PubMed Health⌕ Search

Biomedical subjects

E Kebebew

Publications and source records attributed to E Kebebew.

18 recordsLinked to original sources
PubMed2006

How to localize parathyroid tumors in primary hyperparathyroidism?

The management of primary hyperparathyroidism (PHPT) has dramatically changed in the last 5 yr. Many more patients now undergo focused, limited or minimally invasive parathyroidectomy instead of traditional bilateral neck exploration. This change has taken place because of the improved accuracy of pre-operative localizing studies in selecting patients who have single-gland parathyroid disease (single adenoma) and can therefore have a minimally invasive parathyroidectomy. Sestamibi scanning followed by ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans are most accurate for localizing parathyroid tumors in patients with PHPT. Selective venous catheterization for PTH levels is useful when other localizing studies are negative or discordant in patients with persistent or recurrent PHPT. The routine use of one or more localizing studies commonly identifies the parathyroid tumor in patients with single-gland disease; but if localizing studies are negative or discordant, patients should have intra-operative PTH levels monitored or have a bilateral neck exploration to ensure a high rate of biochemical cure.

Adenoma↗
PubMed2006

Selective modified radical neck dissection for papillary thyroid cancer-is level I, II and V dissection always necessary?

BACKGROUND: There is ongoing controversy as to the indications for and extent of lateral cervical lymphadenectomy for patients with papillary thyroid cancer (PTC). While most now agree that prophylactic lymph node dissections (LND) play no role, at the University of California, San Francisco (UCSF) we limit LND selectively on a level by level basis, and resect only the levels thought to harbor disease or to be at increased risk of metastases. This initial 'selective LND' usually includes levels III and IV (due to the well-documented increased likelihood of metastases to these levels) and levels I, II, and V are included when there is clinical or radiological evidence of disease or increased risk of it. METHODS: A retrospective review of the clinical charts and hospital records of 106 consecutive patients who had metastatic PTC and who underwent at least one lateral cervical LND at UCSF between January 1995 and December 2003 was carried out. Data were collected to assess which patients had levels I, II, and/or V included in their initial ipsilateral and/or contralateral LND and to determine the recurrence rates at these levels if they had previously been excised compared with if they had not. Chi-squared and Fisher exact tests were utilized for statistical comparison, where appropriate. RESULTS: A total of 140 initial lateral LND were performed: 104 ipsilateral and 36 contralateral. In these initial LND, 3.9%, 72.5%, and 18.6% of patients had levels I, II, and V resected on the ipsilateral side, and 2.9%, 60.0%, and 37.1% of patients had levels I, II, and V resected on the contralateral side. Recurrence at levels I and V was uncommon in all patient populations. Recurrence at level II was 19% ipsilaterally and 10% contralaterally when the level was previously resected and 21% ipsilaterally and 14% contralaterally when the level was not previously resected. There was no statistically significant difference in recurrence at level II when the level had previously been resected compared with when it had not. CONCLUSIONS: If utilized in the appropriate patient population, a selective approach to lateral cervical LND for PTC can be a successful alternative to the routine modified radical LND. Levels I and V do not require resection unless there is clinical or radiological evidence of disease. Guidelines for which patients may be considered for this less aggressive approach to level II nodal metastases are suggested.

Adenocarcinoma, Papillary↗
PubMed2004

Prognostic scoring systems in patients with follicular thyroid cancer: a comparison of different staging systems in predicting the patient outcome.

BACKGROUND: The use of prognostic scoring systems is important for predicting the survival of individuals with thyroid carcinoma. Relatively few studies have addressed this issue for patients with follicular thyroid cancer. The goal of this retrospective study was to establish the best and most pertinent prognostic scoring system to predict survival in patients with follicular thyroid cancer. METHODS: We selected 86 patients with follicular thyroid cancer treated at University of California, San Francisco (UCSF) hospitals from January 1954 to April 1998. The mean follow-up time was 11.5 years. There were 60 women (70%) and 26 men (30%), with a mean age if 48.6 years. Prognostic scoring systems included tumor, node, metastases (TNM), European Organization for Research and Treatment of Cancer (EORTC), Age, Grade, Extent, Size (AGES), Age, Metastases, Extent, Size (AMES), and the Metastases, Age, Completeness of resection, Invasion, Size (MACIS). Survival time was calculated using the Kaplan-Meier method. Using Cox proportional hazards analysis, the relative importance of each scoring method was determined by calculating the proportion of variation in survival time explained (PVE). RESULTS: Kaplan-Meier analysis indicated that all scoring systems were significant predictors of survival time (p < 0.0001). The PVE associated with each system was (from highest to lowest) 0.48 for MACIS, 0.46 for AGES, 0.44 for EORTC, 0.40 for AMES, and 0.33 for TNM. These results indicate that the MACIS scoring system accounted for a great proportion of explained variance in survival and is a more precise predictor of survival compared to the other scoring systems. CONCLUSIONS: TNM, EORTC, AGES, AMES, and MACIS, all provided useful prognostic information about the survival in our 86 patients with follicular thyroid cancers. The MACIS classification, however, was the most accurate predictor using PVE as a method of evaluation. Future scoring systems considering additional prognostic factors, may obtain a higher PVE.

Adenocarcinoma, Follicular↗
PubMed2003

Intraoperative parathyroid hormone assay and parathyroid reoperations.

BACKGROUND: The purpose of this study was to determine whether intraoperative parathyroid hormone (IOPTH) assay improved results of reoperations. METHODS: One hundred two patients with persistent/recurrent sporadic primary hyperparathyroidism underwent 108 reoperations (1996-2002). IOPTH was not used (n=58) from 1996-1998 (group 1). IOPTH was used (n=50) from 1999-2002 (group 2). Sensitivity and positive predictive value of IOPTH and its influence on surgical strategy were analyzed. A 50% decrease occurring 10 minutes after removal of parathyroid tumor was used to determine if all abnormal tissue had been removed. RESULTS: Groups 1 (58 patients) and 2 (50 patients) were comparable except for duration of follow-up. The cure rate was 84% (group 1, 87%; group 2, 82%, P=0.7). Hypocalcemia developed in 20 patients (permanent in 2 patients). There was 1 permanent vocal cord paralysis and 1 patient died of toxic shock syndrome. IOPTH successfully predicted cure in 44 of 49 patients (sensitivity, 90%); the positive predictive value was 90%. Values for parathyroid hormone level and the ratio parathyroid hormone/calcium at day 1 were at least as accurate as IOPTH in predicting cure. IOPTH was helpful in 1 patient but misleading in 4 patients. It failed to modify intraoperative strategy in most other patients. CONCLUSIONS: IOPTH testing was relatively reliable in patients with persistent or recurrent sporadic primary hyperparathyroidism, but the test unfortunately failed to improve the overall success rate at reoperation.

Adolescent↗
PubMed2001

Localization and reoperation results for persistent and recurrent parathyroid carcinoma.

HYPOTHESIS: Reoperation is safe and benefits patients with persistent and recurrent parathyroid carcinoma. DESIGN: Retrospective study. The mean follow-up time was 8.1 years (median, 7 years; range, 1-23 years). SETTING: A university tertiary referral center. PATIENTS: Eighteen patients treated for parathyroid carcinoma from 1966 to 1999. RESULTS: The mean serum calcium level was 13.7 mg/dL (3.43 mmol/L), and the parathyroid hormone (PTH) level was 1.6 to 20 times the upper limit of normal. Fourteen of 18 patients had persistent or recurrent parathyroid carcinoma and underwent 54 reoperations (28 at our institution). Mean time to recurrence was 4.8 years (range, 1-20 years). Symptoms of hyperparathyroidism were relieved in 86% of patients who had reoperation (P<.05). Reoperation for parathyroid carcinoma (25 locoregional and 3 distant) significantly reduced and normalized the serum calcium and PTH levels in 75% and 62% of the cases, respectively (P<.001). The preoperative serum calcium level was a significant predictor of postreoperative normalization of the serum calcium level but not extent of initial resection, PTH level, time to recurrence, concordance of localization studies, or patient age and sex (P<.01). Surgical complications consisted of 5 unilateral and 1 bilateral permanent recurrent laryngeal nerve palsies (2 intentionally resected en bloc), 1 transient hypoparathyroidism, 1 wound seroma, and 1 tracheoesophageal fistula. The sensitivity rates of sestamibi scan (n = 14), magnetic resonance imaging (n = 15), computed tomographic scan (n = 6), ultrasound (n = 13), and selective venous catheterization with PTH measurement (n = 6) were 79%, 93%, 67%, 69%, and 83%, respectively. CONCLUSIONS: Recurrence is common in patients with parathyroid carcinoma. Patients with this disease should have frequent, lifelong follow-up to ensure early detection of recurrence. Although reoperation for persistent or recurrent parathyroid carcinoma provides significant symptomatic relief and normalizes serum calcium and PTH levels in most patients, it is associated with some morbidity. Localizing studies of parathyroid carcinoma are helpful but do not detect all tumor foci.

Adult↗
PubMed2001

Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited.

The effect of chronic lymphocytic thyroiditis (CLT) on the behavior of papillary thyroid cancer (PTC) remains unclear. In recent studies the presence of CLT in patients with PTC was reported to be associated with a lower recurrence rate and an improved survival rate. Furthermore, patients with PTC and tumor infiltrating lymphocytes (TILs) have been reported to have lower recurrence rates and a lower frequency of distant metastases. Because of these and other observations, a tumor immune response in PTC has been suggested. The aim of our study was to determine: (1) the relative frequency of CLT in PTC; (2) the prognostic significance of CLT in patients with PTC; and (3) if TIL occurs independently or in association with CLT. A 10-year retrospective study of patients who underwent initial thyroidectomy for PTC from 1986 to 1996 was completed. The extent of thyroid lymphocytic infiltration was determined within the tumor, surrounding the tumor, and in the distant parenchyma by two independent observers blinded to the clinical data. Dense focal/diffuse lymphoid aggregates throughout the thyroid gland were diagnostic of CLT and when present within or surrounding the tumor were designated TILs. A total of 136 patients with PTC (typical and follicular variant of PTC histologic subtypes) were identified with a mean follow-up of 4.4 years and a 8% mortality rate at 10 years. Thirty percent of the patients with PTC had coexisting CLT, and 65% of these patients with CLT had positive anti-thyroglobulin antibodies. Patients with coexisting CLT and PTC were younger (p < 0.05), more likely to be female (p < 0.05), and more likely to have multicentric tumors (p < 0.001) compared to patients without CLT. Only 5% of patients had TILs without CLT, but 82.5% of patients with CLT had TILs identified (p < 0.0001). By univariate analysis CLT, age, gender, stage of PTC, tumor multicentricity, and tumor size were significant prognostic factors. Only age and TNM stage of PTC remained independent prognostic factors by multivariate analysis. We found a similar frequency (30%) of coexisting CLT and PTC as reported by others; but, more importantly, the presence of TILs primarily occurred in association with CLT. The presence of CLT in patients with PTC correlated with an improved prognosis. It was not an independent prognostic factor, however, and was not associated with a lower recurrence rate or a lower frequency of distant metastasis.

Chronic Disease↗
PubMed2001

Parathyroid carcinoma.

Although parathyroid neoplasms are common and cause primary hyperparathyroidism, parathyroid carcinoma is a rare entity. At times it can be difficult to diagnose. Patients with parathyroid carcinoma usually present with profound symptoms of hyperparathyroidism and highly elevated serum calcium and parathyroid hormone (PTH) levels. At the time of neck exploration, a large, gray-white, locally invasive tumor is commonly encountered. The course of patients with parathyroid carcinoma is variable; unfortunately, more than 50% have persistent or recurrent disease due to regional or distant disease. Surgical resection is the principal treatment for patients with parathyroid carcinoma. The optimal surgical treatment is en bloc tumor resection with ipsilateral thyroid lobectomy when the diagnosis is suspected and until it is proven otherwise. Patients who have persistent or recurrent parathyroid carcinoma should have localizing studies to identify loco-regional or distant tumor sites. Reoperation in patients with localized parathyroid carcinoma is recommended because it relieves symptoms of hypercalcemia, and it normalizes serum calcium and PTH levels in most patients. For patients who have unresectable parathyroid carcinoma, a protocol-based treatment with chemotherapy and external radiotherapy should be considered. Additionally, second-generation bisphosphonates and the NPS R-568 calcimimetic agent may be useful in normalizing the serum calcium and improving symptoms of hypercalcemia. However, they do not treat the tumor and are rarely effective in the long term.

Adenocarcinoma↗
PubMed2001

Laparoscopic adrenalectomy: the optimal surgical approach.

BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy has emerged as the treatment of choice for most adrenal surgical disorders. We describe our experience with 176 laparoscopic operations. PATIENTS AND METHODS: The patients were treated for hyperaldosteronism (N = 62), pheochromocytoma (N = 43), "incidentaloma" (N = 21), Cushing's syndrome (N = 20), suspected adrenal metastasis (N = 16), Cushing's disease (N = 8), adrenal hemorrhage (N = 3), or virilizing tumor (N = 1). In 154 of the 176 laparoscopic operations, a lateral transabdominal approach (15 bilateral, 76 left, and 63 right) was used. In the remaining 22, a posterior laparoscopic approach (3 bilateral, 10 left, and 9 right) was used. RESULTS: The average total operating time for unilateral laparoscopic adrenalectomy was 2.8 hours, and for bilateral adrenalectomy, it was 5.2 hours. The mean tumor size was 4.6 cm (range 1-15 cm). There was no significant difference in operating time according to the tumor size. The average length of hospitalization was 1.7 days (range 1-9 days). The perioperative complication rate was 5.1%. There were no conversions to an open procedure. The operating time, length of hospitalization, and perioperative complication rate were stable over the period. Although we used the posterior laparoscopic approach only for smaller tumors (<6 cm), we found no differences in patient outcome between the lateral and posterior laparoscopic approaches. CONCLUSION: For almost all adrenal surgical disorders, an initial laparoscopic approach is optimal. It is safe and is associated with the best patient outcome.

Adolescent↗
PubMed2000

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

BACKGROUND: The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. METHODS: The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. RESULTS: Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. CONCLUSIONS: Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value.

Adult↗
PubMed2000

Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer.

HYPOTHESIS: Reoperation benefits patients with locoregional, persistent, or recurrent medullary thyroid cancer (MTC). Currently available localizing studies have limited utility for detecting all foci of residual MTC. DESIGN: A retrospective study with a mean follow-up time of 7.5 years (median, 13 years; range, 2.2-29 years). SETTING: A tertiary referral medical center. PATIENTS: Thirty-three patients who underwent 46 reoperations for locoregional residual MTC. RESULTS: Sixty-four percent of residual MTC was located in the lateral cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by greater than 50% in 10 patients, and either increased or were not reduced by greater than 50% in the remaining patients. On reoperation, one patient had a thoracic duct injury that required reexploration and ligation. Patients who had a greater than 50% decrease in calcitonin levels after reoperation were less likely to develop distant metastases compared with patients who did not have a greater than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n = 31), computed tomographic scan (n = 16), ultrasound (n = 9), and dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively. CONCLUSIONS: Although reoperation in patients with residual MTC rarely results in biochemical cure, cervical reexploration is safe and in selected patients may limit MTC progression. Lateral cervical node dissection could be beneficial at the time of initial surgical treatment because of the high frequency of residual MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but far from perfect for guiding the reexploration for locoregional residual MTC.

Adult↗
PubMed2000

Differentiated thyroid cancer: "complete" rational approach.

Controversy continues regarding the optimal management of patients with differentiated thyroid cancer because no prospective randomized studies evaluating the merits of (1) extent of thyroidectomy, (2) postoperative radioactive iodine ablation, or (3) thyroid-stimulating hormone (TSH) suppressive therapy exist. Patients with low risk differentiated thyroid cancer enjoy a relatively good prognosis with a mortality rate of about 2% to 5% and a recurrence rate of about 20%. Despite the excellent prognosis in patients considered to be at low risk, total or near-total thyroidectomy in patients with differentiated thyroid cancer has the advantages that: (1) postoperative radioactive iodine can be used to detect and treat residual normal thyroid tissue and local or distant metastases; (2) follow-up serum thyroglobulin levels are a more sensitive marker of persistent or recurrent disease when all thyroid tissue has been removed; and (3) total or near-total thyroidectomy with postoperative (131)I ablation and TSH suppressive therapy is associated with better survival and lower recurrence rates. Patients with occult papillary thyroid cancer and minimally invasive follicular thyroid cancer can be treated by thyroid lobectomy because they have a near-normal life expectancy. Virtually all other patients with differentiated thyroid cancer appear to benefit from more extensive initial treatment.

Diagnosis, Differential↗
PubMed2000

Total thyroidectomy or thyroid lobectomy in patients with low-risk differentiated thyroid cancer: surgical decision analysis of a controversy using a mathematical model.

There is a general consensus that total or near-total thyroidectomy is the optimal treatment for patients with high risk differentiated thyroid cancer (DTC), but the optimal extent of thyroidectomy in patients with low risk DTC continues to be controversial. To determine the optimal extent of thyroidectomy in patients with low risk DTC, we used decision analysis to compare the trade-offs of total thyroidectomy (TT) to thyroid lobectomy (TL). The decision analysis model included the probabilities of thyroidectomy complications, risk of DTC recurrence, and death from DTC. This information was obtained from the literature and from outcome data for patients with low risk DTC from our institution. In addition, the concept of utilities was used in the analysis. To determine the utility of each health outcome state (thyroidectomy complication, DTC recurrence, and DTC mortality for low risk patients) a survey was conducted. Overall, prospective patients viewed DTC recurrence as less desirable than thyroidectomy complication. The utilities assigned by the survey participants varied over a wide range, with 61.5% of the individuals viewing the occurrence of a thyroidectomy complication as better than DTC recurrence. At baseline utilities and probabilities, TT had a higher expected utility than TL. One-way sensitivity analysis varying the rates of (1) thyroidectomy complication, (2) DTC recurrence, and (3) DTC mortality over the possible range showed that complication from initial thyroidectomy was the most important factor that determined the preferred extent of thyroidectomy. TL was the preferred surgical approach only if a complication rate of > 33:1, TT/TL complication rate ratio, was assumed. When no differences in DTC recurrence between the two approaches was assumed in the model, TL had a higher expected utility using the baseline utilities of thyroidectomy complication and DTC mortality. The analysis indicates that TT in patients with low risk DTC is preferable to TL. However, TL is preferred if (1) no difference in the DTC recurrence rate between the two approaches is assumed, (2) a higher complication rate for TT is used (> 33 times higher), or (3) the utility ratio of thyroidectomy complication to DTC recurrence is < 0.8 TL. We believe this decision analysis model provides an objective approach that others can use to select the optimal extent of thyroidectomy based on patient preference of health outcome states, institution-specific outcome data for DTC recurrence or mortality, and the surgeon-specific complication rate.

Adenocarcinoma, Follicular↗
PubMed2000

Medullary thyroid cancer.

Patients with clinically evident medullary thyroid cancer should have a total extracapsular thyroidectomy with bilateral central neck dissection and an ipsilateral prophylactic or therapeutic modified (functional) radical neck dissection when the primary tumor is greater than 1 cm and when the central neck nodes are positive. A prophylactic contralateral neck dissection should be done when the primary tumor is bilateral and when there is extensive lymphadenopathy on the side of the primary tumor. Patients who have gross, unresectable residual medullary thyroid cancer should receive postoperative external radiotherapy. Patients who are carriers of germ-line RET proto-oncogene point mutations or have an elevated (basal or stimulated) calcitonin levels on screening should have a prophylactic total thyroidectomy before age 6 years. In patients with an elevated basal or stimulated plasma calcitonin level and an intrathyroidal nodule on ultrasound, a total thyroidectomy and central neck lymph node dissection should be done. Patients with persistent or recurrent medullary thyroid cancer should have a complete thyroidectomy (if not done initially) and bilateral central and modified radical neck dissection, including upper mediastinal lymphadenectomy. Patients who are symptomatic from distant medullary thyroid cancer metastases (diarrhea, flushing, weight loss, or bone pain) should be treated with somatostatin analogs. Bone metastases should be resected if possible, and symptomatic lesions that are unresectable should be treated with external radiotherapy. Cytoreductive procedures such as radiofrequency ablation or cryoablation for liver metastases should be considered in symptomatic patients to reduce tumor burden. Localized pulmonary metastases should be resected. Chemotherapy or radioactive immunotherapy (iodine 131 labeled carcinoembryonic antigen monoclonal antibody) protocols should be considered in patients with nonoperative widely metastatic progressing medullary thyroid cancer.

Antineoplastic Agents↗
PubMed2000

The helix-loop-helix transcription factor, Id-1, is overexpressed in medullary thyroid cancer.

BACKGROUND: The Id-1 helix-loop-helix protein inhibits differentiation and enhances cell proliferation. It is required for cell cycle progression. The Id-1 gene is highly expressed in a variety of tumor-derived cell lines. It increases after mitogen stimulation and is overexpressed in some human neoplasms. Therefore, we hypothesized that the Id-1 gene may play a role in medullary thyroid carcinogenesis. METHODS: The expression of the Id-1 protein in human medullary thyroid cancer (MTC) and the corresponding normal thyroid tissue was determined by Id-1 immunohistochemistry. In a human MTC cell line (TT), the effects of growth stimulation and redifferentiation on Id-1 expression were determined by Northern blot analysis. RESULTS: Id-1 immunostaining intensity in 9 MTC samples (6 sporadic, 2 familial, and 1 MEN 2A) was moderate to strong. However, it was absent or faint in the corresponding normal thyroid tissue. The Id-1 protein was significantly overexpressed in MTC compared with corresponding normal thyroid tissue on the basis of the percentage of positive cells and immunostaining intensity (P =.002). In the TT cell line, Id-1 messenger RNA (mRNA) expression was increased 4-fold after growth stimulation with serum. Phorbol ester (which induces redifferentiation in the TT cell line) downregulated Id-1 mRNA expression. CONCLUSIONS: Id-1 is overexpressed in MTC. The Id-1 gene may play a role in the regulation of MTC differentiation and proliferation.

Adult↗
PubMed1999

Normal thyroid pathology in patients undergoing thyroidectomy for finding a RETgene germline mutation: a report of three cases and review of the literature.

Genetic screening for germline RET proto-oncogene mutation in hereditary medullary thyroid cancer (MTC) is accurate and allows for preventive total thyroidectomy to be performed early in patients who are gene carriers. We report 3 children who underwent preventive total thyroidectomy based on the finding of a RETgene germline mutation, but who had no evidence of MTC or C-cell hyperplasia on permanent histology, even after calcitonin immunostaining. Review of the English literature of patients undergoing preventive thyroidectomy for a positive RETgene germline mutation, shows that 3.4% of these patients (a total of 209 patients) had normal thyroid glands. Also, 8.6% of patients undergoing preventive total thyroidectomy with prophylactic central neck node dissection had cervical node metastases. We conclude that preventive thyroidectomy in patients screened early for germline RETgene mutation allows for earlier diagnosis and treatment of patients, sometimes even before any hyperplasia or neoplasia can be demonstrated because cervical node metastases can occur early and be demonstrated even with small tumors (< 1 cm), we recommend prophylactic central neck node dissection at the time of preventive thyroidectomy.

Adolescent↗
PubMed1999

Phenylacetate inhibits growth and vascular endothelial growth factor secretion in human thyroid carcinoma cells and modulates their differentiated function.

There is increasing evidence that phenylacetate inhibits growth and modulates differentiation in a variety of tumors with effects on gene expression, and protein prenylation and glycosylation at concentrations that have been safely used in humans. We evaluated the antineoplastic effects of phenylacetate in five thyroid cancer cell lines of follicular cell origin in vitro. We found early growth inhibition occurred with phenylacetate treatment at a dose of 2.5-10 mmol/L. The growth inhibition was cytostatic with the thyroid carcinoma cells arrested in the G0-1 cell phase. When evaluating the effect of phenylacetate on the differentiated functions of thyroid carcinoma cells, phenylacetate exposure: 1) decreased the TSH (10 mU/mL) growth response; 2) increased radioactive iodine (125I) uptake in two out of five cell lines; and 3) inhibited thyroglobulin secretion. Phenylacetate also inhibited the secretion of vascular endothelial growth factor (a glycoprotein dependent on glycosylation for efficient cellular excretion) from the thyroid cancer cell lines. Our results support that phenylacetate has an antiproliferative effect in many cell types, but the differentiating effects were not uniform. Importantly, we have identified that phenylacetate inhibits the secretion of vascular endothelial growth factor, which possibly mediates the antiangiogenic effects observed in vivo. Because of the minimal toxicity associated with phenylacetate treatment in humans, at concentrations we show to have a significant antineoplastic effect in thyroid carcinoma cells, phenylacetate could be useful in patients with differentiated thyroid cancer who fail conventional therapy or as an adjuvant to radioactive iodine therapy in patients with aggressive tumors.

Antineoplastic Agents↗
PubMed1998

Benign and malignant pheochromocytoma: diagnosis, treatment, and follow-Up.

The clinical manifestation of pheochromocytoma is presented with specific emphasis on accurate diagnostic approach. The sensitivity, specificity, and indication of localizing studies of pheochromocytomas are reviewed. Management of benign and malignant pheochromocytomas are discussed with follow-up recommendations.

Adrenal Gland Neoplasms↗