Hiroshi Takeyama

Breast-conserving surgery after chemotherapy: value of MDCT for determining tumor distribution and shrinkage pattern.

OBJECTIVE For this study, we investigated the usefulness of MDCT in assessing the extent of residual breast cancer after neoadjuvant chemotherapy. To ensure the success of breast-conserving surgery, we evaluated the usefulness of determining the tumor distribution before neoadjuvant chemotherapy and the shrinkage pattern after neoadjuvant chemotherapy. SUBJECTS AND METHODS MDCT before and after neoadjuvant chemotherapy was performed in 46 consecutive patients with 47 locally advanced breast cancers. The distribution pattern of contrast enhancement on MDCT before neoadjuvant chemotherapy was classified into five categories: solitary lesion, grouped lesion (localized lesion with linear, spotty, or linear and spotty enhancement), separated lesion (multiple foci of contrast enhancement), mixed lesion (grouped lesion with multiple foci), and replaced lesion (diffuse contrast enhancement in whole quadrants). RESULTS There was agreement between the MDCT assessment and pathologic findings in 44 (94%) of the 47 tumors. In the partial response group with nonreplaced lesions, MDCT revealed three shrinkage patterns: pattern 1a, concentric shrinkage without surrounding lesions; pattern 1b, concentric shrinkage with surrounding lesions; and pattern 2, shrinkage with residual multinodular lesions. Breast-conserving surgery was performed successfully in 14 patients including complete response cases that were detected on the basis of MDCT findings and partial response cases that were detected on the basis of observation of pattern 1 shrinkage. In all five patients with pattern 2 shrinkage, CT underestimated the residual tumor extent by more than 2 cm. CONCLUSION MDCT classification of tumor distribution before neoadjuvant chemotherapy and of shrinkage patterns after neoadjuvant chemotherapy is important in the preoperative evaluation of patients undergoing breast-conserving surgery.

Primary small-cell neuroendocrine carcinoma of the breast: Report of a case

Primary small-cell neuroendocrine carcinoma of the breast is a rare and aggressive neoplasm without an established treatment protocol because so few cases have been described. We report a case of primary smallcell neuroendocrine carcinoma in a 31-year-old woman. The patient came to our hospital 10 days after consulting another clinic, where a diagnosis of locally advanced breast cancer suitable for neoadjuvant chemotherapy had been made. Core needle biopsy under ultrasonographic guidance revealed invasive carcinoma. The doubling time of the tumor progression was calculated as 12 days based on ultrasonographic measurement. After three cycles of chemotherapeutic regimens consisting of adriamycin plus docetaxel, the disease was judged to be progressive and the patient underwent surgery. Definitive histopathological examination revealed primary small-cell neuroendocrine carcinoma. Local and mediastinal recurrence with multiple liver metastases developed only 5 weeks after surgery. Cisplatin plus irinotecan combination chemotherapy was started; however, the patient died of aggressive recurrent tumor progression 6 months after surgery, in spite of the transient tumor regression achieved by chemotherapy. This case reinforces the importance of an early correct diagnosis and the standardization of a treatment regimen for this very rare tumor.

Usefulness of radio-guided surgery using Technetium-99m. Methoxyisobutylisonitrile for primary and secondary hyperparathyroidism

The efficacy of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI)-guided surgery for detecting abnormal parathyroid glands in patients with secondary hyperparathyroidism (2-HPT) was evaluated and compared with the results from the same examination in patients with primary hyperparathyroidism (1-HPT). The results were also compared with those found by ultrasonography (US) and preoperative 99mTc-MIBI scintigraphy was also made. At operation 99mTc-MIBI accumulated in 64 nodules of 15 cases of 2-HPT, and all of 60 parathyroid swellings were detected (true-positives 60, sensitivity 100%, accuracy 94%). In the cases of 1-HPT, 99mTc-MIBI revealed 11 hot nodules in 10 cases, and the evaluation was true-positive 10, sensitivity 100%, and accuracy 91%. US and preoperative 99mTc-MIBI scintigraphy in patients with 2-HPT had a sensitivity of 75% and 67% and an accuracy of 70% and 66%, respectively. The usefulness of 99mTc-MIBI-guided surgery for detecting abnormal parathyroid tissue in 2-HPT patients was similar to that in 1-HPT patients but was superior to US and preoperative 99mTc-MIBI scintigraphy. Intraoperative 9mTc-MIBI for patients with 2-HPT is effective and makes the surgery easier, especially when the parathyroid glands are ectopic or when a few glands are markedly enlarged but the other glands are atrophied.

An extremely large solitary primary paraganglioma of the lung: report of a case.

We present herein the case of a 38-year-old woman found to have an extremely large solitary primary paraganglioma of the lung. The patient presented with chest pain on exertion and a mass was discovered in the left lower lobe of the lung by chest X-rays and computed tomography (CT). As no other neoplasms were detected elsewhere, a left lower lobectomy was performed. The patient has remained well without any evidence of recurrence for 5 years since her operation. The tumor, measuring 13×12×7 cm, was composed of ovoid cells (Zellballen), which were positive for Fontana-Masson and Grimelius stains, and sustentacular cells. Immunohistochemically, the ovoid cells were positive for neuron-specific enolase, S-100, CAM5.2, Leu7, and chromogranin A, and negative for carcinoembryonic antigen and epithelial membrane antigen. The sustentacular cells were positive for S-100 protein and CAM5.2, and negative for glial fibrillary acid protein. Therefore, the tumor was diagnosed as a paraganglioma. The tumor from our patient is the largest of the 17 solitary primary pulmonary paragangliomas reported thus far in the English-language literature.

Retrospective Comparison of Non-Skin-Sparing Mastectomy and Skin-Sparing Mastectomy with Immediate Breast Reconstruction

Background. We compared Skin-sparing mastectomy (SSM) with immediate breast reconstruction and Non-skin-sparing mastectomy (NSSM), various types of incision in SSM. Method. Records of 202 consecutive breast cancer patients were reviewed retrospectively. Also in the SSM, three types of skin incision were used. Type A was a periareolar incision with a lateral extension, type B was a periareolar incision and axillary incision, and type C included straight incisions, a small elliptical incision (base line of nipple) within areolar complex and axillary incision. Results. Seventy-three SSMs and 129 NSSMs were performed. The mean follow-up was 30.0 (SSM) and 41.1 (NSSM) months. Respective values for the two groups were: mean age 47.0 and 57; seven-year cumulative local disease-free survival 92.1% and 95.2%; post operative skin necrosis 4.1% and 3.1%. In the SSM, average areolar diameter in type A & B was 35.4 mm, 43.0 mm in type C and postoperative nipple-areolar plasty was performed 61% in type A & B, 17% in type C, respectively. Conclusion. SSM for early breast cancer is associated with low morbidity and oncological safety that are as good as those of NSSM. Also in SSM, Type C is far superior as regards cost and cosmetic outcomes.

Detection of MUC1 and Keratin 19 mRNAs in the Bone Marrow by Quantitative RT-PCR Predicts the Risk of Distant Metastasis in Breast Cancer Patients

BackgroundEarly detection of micrometastasis in bone marrow is critical for the prognosis of breast cancer patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) has been used to detect cancer cells in bone marrow, but its utility as a prognostic factor still remains obscure.Materials and MethodsBone marrow samples were aspirated from the anterosuperior iliac spine of 34 patients, immediately after their surgical procedures had been completed. Control samples were also obtained from 10 healthy adult volunteers. The total RNA was extracted from the mononuclear cells, and the expression levels of β-actin, MUC1 and keratin 19 mRNAs were studied by quantitative RT-PCR. Each mRNA level was scored according to the expression level. The sum of these expression scores was defined as the composite expression score, which was employed as the basis of the evaluation.ResultsThe mean follow-up period was 45 months. Nine patients developed distant metastases, and one developed local recurrence. The 4-year disease relapse rates were 75% (RR= 19.38; 95% CI: 1.94-193.20), 28% (RR=3.64; 95% CI: 0.43-31.18), and 8.3% for patients with composite expression scores of 5/6, 3/4 and 2, respectively. The difference among the three groups was statistically significant (log-rank test:p = 0.0029), and multivariate analysis also found the composite expression score to be an independent prognostic factor.ConclusionsBreast cancer patients who show a high composite expression score in bone marrow have a significantly higher risk of recurrence.

Sentinel node biopsy for follicular tumours of the thyroid gland

It is difficult to differentiate histologically between benign and malignant follicular‐type tumours of the thyroid gland. The present study evaluated whether sentinel lymph node (SLN) biopsy was helpful in obtaining the correct diagnosis of malignant follicular‐type tumours, as metastasis to the lymph nodes is sufficient evidence for a diagnosis of cancer.

The usefulness of radio-guided surgery in secondary hyperparathyroidism

Recent reports have shown that radio-guided surgery with an intraoperative gamma probe (IGP) is useful for identifying parathyroid adenomas. The aim of this study was to evaluate the usefulness of IGP mapping in patients with secondary hyperparathyroidism. Seven patients with secondary hyperparathyroidism underwent technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) scintigraphy immediately before undergoing surgical resection of all parathyroid tissues. We compared the sensitivity of Tc-99m MIBI scintigraphy alone with that of the combination of Tc-99m MIBI scintigraphy and IGP mapping. The sensitivity of the combination of Tc-99m MIBI scintigraphy and IGP mapping was 100% (28 of 28 lesions) and was significantly higher than that of Tc-99m MIBI scintigraphy alone (71.4%, 20 of 28 lesions). The combination of the Tc-99m MIBI scintigraphy and IGP mapping has increased sensitivity for identifying parathyroid lesions during parathyroidectomy in patients with secondary hyperparathyroidism.

Conjugation of Quantum Dots and JT95 IgM Monoclonal Antibody for Thyroid Carcinoma Without Abolishing the Specificity and Activity of the Antibody

Among the immunoglobulins, IgM class-antibodies are now considered to be potent immunological reagents for anticancer remedies. However, only a few reports are available about the effective labeling of IgM with enzymes, fluorescence, or other bioreactive reagents. Here, we report an effective application of luminescent semiconductive nanoparticles, quantum dots (QDs), as a labeling material of the IgM antibody. The CdSe carboxyl QDs were reacted with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysulfo- succinimide in 2-(morpholino) ethanesulfonic acid. The reacted QDs were then coupled to JT95 IgM antibody, which recognizes thyroid carcinoma associated antigen. The specificity and activity of the conjugates were tested by immunoblot, immunoquantitive assay and immunohistological imaging. The QDs were firmly conjugated with JT95 IgM monoclonal antibody. In immunoblot assay, QD-JT95 conjugates directly detected the target molecules without obstructing the binding site. In immunoquantitive assay, the conjugates could quantify the antigen in the range of 1.56-100 μg/mL. Also, QDs-labeled antibody detected the antigen on plasma membrane. Our results demonstrate that labeling of JT95 and other IgM class antibodies with QDs is feasible. This approach may be an important method for the medical application of IgM in the diagnosis and treatment of cancers.

Dihydropyridine‐ and voltage‐sensitive Ca2+ entry in human parathyroid cells

Patch‐clamp and fluorescence measurements of cytoplasmic Ca2+ concentration ([Ca2+]i) were performed to directly detect extracellular Ca2+ entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo‐3 AM or fluo‐4 AM showed a transient increase in fluorescence (Ca2+ transient) following 10 s exposure to 150 mm K+ solution in the presence of millimolar concentrations of external Ca2+. The Ca2+ transient was completely inactivated after 30–40 s exposure to the high‐K+ solution, was reduced by dihydropyridine antagonists and was enhanced by FPL‐64176, an L‐type Ca2+ channel agonist. The electrophysiological and pharmacological properties of the whole‐cell Ca2+ and Ba2+ currents were similar to those of L‐type Ca2+ channels. The Ca2+ transients induced by 10 s exposure to 3.0 mm extracellular Ca2+ concentration ([Ca2+]o) were inhibited by dihydropyridine antagonists and were partly inactivated following 30–40 s exposure to the high‐K+ solution. These results demonstrate, for the first time, that human parathyroid cells express L‐type‐like Ca2+ channels that are possibly involved in the [Ca2+]o‐induced change in [Ca2+]i. This Ca2+ entry system might provide a compensatory pathway for the negative feedback regulation of parathyroid hormone secretion, especially in hyperplastic conditions in which the Ca2+‐sensing receptor is poorly expressed.