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Biomedical subjects

O H Clark

Publications and source records attributed to O H Clark.

At least 73 records · Page 4Linked to original sources
PubMed1998

Pulmonary metastases of endocrine origin: the role of surgery.

PURPOSE: To determine the clinical course and outcome of patients undergoing pulmonary resection for metastatic endocrine tumors. METHODS: Retrospective review of 47 patients with known endocrine tumors and pulmonary metastases who were evaluated for surgical resection between 1975 and 1996. RESULTS: Tumors evaluated included the following: carcinoid (16), thyroid (12), pancreatic adenocarcinoma (10), adrenocortical carcinoma (6), pheochromocytoma (2), and parathyroid (1). Thirty-three patients were asymptomatic. Hormone secretion was noted in five patients. Twenty-five patients, who had isolated lung metastases, good control of the primary tumor, and no medical contraindication had surgical resection. The number of pulmonary nodules was not a limiting factor as long as all disease could be resected with adequate residual pulmonary function. CT was successful in directing resection in all patients. Twenty-six operations were performed in 25 patients and 22 patients were treated medically. Wedge resection was performed for lesions <2 cm (15), and lobectomy for larger or multiple nodules (10). Four patients had bilateral nodules resected. There was no operative mortality and no major complications. Actuarial 5-year survival was 61% for surgically treated patients. Independent predictors of poor survival included positive mediastinal lymph nodes at time of surgery (p=0.004) and shorter disease-free interval (p=0.01). At a median of 6.7+/-1.2 years, six patients have developed radiographic appearance of a recurrence. A single patient with recurrent Hürthle cell cancer has had a successful reresection. The remaining patients have received chemotherapy. No patient with pancreatic carcinoma or adrenocortical carcinoma was a candidate for resection. All medically treated patients died within 6 months. CONCLUSION: Patients with endocrine tumors and pulmonary metastases are usually asymptomatic, their conditions are diagnosed accurately with CT, and they can achieve long-term survival comparable to other tumors (sarcoma) after pulmonary metastasectomy. CLINICAL IMPLICATIONS: Patients with carcinoid, thyroid, pheochromocytoma, and parathyroid tumors with pulmonary metastases should undergo surgical resection if there is the following: (1) no evidence of extrathoracic disease; (2) good control of the primary tumor; (3) no medical contraindications for surgery; and (4) pulmonary function that can tolerate resection of all documented disease. The role of adjuvant chemotherapy in patients with positive lymph nodes needs further study.

Adolescent↗
PubMed1998

[Transfection of follicular thyroid gland carcinoma cells with human TSH receptor changes growth, invasion and adhesion].

TSH is the classic stimulator of thyroid cell function. Clinically, treatment with thyroxin to suppress TSH decreased the risk of thyroid cancer recurrence and improved patient survival. This study analyzed the effect of stably transfected human TSH receptor cDNA in an established model of metastatic follicular thyroid cancer cells (FC) compared to wild type FTC. Wild type FTC lack TSH receptors and do not depend on TSH for growth. However, they contain thyroglobulin, have intact thyroid functions and response to TSH. We tested growth, invasion, and adhesion of transfected tumor cells (FTC-TSHr) compared to parental cells. All transfected FTC-TSHr expressed TSHr mRNA. Compared to wild type cells invasion and growth of TSHr-transfected FTC were significantly inhibited (p < 0.001). All FTC adhered best to collagen IV and fibronectin. Compared to parental cells adhesion of unstimulated FTC-TSHr was significantly enhanced (p < 0.001). These in vitro data underline the important role of the human TSH receptor as the main regulator of thyroid growth and functions.

Adenocarcinoma, Follicular↗
PubMed1998

Insulinoma--experience from 1950 to 1995.

Insulinomas are rare tumors that originate from the islet cells of the pancreas. The purpose of this study was to analyze our experience in patients with insulinoma and present our approach to these patients. Medical records of 67 patients treated at the University of California, San Francisco (UCSF) Medical Center, 56 surgically and 11 medically, from 1954 to 1995 were retrospectively reviewed. Presenting symptoms, physical findings, laboratory data, pre and intraoperative localization studies, operative management, operative success, and post-operative complications were analyzed. Among the entire cohort, there were 11 patients with Multiple Endocrine Neoplasia type I (MEN 1) and 7 patients with multiple tumors. 46 out of 48 patients (96%) having first operations for benign tumors and 5 out of 8 patients (63%) having reoperations for benign tumors were successful, as were 6 out of 12 patients (50%) having operations for islet cell carcinoma. Overall, preoperative localization studies were positive in only 46% of patients and therefore failed to improve our surgical outcome. Careful palpation with intraoperative ultrasonography gave the best localization results. Enucleation of solitary tumors is curative in sporadic cases and gives the lowest complication rate. In patients with MEN 1, subtotal pancreatectomy with enucleation of tumours from the pancreatic head and uncinate process is recommended over simple enucleation because of frequent multiple tumors.

Adolescent↗
PubMed1997

Sestamibi scanning is inadequate for directing unilateral neck exploration for first-time parathyroidectomy.

OBJECTIVE: To determine whether technetium Tc 99m sestamibi scanning is accurate enough to allow surgeons to perform unilateral neck exploration for first-time parathyroidectomy in patients with primary hyperparathyroidism. DESIGN: Retrospective review. SETTING: University tertiary care center. PATIENTS: Forty patients with primary hyperparathyroidism who underwent sestamibi scanning before first-time parathyroidectomy, of whom 28 had single adenomas, 9 had multiple adenomas, and 3 had hyperplasia. INTERVENTIONS: All 40 patients underwent bilateral neck exploration with identification of 4 parathyroid glands. MAIN OUTCOME MEASURES: We compared the results of preoperative sestamibi scanning with operative and histologic findings. We then used these data to calculate the projected success rates of parathyroidectomy if unilateral neck explorations had been performed based on the results of sestamibi scanning, instead of bilateral explorations. RESULTS: Sestamibi scanning was correct in 20 (71%) of 28 patients with single adenomas, 4 (44%) of 9 patients with multiple adenomas, and 0 (0%) of 3 patients with hyperplasia. If unilateral neck explorations had been performed on the basis of localization by sestamibi scanning, parathyroidectomy would have failed in 4 (10%) of 40 patients. CONCLUSIONS: Sestamibi scanning, although helpful, is inadequate for directing unilateral neck exploration for first-time parathyroidectomy. Surgeons who perform unilateral neck exploration based on the results of sestamibi scanning will record a higher failure rate and incur higher costs than those who perform bilateral neck exploration for first-time parathyroidectomy.

Adolescent↗
PubMed1997

Antiproliferative effect of suramin on primary cultures of human pheochromocytomas and rat PC12 pheochromocytoma cells.

BACKGROUND: Suramin inhibits growth of neural crest-derived cells and is used to treat adrenocortical cancer and neuroblastoma in clinical trials. The antiproliferative effect of suramin was evaluated in primary cultures of human pheochromocytoma and the PC12 rat pheochromocytoma cell line in vitro and in vivo. METHODS: Human pheochromocytoma and PC12 rat pheochromocytoma cells were grown in medium supplemented with suramin at concentrations of 1-1,000 micrograms/ml (1.43-1.43 mM) for up to five generations. Suramin did not induce neuronal differentiation, but inhibited growth of cultured human pheochromocytoma cells with IC50 (inhibitory concentration at which a 50% reduction of proliferation is observed) of 50-250 micrograms/ml. Also, suramin inhibited proliferation of PC12 cells with IC50 of 228 micrograms/ml after 5 days and 161 micrograms/ml at 10 days of treatment. Colony formation assays demonstrated these effects to be cytotoxic rather than cytostatic. Thus when reproductive integrity of PC12 cells was taken into account, IC50 was calculated with 118 micrograms/ml and 129 micrograms/ml, respectively. In vivo experiments were performed with subcutaneously xenotransplanted PC12 cells (BALB/c NCR-NU mice). Suramin did not alter tumorigenicity and did not inhibit local tumor growth. RESULTS: These data determine for the first time an antiproliferative effect of suramin in pheochromocytoma cells. Suramin is cytotoxic to pheochromocytoma cells in vitro at levels that are clinically achievable. CONCLUSIONS: Suramin may have potential as an antiproliferative drug in nonresectable pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1997

Familial hyperparathyroidism without multiple endocrine neoplasia.

Hyperparathyroidism occurs sporadically, in association with multiple endocrine neoplasia (MEN) types I and II, or rarely as familial hyperparathyroidism (FHPT) without other manifestations. We analyzed our experience in 16 FHPT patients from 14 families treated between 1934 and 1991 and reviewed 51 other FHPT patients reported in the literature to determine the clinical course of these patients. Among our 16 patients, 7 (44%) had a serum calcium level >/= 3.75 mmol/L, 5 (31%) presented with hypercalcemic crisis, 3 (19%) had osteitis fibrosa cystica, 5 (31%) had nephrolithiasis, 1 had pancreatitis, 12 (75%) had multiple abnormal parathyroid glands, 3 (19%) had supernumerary glands, and 7 (44%) required reoperation for persistent (n = 4) or recurrent (n = 3) hyperparathyroidism. Three patients (19%) also had papillary thyroid cancer, and 7 (44%) had other coexistent thyroid disorders. Among 51 patients with FHPT reported in the literature, 23 (45%) had serum calcium >/= 3.75 mmol/L, and 23 (45%) had multiple abnormal parathyroid glands; 10 (20%) had recurrent hyperparathyroidism. FHPT without other endocrinopathies is a distinct entity. Patients with FHPT have multiple abnormal parathyroid glands and are prone to both recurrent and persistent hyperparathyroidism. They frequently present with profound hypercalcemia or hypercalcemic crisis, in contrast to patients with MEN-associated hyperparathyroidism or sporadic hyperparathyroidism.

Adolescent↗
PubMed1997

Management of thyroid carcinosarcoma.

BACKGROUND: Thyroid carcinosarcoma is a rare and aggressive malignant thyroid tumor that has been described pathologically, but there is little clinical information regarding tumor behavior. METHODS: We retrospectively analyzed the course of our patient and 16 others reported in the literature to determine optimal management. We review the case history of our patient and the literature concerning patients with carcinosarcoma of the thyroid. RESULTS: Seventeen patients, 52 to 80 years of age (mean, 60 years), have had a thyroid carcinosarcoma of the thyroid. Five of seven patients for whom the information is available were treated by partial thyroidectomy and two by total thyroidectomy. Among these patients five (71%) died within the first 3 months and two (29%) survived more than 6 months. The mean survival was 5 months. At autopsy in seven patients, six had lymph node or distant metastases. CONCLUSIONS: Carcinosarcoma of the thyroid is a very aggressive tumor with a clinical course similar to anaplastic thyroid carcinoma. Like patients with anaplastic thyroid carcinoma, few survive more than 6 months despite aggressive multimodal treatment. Our patient's exposure to raw phosphorus, radiation, and 1,3-bis-(2-chloroethyl)-1-nitrosourea may have predisposed her to this aggressive tumor.

Aged↗
PubMed1997

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid.

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.

Adenocarcinoma↗
PubMed1997

Prognostic factors in thyroid carcinoma.

Thyroid carcinomas range from the most indolent to the most aggressive human malignancies. A variety of clinical and pathologic factors can be used to help predict behavior and determine appropriate therapy. New molecular biologic techniques show promise in further refining the assessment of prognosis in thyroid cancer patients.

Biomarkers, Tumor↗
PubMed1996

Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association.

A set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with thyroid nodules or thyroid cancer was developed by consensus by an 11-member Standards of Care Committee (the authors of the article) of the American Thyroid Association, New York, NY. The participants were selected by the committee chairman and by the president of the American Thyroid Association based on their clinical experience. The committee members represented different geographic areas within the United States, to reflect different practice patterns. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. Each committee participant was initially assigned to write a section of the document and to submit it to the committee chairman, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. Several of the committee members further revised and refined the document, which was then submitted to the entire membership of the American Thyroid Association for written comments and suggestions, many of which were incorporated into a final draft document, which was reviewed and approved by the Executive Council of the American Thyroid Association.

Adenocarcinoma, Follicular↗
PubMed1996

Tamoxifen antagonizes proliferation and invasion of estrogen receptor-negative metastatic follicular thyroid cancer cells via protein kinase C.

Tamoxifen inhibits invasion and growth of estrogen-receptor negative follicular thyroid cancer (FTC) cells in vitro and in vivo. To study the mechanisms involved, we documented the effects of tamoxifen and staurosporine on three metastatic FTC-cell lines. TPA (10 ng/ml) enhanced invasion and growth of FTC by 15% (P < 0.02). Tamoxifen (1.5 micromol/l) inhibited invasion of FTC133 by 36% (FTC236 30%; FTC238 32%; P < 0.01). TPA reversed the tamoxifen-mediated inhibition of invasion by 35% in FTC133 and 30% in FTC238 (P < 0.02). Staurosporine (10 ng/ml) inhibited invasion and growth of all FTC. At 0.1-1 ng/ml it enhanced the inhibitory effects of tamoxifen, but did not further inhibit invasion or growth at higher concentrations. We conclude that the antiproliferative and antiinvasive effects of tamoxifen on follicular thyroid cancer cells are at least partly mediated by an inhibition of protein kinase C.

Alkaloids↗
PubMed1996

Reoperation for persistent or recurrent primary hyperparathyroidism.

OBJECTIVE: To analyze the causes and outcomes of reoperation for persistent or recurrent primary hyperparathyroidism. DATA SOURCES: Medical records of 102 patients with persistent or recurrent primary hyperparathyroidism who underwent reoperation by 1 surgeon between 1985 and 1995. STUDY SELECTION: Only patients with persistent or recurrent primary hyperparathyroidism were selected; patients with secondary hyperparathyroidism, parathyroid cancer, familial hyperparathyroidism, and previous thyroid operations were omitted. DATA EXTRACTION: Performed by a single unblinded researcher. DATA SYNTHESIS: Reasons for failed parathyroid operations included tumor in ectopic position (53%), incomplete resection of multiple abnormal glands (37%), adenoma in normal position missed during previous surgery (7%), and regrowth of previously resected tumor (3%). Of the ectopic glands, 28% were paraesophageal, 26% in the mediastinum (nonthymic), 24% intrathymic, 11% intrathyroidal, 9% in the carotid sheath, and 2% in a high cervical position. Eighty-three percent of ectopic glands were accessible via cervical incision. The success rate of reoperations was 95%. One patient (1%) became permanently hypocalcemic after reoperation; 1 patient (1%) suffered permanent unilateral vocal cord paralysis. The sensitivities of preoperative localization studies were as follows: technetium Tc 99m sestamibi scan, 77%; magnetic resonance imaging, 77%; selective venous catheterization for intact parathyroid hormone, 77%; thallium-technetium scan, 68%; ultrasonography, 57%; and computed tomography, 42%. CONCLUSIONS: Repeated parathyroidectomy can be avoided in more than 95% of patients if an experienced surgeon performs bilateral cervical exploration during the initial parathyroid operation. For patients with persistent or recurrent primary hyperparathyroidism, preoperative localization studies and a focused surgical approach can result in a 95% success rate with minimum complications.

Adult↗
PubMed1996

Laparoscopic adrenalectomy. Comparison of the lateral and posterior approaches.

OBJECTIVE: To compare the lateral transabdominal and posterior retroperitoneal laparoscopic methods for performing adrenalectomy. DESIGN: Nonrandomized. SETTING: Hospitals affiliated with the University of California, San Francisco. PATIENTS: Thirty-six patients (15 men and 21 women), aged 5 to 78 years (mean age, 49 years), were treated for the following conditions: aldosteronoma, 18 patients; pheochromocytoma, 4 patients; Cushing syndrome, 6 patients; androgen-secreting tumor, 1 patient; nonfunctioning adenoma, 3 patients; adrenal hemorrhage, 1 patient; metastatic neoplasm, 2 patients; and myelolipoma, 1 patient. INTERVENTIONS: Twenty-three lateral and 14 posterior laparoscopic adrenalectomies. MAIN OUTCOME MEASURES: Success rate, operating time, complications, and length of hospital stay. RESULTS: The tumors, which ranged in size from 1 to 13 cm (mean, 4.2 cm; median, 2.5 cm), were all successfully resected laparoscopically. All 8 tumors larger than 6 cm were resected by the lateral approach. One critically ill patient died. No patient required blood transfusions or conversion to laparotomy. Mean operating time was 3.8 hours vs 3.4 hours (median, 3.5 hours vs 3 hours) and mean hospital stay was 2.2 days vs 1.5 days (median, 2 days vs 1 day) for the lateral and posterior approaches, respectively. All patients without concomitant procedures were ready to be discharged within 48 hours. CONCLUSIONS: Both approaches were effective and safe. We prefer the lateral approach for tumors larger than 6 cm and the posterior approach for bilateral tumors.

Adolescent↗
PubMed1996

Desensitization of cyclic adenosine 3,5'-monophosphate response to thyrotropin in normal and primary or metastatic papillary thyroid cancer cells in vitro.

BACKGROUND: Desensitization is an important physiologic process resulting in a decreased functional response after continuous or repeated stimulation. Prior exposure of normal human thyroid tissue to thyrotropin either in vivo or in vitro causes desensitization of adenylate cyclase. Little is known, however, about whether the thyrotropin-adenylate cyclase-cyclic adenosine 3,5'-monophosphate (cAMP) signal transduction system desensitizes in human thyroid carcinomas. Failure to desensitize could result in increased growth or metastases. METHODS: Cell cultures from Chinese hamster ovary (CHO) cells transfected with normal human thyrotropin receptor (hTSHr) and thyroid neoplasms including one papillary carcinoma and one papillary lymph node metastases were evaluated for desensitization. CHO cells were stably transfected with plasmid DNA containing hTSHr. Cells were incubated with thyrotropin (10 mU/ml) for different periods (1 to 24 hours). A second incubation (30 minutes) was done with and without thyrotropin in medium including 3-isobutyl-1-methylxanthine (1 mmol/L). Intracellular cAMP accumulation was determined by means of radioimmunoassay. RESULTS: Maximal stimulation and desensitization to thyrotropin were observed at 30 minutes and 4 hours, respectively. The cAMP response to a second incubation with thyrotropin was 52% and 48% lower than the initial response to thyrotropin in CHO-hTSHr and papillary thyroid cancer cells, respectively (p < 0.001). A papillary carcinoma lymph node metastases had an increased basal cAMP level and also an increased cAMP level in response to thyrotropin stimulation (227%) but failed to desensitize (p < 0.001). CONCLUSIONS: Desensitization of the cAMP response to thyrotropin occurred in a papillary thyroid cancer but not in a metastatic thyroid cancer. Failure to desensitize might play a role in tumor progression.

Animals↗