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Biomedical subjects

Steven Goodman

Publications and source records attributed to Steven Goodman.

5 recordsLinked to original sources
PubMed2004

Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors.

PURPOSE: Patients with a preoperative cytologic diagnosis of a suspicious thyroid nodule present a therapeutic dilemma because surgery differs for benign and malignant lesions. To address this issue, several molecular markers, including human telomerase reverse transcriptase (TERT), have been tested as markers of thyroid cancer. Because most studies select cases falling into well-defined categories to test new markers, they may overestimate their discriminatory power when applied to samples that are difficult to classify. Fine-needle aspirates (FNAs) of the thyroid with indeterminate cytology are an example of such cases. EXPERIMENTAL DESIGN: We examined whether assessing TERT mRNA by reverse transcription-PCR could have improved the surgical management in a cohort of 100 patients undergoing thyroidectomy for indeterminate FNA results. RESULTS: Ninety percent of 48 cancers were TERT positive, as were 35% of 52 benign lesions. When 10 cases with concomitant lymphocytic thyroiditis were excluded, the overall sensitivity of TERT was 91% (95% confidence interval, 80-98%) and specificity was 79% (64-90%). No clinical or tumor variable contributed to the predictive ability of TERT except for tumor size, which added only marginally. Basing the surgical approach on the TERT assay alone would have reduced lobectomies performed for malignant disease from 11 to 4 cases and reduced total thyroidectomies for benign lesions from to 15 to 9, an overall 50% reduction in suboptimal treatment. CONCLUSIONS: The overall performance of preoperative differential diagnosis for thyroid tumors with indeterminate FNA results can be substantially improved by the inclusion of molecular markers such as TERT.

Adenocarcinoma, Follicular↗
PubMed2003

Gene promoter hypermethylation in tumors and lymph nodes of stage I lung cancer patients.

Promoter hypermethylation is an important pathway for repression of gene transcription in cancer cells and a promising marker for cancer detection. We tested five gene promoters [CDKN2A (p16), O(6)-methylguanine-DNA-methyltransferase, glutathione S-transferase P1 (GSTP1), adenomatous polyposis coli (APC), and death-associated protein kinase (DAPK)] by real-time methylation-specific PCR in primary tumors from 90 stage I lung cancer patients for aberrant DNA methylation. We then used the presence of tumor methylation as a marker to investigate the presence of occult metastasis in corresponding histologically negative lymph nodes. Of the primary tumors, 73 of 90 (81%) displayed promoter hypermethylation in at least one of the genes studied: 17% (15 of 90) at p16 (CDKN2A); 16% (14 of 90) at O(6)-methylguanine-DNA-methyltransferase; 8% (7 of 90) at GSTP1; 72% (65 of 90) at APC; and 17% (15 of 90) at DAPK. Squamous histology was predictive of worse overall survival (P = 0.074, log-rank test). APC methylation and GSTP1 methylation in the primary tumor were both correlated with nonsquamous histology (P = 0.02 and P = 0.01 likelihood ratio respectively). The presence of both APC methylation and DAPK methylation in the primary tumor predicted a worse outcome, with 7 of 13 (54%) deaths in this group compared with 21 of 77 (27%) deaths in cases without both genes methylated (P = 0.229, log-rank test). The same methylation pattern was detected in DNA from at least one of the corresponding lymph nodes in 11 of 73 (15%) cases. Five of 11 (45%) patients with occult metastasis detected by methylation analysis have died compared with 17 of 62 (27%) patients with negative lymph nodes, although survival analysis did not reach statistical significance (P = 0.632, log-rank test). Promoter hypermethylation is common in lung cancer and represents a promising marker for the molecular staging of lung cancer patients. Although this study showed important trends, a larger prospective study is required to better understand the value of methylation analysis in detecting occult metastasis.

Adenomatous Polyposis Coli Protein↗
PubMed2002

Do basic laboratory tests or clinical observations predict bleeding in thrombocytopenic oncology patients? A reevaluation of prophylactic platelet transfusions.

The purpose of this study was to determine which clinical and laboratory features correlate with serious hemorrhage in thrombocytopenic oncology patients. A retrospective review was conducted of all thrombocytopenic adult patients admitted to the Johns Hopkins Oncology Center, Baltimore, MD, over the last 10 years. We performed multiple logistic regression analysis on 2942 patients looking at the frequency of serious bleeding as a function of platelet count and numerous features that may correlate with hemorrhage. Multivariate analyses showed no relationship between either the first morning platelet count or the lowest platelet count of the day and the risk of hemorrhage. Of the other features we examined, several correlated independently with bleeding, including uremia (odds ratio [OR] 1.64; 95% confidence interval [CI], 1.40 to 1.92), hypoalbuminemia (OR 1.54; 95% CI, 1.33 to 1.79), recent bone marrow transplantation (OR 1.32; 95% CI, 1.22 to 1.43), and recent hemorrhage (OR 6.72; 95% CI, 5.53 to 8.18). Leukopenia was associated with a decreased risk of bleeding (OR 0.70; 95% CI, 0.60 to 0.82). Although this large study identified a number of clinical and laboratory features that correlated significantly with bleeding, the ORs of these factors were not large and all were much less than previous bleeding. These findings suggest that the major goal of transfusion support should be the aggressive therapeutic use of blood products rather than prophylactic use based on such weak clinical correlates and on the platelet count, which was not a correlate at all in multivariate analysis.

Acute Disease↗
PubMed2002

High-resolution scintimammography: a pilot study.

UNLABELLED: This study evaluated a novel high-resolution breast-specific gamma camera (HRBGC) for the detection of suggestive breast lesions. METHODS: Fifty patients (with 58 breast lesions) for whom a scintimammogram was clinically indicated were prospectively evaluated with a general-purpose gamma camera and a novel HRBGC prototype. The results of conventional and high-resolution nuclear studies were prospectively classified as negative (normal or benign) or positive (suggestive or malignant) by 2 radiologists who were unaware of the mammographic and histologic results. All of the included lesions were confirmed by pathology. RESULTS: There were 30 benign and 28 malignant lesions. The sensitivity for detection of breast cancer was 64.3% (18/28) with the conventional camera and 78.6% (22/28) with the HRBGC. The specificity with both systems was 93.3% (28/30). For the 18 nonpalpable lesions, sensitivity was 55.5% (10/18) and 72.2% (13/18) with the general-purpose camera and the HRBGC, respectively. For lesions < or = 1 cm, 7 of 15 were detected with the general-purpose camera and 10 of 15 with the HRBGC. Four lesions (median size, 8.5 mm) were detected only with the HRBGC and were missed by the conventional camera. CONCLUSION: Evaluation of indeterminate breast lesions with an HRBGC results in improved sensitivity for the detection of cancer, with greater improvement shown for nonpalpable and < or =1-cm lesions.

Breast↗