growth (P<0.0001): metastasis weight was 5.96±0.87 g in non-treated controls, 2.67±1.89 g in cases receiving AT and 0.85±0.68 g in those receiving 131 I-A7 RIT. Combination of AT and 131 I-A7 RIT more effectively suppressed the growth to 0.28±0.32 g (P<0.05 vs RIT alone). The effect of 131 I-HPMS-1 RIT, which suppressed metastasis growth to 2.25±0.88 g, was significant in comparison with the control (P<0.0001); however, the combination of AT and 131 I-HPMS-1 RIT (which suppressed growth to 1.41±0.68 g) was far less effective than the combination of AT and 131 I-A7 RIT. AT did not decrease 131 I-A7 accumulation in metastases. AT did not affect RIT myelotoxicity. The results of this study demonstrating the combined effects of AT and 131 I-A7 RIT in a small metastasis model indicate that such combination therapy may be suitable for the treatment of minimal disease.

Clinical Nuclear Medicine, 1988

A case is presented in which uptake of Tc-99m DTPA has been demonstrated in an extramedullary pla... more A case is presented in which uptake of Tc-99m DTPA has been demonstrated in an extramedullary plasmacytoma of the retroperitoneum. Because Ga-67 citrate does not concentrate in the same areas as Tc-99m DTPA, a radionuclide-specific uptake mechanism may be present. Extramedullary plasmacytoma should be included in the list of possible causes if extrarenal or extracentral nervous system uptake of Tc-99m DTPA occurs.

Clinical Nuclear Medicine, Jun 1, 2010

A 61-year old woman after total thyroidectomy for papillary thyroid cancer underwent I-131 therap... more A 61-year old woman after total thyroidectomy for papillary thyroid cancer underwent I-131 therapy. Focal uptake was seen in the chest on whole body imaging. SPECT/CT delineated I-131 accumulation in an iso-dense mediastinal lesion which was histologically diagnosed as thymic cyst. I-131 uptake in thymic cyst has never been reported and should be included in the gamut of false positive entities of I-131 scintigraphy.

Annals of Nuclear Medicine, Dec 1, 2001

Antiphospholipid antibodies (AA) are immunoglobulins that cross-react with phospholipid on cell m... more Antiphospholipid antibodies (AA) are immunoglobulins that cross-react with phospholipid on cell membrane, and are therefore associated with a hypercoagulable state manifested by arterial/venous thromboses. We aimed to determine the prevalence of deep venous thrombosis in the lower limbs and the pelvic region (DVT) and pulmonary embolism (PE) in patients with positive AA. Sixty-six patients (48 female, 18 male) with positive lupus anticoagulant (LA) and/or positive anticardiolipin antibody (aCL) underwent radionuclide (RN) venography with 370 MBq of 99mTc-MAA. Pulmonary perfusion scintigraphy was performed in 58 patients. Fifteen patients had positive LA and positive aCL (LA+/aCL+), 33 patients had positive LA only (LA+/ aCL-) and 18 patients had positive aCL only (LA-/aCL+). 43 patients were diagnosed with primary antiphospholipid syndrome (APS) and 19 were diagnosed with APS associated with SLE. DVT was detected in 21 of 66 patients (32%). Patients with LA+/aCL+ showed higher prevalence of DVT (53%) as compared to LA+/aCL- (27%) and LA-/aCL+ (22%). PE was found in 13 of 58 patients (22%). The prevalence of PE was higher in patients with positive aCL (33% in LA+/aCL+; 36% in LA-/aCL+) than in patients with negative aCL (10%). Because of the high prevalence of DVT and PE in patients with AA, RN scintigraphy must be recommended in screening for these clinical troubles. These results indicate that the prevalence of DVT and PE may vary in subgroups of AA.

Journal of Nuclear Medicine, Jul 1, 2000

Induced hypertension and kininase inhibition can enhance tumor targeting of radiolabeled monoclon... more Induced hypertension and kininase inhibition can enhance tumor targeting of radiolabeled monoclonal antibody (MAb) by altering tumor circulation. This study investigated the effect of this manipulation on the antitumor efficacy of radioimmunotherapy (RIT). Methods: Mice bearing human colon cancer xenografts were administered 2.0 ug/kg/min of angiotensin II (AT-II) for 1 h and 30 ug of a kininase inhibitor, enalapril malÃ©ate, before the administration of 3.7 MBq 13'I-A7, an lgG1 against 45-kDa glycoprotein on colorectal cancer, and tumor growth was ob served thereafter. The mechanism of the manipulation effect was investigated by estimation of the tissue absorbed dose and radioluminography of tumors. Results: The pharmacologie ma nipulation with AT-II and enalapril improved the tumor quadru pling time (Tq) of 3.7 MBq RIT from 24.3 Â±2.75 d to 33.1 Â±2.83 d (P < 0.05). Addition of this manipulation made 3.7 MBq RIT as effective as 9.25 MBq RIT alone (Tq, 37.2 Â±2.97 d). Dose estimation showed that the manipulation increased the tumor absorbed dose 1.55-fold without affecting the doses to normal tissues. Uniform intratumoral distribution in the manipulated tumors was shown by radioluminography. Conclusion: Larger and more uniform tumor radiation produced by this pharmaco logie manipulation can benefit RIT with 131l-MAb.