We established the first extensive database for Asian patients with MEN1. Although the clinical features of Japanese patients were similar to those in western countries, there were several characteristic differences between them.

Preoperative sestamibi (MIBI) and ultrasonography (US) are used to localize parathyroid tumors in patients with primary hyperparathyroidism (pHPT). The intraoperative quick PTH assay (qPTH) has been recommended to determine whether all hyperfunctioning parathyroid tissue has been removed. We questioned whether qPTH improves the results of parathyroidectomy in patients with pHPT. We analyzed 115 unselected patients with pHPT without a family history or multiple endocrine neoplasia but who had undergone parathyroidectomy. All 115 patients had successful operations without complications. Of these patients, 88 (77%) had solitary adenomas, 13 had double adenomas, 1 had triple adenomas, 12 had hyperplasia, and 1 had carcinoma. Overall, MIBI was correct in 72% (76/106), US in 49% (49/99), and qPTH in 80% (92/115). For preoperative studies showing a single tumor, MIBI was correct in 83% (73/88), US was correct in 71% (45/63), and combined MIBI and US were correct in 95% (37/39). Adding qPTH in this subgroup did not improve the successful focused approach: 70% for MIBI, 65% for US, and 87% for combined MIBI and US. However, adding qPTH improved the overall success of parathyroidectomy (MIBI 92%, US 86%, combined MIBI and US 97%), but at the cost of unnecessary further exploration (MIBI 13%, US 6%, combined MIBI and US 8%). We conclude that when the same solitary tumor is identified by both MIBI and US, a focused exploration can be done with a 95% success rate. Adding qPTH to MIBI or US can improve the success rate but at a significant cost. General exploration of all parathyroid glands, however, has the highest success rate (100%).

Hürthle cell thyroid neoplasms are classified as variants of follicular neoplasms, but they have distinct clinicopathological features. Chromosomal aberrations by comparative genomic hybridization (CGH) are common in Hürthle cell neoplasms. However, there is currently only limited information concerning the relationship between the chromosomal aberrations by CGH and tumor behavior. We, therefore, investigated chromosomal aberrations in primary Hürthle cell neoplasms (13 carcinomas and 15 adenomas) using CGH and correlated the aberrations identified with tumor node metastasis (TNM) stage, tumor differentiation, capsular invasion, and tumor recurrence. Chromosomal aberrations were found in 62% (8 of 13) of carcinomas and 60% (9 of 15) of adenomas. Overall, common chromosomal gains were found on 5p (29%), 5q (36%), 7 (29%), 12p (14%), 12q (21%), 17p (29%), 17q (32%), 19p (32%), 19q (25%), 20p (21%), 20q (29%), and 22q (18%). Common chromosomal losses were found on 2q (18%) and 9q (18%). Thirty-eight percent (5 of 13) of carcinomas were TNM stage III, 31% (4 of 13) were moderately to poorly differentiated, and 46% (6 of 13) were intermediately to widely invasive. Recurrence occurred in 38% (5 of 13). Carcinomas that subsequently recurred had a greater number of chromosomal gains (9.0 vs. 1.3; <0.005) and had more frequent chromosomal gains on 12q, 19q, and 20p (<0.001), 5p, 7, 19p, and 20q (<0.005), and 12p (<0.01) than those that did not recur. Five of the eight (63%) patients with aberrations developed recurrence, whereas none of the five patients without aberrations developed recurrence. In conclusion, chromosomal gains by CGH on 5p, 7, 12p, 12q, 19p, 19q, 20p, and 20q in Hürthle cell carcinomas are associated with tumor recurrence. Such chromosomal aberrations may be predictive for recurrent disease in patients with Hürthle cell thyroid carcinoma.

These results suggest that intensive psychological intervention is necessary for breast cancer patients with large tumors, as well as for women with suspected breast cancer with high HADS scores at pre-consultation.

Parathyroid glands arise from the third and fourth pharyngeal pouches. Parathyroid lesions sometimes develop ectopically. The aim of this article is to illustrate the knowledge of pharyngeal apparatus development to assist with diagnostic localization of ectopic parathyroid lesions. We retrospectively reviewed charts of 23 patients who received a diagnosis of ectopic parathyroid lesions. The ectopic lesions were widely distributed; cranially lesions were located on the carotid bifurcation, caudally in the right paraaortic region, ventrally on the surface of the sternohyoid muscle, and dorsally in the paraesophageal region. In most cases, parathyroid tissues were associated with structures related to the third or fourth pharyngeal pouches that traveled to regions where the ectopic lesions ultimately developed. In a few cases, lesions were not associated with these pouches and might have developed from parathyroid tissue that migrated due to an anomalous pathway of parathyroid travel. When patients present without entopic lesions, the presence of ectopic lesions should be evaluated based on an understanding of the developmental mechanisms of parathyroid glands and the frequency with which ectopic lesions have been found in specific locations. Systematic diagnosis can minimize the frequency with which ectopic lesions are missed during clinical care and maximize their accurate localization.

PurposeZoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT).MethodsAsian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2), followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.ResultsThis randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher’s exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher’s exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and patients with triple-negative breast cancer. Further investigation is warranted.Trial RegistrationUniversity Hospital Medical Information Network. UMIN000003261.

We studied chromosomal abnormalities by comparative genomic hybridization (CGH) and flow cytometry in anaplastic thyroid cancer (ATC), and when present in coexisting or previous differentiated thyroid cancer (DTC). Overall 10 frozen tissues from patients with ATC and 5 cell lines (1 ATC and 4 DTCs) were analyzed. We found chromosomal abnormalities in 5 of 10 ATC tissues, with 24 abnormalities (22 gains and 2 losses). Among 8 ATCs that were associated with prior or concurrent DTC, more chromosomal abnormalities were found in ATC associated with follicular thyroid cancer (FTC) than those associated with PTC (median numbers 9.5 and 0.5, respectively, p = 0.046) or no associated differentiated thyroid cancer. Gain of 1q was relatively common in ATCs (30%). By flow cytometry, we found aneuploidy in 6 of 10 ATC tissues and diploidy in 4. There was concordance between DNA aneuploidy and the presence of chromosomal abnormalities by CGH in 4 of the 5 ATCs (p = 0.048). We also found 26 chromosomal abnormalities in an ATC cell line, 14.3 in 3 FTC cell line, and 3 in a PTC cell line. In conclusion, chromosomal abnormalities are frequent in ATCs associated with FTC, but uncommon in those associated with PTC and in ATCs with no associated differentiated thyroid cancer. These findings support the concept that PTC and FTC have different genetic backgrounds and, even after the transformation to ATC, they may retain some of their cytogenetic characteristics.

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