Biomedical subjects

Hiroki Koyama

Publications and source records attributed to Hiroki Koyama.

At least 19 recordsLinked to original sources

PubMed2004

Controversies in sentinel node biopsy for breast cancer.

Sentinel node biopsy for breast cancer patients has recently been applied as a less invasive, highly accurate alternative to axillary lymph node dissection. Numerous studies have shown that sentinel nodes accurately diagnose axillary staging. However, many problems remain to be answered and must be addressed before sentinel node biopsy becomes the standard surgical procedure for patients with breast cancer. We reviewed and discussed here three of these problems; axillary sampling as an alternative to sentinel node biopsy, dye method vs. combination of dye and radiocolloid for sentinel node biopsy, and intraoperative sentinel node examination. Further investigation will continue to be necessary as we learn how to better provide procedure of sentinel node biopsy.

Axilla↗

PubMed2004

[Controversies in breast conservation treatment for breast cancer].

Breast conservation treatment has become the standard treatment for early breast cancer patients, after the equivalence of mastectomy and breast conservation treatment was demonstrated in prospective, randomized trials and large retrospective studies. New questions, such as the feasibility of neoadjuvant chemotherapy in improving breast conserving rate, the appropriateness of breast conservation treatment in ductal carcinoma in situ, the effectiveness of radiation therapy in patients treated by breast conservation, and patient selection for breast conservation without radiation, are now being raised. Future work that needs to be done to answer these questions is discussed in this review.

Breast Neoplasms↗

PubMed2004

[Technical aspects of sentinel node biopsy].

Many studies have demonstrated that sentinel nodes can accurately determine the regional nodal status in breast cancer and malignant melanoma. Since this was demonstrated sentinel node biopsy has been performed for various solid malignancies. However, the optimal procedure for sentinel node biopsy remains unknown. It is considered that the combination of dye and radiocolloid injection is needed for sentinel node biopsy in breast cancer. As for gastrointestinal tract malignancies, good results were reported in several feasibility studies. A large clinical trial on sentinel node biopsy for gastric cancer will be conducted in the near future, the results of which are highly anticipated.

Breast Neoplasms↗

PubMed2004

1-hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: a randomized controlled trial.

We studied the usefulness of the oral 5-FU anti-cancer drug 1-hexylcarbamoyl-5-fluorouracil (HCFU) + cyclophosphamide (CPM) + tamoxifen (TAM) (HCT group) in comparison with CMF + TAM (CMFT group) in adjuvant therapy for breast cancer by a non-inferiority study based on a multi-institutional joint study. Clinical stage I, II primary breast cancers with histologically positive axillary lymph node metastasis were randomly assigned to the HCT group or the CMFT group after primary surgery. We registered 136 cases (HCT group 68 cases, CMFT group 68 cases). No significant difference in the 5-year overall survival rate (OS) and the 5-year disease-free survival rate (DFS) was found between the two groups. In the stratified analysis, DFS in cases in which the number of metastatic lymph nodes was 1-3 was significantly better in the HCT group (HCT group 84.3%, CMFT group 69.4%, log-rank test p=0.0496). No significant difference in the total incidence of adverse effects was found between the two groups, but there were significantly less adverse effects of grade 2 or over in the HCT group (p=0.034). The QOL survey at 3 months after surgery showed a significant decline of the QOL regarding lassitude, degree of difficulty in daily life, satisfaction with treatment and present mood in the CMFT group. Study results suggest that 2-year HCT therapy including the oral 5-FU anti-cancer drug HCFU is a useful adjuvant therapy which can replace CMFT therapy in early breast cancer cases with 3 or lower metastatic lymph nodes.

Adult↗

PubMed2003

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.

Administration, Oral↗

PubMed2003

Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patients.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients. METHODS: Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc-99m tin colloid, with a larger particle size (0.4-5 microm), rather than sulfur colloid and colloidal albumin. RESULTS: The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P = 0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False-negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P < 0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%). CONCLUSIONS: A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc-99m tin colloid with a large particle size than by subdermal injection.

Axilla↗

PubMed2003

Increased expression of BRCA1 mRNA predicts favorable response to anthracycline-containing chemotherapy in breast cancers.

Clinical significance of BRCA1 and BRCA2 mRNA levels in tumor tissues as predictors of response to anthracycline-containing chemotherapy was studied in breast cancer patients. Fifty-one patients with locally advanced breast tumors (n = 43) or locally recurrent tumors (n = 8) underwent tumor biopsy and were treated with CE (cyclophosphamide (600 mg/m2) plus epirubicin (60 mg/m2), q3w). BRCA1 and BRCA2 mRNA levels in the tumors were determined by a real-time PCR assay, and the expression of p53 and erbB2 in tumors was determined by immunohistochemistry. BRCA1 mRNA levels (1.317 +/- 0.277, mean +/- S.E.) of responders were significantly (p < 0.05) higher than those (0.609 +/- 0.097) of non-responders but there was no significant difference in BRCA2 mRNA levels between responders (1.590 +/- 0.326) and non-responders (1.586 +/- 0.410). Tumors were dichotomized into the BRCA1 mRNA levels high and low group according to the cut-off value of 0.55. Response rate (65%) of tumors with high BRCA1 mRNA levels was significantly (p < 0.05) higher than that (32%) of tumors with low BRCA1 mRNA levels. There was no significant association between response to CE and the expression of p53 or erbB2. Positive predictive value, negative predictive value, and diagnostic accuracy of BRCA1 mRNA determination in the prediction of response to CE were 65, 68, and 67%, respectively. These results suggest a possibility that BRCA1 mRNA levels in tumor tissues might be useful in the prediction of response to CE treatment in breast cancer patients.

Antibiotics, Antineoplastic↗

PubMed2003

Long-term results of breast-conserving treatment for early-stage breast cancer in Japanese women from multicenter investigation.

BACKGROUND: Although many clinical data regarding breast-conserving treatment have already been reported from European and North American countries, few clinical data with long-term follow-up have been reported from Japan. METHOD: We collected information on therapeutic and possible or developed prognostic factors and follow-up data for Japanese women who had received breast-conserving treatment consisting of wide excision of the primary tumor, axillary dissection and radiotherapy for unilateral breast cancer considered suitable for breast-conserving treatment from 18 Japanese major breast cancer treating hospitals; 1561 patients were registered. RESULTS: The median follow-up period was 77 months. Five-year disease-free and overall survival rates were 89.4 and 95.9%, respectively. The 5-year local recurrence-free rate was 96.3%. The patients with histologically positive margins (P < 0.0001) or estrogen receptor negative tumor (P = 0.0340) or younger than 40 years old (P < 0.0001) developed statistically significantly more local recurrences. Adjuvant endocrine therapy was essential for the estrogen receptor positive patients to have a lower local recurrence rate. Endocrine therapy did not change the local recurrence rate among estrogen receptor negative patients at all. Multivariate analysis showed histological margin status and the combination of estrogen receptor status and endocrine therapy were independent prognostic factors for local recurrence. CONCLUSION: The 5-year local recurrence rate of Japanese breast cancer patients who were treated with breast-conserving treatment using radiotherapy was 3.7%. Independent prognostic factors for local recurrence were histological margin status and the combination of estrogen receptor status and adjuvant endocrine therapy.

Adult↗

PubMed2003

Lymphoscintigraphic visualization of internal mammary nodes with subtumoral injection of radiocolloid in patients with breast cancer.

OBJECTIVE: To determine whether subtumoral injection of radiocolloid is useful for lymphoscintigraphic visualization of the internal mammary node and in sentinel lymph node (SLN) biopsy of the axilla in breast cancer patients. SUMMARY BACKGROUND DATA: The presence of retromammary lymphatics connecting to the axillary and internal mammary basins has been demonstrated by early anatomic studies. Thus, it is hypothesized that some lymph, especially that from the parenchyma under the tumor, may drain into both the axillary and internal mammary basins. METHODS: Patients (n = 196) with T1-2, N0 breast cancer underwent preoperative lymphoscintigraphy with radiocolloid (technetium 99m tin colloid) injection into various sites of the breast, followed by SLN biopsy using the combined method with blue dye. Patients were divided into four groups: group A (n = 41), peritumoral injection of both radiocolloid and blue dye; group B (n = 70), periareolar radiocolloid and peritumoral blue dye; group C (n = 45), intradermal radiocolloid and periareolar blue dye; and group D (n = 40), subtumoral radiocolloid and intradermal blue dye. A retrospective analysis of 1,297 breast cancer patients who underwent extended radical mastectomy with internal mammary node dissection was also conducted to determine the relationship between vertical tumor location (superficial or deep) and frequency of axillary and internal mammary node metastases. RESULTS: One patient (2%) in group A, 3 (4%) in group B, 0 (0%) in group C, and 15 (38%) in group D exhibited hot spots in the internal mammary region on lymphoscintigraphy (P <.001, group D vs. the other groups). The concordance rate of radiocolloid and blue dye methods in detection of SLNs in the axillary basin was significantly lower in group D than in the other groups. In contrast, the mismatch rate (some SLNs were identified by radiocolloid and other SLNs were identified by blue dye, but no SLN was identified by both in the same patient) was significantly higher in group D than in the other groups. In patients treated with extended radical mastectomy, positivity of axillary and internal mammary metastases was significantly higher in patients (n = 215) with deep tumors than those (n = 368) with superficial tumors. CONCLUSIONS: These results suggest the presence of a retromammary lymphatic pathway from the deep portion of the breast to both axillary and internal mammary basins, which is distinct from the superficial pathway. Therefore, SLN biopsy with a combination of subtumoral and other (peritumoral, dermal, or areolar) injections of radiocolloid will improve both axillary and internal mammary nodal staging.

Adult↗

PubMed2003

Repeat lumpectomy for patients with ipsilateral breast tumor recurrence after breast-conserving surgery. Preliminary results.

In this study, we assessed the appropriateness of conducting repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) based on the characteristics of recurrence after primary breast conserving surgery (BCS). Of 41 patients who had developed IBTR from October 1986 to June 2000 at our institute, 11 underwent mastectomy of the remaining breast and 30 underwent repeat lumpectomy. The 5-year overall survival rate at a median follow-up of 43 months after salvage surgery was 90.9% for the mastectomy group and 90.0% for the lumpectomy group. The 5-year distant disease-free survival rate was 70.1% for the mastectomy group and 83.0% for the lumpectomy group. The survival rates were remarkably high in both treatment groups, with no significant difference between them. IBTRs in the majority of our patients were small lesions less than 1 cm in diameter. They did not feature lymphatic invasion and had low histological grade. Compared with that of primary lesions, the malignancy of recurrent tumors was not increased in many patients. In contrast to these preferable features, 9 of 30 patients who underwent repeat lumpectomy developed second local relapse within 3 years after salvage operation. Young age (<or=35 years), positive family history and omission of adjuvant systemic therapy were found to exhibit trends as a discriminate for further local recurrences. In view of the relatively good prognosis of IBTRs and excellent results of repeat lumpectomy, we consider this method a treatment option that deserves serious consideration if we can select the patients who will not likely develop second local relapse.

Adult↗

PubMed2003

[Sentinel node biopsy using dye methods].

At first, sentinel node identification was performed using dyes such as isosulfan blue dye and patent blue dye. Although dye localization is a simple and cheap method, this procedure requires training and the success rate and accuracy are not very good. It is considered that the addition of a radiocolloid injection is needed for sentinel node biopsy in melanoma and breast cancer. For gastrointestinal tract malignancies, good results were reported in several feasibility studies. However, the validity of sentinel node biopsy for those malignancies depends on the results of a large ongoing clinical trial.

Animals↗

PubMed2002

Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer.

Several recent trials have demonstrated that neoadjuvant chemotherapy can allow more patients to successfully undergo breast-conserving treatment (BCT), and does not confer a survival disadvantage compared with standard adjuvant chemotherapy. In addition, the pathological response of primary breast tumors to neoadjuvant chemotherapy appears to be a surrogate marker for patient outcome. In our series, during the period from May 1995 to December 2000, 86 patients with tumors between 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. The margin positive rate was 14.1%(9/64), similar to the rate after BCT for early-stage breast cancers, the largest diameter of which was smaller than 3 cm. At a median follow-up of 30 months, only 3 patients in the BCT group have developed local recurrence; the local recurrence rate appears to be comparable to that after BCT for early stage breast cancers. Long term follow-up is required, however, to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.

Antineoplastic Agents↗

PubMed2002

Long-term results of breast conserving surgery for stages I and II breast cancer: experiences at Osaka Medical Center for Cancer and Cardiovascular Diseases.

PURPOSE: The purpose of this study is to summarize the long-term results of breast conserving surgery (BCS) for Japanese patients with stage I and II breast cancer at a single institute and to identify risk factors for local recurrence after BCS. PATIENTS AND METHODS: Between October 1986 and June 2000, 979 women underwent BCS with or without radiation therapy (RT). Overall survival, disease free survival and local recurrence rates were calculated by the Kaplan-Meier method. Risk factors for local recurrence were examined by multivariate analysis using the Cox proportional regression model. RESULTS: The 10-year overall survival rates were 90.9% for the surgery and radiation therapy (RT group) and 89.3% for the surgery only group with a median follow-up time of 46 months. The 10-year disease free survival rates were 85.1% in the RT group and 69.2% in the surgery only group (p=0.0001). The positive margin rate was 14.1% (138/979). The 10-year overall survival rate of the patients with positive margins was 87.9%, compared with 90.8% for patients with negative margins (N.S.). The cumulative incidence of local recurrence at 10 years was significantly lower in the RT group (7.2% ) than in the surgery only group (27.5% ) (p<0.0001). Multivariate analysis showed that positive margins and lack of post-operative irradiation or adjuvant endocrine therapy were risk factors for non-inflammatory local recurrence. CONCLUSIONS: Our study indicates that BCS can be performed for Japanese women with early breast cancer. The margin status and post-operative irradiation had no influence on overall survival while but were significantly related to local recurrence.

Adult↗

PubMed2002

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer.

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.

Axilla↗

PubMed2002

Patient age affects identification rate of sentinel nodes in breast cancer.

BACKGROUND: The aim of this study was to investigate whether clinicopathological features affect the success rate of identifying sentinel nodes using a combination method of dye and radioisotope in breast cancer patients. METHODS: Sentinel node biopsy was performed in patients (n = 154) with stage I and II breast cancer using a combination method. The association between the clinicopathological features of breast cancer and the success rate in the identification of sentinel nodes was investigated. RESULTS: Sentinel nodes were successfully identified in 147 (95.5%) of the 154 patients. There was a concordance between the sentinel-node and axillary-node status in 146 (99.3%) of 147 cases. The false negative rate of the sentinel node biopsy was 2.4% (1/42). The identification rate of sentinel nodes was significantly (P = 0.005) lower in patients > or = 60 years (84.4%) than in those < 60 years (98.4%). The tumor size, histological node status, lympo-vascular invasion, history of previous surgical biopsy, operative procedure, tumor location, and histological type were not related with the identification rate of sentinel nodes. The mean count ratio of all hot nodes was 14.0 (range 2.0-73.6) in patients > or = 60 years and 73.4 (2.0-1700.6) in patients < 60 years, and this difference was statistically significant (P < 0.0001). In addition, the mean number of sentinel nodes was significantly (P = 0.0006) lower in patients > or = 60 years (1.3; range one to four) than in patients < 60 years (2.1; range one to 12). CONCLUSIONS: Patient age affects the identification rate of sentinel nodes using a combination method in breast cancer.

Adult↗

PubMed2002

Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation.

This study evaluated if melatonin would increase bone mass in mice. Four groups of 4-week-old male ddy mice received daily injections of vehicle or 1, 5, or 50 mg/kg of melatonin, respectively, for 4 weeks. Treatment with 5 mg/kg per day or 50 mg/kg per day of melatonin significantly increased bone mineral density (BMD; by 36%, p < 0.005) and bone mass (bone volume per tissue volume [BV/TV] by 49%, p < 0.01, and trabecular thickness [Tb.Th] by 19%, p < 0.05). This treatment significantly reduced bone resorption parameters (i.e., osteoclast surface [Oc.S/bone surface [BS]] by 74%,p < 0.05, and osteoclast number [N.Oc/BS] by 76%,p < 0.005) but did not increase histomorphometric bone formation parameters (i.e., bone formation rate [BFR/ BS], mineral apposition rate [MAR], and osteoid volume [OV/TV]), indicating that melatonin increases bone mass predominantly through suppression of bone resorption. Melatonin (1-500 microM) in vitro caused dose-dependent reduction (p < 0.001 for each) in the number and area of resorption pits formed by osteoclasts derived from bone marrow cells but not those formed by isolated rabbit osteoclasts. Because RANKL increases, while osteoprotegerin (OPG) serves as a soluble decoy receptor for RANKL to inhibit osteoclast formation and activity, the effect of melatonin on the expression of RANKL and OPG in mouse MC3T3-E1 osteoblastic cells was investigated. Melatonin (5-500 microM) increased in a dose-dependent manner and reduced the mRNA level of RANKL and both mRNA and protein levels of OPG in MC3T3-E1 cells (p < 0.001 for each). In summary, these findings indicated for the first time that melatonin at pharmacologic doses in mice causes an inhibition of bone resorption and an increase in bone mass. These skeletal effects probably were caused by the melatonin-mediated down-regulation of the RANKL-mediated osteoclast formation and activation.

Animals↗

PubMed2002

The effect of adjuvant 5'-deoxy-5-fluorouridine in early stage breast cancer patients: results from a multicenter randomized controlled trial.

To assess the efficacy of 5'-DFUR, an intermediate of capecitabine, for adjuvant treatment of early breast cancer, we conducted an open-labeled multi-center randomized controlled trial to compare postoperative 5'-DFUR treatment with surgery alone. We enrolled 1217 primary breast cancer patients and randomly assigned them into two treatment groups; one received six-month postoperative 5'-DFUR treatment by consecutive or intermittent administration, and the other surgery alone. Follow-up surveys were conducted once a year for all subjects simultaneously and examined their outcome/presence or absence of the cancer recurrence. The central study committee reviewed all follow-up data and judged the recurrence data to be used for the analysis. Eight-year follow-up data showed no significant differences in relapse-free and overall survival between the two groups, and 5'-DFUR treatment regimen showed an extremely high tolerance. Possible explanations are discussed for the finding of no significant survival difference between adjuvant 6-month 5'-DFUR monotherapy and surgery alone in early breast cancer.

Adult↗

PubMed2002

[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no. 1)--investigation of recommended clinical dose CGS20267 Study Group].

To determine the recommended clinical dose of CGS20267 (Letrozole), we conducted a randomized comparative study as a late phase II study (first part) in postmenopausal women with advanced or recurrent breast cancer. Forty-one patients were randomly assigned to receive 0.5 mg or 1.0 mg once daily. There were no statistically significant differences in background between the two groups. Although there was no significant difference in the objective response rates between the two groups, the rate was higher at 1.0 mg (44.4%) than at 0.5 mg (38.1%). We also combined these data with the results of an early phase II study. The objective response rates (CR + PR) were 31.4% at 0.5 mg and 42.2% at 1.0 mg, and response rates consisting of CR, PR, and NC for longer than 6 months were significantly higher at a dose of 1.0 mg (68.9%) than 0.5 mg (41.2%). Side effects included drug-related adverse events in 36.8% at 0.5 mg and in 31.6% at 1.0 mg. All of the events were grade 2 or lower, indicating a favorable tolerability of CGS20267. These results demonstrated that CGS20267 1.0 mg once daily is more effective than 0.5 mg, and has comparable safety, in the treatment of postmenopausal women with advanced or recurrent breast cancer. We conclude the recommended clinical dose of CGS20267 should be 1.0 mg once daily.

Adult↗