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P Ladenson

Publications and source records attributed to P Ladenson.

5 recordsLinked to original sources
PubMed2005

Quantitative assessment of promoter methylation profiles in thyroid neoplasms.

CONTEXT: Cancer-specific molecular markers are needed to supplement the cytopathological assessment of thyroid tumors, because a majority of patients with cytologically indeterminate nodules currently undergo thyroidectomy without a definitive diagnosis. OBJECTIVE: The aim of this study was the quantitative assessment of promoter hypermethylation and its relation to the BRAF mutation in thyroid tumors. DESIGN: Quantitative hypermethylation of Rassf1A, TSHR, RAR-beta2, DAPK, S100, p16, CDH1, CALCA, TIMP3, TGF-beta, and GSTpi was tested on a cohort of 82 benign and malignant thyroid tumors and five thyroid cancer cell lines. SETTING: The study was conducted at a tertiary research hospital. PATIENTS: Patients underwent surgical resection for a thyroid tumor from 2000 to 2003 at our institution. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Final surgical pathology diagnosis was the main outcome measure. RESULTS: Thyroid tumors showed hypermethylation for the following markers: Rassf1A, TSHR, RAR-beta2, DAPK, CDH1, TIMP3, and TGF-beta. A trend toward multiple hypermethylation was evident in cancer tissues, with hypermethylation of two or more markers detectable in 25% of hyperplasias, 38% of adenomas, 48% of thyroid cancers, and 100% of cell lines. A rank correlation analysis of marker hypermethylation suggests that a subset of these markers is epigenetically modified in concert, which may reflect an organ-specific regulation process. Furthermore, a positive correlation was found between the BRAF mutation and RAR-beta2, and a negative correlation was found between the BRAF mutation and Rassf1A. CONCLUSIONS: Methylation-induced gene silencing appears to affect multiple genes in thyroid tissue and increases with cancer progression. Additional markers with better discriminatory power between benign and malignant samples are needed for the diagnostic assessment of cytologically indeterminate thyroid nodules.

Cell Line, Tumor↗
PubMed1998

Outcome after treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma. DESIGN: Analysis of data from a multicenter study. SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). MEASUREMENTS: Death, disease progression, and disease-free survival. RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.

Adenocarcinoma, Follicular↗
PubMed1996

Optimal surgery for papillary thyroid carcinoma.

There has been a long, unresolved debate regarding the operation of choice for well differentiated carcinoma of the thyroid. We therefore analyzed the feasibility, scope, sample size, and length of follow-up required to determine the optimal operation for papillary thyroid carcinoma. A statistical approach was used to design a randomized prospective trial comparing the endpoints of complications, recurrence, and cause-specific mortality. A complication comparison trial is prohibitive owing to the large population required--approximately 12,000 randomized patients. A recurrence trial appears feasible based on sample size: approximately 360 to 800 patients with a 6 to 10-year follow-up. However, recurrence detection would be severely compromised in the lobectomy arm, and a unilateral lag-time bias would occur. A cause-specific mortality trial proves to be the least objectionable, although a large sample size (n = 3100) would be required. Such a trial is critically dependent on the ability to select an appropriate endpoint. A cause-specific mortality trial proves to be the most objective and statistically valid endpoint.

Carcinoma, Papillary↗