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O H Clark

Publications and source records attributed to O H Clark.

At least 19 recordsLinked to original sources

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↗

Parathyroid surgery: we still need traditional and selective approaches.

Since the first parathyroidectomy in 1925, the traditional bilateral cervical approach has been the gold standard surgical treatment for patients with primary hyperparathyroidism, with a success rate >95%. Over the past decade, the focus on minimally invasive surgery has led to the development of several innovative approaches to the parathyroid glands including the focused, radio-guided, video-assisted and videoscopic parathyroidectomy. Improvements in pre-operative parathyroid localization studies as well as the use of the intraoperative PTH assay have made these minimally invasive approaches possible, and they have been proven to be safe and effective for the solitary parathyroid adenoma. For patients with multiple gland disease or equivocal localization studies, the traditional bilateral approach remains the standard of care.

Adenoma↗

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↗

Accuracy of fine-needle aspiration cytology in patients with radiation-induced thyroid neoplasms.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is useful for selecting patients with thyroid nodules for thyroidectomy. Its value in patients who have been exposed to low-dose therapeutic radiation is questionable because these patients have an increased risk of multifocal benign and malignant tumours, and thyroid cancer is common in such patients. METHODS: Between 1960 and 1999, 171 patients with one or more thyroid nodules who had a history of exposure to radiation underwent operation; 49 of these patients had preoperative FNAC. The cytology results in these 49 patients were compared with those of an age- and sex-matched control group of patients with thyroid nodules who did not have a history of radiation exposure. RESULTS: Of those who had been exposed to radiation, six of 20 patients with 'benign' cytology by FNAC and six of 16 patients with 'suspicious' cytology had thyroid cancer. All 13 specimens considered to be malignant on FNAC were indeed malignant. There was a higher rate of false-negative cytological examinations among patients with a history of irradiation that in those without. CONCLUSION: FNAC of thyroid nodules in patients with a history of irradiation is not as accurate as that in non-irradiated patients, primarily because of coexisting occult thyroid cancers.

Biopsy, Needle↗

Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing apoptosis-related genes.

Oxyphilic tumors of the thyroid are characterized by mitochondrion-rich cells and extensive DNA fragmentation. In order to clarify if a different expression of apoptosis-related genes could be responsible for DNA fragmentation in oxyphilic cell tumors, two thyroid follicular carcinoma-derived cell lines, having oxyphilic (XTC.UC1) and non-oxyphilic (WRO) features, were compared applying a gene array technique. Under basal culture conditions, several pro-apoptotic genes [caspases 3 and 10, Fas and the tumor necrosis factor-related apoptosis-inducing ligand (trail) genes] were switched on in oxyphilic, but not in non-oxyphilic cells. No difference in the mitochondrial apoptosis-related genes (bax, bad, bcl family etc.) was observed. Using the ISEL technique, the extent of DNA fragmentation did not differ under basal conditions in the two cell lines. Conversely, following an oxidative pro-apoptotic stress (6-h methylene blue treatment and light exposure), XTC.UC1 cells showed an extensive DNA fragmentation (up to 70% of cells), dramatically exceeding that observed in WRO cells (up to 20% of cells). In contrast, the oxidative stimulus induced a remarkable apoptosis gene activation in non-oxyphilic WRO cells only. These results suggest that oxyphilic cells may have a unique silent activation of a pro-apoptotic phenotype, which could be responsible for DNA instability and lead to cell death as the consequence of an increased sensitivity to ischemic stresses, as frequently observed in vivo.

Adenocarcinoma↗

A critical analysis of intraoperative time utilization in laparoscopic adrenalectomy.

BACKGROUND: Time and efficiency analysis is a technique common in industry that is being applied to surgical procedures. The aim of this study is to analyze the time spent performing the component parts of laparoscopic adrenalectomy by both the lateral transabdominal and the posterior retroperitoneal approaches. METHODS: Operational videotapes of 33 patients undergoing laparoscopic adrenalectomy (12 lateral, 21 posterior) were reviewed. The operation was divided into six steps: trocar entry, laparoscopic ultrasonography, exposure of the adrenal gland, dissection of the adrenal, extraction of specimen, and irrigation-aspiration. Time spent for each step and the relation with age, gender, body mass index (BMI), tumor size, side, and histology were assessed using Student's t-test, Pearson correlation, and regression analysis. RESULTS: Although tumor size was larger in the lateral compared to the posterior approach (5.5 vs 2.5 cm, p < 0.001), there was no difference between the groups regarding total operating time (116.1 vs 112.8 min). Most of the operating time was spent on dissection of the adrenal gland with both techniques (lateral, 60%; posterior, 66%). Exposure of the adrenal gland was longer in the lateral compared to the posterior approach (15.1 vs 5.8 min, respectively; p < 0.05). In the transabdominal technique, this step was longer on the right side than on the left (18.9 vs 11.4 min, respectively; p < 0.05). In the lateral approach, dissection time was dependent on tumor size (r = 0.90, p < 0.05) but not on BMI, whereas in the posterior approach both tumor size and BMI were positively correlated (r = 0.56 and r = 0.64, respectively). CONCLUSIONS: To our knowledge, this is the first study to apply time analysis techniques to laparoscopic adrenal surgery. Understanding the variables that affect operative time may influence the choice of the surgical approach in a given patient. This study also suggests that efforts to improve operative efficiency are best directed at the dissection of the adrenal.

Adrenalectomy↗

Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival.

BACKGROUND: The prognosis of anaplastic thyroid carcinoma (ATC) has been dismal. The objective of this study was to identify prognostic factors in patients who had prolonged survival. METHODS: Patients with ATC were identified from a computer database at a tertiary referral center. Univariate and multivariate analyses for survival differences were performed using the Kaplan-Meier log-rank statistic and the Cox proportional hazards model, respectively. RESULTS: Of the 33 evaluable patients, median survival was 3.8 months. Median age was 69 years. Prior goiter was present in 6 patients (18%), and 6 (18%) had prior thyroid carcinoma. Median tumor size was 6 cm, and 12 (36%) had adjacent well-differentiated carcinoma. Of the 26 patients who underwent neck exploration, 8 patients were potentially cured and received postoperative chemotherapy and irradiation; 4 (50%) were surgically macroscopically free of disease, and 4 (50%) patients had minimal residual disease after total thyroidectomy and resection of tumor adherent to adjacent structures. Four of these 8 patients survived longer than 2 years; their 5-year survival estimate was 50%. Eighteen patients underwent palliative resection of neck disease, leaving macroscopic residual disease or distant metastases; postoperative adjuvant chemotherapy and irradiation were administered in 16 of these 18 patients. Seven patients were treated with only chemotherapy and irradiation. In patients treated with potentially curative resection, median survival was 43 months compared with 3 months with palliative resection (P =0.002); the median survival of 3.3 months with only chemotherapy and irradiation was no different than palliative resection (P =0.63). No association was found between survival and age, prior goiter, prior thyroid carcinoma, adjacent differentiated carcinoma, or tumor size. CONCLUSIONS: Although the prognosis of most patients with ATC continues to be poor, complete resection of ATC combined with postoperative adjuvant chemotherapy and irradiation resulted in long-term survival, even with persistent minimal disease that remained on vital structures. An aggressive attempt at maximal tumor debulking followed by adjuvant therapy was found to be warranted in patients with localized ATC.

Age Factors↗

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↗

Association between residual thyroid carcinoma and diffuse hepatic uptake of 131I following radioiodine ablation in postoperative total thyroidectomy patients.

In patients with differentiated thyroid cancer (DTC) total or near-total thyroidectomy, postoperative 131I ablation, and thyroid suppression therapy are reported to be associated with fewer recurrences than other treatments. Many patients with DTC after total thyroidectomy and radioablation therapy have diffuse hepatic uptake of radioiodine, and its clinical importance is debated. Some investigators report that diffuse liver uptake correlates with uptake in the thyroid bed or the presence of metastatic thyroid cancer somewhere in the body, whereas others note no such correlation. The purpose of this research was to determine the clinical importance of diffuse hepatic uptake of radioiodine after 131I ablative therapy in patients with DTC. We retrospectively reviewed 141 posttherapy scans done in 118 patients with DTC. Patients had had total thyroidectomy and were hypothyroid when serum thyroglobulin (Tg) levels were obtained, and they were treated with 30 to 200 mCi of 131I. Scans were performed 3 to 21 days after radioablation therapy. Information was collected regarding the patients' age and gender, the interval between the ablation therapy and scan, uptake of radioiodine, serum thyroglobulin level, thyroid-stimulating hormone (TSH) level, thyroglobulin antibodies, TNM classification, mortality, and recurrence. Diffuse liver uptake was classified from 0 to 4 depending on hepatic brightness. Radioiodine scans were done to determine whether there was uptake in the thyroid bed or elsewhere. Statistical analyses included analysis of variance and Kaplan-Meier survival analysis. Diffuse hepatic uptake was observed (grades 1-4) in 96.4% of the patients; thus 3.6% had no hepatic uptake. There was no significant association between liver uptake and the uptake in the thyroid bed, the dose of 131I administered for ablation therapy, thyroglobulin levels, age, stage of the disease, presence of local or distant metastases, recurrence, or survival. Diffuse hepatic uptake was therefore not associated with residual normal thyroid or metastases as suggested by some but not all previous investigators.

Adult↗

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↗

Hürthle cell carcinoma.

Patients with Hürthle cell carcinoma (HCC) of the thyroid often have aggressive tumors and generally have a worse prognosis than those with papillary or follicular thyroid carcinomas. A total thyroidectomy with ipsilateral central neck lymphadenectomy and a modified radical neck dissection, if central or lateral nodes are positive, are indicated for HCC. The completeness of this procedure should be assessed by radioiodine scan 3 to 4 months after surgery. Any thyroid remnant should be ablated with radiolabeled iodine 131 to eliminate all tissue at risk and to facilitate the use of serum thyroglobulin in surveillance for tumor recurrence. Fewer than 10% of these cancers take up radioiodine. Recurrent disease is treated surgically with good palliation and appreciable prolongation of life. Local excision and neck dissection for recurrent neck disease or pulmonary wedge resection for lung metastasis has been shown to be effective. All patients with HCC should be given thyroid hormone because most of these tumors have thyrotropin receptors. External beam radiation may be considered for patients with unresectable disease, but this is considered palliative.

Adenoma↗

Can localization studies be used to direct focused parathyroid operations?

BACKGROUND: There is considerable controversy today concerning the most appropriate surgical approach for patients with primary hyperparathyroidism. The conventional surgical operation involves a bilateral neck exploration through a collar incision with identification of all parathyroid tissue and removal of abnormal parathyroid glands while the patient is under general anesthesia. The success rate of this operation is about 95% or greater in the hands of an experienced endocrine surgeon. Preoperative localization techniques are generally considered to be unnecessary before initial parathyroid operations. The purpose of this investigation was (1) to evaluate the individual and combined accuracy of ultrasonography and technetium 99m sestamibi scans in localizing abnormal parathyroid glands and (2) to determine whether such scans could be used to direct a focused operation. METHODS: We retrospectively studied 338 patients with sporadic primary hyperparathyroidism who had preoperative neck localization studies, ultrasonography and/or technetium 99m sestamibi scans, and parathyroid exploration (238 patients or, reexploration, 60 patients) from January 1996 to April 2000 at the University of California San Francisco/Mount Zion Medical Center. The preoperative localization studies were recorded as true-positive, false-positive, and false-negative and compared with the surgical and pathologic findings and with the outcome of the operation. RESULTS: All of the abnormal parathyroid glands were correctly identified by ultrasonography in 184 of 303 patients (60.7%) and by technetium 99m sestamibi scanning in 183 of 237 patients (77.2%). The sensitivities of ultrasonography and sestamibi were 65% and 80%, respectively. Among the 202 patients who received both ultrasonography and sestamibi scans, a parathyroid tumor was identified at the same site in 105 (52%) of them. When both techniques identified a parathyroid tumor at the same site, the tests were correct in 101 of 105 patients and the sensitivity increased to 96%. CONCLUSIONS: When both the ultrasonography and sestamibi scans identified the same, solitary parathyroid tumor in patients with sporadic primary hyperparathyroidism, this was the only abnormal parathyroid gland in 96% of the patients. A focused parathyroidectomy could therefore be performed in such patients with an acceptable ( approximately 95%) success rate.

Adenoma↗

Phenylacetate enhances the antiproliferative effect of retinoic acid in follicular thyroid cancer.

BACKGROUND: Retinoic acid (RA) has antiproliferative as well as redifferentiating effects in thyroid cancers. Similar effects have been seen with phenylacetate (PA) therapy. These observations prompted us to evaluate the potential antiproliferative effects of the combination of RA and PA in follicular thyroid cancer. METHODS: Three follicular cell lines were treated in vitro with varying concentrations of all-trans RA or PA alone or in combination. Growth was measured by dimethyl-thiazol-diphenyltetrazolium bromide assays. RESULTS: RA (1-2.5 micromol/L) and PA (1-10 mmol/L) alone inhibited cell growth in a time- and dose-dependent manner, with maximum effect at 5 days. The combination of RA and PA had synergistic antiproliferative effects. In the FTC-133 cell line, RA alone (2.5 micromol/L) inhibited growth 16% and PA alone (10 mmol/L) inhibited growth 35% versus controls, whereas the combination of the 2 inhibited growth by 60% at 5 days (P < .005). Similar results were seen with FTC-236 and FTC-238 cell lines. CONCLUSIONS: Our results support that RA and PA have antiproliferative effects in follicular thyroid cancer and are synergistic. The combination of RA and PA may be beneficial in the treatment of advanced thyroid cancers for which conventional therapy fails or as an adjuvant to radioactive iodine therapy in aggressive tumors.

Antineoplastic Agents↗

Familial thyroid cancer.

Familial thyroid cancer can arise from parafollicular cells (familial medullary thyroid cancer) or from follicular cells (familial nonmedullary thyroid cancer). Familial medullary thyroid cancer may occur in isolation or as part of multiple endocrine neoplasia (MEN) type II syndromes. Genetic testing for a RET mutation on chromosome 10 is used to identify new family members who are gene carriers. Total thyroidectomy should be used in gene carriers without clinical disease before age 6 in medullary thyroid cancer and MEN type IIA, and as soon as the diagnosis is made in MEN type IIB after the first year of life. Those with clinical disease should have at least a bilateral central neck dissection. Modified radical neck dissection is recommended for patients when the primary tumor is 1.5 cm. A normal postoperative serum calcitonin level suggests that the operation has been curative. Physicians need to be aware of ethical and lifestyle issues related to patients with familial disease and their family members. Familial nonmedullary thyroid cancer occurs as a discrete entity or as part of other family cancer syndromes such as Gardner syndrome, Cowden disease, and other rare syndromes. Familial nonmedullary thyroid cancer almost exclusively includes patients with papillary or Hurthle cell cancers. These families appear to have more benign thyroid conditions. The gene (or genes) for familial papillary thyroid cancer is yet to be identified, whereas that for some Hurthle cells (TCO) has been mapped to chromosome 19p13.2. Familial nonmedullary thyroid cancer is somewhat more aggressive than its sporadic counterpart, but is less aggressive than medullary thyroid cancer. Total thyroidectomy and central neck dissection followed by radioactive iodine ablation and thyroid hormone suppression appear to be the most effective therapy.

Adolescent↗

Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism.

PURPOSE: To compare the sensitivity and positive predictive value of magnetic resonance (MR) imaging and technetium 99m 2-methoxyisobutyl-isonitrile (MIBI) scintigraphy for the detection of hyperfunctioning parathyroid tissue when used alone and in combination in a large patient population with recurrent or persistent hyperparathyroidism (HPT). MATERIALS AND METHODS: In 98 consecutive patients with biochemically proved recurrent or persistent HPT after surgery, MR imaging and 99mTc MIBI study findings were retrospectively reviewed and compared with surgical and histopathologic findings. The sensitivity and positive predictive value of MR imaging and 99mTc MIBI scintigraphy were compared with each other and in combination. RESULTS: In these patients, 130 abnormal parathyroid glands were identified at surgery. The sensitivity and positive predictive value of MR imaging were 82% (95% CI: 75%, 89%) and 89%, respectively; those for (99m)Tc MIBI scintigraphy were 85% (95% CI: 79%, 91%) and 89%. No significant difference was found between MR imaging and 99mTc MIBI scintigraphy for sensitivity (P =.7). The sensitivity and positive predictive value for the detection of abnormal parathyroid tissue on a per-gland basis increased to 94% (95% CI: 90%, 98%) and 98%, respectively, when only one of the two tests was required to be positive. CONCLUSION: MR imaging and 99mTc MIBI scintigraphy have similarly good sensitivity and positive predictive value for the detection of hyperfunctioning parathyroid tissue in patients after surgery. The combination of the two tests provided a substantial increase in sensitivity and positive predictive value.

Adolescent↗

Monitoring signal transduction in cancer: tyrosine kinase gene expression profiling.

Abnormal expression of tyrosine kinase (TK) genes is common in tumors, in which it is believed to alter cell growth and response to external stimuli such as growth factors and hormones. Although the etiology and pathogenesis of carcinomas of the thyroid or breast remain unclear, there is evidence that the expression of TK genes, such as receptor tyrosine kinases, or mitogen-activated protein kinases, is dysregulated in these tumors, and that overexpression of particular TK genes due to gene amplification, changes in gene regulation, or structural alterations leads to oncogenic transformation of epithelial cells. We developed a rapid scheme to measure semiquantitatively the expression levels of 50-100 TK genes. Our assay is based on RT-PCR with mixed based primers that anneal to conserved regions in the catalytic domain of TK genes to generate gene-specific fragments. PCR products are then labeled by random priming and hybridized to DNA microarrays carrying known TK gene targets. Inclusion of differently labeled fragments from reference or normal cells allows identification of TK genes that show altered expression levels during malignant transformation or tumor progression. Examples demonstrate how this innovative assay might help to define new markers for tumor progression and potential targets for disease intervention. (J Histochem Cytochem 49:673-674, 2001)

Breast Neoplasms↗