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Biomedical subjects

H Inaji

Publications and source records attributed to H Inaji.

At least 19 recordsLinked to original sources

Combination technique is superior to dye alone in identification of the sentinel node in breast cancer patients.

BACKGROUND: The purpose of the present study was to evaluate whether the combination of dye and radioisotope would improve the detection rate of sentinel nodes (SN) and the diagnostic accuracy of axillary lymph node status over dye alone in patients with breast cancer. METHODS: Sentinel node biopsy (SNB) was performed in stages I or II breast cancer patients with clinically negative nodes using dye alone (indocyanine green) or a combination of dye and radioisotope (99mTc-radiolabelled tin colloid). RESULTS: SNB guided by dye alone was performed in 93 patients and SNB guided by a combination of dye and radioisotope was performed in 138 patients. The detection rate of SN was significantly (P = 0.006) higher in the combination group (94.9%) than in the dye alone group (83.9%). The sensitivity, specificity, and overall accuracy of SNB in the diagnosis of axillary lymph node status were 100, 100, and 100%, respectively, for the combination group, and 81.0, 100, and 94.9%, respectively, for the dye alone group. There were no false negatives in the combination group, but four false negatives (19.0%) in the dye alone group. The combination method was significantly superior to the dye alone method for sensitivity (P = 0.011) and accuracy (P = 0.018). CONCLUSIONS: The addition of a radioisotope to the dye in SNB increases the detection rate of SNs in breast cancer patients, and SNs detected by the combination method predict the axillary lymph node status with greater accuracy than those detected by the dye alone method.

Breast Neoplasms↗

Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients.

AIM: The purpose of the present study was to evaluate the usefulness of gamma probe and ultrasonographically-guided fine-needle aspiration biopsy (FNAB) in the pre-operative detection of sentinel node (SN) metastasis in breast cancer patients. METHODS: Sentinel node biopsy (SNB) was performed in patients with stage I or II breast cancer with clinically negative nodes using dye and radio-isotope. Axillas of 60 patients in whom a hot spot was detected by gamma probe were examined by ultrasonography. Pre-operative diagnosis of SN metastasis by gamma probe and ultrasonographically-guided FNAB was compared with the histological results of SN. RESULTS: The sensitivity, specificity and overall accuracy of ultrasonography in the diagnosis of SN metastasis were 50.0%, 92.1% and 76.7%, respectively. SNs were visualized by ultrasonography in 29 of 60 patients. Of 14 patients with positive results by ultrasonography, four had positive and two had negative cytology. The combination of ultrasonography and ultrasonographically-guided FNAB for visualized nodes had a sensitivity of 78.5%, specificity of 93.3% and overall accuracy of 86.2%. Blind FNAB in the hot spot was not useful in the detection of SN metastasis in patients whose SNs failed to be detected by ultrasonography. CONCLUSIONS: Gamma probe and ultrasonographically-guided FNAB is a potentially useful method for pre-operative detection of SN metastasis. In patients with positive SNs, SNB is not indicated and complete axillary lymph-node dissection can be performed as a primary procedure.

Biopsy, Needle↗

Diagnosis of ductal carcinoma in situ (DCIS) and intraductal papilloma using fluorescence in situ hybridization (FISH) analysis.

BACKGROUND: It is often difficult to pre-operatively diagnose ductal carcinoma in situ (DCIS)or intraductal papilloma (IDP). Current reports show that breast cancer frequently has numerical aberrations of chromosomes 1, 11 and 17. We investigated whether fluorescence in situ hybridization (FISH) analysis using three centromere-specific probes for chromosomes 1, 11 and 17 was feasible for diagnosing intraductal breast lesions. METHODS: Fine-needle aspiration specimens from 102 breast lesions including DCIS (10), invasive ductal carcinoma (IDC) (78), IDP (7), fibroadenoma (6) and mastopathy (1) were examined for numerical aberrations on chromosomes 1, 11, 17 using FISH. If over 15% of all cells showed one signal, the sample was judged monosomic. If over 20% of cells showed three or more signals, it was considered polysomic. If the specimen had an aberration of at least one chromosome, it was judged positive. RESULTS: Nine of 10 DCISs showed numerical aberrations of at least one chromosome whereas 65 of 78 IDCs and 2 of 14 benign lesions (containing 7 IDPs of which one case was positive) showed numerical aberrations on these chromosomes. The proportion of positive results was highest with DCIS. Moreover 6 out of 7 DCISs showed an aberration of all three chromosomes simultaneously and one case showed an aberration of two chromosomes. All aberrations in case of DCIS were polysomic while two benign lesions and 15 IDCs showed a monosomic pattern. CONCLUSION: FISH may enable more accurate diagnosis of intraductal breast lesions.

Breast Neoplasms↗

Intraoperative sentinel lymph node examination by imprint cytology and frozen sectioning during breast surgery.

BACKGROUND: The purpose of the present study was to evaluate the usefulness of intraoperative imprint cytology and frozen sectioning of sentinel lymph nodes in patients with clinically node-negative breast cancer. METHODS: Sentinel node biopsy was performed in 101 patients with stage I or II breast cancer with clinically negative nodes using a dye-guided method. Intraoperative evaluation of sentinel node involvement by imprint cytology and frozen sectioning was compared with the final histopathological results of permanent sections. Tumour-negative nodes in paraffin sections stained by haematoxylin and eosin were further studied using an anticytokeratin antibody. RESULTS: The results of imprint cytology and frozen-section analysis were compared with those of haematoxylin and eosin-stained sections. The sensitivity, specificity and overall accuracy of imprint cytology were 96.0, 90.8 and 92.1 per cent respectively, and those of frozen-section examination were 52.0, 100 and 88.1 per cent. Ten sentinel nodes were tumour positive on imprint cytology and tumour negative on stained paraffin sections. Micrometastasis was found in eight of these nodes on immunohistochemistry. Taking these immunohistological results into consideration, the final sensitivity, specificity and overall accuracy of imprint cytology were 90.9, 98.5 and 96.0 per cent respectively. CONCLUSION: Intraoperative imprint cytology is a useful method for evaluating the status of sentinel nodes and is more accurate than frozen-section analysis. In addition, imprint cytology can detect micrometastasis more accurately than conventional haematoxylin and eosin-stained sectioning.

Adult↗

Prognostic significance of occult bone marrow micrometastases of breast cancer detected by quantitative polymerase chain reaction for cytokeratin 19 mRNA.

Amplification of cytokeratin 19 (CK19) transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a highly sensitive assay for the detection of bone marrow micrometastases (BMM) of breast cancer, but recent studies have demonstrated the occurrence of false-positive results due to low-level, illegitimately transcribed CK19 in normal bone marrow tissue. One approach to solve this problem is to develop a quantitative CK19 RT-PCR assay and to introduce a cut-off value which can distinguish between illegitimate expression and cancer-specific expression levels. In the present paper, we describe a quantitative CK19 RT-PCR assay using a real-time automated PCR system. The number of CK19 transcripts was normalized to that of GAPDH transcripts as an internal control for quality and quantity of cDNA. The cut-off value for the ratio of CK19 to GAPDH transcripts was set at 10(-4) since the ratio never exceeded this value in the control bone marrow samples (n = 12). In total, 117 bone marrow aspirates from stage I - III patients with invasive breast cancers were subjected to CK19 RT-PCR assay and immunocytological examination. Forty (34.2%) were found to be BMM-positive by CK19 RT-PCR assay whereas only three (2.6%) were found to be BMM-positive by immunocytology. Multivariate analysis has shown that occult BMM detected by CK19 RT-PCR is a significant risk factor for relapse, being independent of axillary lymph node metastases.

Bone Marrow Neoplasms↗

Demonstration and diagnostic significance of pro-gastrin-releasing peptide in medullary thyroid carcinoma.

The expression of pro-gastrin-releasing peptide (proGRP) in medullary thyroid carcinoma (MTC) and other histological types of thyroid carcinoma was studied by an immunohistochemical technique, using polyclonal anti-proGRP antiserum. Immunoreactivity for proGRP was detected exclusively in MTC (n = 7); other histological types (n = 12) were all negative for proGRP. In addition, serum proGRP levels were elevated in patients with primary or recurrent MTC (n = 3), and they changed in parallel with serum calcitonin (CT), and carcinoembryonic antigen (CEA). These results show that proGRP, which is considered to be a specific marker for small-cell lung carcinoma, may be also a potential tumor marker for MTC, in addition to CT and CEA.

Biomarkers, Tumor↗

Endocrine therapies for patients with recurrent breast cancer: predictive factors for responses to first- and second-line endocrine therapies.

Breast cancer patients have been treated with four different hormonal agents, antiestrogen, progestin, luteinizing hormone-releasing hormone agonist and aromatase inhibitor, during the past 7 years in Japan. To investigate the efficacy of these agents for the treatment of recurrent breast cancer patients, we conducted a retrospective multi-institute survey in Japan. The clinico-pathological data of 131 patients, who received endocrine therapy as first-line treatment between 1993 and 1998, were collected from seven institutes. The median age of the patients was 55 (range 27-92) years, 75% of their primary tumors were estrogen receptor (ER)-positive or unknown, and 95% of the dominant metastatic sites were bone, soft tissue or lungs. The objective response rate to first-line endocrine therapy was 42.7%, and that to second-line therapy 42.5% (17 of 40 patients). Multiple regression analyses of predictive factors for a response to first- and second-line endocrine therapies indicated two independent factors, ER status of the primary tumors and dominant site of metastasis, for the former, and one independent factor, a response to first-line endocrine therapy, for the latter. Analysis of relationships between sequences of use of hormonal agents and objective response rates revealed that the choice of first-line hormonal agent did not influence the overall efficacy of first- and second-line endocrine therapies. Overall survival after first recurrence in patients with tumors exhibiting an objective response or stable disease to first-line endocrine therapy was significantly better than that in patients with tumors exhibiting progressive disease (p < 0.01). These findings suggest that an adequate selection of recurrent breast cancer patients referring the ER status, dominant site of metastasis and a prior response to endocrine therapy may contribute to better clinical outcomes of the patients.

Antineoplastic Agents, Hormonal↗

Sentinel Node Biopsy in Breast Cancer.

Axillary lymphnode dissection (ALND) for breast cancer patients provides local control and information for the determination of the type of adjuvant therapy.The benefit of axillary surgery itself for survival is considered to be limitedto patients with positive nodes. Sentinel node biopsy is a recently developed, minimally invasive technique for precisely predicting axillary nodal status. As this technique has less morbidity and greater accuracy than ALND, it replaces ALND for patients with node negative breast cancer. In this report, we outline thecurrent status of sentinel node biopsy for breast cancer patients and introduceour preliminary results.

Journal Article↗

Current Status and Controversial Issues concerning Endocrine Therapy for Patients with Recurrent Breast Cancer in Japan.

BACKGROUND: Four different endocrine therapeutic agents have been used in Japan since 1996. However, a consensus regarding proper use of these agents has notyet been established. Therefore, a questionaire survey of Japanese breast cancer authorities on endocrine therapy and a multi-institute survey to investigate the efficacy of a single first-line endocrine therapy for recurrent breast cancerwere conducted. MATERIALS AND PATIENTS: A total of 279 questionaires were sent to the Councilors of the Japanese Breast Cancer Society. The clinico-pathological data of 77 breast cancer patients who underwent a single first-line endocrine therapy were collected from five institutes. RESULTS: The response rate to this questionaire survey was 67.4%. The resultsshow that many authorities consider that: 1) both ER and PgR in primary tumors should be measured, 2) patient age, the disease-free interval and postoperative adjuvant therapy do not provide enough information for the selection of endocrine therapies, 3) antiestrogen and LH-RH agonists should be used as first-line endocrine therapies, 4) combined endocrine therapies, such as an antiestrogen plus an LH-RH agonist, should be used, 5) the optimal sequence of use of endocrine therapeutic agents is most controversial. The objective response rate to first-line endocrine therapies was 40.3% and the duration of response was over 15 months.The objective response rate to second-line endocrine therapies was 42.1%. A multiple regression analysis of predictive factors for the efficacy of first-line endocrine therapies indicated two factors, the disease-free interval and dominantsite of metastasis, to be significant. Conclusions: This questionaire survey suggests that clinical trials to investigate the optimal sequence of use of endocrine therapies and to clarify the usefulness of combined endocrine therapies should be conducted. Single first- or second-line endocrine therapies for recurrent breast cancer are effective and should be carried out by general clinicians.

Journal Article↗

Sentinel Node Biopsy in Breast Cancer Patients with Clinically Negative Lymph-Nodes.

BACKGROUND: The purpose of the present study is to evaluate the usefulness ofdye-guided sentinel node biopsy in breast cancer patients with clinically negative nodes and to clarify the anatomic distribution of sentinel nodes in the axilla. METHODS: Sentinel node biopsy was performed in patients with T1 or T2 breast cancer who had clinically negative nodes, using an indocyanin green dye-guided method. Thereafter, complete axillary dissection was performed. Sentinel node andcomplete axillary lymph-node dissection specimens were examined separately, andthe incidence of metastases was compared. RESULTS: We identified sentinel nodes in 115 (76.7%) of 150 patients with clinically negative nodes. The mean number of sentinel nodes was 1.7 (range, one toeight nodes). The mean size of sentinel nodes was 9.0 mm (range, 2.0 to 28.0 mm). Of the 31 patients who had a tumor-positive sentinel node, 14 (45.2%) patients had only the sentinel node involved. There was concordance on histological examination between sentinel node and axillary node status in 111 (96.5%) of 115 cases. Of the sentinel nodes 89.1% were located cranially to the intercostobrachial nerve and within 2 cm of the lateral edge of the pectoralis minor muscle. CONCLUSIONS: Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable detection rate of sentinel nodes for breast cancer patients with clinically negative nodes. Most of the sentinel nodes were locatednear the lateral edge of the pectoralis minor muscle and cranial to the intercostobrachial nerve.

Journal Article↗

Surgical Margin Status as a Cause of Local Failure after Breast Conserving Therapy.

BACKGROUND: To elucidate the cause of in-breast recurrence after breast conserving surgery, we analyzed the characteristics of resected specimens histopathologically, especially the surgical margin status. MATERIALS AND METHODS: 1) Pathological surgical margin positivity was reevaluated in terms of the distance from the resected surgical margin by pathologists from seven institutions in 486 cases with complete stepwise pathological examination. 2) We reviewed pathological specimens including surgical margins from 30 patients with in-breast recurrence for whom serial sections of resected primary breast cancer specimens were available and made comparisons of the time to in-breast recurrence. RESULTS: Cancer cells at the surgical margin were present at a rate of 4.1% on the surface and 15.2% within 5 mm on the areolar side of the surgical margin. Histopathologically, the reasons for local recurrence after breast conserving therapy included a positive surgical margin (21/30), lymphatic permeation (4/30), and others (5/30). The last category included cases with an inadequate margin diagnosis because of a biopsy scar. Disease-free intervals for the patients without postoperative radiotherapy decreased as the volume of cancer cell nests in thesurgical margin increased (P=0.06). On the other hand, this trend was not observed in the group with postoperative radiotherapy. CONCLUSION: Adequate materials are essential for accurate evaluation of surgical margin status. Quantitative evaluation of surgical margin status, apart fromwhether or not radiotherapy was performed, is important for estimating the riskand disease-free period to in-breast recurrence.

Journal Article↗

Mediastinal lymph node involvement as the initial manifestation of occult thyroid cancer in the surgical treatment of lung cancer: report of a case.

A 63-year-old man was referred to our institute for the treatment of squamous cell carcinoma of the upper lobe of his right lung. A right upper lobectomy of the lung was performed with a mediastinal lymph node dissection. The postoperative pathological examination of the dissected specimens revealed one of the superior mediastinal lymph nodes to be morbid with micrometastasis of occult thyroid cancer, while no node involvement was seen due to lung cancer. A right lobectomy of the thyroid gland with a modified radical neck dissection was done 4 years later after the confirmation of the absence of any recurrent sign of lung cancer. In the resected specimen, papillary thyroid microcarcinoma was observed with several intraglandular metastases and right regional lymph node involvement. Eight months later, a new primary lung cancer developed in the left lung, and a left upper lobectomy of the lung with a mediastinal lymph node dissection was performed. At that time, the absence of mediastinal lymph node metastasis from lung cancer or thyroid cancer was confirmed. Mediastinal lymph node involvement as the initial manifestation of occult thyroid cancer in surgical treatment for lung cancer is rare, but it is important to be aware of the possibility of incidentally detecting occult thyroid cancer in surgical dissections in this area for lung cancer. The appropriate surgical treatment should be determined while carefully considering the prognosis of the lung cancer as well as that of any coexisting malignancy.

Carcinoma, Papillary↗

Sentinel node biopsy guided by indocyanine green dye in breast cancer patients.

BACKGROUND: We aimed to evaluate whether dye-guided sentinel node biopsy is a useful indicator of axillary node involvement in breast cancer patients and whether clinicopathological features affect its success in identifying sentinel nodes. METHODS: Sentinel node biopsy was performed in patients with stage I or II breast cancer using an indocyanin green dye-guided method. RESULTS: We could identify sentinel nodes in 127 (73.8%) of 172 patients. The mean number of sentinel nodes per patient was 1.7 (range, 1-8) and the mean node size was 9.3 mm (range, 3.0-28.0 mm). Of the 127 patients, 40 (31.5%) also had axillary node involvement. In 16 (40.0%) of these, the sentinel node was the only node involved. There was concordance between sentinel node and axillary node status in 122 (96.1%) of the 127 patients. Success in identifying sentinel nodes was not affected by tumor size, operative procedure, histological type of tumor or tumor location; however, the success rate was significantly lower in patients with axillary node involvement (65.7 vs 79.0% in axillary node-negative patients, p = 0.039) and the presence or absence of lymphatic or vascular invasion in the tumor (63.8 vs 78.9% in patients without lymphatic or vascular invasion, p = 0.043). Sentinel nodes could also be identified significantly more frequently in patients under 50 years old (83.3%) than in those over 50 years old (64.8%, p = 0.009). CONCLUSIONS: Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable success rate in detecting sentinel nodes and predicting axillary nodal status. Axillary node status, the presence or absence of lymphatic or vascular invasion in the tumor and patient age affect its success in identifying sentinel nodes.

Adult↗

Malignant seeding of the lumpectomy cavity upon breast-conserving surgery.

One of the etiologic factors involved in local recurrence after breast-conserving surgery may be malignant seeding of the wound during the lumpectomy procedure. A total of 340 patients with stage I and II breast cancer were entered into the study. Of these, 270 patients received breast-conserving surgery (BCS group), and the other 70 patients underwent mastectomy (control group). After resection, lavage cytology was performed at the surgical wound. There were 55 patients (20.4%) who showed positive lavage cytology in the BCS group. In the control group, there were only 3 patients (4.3%) with positive cytology. Positivity was significantly higher in the former group (p = 0.00064). Patients with evidence of cutting across cancer lesions showed significantly higher positive rates in lavage cytology (p < 0.00001). Positivity in lavage cytology was significantly higher in patients with positive surgical margins evaluated by frozen sections (p = 0.0017), touch cytology (p < 0.0001) and formalin-fixed, paraffin-embedded sections (lateral or medial margin; p = 0.0036, anterior and posterior margin: p = 0.0210). The positivity was also significantly higher in patients with an extensive intraductal component (p < 0.0001), and less than or equal to 50 (p = 0.0061) years of age. Multivariate analysis revealed that the highest relative risk factor for positive cytology was evidence of cutting across cancer lesions (relative risk = 8. 166; p < 0.00001).

Adult↗

[Detection of numerical aberrations in chromosomes by fluorescence in situ hybridization in fine needle aspirates in the preoperative diagnosis of cancer].

Fine needle aspiration (FNA) samples were obtained from 176 breast tumors suspected of malignancy, which were then subjected to conventional cytological and fluorescence in situ hybridization (FISH) analyses using the centromeric probes for chromosomes 1, 11, and 17. Histological examination revealed 157 breast cancers and 19 benign diseases (ten fibroadenomas, six intraductal papillomas, one intracystic papilloma, and two ADH). Sensitivity, specificity, and diagnostic accuracy were 85.4% 94.7%, and 86.4%, respectively, for cytology and 90.4%, 100%, and 91.5%, respectively, for FISH. These results demonstrate that FISH diagnosis of FNA samples has a diagnostic accuracy comparable to that of conventional cytology.

Biopsy, Needle↗

The Current Status of the Treatment of Ductal Carcinoma In Situ of Japanese Women, Especially Breast Conserving Operation in Relation to the Surgical Margin and Short Term Outcome.

The indications for a breast conserving operation in the treatment of ductal carcinoma in situ (DCIS) of the breast with clinical manifestations other than mammographically detected calcifications are controversial. A positive surgical margin has been suggested to be an improtant risk factor for local recurrence after a breast conserving operation. We attempted to clarify the frequency of positive surgical margins when performing breast conserving operations for DCIS, identify the risk factors for positive margins, and also to evaluate the short-term outcome. Between 1988 and 1992, 5571 breast cancer cases were surgically treated at the 7 institutions of the authors, of which 375 cases (6.7%) were histologically diagnosed as DCIS. The most frequent clinical manifestation was a tumor in 64% of the cases, followed by nipple discharge in 23% and calcification on mammography in 12%. Of these 375 cases, 242 cases were analyzed. Sixty-six cases had undergone a breast conserving operation. Axillary dissection was not performed in 29 cases. The median follow up period was 61.4 months. The initial surgical margin was positive in 29% of the cases. The most significant factor for a positive surgical margin was young age fllowed by large tumor size. There were four cases with local recurrence. Three recurrences developed in the same quadrant. All four cases remain alive after total mastectomy. There were no cases with distant metastasis or axillary recurrence. Breast cancerving operation for DCIS have shown satisfactory results to date, and when clear surgical margins can be obtained, this procedure, without axillary dissection, should be considered even for patients with clinical manifestations other than mammographically detected calcifications.

Journal Article↗