Biomedical subjects

Noriaki Wada

Publications and source records attributed to Noriaki Wada.

10 recordsLinked to original sources

PubMed2007

Serum c-erbB-2 protein is a useful marker for monitoring tumor recurrence of the breast.

C-erbB-2 oncogene protein (ErbB-2/HER-2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB-2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I-IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ml for postoperative patients. Twenty-nine patients (34%) had higher preoperative serum ErbB-2 levels (>or=5.4 ng/ml). A higher preoperative serum ErbB-2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB-2. Seventeen patients died of tumor progression. The recurrence-free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB-2 and 41% in 29 patients with a higher preoperative serum ErbB-2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB-2 was an independent prognostic factor for recurrence-free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15-3 and ErbB-2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast.

Biomarkers, Tumor↗

PubMed2007

Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy.

BACKGROUND: Previous studies have shown cognitive impairment in breast cancer survivors who were exposed to adjuvant chemotherapy. Neural damage by chemotherapy might have played some part in these findings. The current study explored the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy (C+) and those unexposed (C-). METHODS: High-resolution 1.5-tesla brain magnetic resonance imaging (MRI) databases of breast cancer survivors and healthy controls were used. Brain images were preprocessed for optimal voxel-based morphometry. Comparisons of gray matter and white matter were performed between the C+ and the C- groups, by using MRI scans from within 1 year (the 1-year study, n = 51 and n = 55, respectively) or 3 years after their cancer surgery (the 3-year study, n = 73 and n = 59, respectively). As exploratory analyses, correlation analyses were performed between indices of the Wechsler Memory Scale-Revised and regional brain volume where the volume were significantly smaller. As a reference, MRI scans of cancer survivors were compared with those of healthy controls (n = 55 for the 1-year study and n = 37 for the 3-year study). RESULTS: The C+ patients had smaller gray matter and white matter including prefrontal, parahippocampal, and cingulate gyrus, and precuneus in the 1-year study. However, no difference was observed in the 3-year study. The volumes of the prefrontal, parahippocampal gyrus, and precuneus were significantly correlated with indices of attention/concentration and/or visual memory. Comparisons with healthy controls did not show any significant differences. CONCLUSIONS: Adjuvant chemotherapy might have an influence on brain structure, which may account for previously observed cognitive impairments.

Adolescent↗

PubMed2006

Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance.

Lymph vessel tumor emboli (LVTEs) within tumors are difficult to distinguish from stroma-invasive tumor foci. The purpose of this study was to evaluate staining of LVTEs with hematoxylin-eosin (HE) and with D2-40 to determine whether LVTEs identified by HE staining alone are D2-40-positive LVTE and whether the presence of LVTE identified by HE or D2-40 staining is an accurate predictor of outcome in 151 patients with invasive ductal carcinoma (IDC) of the breast. We first attempted to identify LVTE in the stroma-invasive tumor area (intratumor area), the advance area, and the nontumor area by HE staining alone, and then LVTE identified by HE staining was confirmed by D2-40 staining. The number of LVTE identified by HE staining and D2-40 staining successively increased from the intratumor area to the nontumor area. Although D2-40 staining detected larger numbers of LVTE than HE staining in all tumor areas, the highest positive predictive value of LVTE was observed in the intratumor area, and the next was in the advance area, and then the nontumor area, and significant correlations were found between the numbers of LVTE stained by HE and D2-40 in the same tumor areas. LVTE identified by HE staining or D2-40 staining in the intratumor area or nontumor area significantly increased the risk for tumor recurrence or death of patients with IDC, independent of hormone receptor status or nodal status. The results of this study demonstrate that the existence of intratumoral LVTE and that the presence of intratumoral LVTE identified by HE staining or D2-40 staining are accurate predictors of the outcome of patients with IDC of the breast.

Adult↗

PubMed2005

Correlation between concordance of tracers, order of harvest, and presence of metastases in sentinel lymph nodes with breast cancer.

BACKGROUND: There are various methods for the detection of sentinel lymph nodes (SLNs) in breast cancer by using a combined method with blue dye and radioisotope (RI) tracers. The purpose of the study was to reveal any correlation between concordance of the tracers and the order of harvest with the presence of metastases in SLNs. METHODS: The outcomes were reviewed in 408 cases with stage 0 to II breast cancer; the combined method was used in which blue dye and RI were injected subcutaneously around the tumor. The radioactivity and blue staining in each harvested SLN were checked. RESULTS: In 330 cases (81%), SLNs contained both blue dye and RI tracers (blue-hot cases), and in 42 (10%) and 31 (8%) cases, the SLNs contained only the blue stain (blue-only cases) and only RI (hot-only cases), respectively. The overall metastatic rate was 25% on a patient basis. Blue-only cases had a higher rate (42%) of metastasis than hot-only cases (14%). The rate of nodes containing both blue dye and RI gradually decreased from the first SLNs harvested to the third SLNs harvested. The rate of nodes containing RI only increased with the number harvested, and there was not so much change in the rate of nodes containing blue only. CONCLUSIONS: These data suggest that RI tracer could detect a wide range of SLNs and that the blue dye tracer could efficiently detect SLNs with metastasis. The combined methods compensates for the deficiencies of each method and thus will probably help to prevent missing SLNs.

Adult↗

PubMed2004

Inhibition of bone metastasis from breast cancer with pamidronate resulting in reduction of urinary pyridinoline and deoxypyridinoline in a rat model.

BACKGROUND: Breast cancers frequently metastasize to bone, in a process in which osteoclasts play a major role. Bisphosphonate pamidronate, a specific inhibitor of osteoclasts, has been widely used in the treatment of bone metastasis (BM). In this study, using an animal model of BM, we examined the prophylactic and treatment effects of pamidronate against BM and clarified the relationships between BM, pamidronate and bone resorption markers such as urinary pyridinoline and deoxypyridinoline. METHODS: Bone metastases were established by inoculating c-SST-2 (spontaneously developed rat mammary adenocarcinoma) cells into the thoracic aorta of 27 rats, which were then divided into three groups of rats: the untreated control group, the pre-treatment group, consisting of rats treated with pamidronate (10 mg/kg) injected subcutaneously a day before tumor inoculation, and the post-treatment group, in which rats were injected with pamidronate a week after tumor inoculation. Three weeks after tumor inoculation, blood and urine samples were collected. The subjects were then sacrificed to harvest the thoracic and lumbar vertebrae for histological examination, consisting of staining with hematoxylin and eosin and tartrate resistant acid phosphatase (TRACP). RESULTS: The incidence of BM was 70.0%, 44.4% and 37.5% in the control, pre-treatment and post-treatment groups, respectively. Although there was no significant difference among the groups, the rate of BM in the treated groups was lower than that of the control group and no bone destruction was observed in treated rats. The TRACP-stained specimens revealed that there were numerous osteoclasts contributing to the control group tumor burden. The urinary levels of pyridinoline and deoxypyridinoline were reduced by pamidronate. CONCLUSION: Our results suggest that pamidronate prevents the development of BM and the destruction of bone associated with BM. Maintaining the values of Pyr and Dpyr at low levels with pamidronate might lead to inhibition of the incidence and development of BM.

Amino Acids↗

PubMed2004

Evaluation of intraoperative frozen section diagnosis of sentinel lymph nodes in breast cancer.

BACKGROUND: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLNs) can be used to detect metastatic disease, allowing immediate axillary lymph node dissection (ALND). However, pathological inconsistency in the SLNs diagnosis is sometimes encountered when the results of FS and permanent sections are compared. The purpose of this study was to reveal the usefulness and limitations of FS for the diagnosis of SLNs in patients with breast cancer. METHODS: We reviewed the results for 569 patients with breast cancer at stage 0-II who underwent a sentinel node biopsy between February 1998 and December 2002. SLNs were analyzed using standard FS procedures and a single section stained with hematoxylin and eosin was examined. Patients determined to have positive SLNs based on the results of the FS diagnosis immediately underwent ALND. Permanent sections were later prepared from the remaining frozen tissues and examined using hematoxylin and eosin staining without additional immunohistochemical staining. RESULTS: Seven cases (1%) with atypical cells were found in the FS diagnosis intraoperatively, which were counted as "negative" by the following analysis. The final pathology results showed metastasis in the SLN sections in 159 patients (28%), of whom 26 were diagnosed as negative by the FS diagnosis. Accuracy, specificity and the false-negative rate were 95, 100 and 16%, respectively. The mean size of the nodal metastases in the false-negative cases was significantly smaller than that in the true-positive cases (n = 72) (P < 0.01). False-negative rates for T1b, T1c and T2 were 33, 19 and 14%, respectively. The rate of micrometastasis in T1 (43%) was significantly higher than that of T2 (13%) (P < 0.01). CONCLUSIONS: FS diagnosis for SLNs is reliable. Patients with negative SLNs by the FS diagnosis can avoid reoperation for ALND. However, FS may fail to detect micrometastases, especially in cases with small tumors.

Adult↗

PubMed2004

Prognosis of breast cancer patients treated with sentinel node biopsy in Japan.

BACKGROUND: Sentinel node biopsy predicts accurate pathological nodal staging. The survival of node-negative breast cancer patients should be evaluated between the patients treated with sentinel node biopsy alone and those treated with axillary lymph node dissection. METHODS: Ninety-seven patients with negative axillary nodes underwent sentinel node biopsy immediately followed by axillary lymph node dissection between January 1998 and June 1999 (the ALND group). Since then, if sentinel lymph nodes were negative on the frozen-section diagnosis, 112 patients underwent sentinel node biopsy alone without axillary lymph node dissection between July 1999 and December 2000 (the SNB group). We retrospectively observed the outcome of the two study groups. RESULTS: Median follow-up was 52 months in all patients. Relapse-free survival rates at 3 years in the ALND and SNB groups were 94% and 93%, respectively. Five of the 112 patients in the SNB group had overt axillary metastases. Three of them with axillary metastases alone were treated with delayed axillary lymph node dissection. These three patients have been free of other events for 3 years after local salvage treatment. CONCLUSIONS: Sentinel node biopsy will emerge as a standard method to diagnose axillary nodal staging for clinically node-negative breast cancer patients.

Adult↗

PubMed2003

[Current issues in sentinel node navigation surgery in breast cancer].

Sentinel node navigation surgery (SNNS) will become a standard surgical technique to avoid unnecessary axillary lymph node dissection (ALND) in node-negative breast cancer patients. Numerous studies on SNNS have confirmed and demonstrated the reliability of the hypothesis of sentinel lymph nodes in the last decade. In Japan, several feasibility studies on SNNS started in the mid-1990s. Japanese investigators have attempted to perform SNNS using dyes and radiopharmaceuticals. Their results were similar to those reported in Western countries. Now several randomized, phase III trials are underway to assess SNNS in breast cancer in comparison with ALND. On the other hand, observational studies are carried out if sentinel lymph nodes are confirmed to be histologically negative. However, many issues regarding this minimally invasive surgery remain unsolved in Japan: health insurance coverage; guidelines for SNNS; and safe handling of radioactive breast tissues and lymph node specimens. The current status and problems of SNNS in breast cancer are reported.

Breast Neoplasms↗

PubMed2002

[Sentinel node biopsy in breast cancer].

Sentinel node biopsy is a promising surgical technique to avoid unnecessary axillary lymph node dissection for breast cancer patients with histologically negative nodes. Several randomized phase III trials in Western countries are underway to assess sentinel node biopsy in cases of breast cancer in comparison with conventional axillary lymph node dissection. Other investigators have also started observational studies in cases when sentinel lymph nodes are proven histologically negative. In Japan, many issues regarding this minimally invasive surgery remain unresolved: optimal procedure, pathologic work-up, radiation exposure, health insurance coverage, and indication for sentinel node biopsy. The current status and problems of sentinel node biopsy in breast cancer are discussed herein.

Axilla↗

PubMed2002

[Combined chemoendocrine therapy using adriamycin, cyclophosphamide and high dose toremifene in patients with recurrent breast cancer].

We studied a new chemoendocrine therapy against recurrent breast cancer in order to evaluate its efficacy and toxicity. Sixteen eligible patients were treated with the therapy consisting of adriamycin/cyclophosphamide (AC) plus toremifene (TOR). Adriamycin (20 mg/m2) was administered intravenously on days 1 and 8, and cyclophosphamide (100 mg/body) was given orally on days 1 to 14 every 4 weeks. TOR (120 mg/day) was given orally daily. The median age of the patients was 52 years; 6 were premenopausal and 10 postmenopausal. As post-operative adjuvant therapy, anthracycline chemotherapy and tamoxifen were given to 4 and 9 patients, respectively. AC therapy was administered for 8.5 cycles (median). Four complete responses (25%), 8 partial responses (37.5%), 4 no change (25%) (including 2 long NC), and 2 progressive disease (12.5%) were obtained, for an overall response rate of 62.5%. The median duration of time to progression and survival were 13.2 months (0.7-30.4 months) and 22.8 months (13.7-44.8 + months), respectively. The frequent toxicities were leukopenia, nausea/vomiting, and alopecia, but these were clinically well tolerated. Our results suggest that the addition of high dose TOR to AC therapy is useful in the treatment of recurrent breast cancer.

Administration, Oral↗