Biomedical subjects

A E Siperstein

Publications and source records attributed to A E Siperstein.

At least 37 records · Page 2Linked to original sources

PubMed2000

Laparoscopic posterior adrenalectomy: technical considerations.

HYPOTHESIS: Although laparoscopic posterior adrenalectomy (LPA) offers a more direct access to the adrenal gland, it is not as popular as laparoscopic transabdominal adrenalectomy, and the worldwide experience has been limited. We hypothesized that LPA is a safe and efficacious procedure that could best serve certain patients with adrenal tumors. DESIGN: Case series of patients undergoing laparoscopic adrenalectomy in a single institution. SETTING: University teaching hospital. PATIENTS: Medical records of 31 patients with 33 tumors who underwent LPA were reviewed. Indications for operation included hormone secretion in 23 patients (74%), suspected or known malignant neoplasms in 7 patients (23%), and local symptoms in 1 patient (3%). INTERVENTION: The LPAs were performed with the patients in prone position. Preoperative ultrasonography localized the adrenal tumor and kidney to guide balloon trocar placement for the creation of a working retroperitoneal space. The LPAs were performed with three 10-mm trocars using laparoscopic ultrasound to localize the tumor and the harmonic scalpel to perform the dissection. MAIN OUTCOME MEASURES: Demographic data, type and size of tumor, operative time, blood loss, intraoperative and postoperative complications, and hospital stay were analyzed. RESULTS: All operations were successfully completed without conversion. Excluding the bilateral cases, the mean +/- SD operative time was 176 +/- 104 minutes. Estimated blood loss averaged 32 mL (range, 10-200 mL). There were no intraoperative complications. The mean +/- SD tumor size was 3.2 +/- 1.8 cm (range, 0.8-7.0 cm). Pathological evaluation revealed benign tumors in 25 patients (81%) and malignant tumors in 6 patients. The average hospital stay was 1.4 days (range, 1-3 days). There were no deaths. CONCLUSIONS: Although technically more demanding, LPA should be considered in patients with tumors less than 6 cm, bilateral tumors, or extensive previous abdominal surgery.

Adrenal Gland Neoplasms↗

PubMed2000

Intraoperative parathyroid aspiration and parathyroid hormone assay as an alternative to frozen section for tissue identification.

Most people would agree that successful parathyroidectomy depends on two important variables: the surgeon's recognition and excision of the abnormal parathyroid gland(s) and the pathologist's confirmation that the removed tissue is parathyroid tissue. Frozen section is usually employed to confirm the identity of parathyroid tissue, but occasionally confirmation cannot be made without a permanent section, as with intrathyroidal glands. This study proposes a new method of expeditious and easy confirmation of parathyroid tissue utilizing the immunoassay for quick measurement of intraoperative parathyroid hormone (IOPTH). By directly aspirating the suspected adenoma, the assay becomes a rapid diagnostic tool that can be used as an alternative to frozen section. In cases where the surgeon is already planning to employ the assay, the elimination of frozen section is cost-effective. Intraoperative aspiration of histologically confirmed parathyroid adenomas was performed on 12 consecutive patients undergoing parathyroid surgery. Parathyroid glands were aspirated with a 22-gauge syringe after gland excision. Aspirates were placed in 1 to 3 ml of buffered saline. A similar process was performed on 12 thyroid controls. Specimens were centrifuged, aliquotted, and stored at -70 degrees C. The parathyroid hormone value was analyzed electively by rapid assay and the values recorded. For all parathyroid aspirates, the rapid assay value was > 1500 pg/ml, exceeding the uppermost limit of the diagnostic chart. Values for thyroid aspirates ranged from 58 to 85 pg/ml (mean 75.7 pg/ml). In all cases tissue confirmation was achieved with permanent section. Values were 100% sensitive and specific. Measurement of PTH from intraoperative aspiration of suspected parathyroid adenomas is clinically useful in patients for whom frozen section would routinely be employed. Values > 1500 pg/ml secure the tissue diagnosis. There is no additional cost in cases where IOPTH monitoring is already being utilized to confirm cure. The elimination of frozen section could be cost-effective and, for some institutions, actually decrease the operating time as the IOPTH assay takes only 15 minutes. PTH assay is an accurate diagnostic technique and to date is 100% sensitive and specific for differentiating between parathyroid tumors and thyroid nodules.

Biopsy, Needle↗

PubMed2000

Use of CT Hounsfield unit density to identify ablated tumor after laparoscopic radiofrequency ablation of hepatic tumors.

BACKGROUND: When attempting to interpret CT scans after radiofrequency thermal ablation (RFA) of liver tumors, it is sometimes difficult to distinguish ablated from viable tumor tissue. Identification of the two types of tissue is specially problematic for lesions that are hypodense before ablation. The aim of this study was to determine whether quantitative Hounsfield unit (HU) density measurements can be used to document the lack of tumor perfusion and thereby identify ablated tissue. METHODS: Liver spiral CT scans of 13 patients with 51 lesions undergoing laparoscopic RFA for metastatic liver tumors within a 2-year time period were reviewed. HU density of the lesions as well as normal liver were measured pre- and postoperatively in each CT phase (noncontrast, arterial, portovenous). Statistical analyses were performed using Student's paired t-test and ANOVA. RESULTS: Normal liver parenchyma, which was used as a control, showed a similar increase with contrast injection in both pre- and postprocedure CT scans (56.4 +/- 2.4 vs 57.1 +/- 2.4 HU, respectively; p = 0.3). In contrast, ablated liver lesions showed a preablation increase of 45.7 +/- 3.4 HU but only a minimal postablation increase of 6.6 +/- 0.7 HU (p < 0.0001). This was true for highly vascular tumors (neuroendocrine) as well as hypovascular ones (adenocarcinoma). CONCLUSIONS: This is the first study to define quantitative radiological criteria using HU density for the evaluation of ablated tissues. A lack of increase in HU density with contrast injection indicates necrotic tissue, whereas perfused tissue shows an increase in HU density. This technique can be used in the evaluation of patients undergoing RFA.

Adenocarcinoma↗

PubMed2000

Recurrent or persistent thyroid cancer of follicular cell origin.

Most patients with differentiated thyroid cancer of follicular cell origin have a favorable postoperative course, and their prognosis often appears to be unrelated to the extent of initial surgical treatment in some studies. Important questions that need to be addressed include whether the extent of the initial operation has any impact on the subsequent tumor-free survival and total survival, and whether patients with persistent or recurrent disease benefit from reoperation.

Adenocarcinoma, Follicular↗

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↗

PubMed2000

Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series.

BACKGROUND: The aggressiveness of familial non-medullary thyroid cancer (FNMTC) has been a subject of debate. The purpose of the study was to determine whether FNMTC is more aggressive than sporadic thyroid cancer. METHODS: A multicenter retrospective matched-case control study of FNMTC versus sporadic non-medullary thyroid cancer was conducted. Disease-free survival (time to recurrence) for both groups was compared. RESULTS: Forty-eight familial cases were compared with 144 age-, gender-, and stage-matched controls. Patients with FNMTC had a significantly shorter disease-free survival compared with sporadic non medullary thyroid cancer. Patients with FNMTC who presented with evidence of distant metastasis, or who were from families with more than 2 thyroid cancer-affected members, had the worst prognosis. The available staging systems were less likely to predict the outcome in patients with FNMTC than in patients with sporadic non-medullary thyroid cancer unless one accounted for the strength of family history in the staging system. CONCLUSIONS: FNMTC is more aggressive than sporadic non-medullary thyroid cancer. The best predictors of a poor outcome in patients with FNMTC are the number of family members affected by thyroid cancer and evidence of distant metastasis.

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↗