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Biomedical subjects

Y Komoike

Publications and source records attributed to Y Komoike.

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↗

Low gastric toxicity of nitric oxide-releasing aspirin, NCX-4016, in rats with cirrhosis and arthritis.

The gastric toxic effects of aspirin (ASA) and NCX-4016, a nitric oxide (NO)-releasing ASA, were compared in normal, cirrhotic, and arthritic rats. Oral administration of ASA (100 mg/kg) produced hemorrhagic lesions on the gastric mucosa in normal rats. The gastric ulcerogenic response to ASA was significantly worsened in both cirrhotic rats induced by N-nitrosodiethylamine and in arthritic rats induced by Freund's complete adjuvant. By contrast, NCX-4016 at 190 mg/kg (a dose equimolar to 100 mg/kg of ASA) did not induce damage in normal rat stomachs but caused slight lesions in the gastric mucosa of both cirrhotic and arthritic rats. Plasma salicylate levels following administration of ASA or NCX-4016 were not different between normal, cirrhotic, and arthritic rats, although the latter drug gave significantly lower values in any group of rats as compared to the former. Acid secretion was significantly increased in both cirrhotic and arthritic rats. ASA with 150 mM HCl caused severe gastric lesions in normal rats, the degree of damage being significantly greater than that induced by ASA alone. Coadministration of NOR-3, a NO donor, significantly prevented the development of gastric lesions induced by ASA, irrespective of whether or not ASA was given together with HCl. Gastric mucosal application of ASA (100 mg/kg) for 30 min caused a marked reduction of transmucosal potential difference (PD) with a minimal effect on gastric mucosal blood flow in both normal and cirrhotic rats, while that of NCX-4016 did not cause a PD reduction and produced a marked increase in the mucosal blood flow in both groups of rats. These results suggest that gastric mucosal susceptibility to ASA-induced damage is increased in both cirrhotic and arthritic rats (the process being partly accounted for by acid hypersecretion in these animals), NCX-4016 has even less gastric toxicity in both cirrhotic and arthritic rats, and the gastric-sparing effect of NCX-4016 is due, at least partly, to an increase of gastric mucosal blood flow, mediated by NO released from this drug.

Animals↗

Lack of gastric toxicity of nitric oxide-releasing indomethacin, NCX-530, in experimental animals.

The effects of a nitric oxide (NO) releasing derivative of indomethacin (NCX-530) on gastric ulcerogenic and healing responses were evaluated in rats and mice, in comparison with the parent compound indomethacin. Indomethacin (per os) produced damage in the rat stomach in a dose-dependent manner. NCX-530 (per os) itself, however, was not ulcerogenic and even showed a dose-dependent protection against HCl/ethanol-induced lesions in the rat stomach. Likewise, indomethacin given repeatedly delayed healing of gastric ulcers induced in mice by thermal cauterization, while NCX-530 did not affect the healing response and significantly promoted the healing as compared to indomethacin. These actions of NCX-530 were mimicked by the combined administration of a NO donor NOR-3 with indomethacin. The amount of NO metabolites was increased in both the gastric contents and serum when NCX-530, but not indomethacin, was given in pylorus-ligated stomachs. Neither indomethacin nor NCX-530 influenced gastric acid secretion and transmucosal potential difference, yet NCX-530 caused a marked increase of gastric mucosal blood flow, which was preventable by carboxy-PTIO, a scavenger of NO. Gastric motility was increased by indomethacin but not by NCX-530. In addition, NCX-530 inhibited PGE2 generation in both the intact and ulcerated gastric mucosa and showed antiinflammatory action on carrageenan-induced rat paw edema, as effectively as indomethacin. These results suggest that unlike indomethacin, NCX-530 caused neither an irritating action on the stomach nor healing impairment effect on the preexisting gastric ulcers, but conferred gastric protection against HCl/ethanol, despite causing cyclooxygenase inhibition and antiinflammatory action, as effectively as indomethacin. This NO-releasing indomethacin, probably by releasing NO, exerts protective influences, such as an increase of gastric mucosal blood flow, that counteract the potential damaging effects of cyclooxygenase inhibition by indomethacin.

Acetates↗

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↗

Adaptive gastric cytoprotection is mediated by prostaglandin EP1 receptors: a study using rats and knockout mice.

Endogenous prostaglandins (PGs) play a central role in adaptive cytoprotection induced in the stomach by mild irritants. In the present study, we used taurocholate (TC) as a mild irritant in both rats and EP-receptor knockout mice, and examined which EP receptor is responsible for the adaptive gastric cytoprotection. Gastric lesions were induced by p.o. administration of HCl/ethanol (60% ethanol in 150 mM HCl). TC (5-20 mM) or PGE2 was administered p.o. 30 min before HCl/ethanol. HCl/ethanol-induced gastric lesions were dose dependently prevented by TC, and the effect at 20 mM was equivalent to that induced by PGE2 at 0.3 mg/kg. The protective effect of TC was significantly attenuated by indomethacin as well as ONO-AE-829, the EP1 antagonist, but not by either NS-398, the selective cyclooxygenase (COX)-2 inhibitor, or chemical ablation of capsaicin-sensitive sensory neurons. Likewise, the protective action of PGE2 was also antagonized by ONO-AE-829 but not chemical deafferentation. TC significantly increased PGE2 contents in the stomach, with or without chemical deafferentation, and this effect was blocked in the presence of indomethacin but not NS-398 or ONO-AE-829. TC increased the mucosal PGE2 contents similarly in both wild-type and knockout mice lacking EP1 or EP3 receptors, yet the protective action of TC against HCl/ethanol was observed in both wild-type and EP3 receptor knockout mice, but not in mice lacking EP1 receptors. The present findings confirmed a role for endogenous PGE2 produced by COX-1 in adaptive gastric cytoprotection and suggested that this action is mediated by activation of EP1-receptors but not associated with capsaicin-sensitive afferent neurons.

Adaptation, Physiological↗

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↗

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↗

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↗

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↗

Characteristics and prognostic factors in patients with differentiated thyroid cancer who underwent a total or subtotal thyroidectomy: surgical approach for high-risk patients.

Differentiated thyroid cancer grows slowly in general. But some patients repeat recurrence and progress finally to death. To clarify the difference of their prognosis and establish the appropriate thyroid surgery, we studied 105 patients with differentiated thyroid cancer who were treated with total or subtotal thyroidectomy, excluding those with small tumors, under uniform conditions regarding thyroidectomy. There were 77 women and 28 men aged 19 to 76 years (mean 54.7 years). More than 60% (alive) were followed up for longer than 10 years. Thirty-eight (36%) patients had recurrences. There were 19 deaths. Twelve of 31 patients with locoregional recurrence died and 7 of these 12 died of locoregional control failure (neck and mediastinum). Age at first operation, tumor size, and local tumor extension increased the rate of recurrence significantly. Multivariate analysis confirmed that age, locoregional recurrence, and distant metastasis significantly affected survival. Although lymph node metastases were not a prognostic factor, for patients at high risk for recurrence who are older, and have large tumors with invasion, complete resection of cervical lymph nodes is advised to prevent local recurrence and prolong the disease-free interval. Prolongation of the disease-free interval may lead to prolonged survival time.

Adult↗

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↗

Comparative genomic hybridization defines frequent loss on 16p in human anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is one of the malignant tumors with the poor prognosis that is thought to arise from well-differentiated thyroid cancer (DTC). To investigate the molecular mechanism of ATC, we studied genomic alterations of eight ATC cell lines and three DTC cell lines by means of the comparative genomic hybridization (CGH) method. Loss of 16p was observed in five of eight ATC cell lines (62. 5%), but none of the three DTC cell lines showed loss of this chromosome arm. It is notable that loss of 18q [7/8 of ATC (87.5%), 2/3 of DTC (67%)] and gain of 20q [5/8 of ATC (62.5%), 3/3 of DTC (100%)] were frequently seen in both histologic types. Our results suggest that there is a gene in 16p that is closely associated with transformation from well-differentiated thyroid cancer to anaplastic cancer.

Carcinoma↗

Identification of pathologic parathyroid glands in patients with primary hyperparathyroidism.

Localization of the parathyroid glands is not necessarily easy before surgery and can also be troublesome during surgery. This study focuses on the identification of pathologic parathyroid glands. The records of 32 patients who underwent parathyroidectomy at our institution in the past 14 years for primary hyperparathyroidism were reviewed. Twenty-three patients had a single lesion while 9 had multiple-gland involvement. Localization studies identified 17 of 23 patients with a single lesion. All patients with multiple lesions were diagnosed with an enlargement of the parathyroids, but not all glands were identified in each patient preoperatively. At surgery, 8 of 32 patients were explored unilaterally. Solitary enlarged glands were resected, and a subtotal parathyroidectomy was performed for multiple-gland involvement. The intraoperative serum intact parathyroid hormone (PTH) level dropped after resection of the largest gland. The serum PTH level correlated with the gland size (r = 0.861, intact PTH assay). Eight of 9 patients with multiple-gland involvement had an elevated serum PTH (>2000 pg/ml in midportion and >200 pg/ml in intact PTH assays, respectively). No patient developed persistent or recurrent hyperparathyroidism. The serum PTH level was normalized by a resection of relatively enlarged glands in our cases. It is usual to explore all glands during surgery, and in cases with a high serum PTH level, multiple-gland involvement should also be considered.

Adult↗

Transaxillary endoscopic partial mastectomy for comparatively early-stage breast cancer. An early experience.

For optimal cosmetic results in breast cancer surgery, we developed an alternative operation using endoscopy to remove tumors through a small single incision remote from the breast itself. The tumor is endoscopically resected with electrocautery and low constant suction through a short incision in the axilla, 5 cm long, after which axillary dissection is performed through the same wound in the usual manner, under visualization by the naked eye. Primary reconstruction of the breast is performed with the remaining mammary gland and a subcutaneous fat flap on the serratus muscle. Seven patients underwent this surgery. The postoperative shape of the breasts was judged to be cosmetically satisfactory, and the surgical wounds were not visible from the front in all cases. This operation has the same therapeutic oncological effect as a standard lumpectomy and, in addition, offers a greater cosmetic advantage in cases of early breast cancer.

Adult↗

Prognostic factors in patients with recurrent differentiated thyroid carcinoma.

BACKGROUND: Approximately 20% of patients with thyroid carcinoma have relapse. To evaluate the factors affecting their disease-free survival and prognosis, we studied 68 patients with recurrent differentiated thyroid carcinoma, ranging in age from 5 to 73 years (mean: 47.6 years). Three-fourths of patients were followed for >10 years. Thirty-nine patients were treated with total or subtotal thyroidectomy at first operation; the remainder underwent lesser operations. Fifty-six patients had local recurrence, mostly lymph node infiltration. Twenty-six patients died. METHODS: Survival curves were constructed using the Kaplan-Meier method. Factors affecting relapse and survival were tested by univariate or multivariate analysis. RESULTS: Univariate analysis identified age at diagnosis, local tumor extension, and surgical method as significant factors for disease-free survival. These three factors and histology were significant prognostic factors. Multivariate analysis showed age, histology, and disease-free interval as significant and independent variables. CONCLUSIONS: In high-risk patients, complete resection of thyroid tissue and cervical lymph nodes is critical.

Adolescent↗