Biomedical subjects

Electron Kebebew

Publications and source records attributed to Electron Kebebew.

At least 37 records · Page 2Linked to original sources

PubMed2005

Id1 gene expression and regulation in human thyroid tissue.

The Id genes encode helix-loop-helix (HLH) transcription proteins that lack a DNA binding basic domain. Id proteins (Id1, Id2, Id3, and Id4) function as dominant negative regulators of basic HLH transcription factors by forming inactive heterodimers. Recent studies suggest that the Id proteins participate in the regulation of cell growth, differentiation, tumorigenesis and angiogenesis in a variety of cell types. This report summarizes studies done in our laboratory on the expression and regulation of the Id1 gene in human thyroid tissue, the result of activation of the major mitogen signal transduction pathways on Id1 gene expression, and the effect of the Id1 gene on thyroid cancer cell growth and differentiation.

Base Sequence↗

PubMed2005

Should total thyroidectomy become the preferred procedure for surgical management of Graves' disease?

This study aims to evaluate our institution's experience with thyroidectomy for Graves' disease, with an emphasis on indications and long-term outcomes. The study cohort consisted of 103 patients (mean age 34.3 [+/-13.9] years), who underwent thyroidectomy for Graves' disease between 1991 and 2002. Clinical and follow-up data were obtained by retrospective review of medical records and by contacting treating physicians or patients. The most common surgical indications were patient preference (26%), cold nodule (24%), eye symptoms (20%), large goiter size (18%), allergy to antithyroidal medications (15%), and age younger than 16 years (14%). Thyroidectomies performed included 45 (total or near-total), 57 subtotal, and 1 lobectomy. Transient complications included hypocalcemia in 42 patients, and recurrent laryngeal nerve palsy in 5 patients. There was no difference in the frequency of hypocalcemia in patients undergoing total or subtotal resections. One patient developed permanent hypocalcemia and 2 permanent recurrent laryngeal nerve (RLN) injury. Only 3 patients who underwent subtotal resections remain off thyroxine and 2 developed recurrent hyperthyroidism approximately 17 and 54 months after surgery. Subtotal thyroidectomy is associated with a high rate of hypothyroidism and large remnants have potential for recurrence. Total or near-total thyroidectomy obviates these disadvantages and can be performed without increased complication rates, thus appearing to be the preferred extent of thyroidectomy for Graves' disease.

Adolescent↗

PubMed2005

ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy.

OBJECTIVE: The objective of this study was to determine whether genes that regulate cellular invasion and metastasis are differentially expressed and could serve as diagnostic markers of malignant thyroid nodules. SUMMARY AND BACKGROUND DATA: Patients whose thyroid nodules have indeterminate or suspicious cytologic features on fine needle aspiration (FNA) biopsy require thyroidectomy because of a 20% to 30% risk of thyroid cancer. Cell invasion and metastasis is a hallmark of malignant phenotype; therefore, genes that regulate these processes might be differentially expressed and could serve as diagnostic markers of malignancy. METHODS: Differentially expressed genes (2-fold higher or lower) in malignant versus benign thyroid neoplasms were identified by extracellular matrix and adhesion molecule cDNA array analysis and confirmed by real-time quantitative polymerase chain reaction (PCR). The area under the receiver operating characteristic (AUC) curve was calculated to determine diagnostic accuracy of gene expression level cutoffs established by logistic regression analysis. RESULTS: By cDNA array analysis, ADAMTS8, ECM1, MMP8, PLAU, SELP, and TMPRSS4 were upregulated, and by quantitative PCR, ECM1, SELP, and TMPRSS4 mRNA expression was higher in malignant (n = 57) than in benign (n = 38) thyroid neoplasms (P< 0.002). ECM1 and TMPRSS4 mRNA expression levels were independent predictors of a malignant thyroid neoplasm (P < 0.003). The AUC was 0.956 for ECM1 and 0.926 for TMPRSS4. Combining both markers improved their diagnostic use (AUC 0.985; sensitivity, 91.7%; specificity, 89.8%; positive predictive value, 85.7%; negative predictive value, 82.8%). ECM1 and TMPRSS4 expression analysis improved the diagnostic accuracy of FNA biopsy in 35 of 38 indeterminate or suspicious results. The level of ECM1 mRNA expression was higher in TNM stage I differentiated thyroid cancers than in stage II and III tumors (P < or = 0.031). CONCLUSIONS: ECM1 and TMPRSS4 are excellent diagnostic markers of malignant thyroid nodules and may be used to improve the diagnostic accuracy of FNA biopsy. ECM1 is also a marker of the extent of disease in differentiated thyroid cancers.

Biomarkers, Tumor↗

PubMed2004

Prognostic indications for Hürthle cell cancer.

Hürthle cell carcinoma (HCC) has been reported to have variable clinical behavior. The objective of this study was to determine the important prognostic factors in patients with HCC. It was a retrospective investigation of 33 patients with HCC treated in our institution from 1976 to 2002. The average age of our 33 patients with HCC was 55.2 years (range 20-82 years; 23 women, 10 men). Fifteen patients (45.5%) presented with a T2 tumor, 7 (21.2%) with a T3 tumor, and 8 (24.2%) with a T4 tumor; the tumor stage was unknown in three patients. Coexisting papillary carcinoma occurred in six patients (18%), 9% of whom presented with metastatic disease. Twelve patients (36.4%) had metastases, four of whom (12.2%) had persistent HCC, and 8 (24.2%) developed recurrent HCC (range 1-9 years). Eight of these twelve patients (66.7%) died from the HCC. The average follow-up time was 5.5 years (range 1-16 years). Altogether, 3 of 23 women and 5 of 10 men died from their HCC ( p < 0.05). Of the 22 patients with T2-T3 tumors, 5 (22.7%) developed metastases and 1 patient died; 5 of 8 patients (62.5%) with T4 tumors developed metastases and died ( p < 0.01). Patients who were treated by less than total thyroidectomy had a worse prognosis by univariate analysis ( p < 0.01) but not by multivariate analysis. Survival time for patients with persistent disease was shorter than for those with recurrent disease ( p < 0.05). Multivariate analysis, however, revealed no difference for extent of operation or those with persistent and recurrent disease. The cause-specific survivals were 74% and 49% at 5 and 10 years, respectively. Disease-free survivals were 65.0% and 40.5% at 5 and 10 years, respectively. Our findings show that gender and stage of disease influence the prognosis of patients with HCC.

Adenoma, Oxyphilic↗

PubMed2004

Predictors of airway complications after thyroidectomy for substernal goiter.

HYPOTHESIS: Airway complications after thyroidectomy for substernal goiter can be predicted by preoperative symptom profiles, radiologic findings, or other factors. DESIGN: Retrospective review. Settings A university tertiary care center and a veterans' hospital. PATIENTS: Sixty patients with substernal goiter who underwent thyroidectomy between 1993 and 2002. MAIN OUTCOME MEASURES: Symptoms, preoperative radiologic findings, extent of thyroid resection, tumor size, and postoperative complications. RESULTS: Dysphagia was the most common preoperative symptom (n = 26), followed by dyspnea (n = 21), orthopnea (n = 13), and hoarseness (n = 6); 18 patients (30%) had superior vena caval obstruction. Thirteen patients (22%) were asymptomatic. Preoperative imaging identified tracheal deviation or compression in 45 patients (75%). Substernal goiter was resected via a cervical approach in 59 patients (98%). Of 47 patients with preoperative symptoms, 41 (87%) reported improvement postoperatively. Seven patients (12%) had postoperative airway complications: 1 developed a neck hematoma requiring reoperation, and 6 could not be immediately extubated; all 6 were successfully extubated after 1 to 10 days. Patients with airway complications were older (mean +/- SEM, 70.3 +/- 3.6 years vs 61.5 +/- 2.2 years), had larger goiters (mean +/- SEM, 210.7 +/- 37.0 g vs 112.2 +/- 7.7 g), and were more likely to have tracheal compression on preoperative imaging than those who did not have complications (P<.05). CONCLUSIONS: Most patients with substernal goiters underwent thyroid resection via a cervical approach with an improvement in symptoms. The few patients who developed postoperative airway complications were older, had larger goiters, and were more likely to have tracheal compression on preoperative imaging than those without airway complications.

Age Factors↗

PubMed2004

Tertiary hyperparathyroidism: histologic patterns of disease and results of parathyroidectomy.

HYPOTHESIS: Patients with tertiary hyperparathyroidism (THPT) commonly have parathyroid hyperplasia and should have a bilateral neck exploration with subtotal or total parathyroidectomy with autotransplantation to obtain long-term cure. DESIGN: A retrospective cohort study. SETTING: Tertiary referral medical center. PATIENTS: Thirty-four consecutive patients (21 women and 13 men; mean age, 48 years) who underwent neck exploration for THPT. MAIN OUTCOME MEASURES: Sites and histologic pattern of parathyroid disease, and postoperative normalization of serum calcium and parathyroid hormone levels. RESULTS: Twenty-seven patients underwent initial bilateral neck exploration and 7 patients underwent repeat neck exploration for persistent or recurrent THPT. The mean serum total calcium level was 11.2 mg/dL (2.8 mmol/L) (range, 10.3-13.5 mg/dL [2.6-3.4 mmol/L]) and the mean intact parathyroid hormone level was 355 ng/L (range, 95-1236 ng/L). The THPT was due to 4-gland hyperplasia in 33 patients and a single adenoma in only 1 patient. The parathyroid glands were in the normal position in 23 patients and in ectopic locations in 11 patients (8 intrathymic, 1 carotid sheath, 1 tracheoesophageal groove, and 1 intramuscular). Preoperative localizing studies did not identify ectopic or supernumerary glands in any of the patients (ultrasonography, 14 patients; technetium Tc 99m sestamibi, 15; and magnetic resonance imaging, 7). Persistent (n = 5) and recurrent (n = 2) THPT was more common in patients who had an initial 1- or 2-gland excision instead of subtotal or total parathyroidectomy with autotransplantation (P<.001). Four patients had transient hypocalcemia (<8.0 mg/dL [<2.0 mmol/L]), and no other permanent complications or deaths occurred. Biochemical cure was achieved in 94% of patients with a mean follow-up of 4.8 years. CONCLUSIONS: Tertiary hyperparathyroidism is usually due to multiple hyperplastic parathyroid glands, and patients who have initial limited parathyroidectomy have a higher risk of persistent or recurrent THPT.

Adolescent↗

PubMed2004

Reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy: review of 261 laparoscopic adrenalectomies from 1993 to 2003.

Over the past decade, laparoscopic adrenalectomy has become the operation of choice for resecting adrenal tumors. However, few reported data exist regarding the reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy. We retrospectively reviewed the records of 261 consecutive laparoscopic adrenalectomies performed by one surgeon between 1993 and 2003. Laparoscopic adrenalectomy could not be completed in 8 of the 261 patients (3%); four of the operations were converted to hand-assisted laparoscopic adrenalectomy and four to open adrenalectomy. The reasons for the conversion were as follows: In three patients the tumor was too adherent to surrounding structures to be resected laparoscopically; in three patients the tumor was found to have malignant features during laparoscopy, and the operation was converted to achieve proper resection margins; in two patients the tumors were too large (15 and 16 cm, respectively) to be safely removed laparoscopically. The eight resected tumors included three pheochromocytomas, one myelolipoma, one angiomyolipoma, one solitary fibrous tumor, one liposarcoma, and one metastatic hepatocellular carcinoma. There were no cases in which conversion was required emergently for bleeding or other intraoperative catastrophes. All eight of the tumors removed were at least 5 cm in size (range 5-16 cm). The mean length of hospitalization was 4.4 days (range 3-8 days).

Adrenal Gland Neoplasms↗

PubMed2004

Multiple endocrine neoplasia type 2.

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome that is transmitted in an autosomal dominant pattern. MEN-2A, MEN-2B, and familial medullary thyroid cancer (MTC) comprise the MEN-2 syndrome. A germline mutation in the RET proto-oncogene is responsible for the MEN-2 syndrome. Recent data indicate that in 99% of MEN-2 cases, a germline RET mutation can be identified by genetic testing. The phenotypic variation of MEN-2 is diverse and partly related to the codon and specific point mutation in the RET proto-oncogene. There are increasing data on the genotype-phenotype correlations in patients with MEN-2 and this information should be used for screening at-risk patients and treatment of RET mutation carriers. All patients (especially if young) with MTC or bilateral pheochromocytoma should have a careful family history taken and genetic screening for RET germline mutations. Patients who are RET germline mutation carriers but without clinical or biochemical evidence of MTC should have a prophylactic total thyroidectomy. The optimal age of thyroidectomy should be based on the RET genotype (eg, high-risk mutations within the first year of life, intermediate-risk mutations by 5 years of age, and low-risk mutations by 10 years of age). Patients who are diagnosed with clinical or biochemical evidence of MTC should have a total or a near total thyroidectomy and at least a central neck lymph node dissection. Patients who have pheochromocytoma and a unilateral adrenal tumor on a localizing study should have a unilateral laparoscopic adrenalectomy after preoperative alpha-blockade. However, patients with bilateral adrenal tumors on localizing studies should have bilateral laparoscopic adrenalectomy. A cortical-sparing (subtotal) adrenalectomy may be considered, if technically feasible, to avoid long-term steroid dependence and to reduce the risk of Addisonian crisis. Patients with biochemical evidence of primary hyperparathyroidism should have a bilateral neck exploration and total parathyroidectomy and autotransplantation (30-60 mg of the most normal parathyroid tissue) to the nondominant forearm if asymmetric parathyroid hyperplasia is present. Rarely, patients may have only single-gland disease and excision may be performed if the other parathyroid glands are not found with biopsy to be hyperplastic. All unresected parathyroid glands should be marked with a clip because patients with MEN-2A have a high risk of persistent and recurrent primary hyperparathyroidism. Patients with familial MTC may have not manifested the other features of MEN-2A, thus these patients should have continued follow-up for pheochromocytoma and primary hyperparathyroidism.

Adrenal Gland Neoplasms↗

PubMed2004

Laparoscopic adrenalectomy for malignancy.

Laparoscopic adrenalectomy for primary malignancies and tumors metastatic to the adrenal is controversial. Most studies demonstrate that results of laparoscopic adrenalectomy for malignant lesions are similar to those of open adrenalectomy, without its morbidity. The results of laparoscopic adrenalectomy for tumor metastases suggest that it may benefit patients who have a metachronous metastasis from any of a variety of primary tumors. Selective laparoscopic adrenalectomy for potentially malignant tumors requires seeking signs of local invasion, lymphadenopathy, or distant metastasis; there are no other reliable preoperative criteria of malignancy. Diagnostic laparoscopy may be useful, and in some cases, may establish a diagnosis. Laparoscopic adrenalectomy should be cautiously performed, with the goals of achieving complete tumor resection without disruption of the adrenal capsule.

Adrenal Gland Neoplasms↗

PubMed2004

Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas.

BACKGROUND: Diagnostic tests cannot reliably distinguish malignant from benign pheochromocytomas. Laparoscopic adrenalectomy for pheochromocytomas >6 cm is controversial because of a perceived increased risk of malignancy that is based on anecdotal reports and small series. The aim of this study was to determine if pheochromocytoma size should affect the choice of surgical approach. METHODS: Malignant pheochromocytomas in the Surveillance Epidemiology and End Results (SEER) database (1988-2000) were compared to benign pheochromocytomas in our institutional database (1993-2003). The sensitivity, specificity and likelihood ratio for tumor size to predict malignancy were calculated for both groups. RESULTS: Ninety malignant and 60 benign pheochromocytomas were compared. Overall, malignant pheochromocytomas were larger than benign pheochromocytomas (7.6 +/- 4.2 cm vs 5.3 +/- 2.3 cm). However, tumor size was not significantly different between malignant pheochromocytomas without local invasion or metastases and benign pheochromocytomas (6.1 +/- 3.1 cm vs 5.3 +/- 2.3 cm). In pheochromocytomas with local disease only, maximum likelihood ratio to predict malignancy was at a tumor size of greater than 8 cm (2.84). CONCLUSIONS: Although risk of malignancy increases with size for all pheochromocytomas, size does not reliably predict malignancy in pheochromocytomas with local disease only. Regardless of tumor size, laparoscopic adrenalectomy for pheochromocytoma should be converted to open adrenalectomy for difficult dissection, invasion, adhesions, or surgeon inexperience.

Adolescent↗

PubMed2004

GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism.

BACKGROUND: The glial cell missing gene, GCMB , encodes a transcription factor, which is a master regulator of parathyroid development. We postulated that the GCMB gene might play a role in parathyroid tumorigenesis in hyperparathyroidism. METHODS: We used real-time quantitative reverse transcriptase polymerase chain reaction to study GCMB mRNA expression in parathyroid tissue: normal (n = 3), hyperplastic (n = 16), adenomas (n = 19), and cancers (n = 8). In primary parathyroid culture, the effect of CaCl 2 on parathyroid hormone secretion and GCMB mRNA expression was studied by using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction, respectively. RESULTS: GCMB mRNA expression was lower in normal (0.4 +/- 0.1, mean +/- standard error of mean) parathyroid glands as compared to adenoma (3.5 +/- 1.7), hyperplasia (3.2 +/- 1.3 primary hyperparathyroidism [n = 11] and 7.6 +/- 4.8 secondary hyperparathyroidism [n = 5]), and cancer (3.6 +/- 1.3) ( P = .001). There was no difference in the level of GCMB mRNA expression between parathyroid adenoma, hyperplasia, and cancer. In primary culture of parathyroid adenoma (n = 9) and hyperplasia (n = 2), parathyroid hormone secretion was increased 2- to 15-fold with low calcium concentration (0.5 to 4.0 mmol/L CaCl 2 from 2 to 6 hours, P < .005). The level of GCMB mRNA expression was down-regulated with lower extracellular CaCl 2 concentration ( P < .005). CONCLUSIONS: GCMB expression is upregulated in abnormal parathyroid glands of hyperparathyroidism and decreases in response to hypocalcemia. The GCMB transcription factor might mediate the effect of calcium on parathyroid cell parathyroid hormone expression/secretion.

Adenoma↗

PubMed2004

Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid cancer cells.

The Id (inhibitor of DNA binding) proteins are a family of helix-loop-helix (HLH) proteins (Id1, Id2, Id3, and Id4) that lack the basic domain necessary for DNA binding. The Id1 protein enhances cell proliferation and inhibits cellular differentiation in a variety of cell types. We have previously demonstrated that the Id1 gene is up-regulated in papillary and medullary thyroid cancers. In this study we characterized the expression and distribution of the Id1 protein in normal, hyperplastic, and neoplastic human thyroid tissue. We also evaluated the effect of the Id1 gene on thyroid cancer cell growth and markers of thyroid cell differentiation. We used semiquantitative immunohistochemistry to characterize Id1 protein expression in normal, hyperplastic (multinodular goiter and Graves' disease), and neoplastic thyroid tissue from 103 patients. Normal thyroid tissue had the lowest level of Id1 protein expression (P < 0.0001). Anaplastic thyroid cancer had the highest level (vs. benign and malignant thyroid tissues, P < 0.01). Id1 protein expression was higher in malignant thyroid tissue than in hyperplastic thyroid tissue (P < 0.02). We found no significant association between the level of Id1 protein expression and patient age, sex, tumor-node-metastasis stage, tumor size, primary tumor vs. lymph node metastasis, primary tumor vs. recurrent tumors, and extent of tumor differentiation. Inhibiting Id1 mRNA expression in thyroid cancer cell lines using Id1 antisense oligonucleotides resulted in growth inhibition (P < 0.03) and decreased thyroglobulin and sodium-iodine symporter mRNA expression (P < 0.02). In conclusion, Id1 is overexpressed in hyperplastic and neoplastic thyroid tissue and directly regulates the growth of thyroid cancer cells of follicular cell origin, but is not a marker of aggressive phenotype in differentiated thyroid cancer.

Adult↗

PubMed2003

Parathyroidectomy for primary hyperparathyroidism in octogenarians and nonagenarians: a plea for early surgical referral.

BACKGROUND: Surgical referral of elderly patients with PHPT is often deferred because of the perceived risks of general anesthesia, increased age, and comorbidities and also because many of the symptoms of PHPT are difficult to distinguish from the aging process. HYPOTHESIS: Parathyroidectomy for primary hyperparathyroidism (PHPT) in elderly patients is beneficial and safe. DESIGN: Retrospective study of patients with PHPT who were 80 years and older. SETTING: Tertiary academic referral medical center. PATIENTS: Fifty-four consecutive patients (43 women and 11 men) with a mean age of 83.6 years who underwent parathyroidectomy for PHPT. MAIN OUTCOME MEASURES: Delay in surgical referral; improvement in symptoms and normalization of serum calcium and parathyroid hormone levels; and perioperative morbidity and mortality. RESULTS: Twelve (22%) of 54 patients had a mean delay of 5 years (range, 1.2-10.0 years) before surgical referral for a known diagnosis of PHPT. No patient had asymptomatic PHPT. There was no significant difference in the preoperative mean serum calcium level and symptoms of PHPT resulting from delay in surgical referral. Parathyroidectomy resulted in significant improvement of PHPT-associated symptoms of fatigue, weight loss, nocturia, bone pain, constipation, and major depression (P<.05). All patients had normal serum calcium and parathyroid hormone levels postoperatively. The average length of hospitalization was 1.9 days. There were 3 complications (9%): 1 urinary tract infection, 1 bladder perforation, and 3 transient hypocalcemia. There was no perioperative mortality. CONCLUSIONS: Parathyroidectomy in elderly patients is safe, curative, and beneficial. Surgical referral for parathyroidectomy should be considered in elderly patients with PHPT.

Aged↗

PubMed2003

Locally advanced differentiated thyroid cancer.

Although most patients with differentiated thyroid cancer (DTC) of follicular cell origin enjoy a relatively good prognosis, some patients unfortunately present with or develop locally advanced DTC which leads to significant local morbidity and mortality. DTC accounts for 54-94% of all locally advanced thyroid cancers. DTC invasion of the recurrent laryngeal nerve, strap muscles and trachea are the most common followed by invasion of the esophagus, internal jugular vein and carotid artery. Surgical resection is the primary treatment for locally advanced DTC. Although the optimal surgical approach (ranging from conservative shave excision to aggressive en bloc resection of tumor and vital structures) in patients with locally advanced DTC is controversial, a curative resection should be the goal unless complete tumor resection results in unwanted perioperative morbidity and mortality or widely metastatic disease is present. Postoperative radioiodine ablation with TSH suppression is imperative after surgical resection of locally advanced DTC. Patients with microscopic or small gross residual disease, after surgical resection, may benefit from postoperative external radiotherapy for local control of disease.

Chemotherapy, Adjuvant↗

PubMed2003

Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma.

BACKGROUND: The purpose of this retrospective investigation was to evaluate the results of preoperative localization studies and intraoperative parathyroid hormone (IOPTH) assay in patients with primary hyperparathyroidism and double adenomas. STUDY DESIGN: Twenty-one of 287 consecutive patients with primary hyperparathyroidism who had double adenomas identified during first-time parathyroid exploration between July 1999 and September 2002 were analyzed. Individual and combined accuracy of preoperative localization studies, and IOPTH assay and their influence on surgical strategy, were compared. RESULTS: Seven percent of these 287 patients had double adenomas. Fifteen of the patients were female and six were male with a mean age of 59 years (range 17 to 76 years). The accuracy of ultrasonography (US) and technetium 99m sestamibi ((99m)TC-sestamibi) was 40% and 30%, respectively, in this select group. Combined accuracy of both tests reached 60% and guided the surgeon to select a bilateral approach. After removal of the first gland, IOPTH failed to decrease by 50% relative to the highest baseline value in 43% of the cases, indicating other hyperfunctioning parathyroid glands. These results prompted the surgeon to explore further after an initially planned focused approach. When the combination of three tests was analyzed, at least one test accurately suggested a double adenoma in 80% of the patients; in 15% of the patients, no test was suggestive of a double adenoma and in 5% the sestamibi scan was false positive. CONCLUSIONS: This retrospective investigation documents that neither preoperative localization tests nor IOPTH assay accurately document double adenomas in patients with primary hyperparathyroidism. The combined accuracy of US, sestamibi, and IOPTH assay predicted a double adenoma in 80% of the patients.

Adenoma↗

PubMed2003

The helix-loop-helix protein, Id-1, is overexpressed and regulates growth in papillary thyroid cancer.

BACKGROUND: Members of the Id helix-loop-helix proteins are key regulators of cell growth and differentiation in a variety of cell types. They are also required for cell cycle progression and regulate tumor angiogenesis. Furthermore, deregulated expression of Id proteins has been observed in some human malignancies. Therefore we hypothesized that the Id-1 gene may play a role in papillary thyroid carcinogenesis. METHODS: Id-1 gene expression was characterized by Northern blot analysis and Id-1 immunohistochemistry in human thyroid tissue. Id-1 gene expression and regulation was evaluated in a human papillary thyroid cancer cell line, TPC-1, by Northern blot analysis. RESULTS: The Id-1 gene was significantly overexpressed in papillary thyroid cancer compared with normal thyroid tissue from the same patients (n = 18) by both Northern blot analysis and semiquantitative Id-1 immunohistochemistry (P <.001). Id-1 immunoreactivity was primarily localized to the cytoplasm of the thyroid follicular cells. In the TPC-1 cell line, stimulation by TSH and serum up-regulated Id-1 mRNA expression 1.5- and 4.0-fold, respectively. Activation of the mitogen intracellular protein kinase A and protein kinase C signaling pathways also up-regulated Id-1 mRNA expression. Inhibition of Id-1 mRNA expression with Id-1 antisense oligonucleotide inhibited growth compared with control Id-1 sense and random oligonucleotides (P <.05). CONCLUSIONS: The Id-1 gene is overexpressed in papillary thyroid cancer. Id-1 may play a role in the regulation of growth in papillary thyroid cancer.

Blotting, Northern↗

PubMed2003

Expression of vascular endothelial growth factor-C in benign and malignant thyroid tumors.

In contrast to vascular endothelial growth factor (VEGF), which stimulates angiogenesis, VEGF-C is thought to stimulate lymphangiogenesis. The role of VEGF-C in thyroid cancer pathogenesis has not been clarified. One might expect a different pattern of VEGF-C expression in the various types of thyroid cancer because of their different means of metastases. In this investigation, we determined whether the differential expression of VEGF-C might explain the different propensity to lymph node metastasis in thyroid cancers. One hundred eleven normal and neoplastic thyroid tissues were analyzed by real-time quantitative PCR. Papillary thyroid cancers had a higher VEGF-C expression than other thyroid malignancies (P < 0.0005 ANOVA). Among the normal thyroid tissues from patients with malignant or benign thyroid diseases, there was no significant difference in VEGF-C expression. Paired comparison of VEGF-C expression between thyroid cancers and normal thyroid tissues from the same patients showed a significant increase of VEGF-C expression in papillary thyroid cancer (1.10 +/- 0.41 vs. 0.70 +/- 0.13; P = 0.001) and a significant decrease of VEGF-C expression in medullary thyroid cancer (0.11 +/- 0.13 vs. 0.78 +/- 0.29; P = 0.001). In contrast, there was no significant difference of VEGF-C expression between cancer and normal tissues in other types of thyroid cancer. In summary, VEGF-C expression is increased in papillary thyroid cancer, compared with paired normal thyroid tissues, but not in other thyroid cancers that are also prone to lymph node metastasis. The lymphangiogenic role of VEGF-C in thyroid cancers therefore appears to be complex and other factors are likely to be also involved.

Carcinoma, Papillary↗

PubMed2002

Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms.

BACKGROUND: Laparoscopic resection for malignant adrenal tumors is controversial, because they are rare and limited data exist in the literature. HYPOTHESIS: Laparoscopic adrenalectomy for malignant adrenal tumors is safe and effective. PATIENTS AND METHODS: Twenty-three patients who had a laparoscopic approach for suspected and unsuspected malignant adrenal tumors were studied retrospectively. The adrenal mass was suspected to be metastatic if the patient had a history of previous extra-adrenal primary malignancy and/or positive fine-needle aspiration cytologic findings. A primary adrenal cancer was suspected if there were positive fine-needle aspiration cytologic findings and/or a malignant adrenal imaging phenotype. MAIN OUTCOME MEASURES: (1) Margins of tumor resection, (2) tumor recurrence (locoregional, port site, and distant), and (3) disease-free survival. RESULTS: Twenty-three patients (15 men and 8 women) had 24 laparoscopic procedures (20 adrenalectomies, 3 biopsies, and 1 diagnostic laparoscopy). Permanent histologic specimens in the 23 patients showed 5 adrenocortical cancers, 1 undifferentiated adrenal cancer, 13 adrenal metastases, 2 lymphomas, and 2 cases with no evidence of tumor. Clinically suspected adrenal metastases were true positive in 19 patients (83%). The sensitivity of fine-needle aspiration cytology was 57% (n = 7). Only 1 of 6 patients with primary adrenal cancer was suspected to have a malignant tumor preoperatively. The tumor resection margin was negative in all adrenalectomies. There were 3 locoregional recurrences (2 local and 1 lymph node metastasis) in the 6 patients with primary adrenal cancer, no port site recurrences, and 4 distant recurrences in 13 patients with metastatic adrenal tumors. The disease-free survival was 65% at a mean follow-up time of 3.3 years (range, 1-7 years). CONCLUSIONS: A laparoscopic approach in patients with suspected adrenal metastasis can be both diagnostic and therapeutic, and achieves complete tumor resection. In contrast, laparoscopic adrenalectomy for clinically unsuspected adrenocortical cancer is associated with a high recurrence rate. Furthermore, preoperative fine-needle aspiration cytology for the evaluation of suspected malignant adrenal tumors is unreliable.

Adrenal Gland Neoplasms↗