[Assessment of the efficacy, safety and pharmacokinetics of SKG-02 (recombinant human TSH) in postoperative diagnosis of well-differentiated thyroid cancer--a Japanese prospective, controlled, multicenter open-label study].

OBJECTIVE: This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC). METHODS: Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated. RESULTS: In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics. CONCLUSIONS: SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.

Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: a multicenter study.

Recent advances permitting high-resolution ultrasonography have made ultrasonographic examination of nodular thyroid diseases an accessible examination for routine practice. However, diagnostic criteria for ultrasonographic examination of thyroid nodules are not surely established. To identify the optimal strategy for well standardized differential diagnosis of papillary thyroid carcinoma and benign nodules, we evaluated the significance of individual ultrasonographic characteristics of thyroid nodules in a multicenter study. Ten characteristics in ultrasonograms from 53 patients scored by 17 investigators from 15 centers were analyzed by t tests and logistic regression analyses. Between benign and papillary thyroid cancer groups, all characteristics but not size or multiplicity of strong echoes, which suggest calcifications, were significant parameters. Logistic regression analyses showed that border character, shape, and internal echo level are highly significant parameters (p < 0.0005). A multiple logistic regression showed to be the most important predictors of pathologic diagnosis. The diagnostic criterion with border character and internal echo level yielded 93% sensitivity and 92% specificity. In conclusion, univariate and multivariate analyses identified border character, shape, internal echo level, but not strong echoes (calcifications), as important characteristics in differentiating papillary thyroid carcinoma from benign nodules. These results will contribute to standardization of accurate ultrasonographic diagnosis of papillary thyroid carcinoma.

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Adult-type ganglioneuroblastoma in the adrenal gland treated by a laparoscopic resection: report of a case.

A case of ganglioneuroblastoma in the adrenal gland of a 50-year-old man is reported. The patient was incidentally found to have a nonfunctioning tumor in the right adrenal gland. The tumor, measuring 4.5 cm, was successfully removed using laparoscopy. Histologically, the tumor was diagnosed to be a ganglioneuroblastoma. Immunohistochemically, a few MIB-1-positive cells and no S-100 protein-positive cells were observed. There has been no evidence of recurrence for 2.5 years to date after the operation. Adrenal ganglioneuroblastoma is extremely rare in adults, and only seven such cases have been previously reported in the literature.