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Orlo H Clark

Publications and source records attributed to Orlo H Clark.

At least 19 recordsLinked to original sources
PubMed2006

Hook needle-guided excision of recurrent differentiated thyroid cancer in previously operated neck compartments: a safe technique for small, nonpalpable recurrent disease.

CONTEXT: As a result of more sensitive techniques to detect recurrent thyroid cancer, the number of patients presenting with small, nonpalpable recurrent thyroid cancer in cervical lymph nodes is increasing. Surgical excision of nonpalpable recurrent thyroid cancer can be difficult, particularly in a previously operated area. OBJECTIVE: The objective of this study was to investigate whether preoperative insertion of a hook needle under ultrasound guidance is useful in neck reoperations for recurrent thyroid cancer. PATIENTS: Ten consecutive patients presenting over a 4-month period with nonpalpable, ultrasound-visible, fine needle biopsy-proven recurrent thyroid cancer in previously operated neck compartment(s) were studied. MAIN OUTCOME MEASURES: We measured whether it was technically possible to insert a hook needle preoperatively, rate of negative neck exploration, and complication rate. RESULTS: The hook needle was inserted in seven patients. In three patients, the hook needle was not inserted; one patient had palpable disease 4 months after the preoperative clinic visit, one patient had a tumor too close to the carotid artery, and one patient had multiple bilateral foci of recurrent disease in the central neck. One patient had bleeding after insertion of the needle due to a penetration of an anterior jugular vein that was easily managed at neck reexploration. No other complication occurred during the hook needle insertion, and the only surgical complication was a transient recurrent nerve palsy. All pathology reports showed malignant disease. CONCLUSION: Hook needle-guided excision of recurrent thyroid cancer is feasible and appears to be a promising tool for safe and successful reoperation of patients with small recurrent thyroid cancer in cervical lymph nodes.

Adolescent↗
PubMed2006

Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy?

BACKGROUND: Laparoscopic adrenalectomy for tumors > 6 cm is controversial because of the risk of malignancy, but data to support this position are mostly from small series. The recent NIH consensus conference did not make a definitive recommendation about management of 4- to 6-cm nonfunctioning incidentalomas. STUDY DESIGN: Adrenocortical carcinomas (ACC) recorded in the Surveillance, Epidemiology, and End Results (SEER) database (1988 to 2000) were compared with benign functional or nonfunctional adrenal cortical adenomas (excluding aldosteronomas) operated on at our institution between January 1, 1993, and July 1, 2003. Data were compared using t-tests, chi-square tests, likelihood ratios, and receiver operating characteristic (ROC) curves. RESULTS: We identified 457 patients with ACC and 47 patients with adrenal cortical adenomas; 376 and 44 neoplasms, respectively, had tumor size data available. Tumor size was larger in ACC (12.0 +/- 5.6 versus 4.2 +/- 1.9 cm, mean +/- SD, p < 0.05). For ACC presenting with local disease, the sensitivity, specificity, and likelihood ratios of tumor size to predict malignancy were 96%, 52%, and 2.0, respectively, for tumors > or = 4 cm; 90%, 80%, and 4.4 for tumors > or = 6 cm; 77%, 95%, and 16.9 for tumors > or = 8 cm; and 55%, 98%, and 24.4 for tumors > or = 10 cm. Assuming a pretest probability of malignancy of 5%, the likelihood ratios derived from this study yield a posttest probability of 10%, 19%, and 47% for cancer in adrenal cortical tumors > or = 4 cm, > or = 6 cm, and > or = 8 cm, respectively. CONCLUSIONS: These data suggest that size is useful for predicting malignancy, and that at a size threshold of > or = 4 cm, the likelihood of malignancy doubles (to 10%) and it is more than ninefold higher for tumors > or = 8 cm (47%).

Adolescent↗
PubMed2006

Selective use of steroid replacement after adrenalectomy: lessons from 331 consecutive cases.

HYPOTHESIS: Only selected patients require steroid replacement therapy following adrenalectomy. DESIGN: Retrospective review. SETTINGS: University tertiary care center and veterans' hospital. PATIENTS: A total of 331 patients who underwent adrenalectomy by 1 surgeon (Q.-Y.D.) between April 1, 1993, and August 31, 2005. INTERVENTIONS: Laparoscopic, open, and hand-assisted adrenalectomy. Steroid replacement therapy was administered using a standardized hydrocortisone taper protocol. MAIN OUTCOME MEASURES: Indications for adrenalectomy, operative approach, requirement for postoperative steroid replacement, and episodes of acute adrenocortical insufficiency. RESULTS: Of the 331 adrenalectomies, 304 were laparoscopic, 23 were open, and 4 were hand assisted. There were 299 unilateral adrenalectomies and 32 bilateral adrenalectomies performed. Fifty-seven (17%) of the 331 patients required steroid replacement after adrenalectomy. Of the 57 patients requiring steroid replacement, 52 had Cushing syndrome and 5 had bilateral pheochromocytomas. The 52 patients with Cushing syndrome included 16 with pituitary tumors who had failed pituitary resection and/or medical therapy, 14 with unilateral adrenal adenomas, 9 with ectopic corticotropin-secreting tumors who had failed resection and/or medical therapy, 7 with incidentalomas and subclinical Cushing syndrome, 4 with macronodular hyperplasia, and 2 with adrenocortical carcinoma. No patients undergoing unilateral adrenalectomy for non-Cushing adrenal disease required steroid replacement. Four (7%) of the 57 patients receiving steroid replacement had episodes of acute adrenocortical insufficiency following operation and required increased steroid supplementation. There were no cases of acute adrenocortical insufficiency in the 274 patients who did not receive steroid replacement. CONCLUSIONS: Steroid replacement therapy after adrenalectomy should be reserved for patients with Cushing syndrome (overt or subclinical) and patients undergoing bilateral adrenalectomy. Patients undergoing adrenalectomy for unilateral non-Cushing adrenal tumors do not require postoperative steroid replacement.

Acute Disease↗
PubMed2006

Predictors of single-gland vs multigland parathyroid disease in primary hyperparathyroidism: a simple and accurate scoring model.

HYPOTHESIS: Preoperative clinical, biochemical, and imaging studies could be used to reliably select patients with single-gland primary hyperparathyroidism who could undergo minimally invasive parathyroidectomy and to determine whether additional perioperative testing is necessary. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: A total of 238 patients who underwent neck surgical exploration and parathyroidectomy for primary hyperparathyroidism from January 7, 2002, to December 23, 2004. MAIN OUTCOME MEASURES: Demographic, clinical, biochemical, and imaging factors that predict single-gland vs multigland parathyroid disease, and biochemical cure. RESULTS: Of the 238 patients, 75.2% had a single adenoma, 21.4% had asymmetric 4-gland hyperplasia, and 3.4% had double adenomas. A biochemical cure was achieved in 99.2% of the patients. Preoperative calcium and intact parathyroid hormone levels were significantly higher (P = .03 and .04, respectively) and ultrasound and sestamibi scan results were more likely to be positive (both P<.001) in single-gland primary hyperparathyroidism. A dichotomous scoring model based on preoperative total calcium level (>/=3 mmol/L [>/=12 mg/dL]), intact parathyroid hormone level (>/=2 times the upper limit of normal levels), positive ultrasound and sestamibi scan results for 1 enlarged gland, and concordant ultrasound and sestamibi scan findings reliably distinguished single-gland vs multigland cases (P<.001). The positive predictive value of this scoring model to correctly predict single-gland disease was 100% for a total score of 3 or higher. CONCLUSIONS: Preoperative biochemical and imaging study results reliably distinguished single-gland vs multigland parathyroid disease in primary hyperparathyroidism. Our findings suggest that patients with a score of 3 or higher can undergo a minimally invasive parathyroidectomy without the routine use of intraoperative parathyroid hormone or additional imaging studies, and those with a score of less than 3 should have additional testing to ensure that multigland disease is not overlooked.

Adolescent↗
PubMed2006

Diagnostic and prognostic value of cell-cycle regulatory genes in malignant thyroid neoplasms.

BACKGROUND: Approximately 30% of patients with thyroid nodules have indeterminate or suspicious fine-needle aspiration (FNA) biopsy results. Because their risk of cancer is approximately 20%, these patients undergo thyroidectomy. We hypothesized that genes that regulate cell-cycle progression would be differentially expressed in malignant versus benign thyroid nodules and could serve as diagnostic markers and markers of disease aggressiveness. METHODS: We used a cDNA array with 96 cell-cycle regulatory genes to identify differentially expressed genes in pooled benign versus malignant thyroid neoplasms. Genes up- or down-regulated by more than 2-fold in malignant thyroid neoplasms were further evaluated by real-time quantitative polymerase chain reaction (PCR) in 95 patients with hyperplastic nodules (n = 19), follicular adenoma (n = 19), follicular thyroid cancer (n = 19), the follicular variant of papillary thyroid cancer (n = 19), and papillary thyroid cancer (n = 19). RESULTS: cDNA array analysis showed that cyclin B1, MCM5, MCM7, RAD9, ubiquitin C, CDK6, SKP2, and APAF1 were up-regulated in malignant thyroid neoplasms. Real-time quantitative PCR showed that MCM5, MCM7, and RAD9 mRNA expression were significantly higher in malignant than in benign thyroid neoplasms (< or = 0.0012). The combined use of MCM5, MCM7, and RAD9 mRNA expression had a sensitivity of 98.2% and a specificity of 65.7%. The level of MCM7 mRNA expression was higher in T4 than in T1, T2, and T3 differentiated thyroid cancers (P < 0.0127). CONCLUSIONS: MCM5, MCM7, and RAD9 are overexpressed in malignant thyroid neoplasms of follicular cell origin. These genes may be useful markers of malignant thyroid neoplasms as an adjunct to FNA biopsy. MCM7 mRNA expression is higher in locally invasive differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed2006

Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress?

BACKGROUND: Adrenocortical carcinoma (ACC), a rare and aggressive malignancy, accounts for up to 14% of adrenal incidentalomas. The only chance of cure for ACC is diagnosis at an early stage; therefore, a main indication for adrenalectomy in patients with adrenal incidentaloma has been the potential risk of ACC. Recent studies suggest that this has led to earlier stage of ACC at diagnosis, more curative operations, and better survival. METHODS: We analyzed data on ACC from The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Four equal time quartiles (1973-1979, 1980-1986, 1987-1993, and 1994-2000) were compared for changes in demographics, pathology, treatment, and cause-specific mortality. RESULTS: The average age was 51.2 years (range: 1-97), and 45.9% of patients were men. The average tumor size was 12 cm (range: 2-36 cm), and only 4.2% were < or = 6 cm. Most (88%) patients had surgical resection of their tumor, and external beam radiotherapy was used in only 12% of patients. Between the time quartiles compared (as well as annually), there was no significant difference at presentation in age at diagnosis, sex, race/ethnicity, tumor size, tumor grade, the frequency of distant metastasis, and overall TNM stage. Low tumor grade, lower stage of ACC, later time quartile, and surgical resection were associated with a lower cause-specific mortality by univariate analysis (P < or = 0.002) and by multivariate analysis (P < or = 0.031). CONCLUSIONS: Although adrenal incidentalomas have become a common indication for adrenalectomy, this has not resulted in patients with ACC being diagnosed earlier or treated at a lower stage of disease at the national level. The most important predictors of survival in these patients are tumor grade, tumor stage, and surgical resection.

Adolescent↗
PubMed2006

Does familial non-medullary thyroid cancer adversely affect survival?

BACKGROUND: Familial non-medullary thyroid cancer (FNMTC) is associated with a higher rate of multifocality and a higher recurrence rate than sporadic thyroid cancer. However, the effect of FNMTC on life expectancy is unknown. MATERIAL AND METHODS: Using data from our FNMTC database, we calculated life expectancy and survival rates after diagnosis of FNMTC and compared the results with the rates for unaffected family members and for the standard US population. Overall life expectancy and survival rates were calculated using the Kaplan-Meier method. We compared patients from families with 2 affected members with patients from families with > or = 3 affected members. We also compared patients diagnosed in a known familial setting (index cases and subsequent cases) with patients diagnosed before the familial setting was recognized. RESULTS: There were 139 affected patients with 757 unaffected family members. The mean age at diagnosis was 40.8 +/- 13.9 years and the mean follow-up time was 9.4 +/- 11.7 years. Ten patients died of thyroid cancer during follow-up. The life expectancy of patients with FNMTC was similar to that of their unaffected family members. Survival was significantly shorter for patients with 3 or more affected family members, for patients diagnosed before the familial setting was recognized, and for patients with anaplastic cancer. CONCLUSIONS: Our results suggest that FNMTC may be more aggressive than sporadic thyroid cancer, particularly in families with 3 or more affected members. However, when recognized and treated appropriately, it does not significantly shorten the overall life expectancy of the affected patients.

Adenocarcinoma, Follicular↗
PubMed2006

Selective use of adrenal venous sampling in the lateralization of aldosterone-producing adenomas.

INTRODUCTION: It has been suggested that routine adrenal venous sampling (AVS) is necessary to lateralize an aldosterone-producing adenoma in patients with primary hyperaldosteronism. However, the success rate of AVS is variable, with potential risks. We review our experience at University of California San Francisco (UCSF), where AVS is used only selectively, to determine outcomes with this approach. METHODS: All patients undergoing adrenalectomy for aldosteronoma at UCSF from January 1995 to October 2004 were included. Outcome after adrenalectomy was determined based on plasma levels of aldosterone and potassium, rates of persistent hypertension, and reduced use of antihypertensive medications. RESULTS: Altogether, 65 patients were included in the study, 52 (80%) of whom had their adrenal tumors lateralized based on computed tomography scans, magnetic resonance imaging, or both. The remaining 13 (20%) patients had doubtful localization of their lesions on imaging. We did not routinely perform AVS in patients with definitive imaging findings. Thus, only 4 (8%) patients with definitive imaging findings underwent AVS, and one was unsuccessful. Of the 13 patients with doubtful lateralization on imaging, 8 underwent AVS. With this practice, biochemical cure rates after adrenalectomy were up to 100%, and hypertension resolved or was improved in 85% of patients. CONCLUSIONS: AVS may be performed selectively only when preoperative imaging cannot definitively lateralize the aldosteronoma. This practice in our center has resulted in high cure rates. During the era of improved imaging resolution and experience, mandatory routine AVS is not necessary to achieve high cure rates for aldosteronomas.

Adenoma↗
PubMed2006

Papillary thyroid cancer.

Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with an excellent prognosis. Overall survival is more than 90%. The first-line treatment is surgical excision, and although the debate continues as to whether a total thyroidectomy or thyroid lobectomy should be recommended, most patients at the University of California, San Francisco are treated with a total thyroidectomy. Not only has this been shown to be superior for overall survival in select patient populations, but local recurrence is also significantly lower with this approach. Total thyroidectomy also optimizes the adjuvant treatment options that are unique to "differentiated" thyroid cancer because these malignant cells retain many of the features of the native thyroid follicular cell. These cellular features are used for specialized investigations and treatment options in patients with PTC. For example, PTC cells retain the ability to produce thyroglobulin, to be stimulated by thyroid-stimulating hormone (TSH), and to take up iodine. These features are vital and separate differentiated thyroid cancer from other epithelial malignancies because such features can be used in clinical follow-up (monitoring serum thyroglobulin levels, whole body radioactive iodine scans) and in the treatment of patients with PTC (TSH suppression, radioactive iodine ablation of thyroid remnant, local recurrences, and regional or distant metastases). In summary, the wide array of treatment options for patients with PTC includes surgery, radioactive iodine, thyroid hormone suppression of TSH, external beam radiation (less commonly), and rarely, chemotherapy. This continues to be an area of exciting research for emerging therapy, much of which concentrates on enhancing or re-establishing the differentiated features of the thyroid cancer cell, in an effort to optimize the adjuvant treatment options. The treatment options that are chosen depend on patient factors, disease factors, and the decisions of the patient and treatment team.

Antineoplastic Agents↗
PubMed2006

Malignant pheochromocytoma.

Malignant pheochromocytoma is a rare disease with a high mortality. Surgical resection is the only effective treatment if extensive metastatic disease is not present. However, differentiating between benign and malignant pheochromocytoma is impossible in the absence of locoregional invasion or distant metastasis. This diagnostic dilemma has several drawbacks, including later detection and treatment of recurrence than if malignancy is determined at the original operation. With emerging molecular markers of malignant disease, optimal extent and approach for surgical treatment and appropriate extent of follow up could be established based on specific tumor behavior and the need for additional systemic therapy.

3-Iodobenzylguanidine↗
PubMed2006

Observation or laparoscopic adrenalectomy for adrenal incidentaloma? A surgical decision analysis.

BACKGROUND: The optimal strategy remains controversial for adrenal incidentaloma, 4 to 6 cm in size, nonfunctioning, and without malignant imaging characteristics. A decision analysis model was used to identify relevant variables for selecting the optimal management (observation versus adrenalectomy). MATERIAL/METHODS: Risk/benefit analysis in tertiary care center. The probabilities of each health outcome states were determined by a review of the literature from 1980 to 2002 (n=2844 patients); and from a retrospective review of experience at University of California San Francisco (UCSF). RESULTS: The baseline probabilities of morbidity after laparoscopic unilateral adrenalectomy and a new indication developing during initial observation (hypersecretion, size increase, malignancy) were 7.8% and 3.1%, respectively. We found observation to be the preferred approach when using baseline probabilities and utilities. Laparoscopic adrenalectomy becomes the preferred approach however if: (1) The morbidity rate from laparoscopic unilateral adrenalectomy is < 3.0%, 2) The probability of a new indication developing for adrenalectomy during observation is > 7.5%, 3) A patient's perspective of observation has a utility of lower than 98.6%, and (4) A patient views having a complication from adrenalectomy is not much deleterious (utility > 88.1%). CONCLUSIONS: This decision analysis model identifies the important variables for selecting the optimal management approach for adrenal incidentalomas. These results can be used to select the optimal management strategy based on individual patient preference and surgeon-specific complication rate.

Adrenal Gland Neoplasms↗
PubMed2005

The missing thyroid.

BACKGROUND: Several patients have been referred to our practice after having undergone attempted thyroidectomy, during which the thyroid gland was not found. These patients were reviewed to identify factors associated with failure to identify or adequately resect the thyroid. STUDY DESIGN: Patients referred for a "missed thyroid" between October 1, 1990 and December 31, 2002, were reviewed retrospectively. Seven patients who underwent neck exploration for thyroid cancer (n=6) or Graves' disease (n=1) were identified. Surgical indications, history of neck operations, means of recognizing the complication, incision location, and intraoperative and pathologic findings were analyzed. RESULTS: The thyroid was missed on initial exploration in four patients and in the second or third operation in three patients. In three patients, the surgeon misidentified the thymus (two patients) or nodal tissue (one patient) as the thyroid gland. In one patient, the thyroid could not be identified. In one patient, the thyroid was deemed unresectable because of scar tissue. In two patients, an inadequate "near-total" thyroidectomy was performed. In five patients with long necks, the neck incision was too far below the cricoid cartilage. CONCLUSIONS: Failure to identify the thyroid gland at the normal anatomic position was associated with low cervical incisions and a history of earlier neck operations. These findings emphasize the need for improved understanding of thyroid anatomy, embryology, localization procedures, and surgical technique.

Female↗
PubMed2005

Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive human malignancies. Several prognostic factors have been observed in patients with ATC, and some experts advocate aggressive multimodal therapy in selected patients. However, it is unclear whether such an approach significantly improves survival. The authors analyzed prognostic factors and treatment outcomes in patients with ATC reported in the National Cancer Institute's Surveillance, Epidemiology, and End Results data base. METHODS: The cohort consisted of 516 patients with ATC reported to 12 population-based cancer registries between 1973 and 2000. Demographic, pathologic, and treatment data were used for univariate and multivariate survival analyses. RESULTS: The mean patient age at diagnosis was 71.3 years, and there were 171 men and 345 women. Eight percent of patients had intrathyroidal tumors, 38% had extrathyroidal tumors and/or lymph node invasion, and 43% of patients had distant metastasis. The average tumor size was 6.4 cm (range, 1-15 cm). Sixty-four percent of patients underwent surgical resection of their primary tumor, and 63% received external beam radiotherapy. The overall cause-specific mortality rate was 68.4% at 6 months and 80.7% at 12 months. Univariate analysis showed that age < 60 years, female gender, intrathyroidal tumor, external beam radiotherapy, surgical resection, and combined surgical resection of tumor and radiotherapy were associated with a lower cause-specific mortality. On multivariate analysis, only age < 60 years, an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. CONCLUSIONS: Although most patients with ATC had an extremely poor prognosis, patients < 60 years old with intrathyroidal tumors survived longer. Surgical resection with external beam radiotherapy for ATC was associated with lower cause-specific mortality.

Adolescent↗
PubMed2005

Papillary thyroid cancer: surgical management of lymph node metastases.

Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with cervical lymph node metastases in 30% to 90% of patients. While surgery is the primary treatment modality for PTC, radioactive iodine and thyroid hormone suppression often complement the treatment plan. Although thyroid hormone suppression may decrease the incidence of recurrent disease and radioactive iodine may diagnose and treat metastases, lymph node dissection (LND) is the mainstay treatment for clinically evident cervical lymph node metastases. The surgical treatment options published in the literature include the traditional radical LND, the modified radical LND, the selective LND (compartment-based resection based on documented lymph node metastases), and a 'berry picking' resection (in which only the grossly abnormal lymph nodes are excised). At the University of California, San Francisco, we prefer the modified radical LND with preservation of the cervical sensory nerves for the first lymph node dissection with the 'berry picking' procedure limited to surgical treatment of recurrent nodal metastases in previously resected lymph node basins. Some centers are evaluating the potential role of sentinel lymph node biopsies for PTC. While the extent of lymphadenectomy is debated, most physicians treating patients with PTC agree that clinical evidence of lymphatic metastases should be surgically exercised and there is no role for prophylactic LND.

Antineoplastic Agents↗
PubMed2005

Extent of disease and practice patterns for medullary thyroid cancer.

BACKGROUND: There have been significant improvements in the management of medullary thyroid cancer (MTC), and consensus treatment guidelines have been established by numerous international and national societies. It is unclear if the advances in diagnosis and treatment of MTC have led to earlier diagnosis and more complete initial treatment of patients with MTC. STUDY DESIGN: Patients with MTC (n=1,070) were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 12 population-based cancer registries between 1973 and 2000. Four equal-time quartiles (group I=1973 to 1979, group II=1980 to 1986, group III=1987 to 1993, and group IV=1994 to 2000) were compared for changes in demographics, extent of disease, and treatment. RESULTS: Mean tumor size was significantly larger in 1988 than in 1989 through 2000 (p=0.044), but there was no significant trend toward smaller tumor size. The number of patients having total or near total thyroidectomy increased significantly in the latter two quartiles (p < 0.001) but not the number of patients having cervical lymph node dissection. Unfortunately, 15% of patients in group IV still had less than total or near total thyroidectomy, and 41% had no cervical lymph node dissection. There were no significant differences in age, gender, rate of lymph node or distant metastasis, SEER stage, TNM stage, and cause-specific mortality among the four time groups and annually. CONCLUSIONS: There was no significant trend toward earlier stage of disease at diagnosis and treatment and no significant increase in the survival of patients with MTC during a 28-year period. A high proportion of patients continue to receive less than optimal initial surgical treatment.

Adolescent↗
PubMed2005

Diagnostic and prognostic value of angiogenesis-modulating genes in malignant thyroid neoplasms.

BACKGROUND: Angiogenesis is an essential biologic event in the pathogenesis of human malignancies. We postulated that expression analysis of genes that modulate angiogenesis would identify differentially expressed genes that would help to distinguish benign from malignant thyroid neoplasms and serve as markers of aggressive differentiated thyroid cancer. METHODS: A complementary DNA (cDNA) array with 96 genes that modulate angiogenesis was used to identify differentially expressed genes (2-fold higher or lower) in malignant versus benign thyroid neoplasms. Real-time quantitative polymerase chain reaction was used to confirm cDNA array expression data in 123 patients (4 normal thyroid, 26 hyperplastic nodules, 27 follicular adenomas, 23 follicular cancers, 18 follicular variant of papillary cancers, 25 papillary cancers). RESULTS: Twenty-two genes were upregulated in malignant thyroid neoplasms by cDNA array analysis, but only 13 genes had higher messenger RNA (mRNA) expression levels in malignant than in benign thyroid neoplasms by real-time quantitative polymerase chain reaction (P < or = .04). Of the 13 differentially expressed genes, the combined use of angiopoietin 2 (ANGPT2) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression levels was best for distinguishing malignant from benign thyroid neoplasms, with a sensitivity of 90%, specificity of 85%, positive predictive value of 75%, and negative predictive value of 94%. Epidermal growth factor receptor and ephrin B2 mRNA expression was elevated in higher TNM stage neoplasms and in patients with high-risk AMES (Age, distant Metastasis, Extrathyroidal invasion, and tumor Size) differentiated thyroid cancers (P < or = .005). CONCLUSIONS: Angiopoietin 2 and tissue inhibitor of metalloproteinase 1 are diagnostic markers of malignant thyroid nodules and could improve the diagnostic accuracy of FNA biopsy. Epidermal growth factor receptor and ephrin B2 are markers of aggressive differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed2005

Valproic acid inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in human thyroid cancer cells.

BACKGROUND: Among the most promising new therapies for thyroid cancer are the histone deacetylase inhibitors. Valproic acid (VA) is an anticonvulsant that inhibits histone deacetylase activity at nontoxic concentrations. We hypothesized that VA would have antineoplastic effects on human thyroid cancer cells. METHODS: We treated 1 papillary and 3 follicular thyroid cancer cell lines with VA (0.5-2 mmol/L) for 24 to 72 hours. Cell proliferation was measured with a cell proliferation assay kit. Annexin V-fluorescein isothiocyanate was used to quantitate cells that were undergoing apoptosis. Quantitative polymerase chain reaction was used to measure expression of apoptosis-regulatory and differentiation genes. RESULTS: VA inhibited growth in all cell lines by 26% to 59% at 48 hours and up to 77% at 72 hours. Nineteen percent to 30% of VA-treated cells underwent apoptosis, compared with 4% to 8% of the control cells. Expression of pro survival genes bcl-2 and bcl-xl was down-regulated by 10% to 60%; expression of the proapoptosis gene bax was up-regulated by 23% to 85%. Sodium-iodide symporter and thyroglobulin messenger RNA expression were up-regulated by 93% to 370% in follicular cell lines but remained unchanged in the papillary cell line. CONCLUSION: VA inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in thyroid cancer cells. These findings suggest that VA may be useful clinically for patients with thyroid cancers of follicular cell origin.

Adenocarcinoma, Follicular↗