Biomedical subjects

A E Siperstein

Publications and source records attributed to A E Siperstein.

At least 19 recordsLinked to original sources

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

Selective use of tube cholecystostomy with interval laparoscopic cholecystectomy in acute cholecystitis.

HYPOTHESIS: Tube cholecystostomy followed by interval laparoscopic cholecystectomy is a sale and efficacious treatment option in critically ill patients with acute cholecystitis. DESIGN: Retrospective cohort study within a 4 1/2%-year period. SETTING: University hospital. PATIENTS: Of 324 patients who underwent laparoscopic cholecystectomy, 65 (20%) had acute cholecystitis; 15 of these 65 patients (mean age, 75 years) underwent tube cholecystostomy. INTERVENTION: Thirteen patients at high risk for general anesthesia because of underlying medical conditions underwent percutaneous tube cholecystostomy with local anesthesia. Laparoscopic tube cholecystostomy was performed on 2 patients during attempted laparoscopic cholecystectomy because of severe inflammation. Interval laparoscopic cholecystectomy was attempted after an average of 12 weeks. MAIN OUTCOME MEASURES: Technical details and clinical outcome. RESULTS: Prompt clinical response was observed in 13 (87%) of the patients after tube cholecystostomy. Twelve patients (80%) underwent interval cholecystectomy. Laparoscopic cholecystectomy was attempted in 11 patients and was successful in 10 (91%), with 1 conversion to open cholecystectomy. One patient had interval open cholecystectomy during definitive operation for esophageal cancer and another had emergency open cholecystectomy due to tube dislodgment. Two patients (13%) had complications related to tube cholecystostomy and 2 patients died from sepsis before interval operation. One patient died from sepsis after combined esophagectomy and cholecystectomy. Postoperative minor complications developed in 2 patients. At a mean follow-up of 16.7 months (range, 0.5-53 months), all patients were free of biliary symptoms. CONCLUSIONS: Tube cholecystostomy allowed for resolution of sepsis and delay of definitive surgery in selected patients. Interval laparoscopic cholecystectomy was safely performed once sepsis and acute infection had resolved in this patient group at high risk for general anesthesia and conversion to open cholecystectomy. Just as catheter drainage of acute infection with interval appendectomy is accepted in patients with periappendiceal abscess, tube cholecystostomy with interval laparoscopic cholecystectomy should have a role in the management of selected patients with acute cholecystitis.

Acute Disease↗

PubMed2000

Hyperparathyroidism after thyroid surgery and autotransplantation of histologically normal parathyroid glands.

BACKGROUND: Parathyroid autotransplantation is a well-established method to prevent hypoparathyroidism during parathyroid and thyroid operations. The reported success rate of parathyroid autotransplantation ranges from 75% to 100%. Recurrent hyperparathyroidism may develop after parathyroid autotransplantation, especially after the transplantation of hyperplastic or adenomatous parathyroid tissue. Hyperparathyroidism recurs most frequently after subtotal parathyroidectomy or total parathyroidectomy and autotransplantation, in patients with renal failure and secondary hyperparathyroidism, and in patients with familial primary hyperparathyroidism or MEN I or MEN II syndrome. We report three patients who experienced primary hyperparathyroidism after autotransplantation of normal parathyroid tissue during thyroid operations (two patients) or after a long period of hypoparathyroidism. STUDY DESIGN: We reviewed our records from 1983 to May 1998 and identified three patients in whom hyperparathyroidism developed after thyroid operations. RESULTS: One patient had a thyroidectomy with left modified radical neck dissection for papillary thyroid cancer, followed by radioiodine ablative therapy. Two patients had thyroid operations for benign thyroid disease. One of these patients had a history of radiation exposure for acne, and in the other one secondary hyperparathyroidism arose 6 years after a thyroidectomy for hyperthyroidism. CONCLUSIONS: Our study documents that hyperparathyroidism may develop after autotransplantation of histologically normal parathyroid tissue and after a period of hypoparathyroidism after thyroid operations. For this reason, it is important to mark the site of the parathyroid transplantation.

Adult↗

PubMed1999

Laparoscopic gastrostomy and jejunostomy: safety and cost with local vs general anesthesia.

BACKGROUND AND HYPOTHESIS: General anesthesia is used for laparoscopic enteral access because pneumoperitoneum requires relaxation of the abdominal muscles. We wanted to determine whether these procedures could be performed with similar results and cost under local anesthesia. DESIGN: Randomized controlled study with 30-day follow-up including a cost-benefit analysis. SETTING: University-affiliated hospitals. PATIENTS: Forty-eight patients (32 men, 16 women; mean age, 67 years) undergoing laparoscopic gastrostomies (n = 32) and jejunostomies (n = 16). INTERVENTION: Twenty-four patients underwent laparoscopic gastrostomy (n = 15) and jejunostomy (n = 9) under local anesthesia with intravenous conscious sedation and monitored anesthesia care. Twenty-four patients had general anesthesia. MAIN OUTCOME MEASURES: Conversion to general anesthesia, complications, and cost. RESULTS: Ten patients under local anesthesia had periods of deep sedation and 1 required conversion to general anesthesia. One patient under general anesthesia required conversion to open gastrostomy. No patients had intraoperative aspiration; however, 4 aspirated after the procedure. One patient died of myocardial infarction during the 30-day follow-up. We found no significant difference in the total mean cost and actual procedure time. The surgeon's fee accounted for 31% of the total cost. CONCLUSIONS: Some patients undergoing laparoscopic enteral access may require deep sedation and a rare patient may require general anesthesia. Clinical conditions and surgeon preference, therefore, should determine whether local anesthesia is suitable for laparoscopic gastrostomies and jejunostomies, and in what setting, since there is no difference in success rate or complications when compared with general anesthesia. Potential savings are possible from the operating room (26% of total cost) or anesthesiologist (12% of total cost) if these procedures are performed in an endoscopy suite without monitored anesthesia care.

Aged↗

PubMed1999

Laparoscopic vs open adrenalectomy for the treatment of primary hyperaldosteronism.

HYPOTHESIS: That the clinical presentations, biochemical profiles, and surgical outcomes of patients treated with laparoscopic vs open adrenalectomy for primary hyperaldosteronism are different. DESIGN, SETTINGS, PATIENTS, AND INTERVENTIONS: The medical records of 80 patients with primary hyperaldosteronism who underwent open adrenalectomy between 1975 and 1986 or laparoscopic adrenalectomy between 1993 and 1998 at the University of California-San Francisco were reviewed by a single unblinded researcher (W.T.S.). MAIN OUTCOME MEASURES: Severity of hypertension and hypokalemia at diagnosis, their improvement after adrenalectomy, and operative complications. RESULTS: Thirty-eight patients underwent open adrenalectomy and 42 patients underwent laparoscopic adrenalectomy. The patients who underwent open adrenalectomy had documented hypertension for a median of 5 years before surgery; all had diastolic blood pressures greater than 100 mm Hg. Laparoscopically treated patients had documented hypertension for a median of 2.5 years preoperatively, and 20 (48%) had diastolic blood pressures greater than 100 mm Hg. The median preoperative serum potassium levels for the open and laparoscopic groups were 2.6 mmol/L and 3.3 mmol/L, respectively; the mean serum aldosterone levels were 1.47 nmol/L and 1.30 nmol/L. Thirty-two (84%) of the 38 patients who underwent open surgery and 41 (98%) of the 42 patients treated laparoscopically had adrenal adenomas. The sensitivity of preoperative computed tomographic scanning for adenomas was 83% for the patients treated with open adrenalectomy and 93% for those treated laparoscopically. There were 4 postoperative complications in the open surgery group and none in the laparoscopic group. Postoperatively, 30(81%) of 37 patients (excluding 1 patient who died of adrenocortical carcinoma) in the open surgery group and 37 (88%) of 42 patients treated laparoscopically were normotensive. Post-operative values were 3.6 to 5.0 of serum potassium per liter and 3.5 to 4.9 of serum potassium per liter in the open and laparoscopic groups, respectively. CONCLUSIONS: Patients who are treated with laparoscopic adrenalectomy for primary hyperaldosteronism are being referred with less severe hypertension and hypokalemia than patients formerly treated with open adrenalectomy. Patients treated laparoscopically had fewer postoperative complications and were equally likely to improve in blood pressure and hypokalemia. Laparoscopic adrenalectomy has become the treatment of choice for patients with primary hyperaldosteronism because of lower morbidity.

Adrenalectomy↗

PubMed1999

Localization of insulinomas.

HYPOTHESIS: Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techniques for localizing insulinoma. DESIGN: Retrospective review. SETTING: A tertiary referral center. PATIENTS: All patients with a biochemical diagnosis of organic hyperinsulinism who were referred to University of California, San Francisco, from 1975 to 1998. METHODS: Sensitivities of the localization techniques for insulinoma were evaluated. RESULTS: The sensitivities of tumor localization with arteriography, computed tomography, preoperative ultrasonography, magnetic resonance imaging, magnetic resonance imaging with gadolinium, transhepatic venous sampling, palpation, and intraoperative ultrasonography were 47%, 24%, 50%, 30%, 40%, 55%, 76%, and 91%, respectively. Nine of the 11 nonpalpable and nonvisible tumors at operation were localized by intraoperative ultrasonography. CONCLUSION: The currently available preoperative localization tests are not reliable enough to be recommended when intraoperative ultrasonography is available.

Adult↗

PubMed1999

Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients.

BACKGROUND: Serum thyroglobulin determination has been reported to be a sensitive indicator of persistent or recurrent differentiated thyroid cancer of follicular cell origin (DTC) after total thyroidectomy. The purpose of this investigation was to determine the accuracy of serum thyroglobulin levels in predicting persistent or recurrent DTC in euthyroid and hypothyroid patients. METHODS: One hundred ninety consecutive patients with DTC of follicular cell origin who had 4 or more thyroglobulin levels measured after total thyroidectomy were retrospectively evaluated. One hundred fifteen patients had serum thyroglobulin levels measured when hypothyroid for radioiodine scanning or ablation. Serum thyroglobulin levels were determined by commercial assays. One hundred twenty-two patients less than 45 years old were considered at low risk, whereas 68 patients more than or equal to 45 years old were considered at high risk on the basis of TNM classification. The mean follow-up period was 62 months. RESULTS: After thyroidectomy with or without central or modified radical neck dissection 120 patients had normal thyroglobulin levels (< or = 3 ng/mL) while receiving thyroid hormone. One hundred thirteen of the 120 patients (94%) with normal serum thyroglobulin levels had no evidence of recurrent tumor, whereas 6% (7 patients) had persistent or recurrent disease. Among 76 patients with persistent (28 patients) or recurrent (48 patients) disease, 70 had a serum thyroglobulin level > 3 ng/mL while receiving thyroid hormone. Overall, 14 of 115 patients, including 2 of 61 (3%) in the high-risk group and 12 of 54 (22%) in the low-risk group, only had elevated serum thyroglobulin levels when hypothyroid with high serum thyroid-stimulating hormone (TSH) levels documenting persistent or recurrent disease. In 1 patient the serum thyroglobulin level (240 ng/mL) was falsely elevated probably as a result of interfering antibodies because no tumor was identified surgically or pathologically, and the thyroglobulin concentration was < 3 ng/mL when analyzed in 3 other laboratories. CONCLUSION: Serum thyroglobulin testing is sensitive (91%) and specific (99%) for identifying patients with persistent or recurrent differentiated thyroid cancer. Serum thyroglobulin levels are most precise when patients are hypothyroid (high TSH) and may be unreliable in patients with antithyroglobulin antibodies. We recommend TSH-stimulated thyroglobulin testing for all patients after total thyroidectomy for differentiated thyroid cancer of follicular cell origin regardless of patient age or risk group.

Adult↗

PubMed1999

Reliability of fine-needle aspiration in patients with familial nonmedullary thyroid cancer.

In this case-control study we describe how often thyroid cancers and occult cancers are diagnosed or not diagnosed by fine-needle aspiration (FNA) in patients with thyroid nodules and a family history of nonmedullary thyroid cancers (FNMTC). Our hypothesis is that patients with thyroid nodules and a family history of FNMTC seem to be similar to patients with thyroid nodules and a history of exposure to low-dose therapeutic radiation. Both have been reported to have multifocal thyroid neoplasms and malignant tumors are common. Cytological examination may therefore be less accurate. From 1979 to 1996, 27 patients from 24 families with FNMTC were examined histologically after a preoperative cytological examination in all of them. A positive cytology examination was defined when biopsy documented thyroid cancer. It was interpreted as a false-negative study when a benign diagnosis was made and thyroid cancer was present anywhere within the thyroid, including in areas sampled or not sampled by FNA and not palpable preoperatively. A randomized control group, matched for age and gender, contained 27 patients with papillary thyroid cancer without familial disease. In our study group, 25 patients were treated with total thyroidectomy, including 7 with neck dissection, and 2 by thyroid lobectomy. At final histological examination 17 of 27 patients (63%) in this study group had multiple nodules and 25 of 27 (92.6%) had thyroid cancer. Thyroid cancer was diagnosed by FNA in 22 of 25 patients (88%), with 3 (12%) false-negative biopsies due to sampling errors (thyroid cancer not in the index nodule), versus 1 (3.7%) false-negative biopsy in the control group. Two patients in the study group with benign nodules were accurately diagnosed. In patients with false-negative biopsies and a history of FNMTC, the cancer was situated in one or more small nodules. Only one cancer was occult (< 1.0 cm). One-third of the patients in our study group (33%) had a history of radiation; 44% of the irradiated group had a single nodule; 56% had multiple nodules. In the control group, 9 of 27 patients (33%) also had a history of radiation; 33% of the irradiated group had a single nodule, 67% had multiple nodules. In conclusion, the reliability of FNA in patients with FNMTC appears to be less accurate than it is for other patients because of the high incidence of multifocal thyroid cancer and coexistence of benign nodules. Patients with thyroid nodules and a family history of thyroid cancer are more likely to have thyroid cancer and because they also have more coexistent benign nodules, they must be followed closely or treated with total or near-total thyroidectomy.

Biopsy, Needle↗

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

Development of reverse transcription-competitive polymerase chain reaction method to quantitate the expression levels of human sodium iodide symporter.

The sodium iodide symporter (NIS) is the plasma membrane protein that mediates active iodide uptake into thyroid follicular cells. To investigate whether human NIS (hNIS) mRNA levels in papillary thyroid carcinomas (PCs) correlate with the ability of tumors to concentrate radioiodide, we developed a reverse transcription-competitive polymerase chain reaction (RT-cPCR) method to quantify the hNIS mRNA levels in thyroid tissues. We studied 7 normal thyroid tissues, 8 PCs, and 1 follicular adenoma. hNIS mRNA levels in PCs were generally lower than those found in normal thyroid tissues. The reduced radioiodide concentrating activity of PCs is due, at least in part, to the reduced expression and/or the decreased stability of hNIS mRNA.

Adenoma↗

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

Heterologous desensitization in neoplastic thyroid cells: influence of the phospholipase C signal transduction system on the thyrotropin-adenylate cyclase signal transduction system.

Desensitization is defined as a decreased functional response after continuous or repetitive stimulation of a receptor with its agonist. Thyrotropin (TSH) increases cAMP levels in normal and neoplastic thyroid tissue. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) activates protein kinase C (PKC). The aim was to determine whether TPA induces heterologous desensitization of the TSH-adenylate cyclase (AC) signal transduction system. Three human thyroid neoplasms in culture for 6 months or longer (one papillary carcinoma, one Hurthle cell carcinoma, one follicular adenoma) were incubated with TSH (10 mU/ml) and TPA (1.6 x 10(-8) M) separately and together for various time periods (from 10 minutes to 24 hours). The mixture was subsequently incubated for 30 minutes with TSH. TPA alone had no effect on cAMP levels, but co-incubation of TPA and TSH caused a significant reduction in cAMP response when compared to the cAMP response that resulted after stimulation with only TSH (p < 0.001). cAMP levels in response to TSH decreased by 31%, 44%, and 57% after preincubation with TSH for 10 minutes, 4 hours, and 24 hours, respectively (p < 0.01; ANOVA). Co-incubation of cells with TPA and staurosporine (10 ng/ml), a PKC inhibitor, prevented the effect of TPA on desensitization at 10 minutes and blunted the effect at 4 hours. This is the first demonstration in human neoplastic thyroid cells that TPA induced heterologous desensitization of the cAMP response to TSH. This TPA-induced effect appears to involve PKC activation, as it can be blocked by staurosporine.

Adenylyl Cyclases↗

PubMed1998

Desensitization in normal and neoplastic human thyroid cell lines.

Because some papillary thyroid cancers continue to grow when thyroid-stimulating hormone (TSH) levels are suppressed, we questioned whether desensitization (i.e., a decreased cAMP response to repeat stimulation with TSH) occurs in normal and neoplastic thyroid tissue. If desensitization does occur, is it similar or different in these human thyroid cells? Normal and papillary thyroid cancer cells from the same patient were cultured as we have previously described. Normal and neoplastic thyroid tissues responded to TSH (0.01-10.0 mU/ml) by increasing cAMP production and growth in a dose-dependent manner. In normal cells there was an 11-fold mean increase in cAMP production at 4 hours, and all thyroid cultures responded. In neoplastic cells cAMP production increased from 1.5-fold to 3.0-fold with a mean 2.0-fold increase at 4 hours. In normal thyroid cells the cAMP response to a second TSH stimulus (desensitization) decreased up to 75% (range 25-75%), and desensitization occurred in all normal thyroid cell cultures. In neoplastic thyroid cells, however, the cAMP response to a second TSH stimulus decreased up to 17% (range 0-17%); and desensitization occurred in only two of the five neoplastic thyroid cell cultures. Thus when normal thyroid and neoplastic cells from the same patients were studied, greater desensitization occurred in the normal cells (75% vs. 17%). These studies document that there is greater desensitization in normal tissue than in neoplastic thyroid tissue, which may account for the increased growth of thyroid neoplasms in the presence of ever-changing low levels of TSH.

Aged↗

PubMed1998

A unique allogenic model of metastatic pheochromocytoma: PC12 rat pheochromocytoma xenografts to nude mice and establishment of metastases-derived PC12 variants.

Local invasion and metastatic spread to distant sites are major causes of death in patients with malignant pheochromocytoma. Since appropriate in vivo models do not exist, little is known about the underlying mechanisms of tumor growth and invasion. We, therefore, developed an animal model of malignant pheochromocytoma and established organotropic metastatic variants of PC12 rat pheochromocytoma cells. PC12 cells were established as xenografts to BALB/c NCR-NU mice. Subsequent to development of tumors or metastases, primary cultures from local tumors, metastases to lymph nodes, lungs and liver were established. These were subcultured in vitro and reinjected for up to five successive in vivo/in vitro cycles. Xenografted PC12 cells grew tumors with a doubling time of 6.78 +/- 0.58 days during log phase of tumor growth, killing hosts within 5-12 weeks depending on the experimental conditions. Tumors reproducibly metastasized to lymph nodes and the lung. Spontaneous metastases to the liver were not observed, but were achieved by intrasplenic injection of parent PC12 cells. In vitro, the metastatic cell lines displayed striking differences in morphology, overall growth patterns and nutritional requirements as well as binding to purified extracellular matrix proteins compared to the parent cell line. In vivo, the metastatic variants showed marked enhancement of metastatic ability. This is the first report of PC12 rat pheochromocytoma cells to exhibit the malignant phenotype in vivo. We also established variant PC12 cell lines that preferentially metastasized to specific sites and that had acquired different in vitro behavior and ability to metastasize. This unique model system should be useful for further studies relating to the invasion and metastases of pheochromocytoma and may prove valuable for investigations of novel antineoplastic therapies in vitro and in vivo.

Animals↗

PubMed1998

Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin.

Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.

Adenocarcinoma↗

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↗