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Biomedical subjects

M Makita

Publications and source records attributed to M Makita.

At least 19 recordsLinked to original sources

Experience with intradermal injection and intradermal-plus-deep injection in the radioguided sentinel node biopsy of early breast cancer patients.

AIMS: Methods of administering (99m)Tc-phytate during sentinel node biopsy of early breast cancer patients were compared to improve the sensitivity of the technique. METHODS: Two injection methods, intradermal vs. intradermal-plus-deep injection, were compared in 648 early breast cancer patients. Intradermal injection was done in 323 consecutive patients (325 breasts), and intradermal-plus-deep injection was done in 325 consecutive patients (329 breasts). The following items were compared: (1) The number of axillary nodes detected scintigraphically and removed surgically, and the breast number of micrometastasis to axillary nodes; (2) The number of internal mammary nodes detected scintigraphically and removed surgically; and (3) The sensitivity of axillary SNB. RESULTS: The number of axillary nodes scintigraphically detected was 1.63+/-0.80 (mean+/-SD) in patients given intradermal injection, and was 1.82+/-0.94 in patients given intradermal-plus-deep injection. The number of axillary nodes surgically removed was 1.78+/-0.93 in patients given intradermal injection, and was 1.95+/-0.99 in patients given intradermal-plus-deep injection. The visualization of internal mammary nodes was superior with intradermal-plus-deep injection (5/325 for intradermal, and 51/329 for intradermal-plus-deep). The putative sensitivity was 71/72 (98.6%) for the intradermal-plus-deep method and 56/62 (90.3%) for the intradermal method. The frequency of detection of micrometastasis was 24 in 71 true positive (38.8%) for the intradermal-plus-deep method and 13 in 56 true positive (23.2%) for the intradermal method. CONCLUSIONS: The SNB procedure with the intradermal-plus-deep injection method detected more axillary and internal mammary nodes, more (not statistically significant) micrometastasis and improved the putative sensitivity more than the SNB procedure with the intradermal injection method.

Axilla↗

Radioactivity thresholds for sentinel node biopsy in breast cancer.

AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.

Axilla↗

The effect of an old surgical scar on sentinel node mapping in patients with breast cancer: a report of five cases.

AIMS: To study the significance of lymphatic drainage disruption due to a surgical scar in sentinel node mapping (SNM) in breast cancer patients. METHODS: We reviewed patients with stage I breast cancer who had undergone SNM and had an old surgical scar in the ipsilateral breast. RESULTS: Of 534 breast cancer patients who had undergone SNM, five patients had an old scar in the ipsilateral breast. Inter-pectoral nodes, internal nodes, intramammary nodes, and contralateral axillary nodes were identified as sentinel nodes in three cases. In the remaining two cases, no sentinel lymph nodes were identified. CONCLUSIONS: An old surgical scar in the breast may cause lymphatic drainage disruption, resulting in abnormal radioactive colloid uptake during SNM.

Aged↗

Comparison of two-year and five-year tamoxifen use in Japanese post-menopausal women.

AIM: Large multicenter, randomized trials have revealed the advantages of using tamoxifen for 5 years vs 2 years in breast cancer patients. The aim of this report is to confirm the optimal duration of tamoxifen administration in a study of Japanese breast cancer patients. METHODS: Japanese post-menopausal estrogen receptor-positive breast cancer patients treated with mastectomy were randomly assigned to either a 5-year or 2-year course of tamoxifen. The primary endpoint was disease-free survival, with secondary endpoints of overall survival and a reduction in the development of metachronous contra-lateral breast cancer. RESULTS: A total of 256 breast cancer patients were randomized to a 5-year or 2-year tamoxifen administration group. After a median follow-up time of 81 months, there were no significant differences seen in terms of disease-free or overall survival (p=0.65 and 0.56, respectively). Furthermore, the impact of the 5-year use of tamoxifen on the development of contra-lateral breast cancer did not reach statistical significance (p=0.0511). However, 5-year tamoxifen use was closely associated with gynaecological complications (p=0.0081). CONCLUSION: We could not show a beneficial effect of using tamoxifen for 5 years over 2 years in Japanese estrogen receptor-positive patients. This is likely due to the small number of patients enrolled in our study; however, racial disparity may influence this result. A reevaluation is necessary to study the advantages of the 5-year use of tamoxifen in the Japanese racial subgroup.

Adult↗

The potential for oral combination chemotherapy of 5'-deoxy-5-fluorouridine, a 5-FU prodrug, and cyclophosphamide for metastatic breast cancer.

Preclinical studies have demonstrated the synergistic anti-tumour activity of combination therapy with the oral cytostatics, 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA), in human breast cancer xenograft models. This study was performed to evaluate the efficacy and safety of this oral combination chemotherapy in the treatment of metastatic breast cancer. In all, 101 patients with metastatic breast cancer were enrolled in the study, and the data for 94 eligible patients of these were evaluated. The patients received twice daily oral combinations of 5'-DFUR (1200 mg/body/day) and CPA (100 mg/body/day) for 2 weeks, followed by a 1-week rest period. After a median of 19 treatment cycles (range 1-66 cycles), 16 patients (17.0%) had a complete response, and 40 patients (42.6%) had partial responses. The response rate was 59.6% (95% CI, 49.0-69.6%). The median time to progression and overall survival times were 11.7 and 40.3 months, respectively. The toxicity was mild and tolerable, and the related grade 3/4 clinical adverse effects consisted of haematological toxicity in 21 patients (22%) and nonhaematological toxicity in five patients (5%). These results suggest that the oral combination chemotherapy of 5'-DFUR and CPA has low toxicity and is a novel, very convenient and effective treatment for metastatic breast cancer.

Administration, Oral↗

Acute lymphoblastic leukemia with large molecular ACTH production.

Ectopic hormone production is very rare in hematological malignancy. Here, we describe an interesting case of acute lymphoblastic leukemia (ALL) with adrenocorticotropic hormone (ACTH) production. A 47-year-old man was admitted to our hospital with a 7-month history of hyperpigmentation. The plasma level of ACTH was markedly elevated without a circadian rhythm and the level of cortisol was normal. Examination of bone marrow aspiration revealed ALL, and no other disease as a cause of the elevated ACTH was detected. Sephadex G-75 chromatography of plasma ACTH extract revealed the existence of an abnormally large molecular ACTH (probably proopiomelanocortin) in addition to authentic 1-39 ACTH. Ectopic ACTH of low biological activity is considered to be the reason for a discrepancy in the plasma levels of ACTH and cortisol. Shortly after remission induction chemotherapy, blast cells in the peripheral blood disappeared, and the plasma level of ACTH became normal, leading to an improvement of skin pigmentation. These clinical findings and laboratory data suggested that leukemia cells in this case may produce the ACTH.

Adrenocorticotropic Hormone↗

Sentinel node detection using 99mTc-rhenium sulphide colloid in breast cancer patients: evaluation of 1 day and 2 day protocols, and a dose-finding study.

Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post-menopausal patients showed lower SN uptake. 99mTc-rhenium sulphide colloid is an efficient radiopharmaceutical for SN detection. Both 1 day and 2 day protocols have equally good efficacy, and the recommended dose is 7.4 MBq for the 1 day protocol and 37 MBq for the 2 day protocol. Patients with larger BMI and older or post-menopausal patients tend to take up less 99mTc colloid.

Adult↗

Breast conserving treatment without radiotherapy.

Radiotherapy (RT) is not always necessary for the prevention of ipsilateral breast recurrence in cases where cancer is not detected in the remaining breast tissue after breast conserving surgery. In addition, under these circumstances, the rate of a second primary cancer of the remaining breast is theoretically equal to the rate of contralateral breast cancer. In performing breast conserving treatment (BCT) at our institution we do not treat with RT if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been safely resected (negative surgical margins). From 1986 to 1998, 827 patients (157 were ductal carcinoma in situ, and 670 were invasive) underwent BCT without RT at the Cancer Institute Hospital. Ipsilateral breast cancer was observed in 46 cases or 5.6% (0.85% annually) during a median observation period of 67 months. Of these 46 cases, 19 (2.3%) were diagnosed as a recurrence and 27 cases (3.3%) were second primary cancers. This recurrence rate is equivalent to the rate observed in 406 cases of BCT (1.7%) that were treated with RT. Most of these cases had shown positive surgical margins. Furthermore, the rate of occurrence of second cancers is not significantly different from the rate of occurrence of contralateral breast cancers. These results suggest that, by selecting irradiation cases based on careful pathological examinations, BCT can be safely performed.

Breast Neoplasms↗

Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes.

Although CD4(+) helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4(+) T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4(+) T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4(+) T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4(+) T lymphocyte clones produced interferon-gamma (IFN-gamma) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-gamma production by CD4(+)T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4(+) T lymphocytes.

Antigen Presentation↗

[Sentinel node detection of patients with breast cancer by radionuclide method: consideration of radiation safety].

Sentinel node was detected by 99mTc labeled nanocolloid in five patients with breast cancer. Surgery of breast cancer was done at 16 hours after the administration of 74 MBq of 99mTc labeled nanocolloid. Sentinel node was searched by scintigraphy prior to surgery and by gamma-probe during surgery. Radioactivity of injected site, sentinel nodes, blood contaminated gauze, and other garbage was measured by GM detector. Radiation to medical staffs was monitored by a pocket radiation detector and film batches. Sentinel nodes were successfully detected both by scintigraphy and gamma-detector. More than 70% of radioactivity remained in the administered site at 16 hours. Small amount of radioactivity was detectable in the sentinel node. Almost no radioactivity was detectable in blood-contaminated gauze and other garbage. Radiation dose to the main surgeon was 4 to 6 microSv per surgery by a pocket radiation detector. Radiation dose to the assistant surgeon was 2 microSv per surgery. Radiation dose by labeling or injection was 0 to 1 microSv per procedure. No detectable radiation was measured by film batches. It is concluded that the detection of sentinel node by 99mTc labeled nanocolloid is a safe procedure from the point of radiation safety consideration.

Breast Neoplasms↗

Surgery for ductal carcinoma in situ.

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Axilla↗

Ultrastructural studies of implantation sites from mice deficient in uterine natural killer cells.

Implantation sites from three strains of immunodeficient mice [tgepsilon26, IL-2Rbeta nullxp56(lck)null and IL-2Rgamma null, now known as common cytokine chain gamma (gamma(c)) null], which lack uterine natural killer (uNK) cells, are histologically abnormal. The related anomalies (found from day 10 of gestation) include the absence of aggregation of lymphocytes in the mesometrial triangle, acellularity of the mesometrial decidua, decidual arteries with relatively thick walls and reduced lumen diameters, unusual prominence of the endothelium in the major decidual vessels, and an overall reduction in placental size. In this study we have characterized implantation sites in a new mouse strain (gammac(-)/RAG2(-)) that is deficient in all lymphoid lineages. We have compared implantation sites in tgepsilon26 to gammac(-)/RAG2(-)at the ultrastructural level in order to determine the earliest-time point at which implantation sites differed from those in immunocompetent mice, and the cell types affected. Implantation sites from both the uNK cell-deficient mice resemble those from random-bred, immunocompetent mice on days 6 and 7 of gestation. On day 8 of gestation, decidual cells on the mesometrial sides of implantation sites in both tgepsilon26 and gammac(-)/RAG2(-)revealed pleotrophic morphology and degeneration. In some vessels, endothelial cells were distorted or displaced from their supporting cells. Progressive changes, suggestive of loss of function of both the mesometrial decidua and endothelial cells, were seen to day 14 of gestation, the latest time-point analysed. In contrast to tgepsilon26 mice, homozygously-mated gammac(-)/RAG2(-)had normal litter sizes, with birthweights and weaning weights similar to congenic C57Bl/6J controls, and no significant perinatal loss. In both strains, the newly-documented endothelial cell lesions predict detrimental alterations to vasomotor function of the uterine vasculature. These studies add strength to the hypothesis that uNK cells may have specialized physiological, rather than classically immune, functions in the pregnant mammalian uterus.

Animals↗

Successful pregnancy following blastocyst vitrification: case report.

A 32 year old woman and her 32 year old spouse were referred to our IVF programme. Following recovery of 12 mature oocytes, nine were fertilized following conventional IVF. Three fresh embryos were transferred to the uterus, but all failed to result in pregnancy. Six supernumerary embryos were cultured in vitro until day 5 in order to create blastocysts. Two grew to the blastocyst stage and were vitrified using a modification of a previous method. Two blastocysts survived the freeze-thaw process and were transferred to the patient's uterus during a natural cycle, 3 months after the previous retrieval cycle. Implantation resulted in a healthy pregnancy; delivery is expected in June 2000. This report documents the first successful pregnancy in Japan, achieved via blastocyst vitrification.

Blastocyst↗

Determination of hydration kinetics of sulfaguanidine anhydrate in aqueous solution by calorimetry.

A heat conduction microcalorimeter was used to evaluate the isothermal transition in water from anhydrate to monohydrate at 298 K. Sulfaguanidine (SGN) anhydrate was used as a model compound for the measurement of hydration kinetics in water. It is the well-known that SGN is very slightly soluble in water and capable of existing as the anhydrate or monohydrate form in the solid state. The transition rates of SGN anhydrate to monohydrate in tablets and granules were investigated. The hydration kinetics of tablets with controlled surface areas, obtained by coating the side with paraffin in aqueous solution, followed an apparent zero-order mechanism. On the other hand, the transition mechanism of the granules involved a phase boundary-controlled contracting interface reaction.

Calorimetry↗