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S Tezelman

Publications and source records attributed to S Tezelman.

18 recordsLinked to original sources

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

Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines.

Mutations in the tumor suppressor gene p53 are the most-common mutations found in human cancers. In thyroid cancers, p53 mutations generally are found only in poorly differentiated and undifferentiated tumors and in cell lines. To determine the prevalence of p53 mutations in thyroid neoplasms and thyroid cell lines, we screened 58 thyroid tissues and 3 thyroid cell lines, p53 primers bracketing exons 4, 5/6, 7, and 8 were used to amplify genomic DNA using the PCR. Mutations were screened by denaturing gradient gel electrophoresis and confirmed by sequencing. The two papillary thyroid cancer cell lines and the follicular thyroid carcinoma cell line (positive control) had transitions (CGT->CAT) in exon 8, codon 273, resulting in the replacement of arginine with histidine. No normal thyroid tissues or primary tumors from which the cell lines were derived demonstrated exon 8 mutations, using this technique. p53 immunocytochemistry demonstrated a progression of p53 immunopositivity between synchronous and metachronous neoplasms, paralleling the neoplastic progression from a benign adenoma to primary carcinoma, regional, and distant metastasis and ultimately, the cell lines, where intense immunopositivity is noted. In addition, fluorescence in situ hybridization, using probes specific for the p53 locus, revealed the presence of 3 homologues of p53 in the follicular cell line and 2 homologues in the papillary and Hürthle cell lines. These results suggest that a point mutation present in a small number of original tumor cells and amplification of the mutant allele may be responsible for immortalizing well-differentiated thyroid cancer cells into cell lines.

Adenocarcinoma, Follicular

Endoscopic retroperitoneal adrenalectomy.

BACKGROUND: The anterior transabdominal approach for adrenalectomy is associated with a longer postoperative recovery period than a posterior extraperitoneal adrenalectomy. The posterior approach is useful for patients requiring bilateral adrenalectomy or in those undergoing unilateral adrenalectomy for benign adenomas smaller than 5 cm. Recently transabdominal laparoscopic adrenalectomy has been used in patients with adrenal tumors. Endoscopic retroperitoneal adrenalectomy (ERA) is an alternative method that provides excellent exposure and should be associated with less postoperative morbidity. METHODS: Between 1993 and 1994 11 ERAs were performed in eight patients in the Department of Surgery, Istanbul Faculty of Medicine. The patients were placed in the prone semijackknife position on the operating table. After the retroperitoneal space was expanded with a balloon trochar, four 10 mm trochars were placed to perform the procedure. RESULTS: Among the eight female patients 23 to 65 years of age (mean, 42 +/- 12.4 years), three had bilateral adrenal hyperplasia caused by Cushing's disease, three patients had functioning adenoma, one patient had nonfunctioning adenoma (three on right and one on left adrenal), and one patient had right adrenal cyst. The mean operation time was 150 minutes (range, 90 to 300 minutes). No changes in PCO2 values have been found during intraoperative blood gas analyses. No intraoperative or postoperative complications occurred. All patients were discharged on the third postoperative day. CONCLUSIONS: ERA is a new and safe method of adrenalectomy. It is less invasive than the posterior approach. Patients treated by ERA seem to experience less postoperative pain and discomfort and have a shorter postoperative hospitalization and recovery period.

Adenoma

Persistent or recurrent hyperparathyroidism in patients with double adenomas.

BACKGROUND: Are double parathyroid adenomas a discrete clinical entity or are all hyperplastic parathyroid glands of varying size? This investigation was done to determine whether patients with persistent or recurrent hyperparathyroidism and double adenomas (DA) differ in clinical profile or in response to treatment from patients with hyperplasia. METHODS: From 1982 to 1993, 37 unselected patients with persistent (11) or recurrent hyperparathyroidism (26) were treated. Twenty-one had DA and 16 had hyperplasia. DAs were defined as two abnormal and two normal parathyroid glands. RESULTS: Patients with persistent or recurrent hyperparathyroidism caused by DA were older and had more muscle weakness, neuropsychiatric disorders, constipation, and weight loss (p < 0.001) than patients with persistent or recurrent hyperparathyroidism caused by hyperplasia. Nephrolithiasis was more common in patients with recurrent hyperparathyroidism caused by hyperplasia than in patients with recurrent hyperparathyroidism caused by DA (p < 0.001). Serum Ca2+ levels before operation were similar in these groups with variable parathyroid hormone levels. No recurrences occurred in either group (DA [mean, 6 yr]; hyperplasia [mean, 5 yr]). Postoperative levels of serum Ca2+ and parathyroid hormone were normal in both groups. CONCLUSIONS: Patients with persistent or recurrent hyperparathyroidism caused by DA are older, have different clinical manifestations, and are cured by resection of the second adenoma. These findings support the concept that DA and hyperplasia are distinct entities.

Adenoma

Immunoprecipitation isolates multiple TSH receptor forms from human thyroid tissue.

Attempts to purify the thyroid-stimulating hormone receptor (TSHR) have been complicated by its susceptibility to proteolysis and its low level of expression in thyrocytes and many transfected cells. Controversy exists over its size and structure. Multiple, single-polypeptide forms of the TSHR (230, 187, and 95-100 kDa) have been recently identified in immunoblots of crude plasma membranes prepared from COS-7 cells transfected with rat or human cDNA, but the relationship of these receptor species to the TSHR in human thyroid tissue has been heretofore unknown. We have developed a technique for immunoprecipitation of the TSHR which employed IgG purified from a polyclonal rabbit antiserum to TSHR residues 352-366. We have used immunoprecipitation to isolate the previously characterized 95-100 kDa TSH-holoreceptor, 187 kDa intermediate, and 230 kDa precursor forms of the TSHR from plasma membrane prepared from transfected COS-7 cells and human thyroid tissue. The presence of all three forms was not altered by the addition of reducing agent to the sample buffer, demonstrating the single polypeptide structure of the TSHR. This is, to our knowledge, the first report of the purification from transfected COS-7 cells of these TSHR species identified previously only in immunoblots of crude plasma membrane, and the first report of the identification by any means of these TSHR forms in human thyroid tissue. The isolation of TSHR from human thyroid tissue requires confirmation by direct means, but promises to make the receptor available in a soluble form for studies of its structure and function.

Cell Line

Biphasic effects of thyrotropin on invasion and growth of papillary and follicular thyroid cancer in vitro.

The rationale for TSH suppression in the treatment of follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC) is to inhibit tumor growth, prevent recurrent disease, and eventually prolong survival. We analyzed the effects of TSH on invasion and growth of 3 FTC cell lines from 1 patient (FTC133, primary; FTC236, lymph node; FTC238, lung metastasis) and 2 PTC cell lines (PTC-UC1, PTC-UC3). Cell growth and invasion through an 8-micron pore polycarbonate membrane coated with Matrigel were measured using the MTT assay. The dose-response to TSH was biphasic, stimulating invasion and growth of FTC and PTC at low concentrations (0.1-10 mU/mL), and inhibiting them at high concentrations (100 mU/mL). Interestingly, the metastatic FTC cell lines had higher basal invasion, but were less responsive to TSH than the primary tumor. TSH (1 mU/mL) stimulated invasion of FTC133 by 21%, FTC236 by 8%, and FTC238 by 8% (p < 0.01). At 100 mU/mL, TSH inhibited invasion of FTC133 by 21%, compared to 11% in FTC236 and 12% in FTC238. Also, TSH dose-dependently influenced proliferation of follicular thyroid cancer cells. At low concentrations it stimulated growth of FTC133 (20%) and inhibited it at high concentrations (23%; p < 0.01). Again, the amplitude of TSH effects was significantly smaller in the cell lines from metastatic tumors. TSH affected invasion and growth of PTC-UC1 and PTC-UC3 also biphasically. These results show that TSH may act as a mitogenic and antimitogenic growth factor for invasion and proliferation of well-differentiated thyroid cancer cells in vitro.

Adenocarcinoma, Follicular

Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy.

BACKGROUND: Primary hyperparathyroidism (HPT) occurs more frequently in persons who have been exposed to low-dose therapeutic radiation. Little information is available concerning whether or not the clinical, metabolic, and pathologic manifestations, as well as outcome, differ in these patients when compared with patients with sporadic HPT. STUDY DESIGN: Records from 438 unselected patients with primary HPT, who were treated from 1982 to 1993 were retrospectively analyzed. All patients prospectively received a standard questionnaire preoperatively and postoperatively concerning clinical manifestations and a history of radiation exposure. Forty-nine patients had a history of radiation exposure (rHPT), whereas 389 did not have sporadic HPT (sHPT). RESULTS: There was no difference in gender (36 women and 13 men versus 289 women and 100 men) or age (mean of 52 +/- 12 versus 57 +/- 16 years) in patients with rHPT or sHPT. Fatigue, neuropsychiatric disorders, memory loss, nocturia, and polyurea were more common in patients with sHPT (p < 0.05), whereas pain in joints was more common in patients with rHPT (63 versus 52 percent; p < 0.001). Serum calcium levels were similar (11.1 +/- 0.8 versus 11.2 +/- 0.8 mg per dL), but serum parathyroid hormone levels were higher in rHPT (448 +/- 14 percent of upper limit of normal versus 371 +/- 12 percent upper limit of normal). The parathyroid pathology was similar in the two groups (single adenoma 74 versus 72 percent, hyperplasia 14 versus 16 percent, and double adenoma 12 versus 12 percent in rHPT versus sHPT, respectively). Thyroid pathology was more common in the rHPT group (multinodular goiter 27 versus 7 percent and papillary thyroid carcinoma 14 versus 0.3 percent). Seven (1.8 percent) of patients not receiving radiation therapy treated by us had persistent HPT, but no patients receiving or not receiving radiation therapy had recurrent HPT during the follow-up period (six years). CONCLUSIONS: Patients who have HPT after radiation treatment have more thyroid neoplasms but are otherwise quite similar to other patients with primary hyperparathyroidism.

Adolescent

Comparison of preoperative imaging techniques (thallium technetium scan and ultrasonography) and intraoperative staining (with methylene blue) in localizing the parathyroid glands.

We carried out a prospective study to compare the predictive value of preoperative thallium technetium scan, ultrasound (US) and intraoperative staining of the parathyroid glands (with methylene blue) in patients with parathyroid adenoma, parathyroid hyperplasia, thyroid carcinoma and thyrotoxicosis, in the Istanbul School of Medicine, Department of General Surgery. Methylene blue was given at a dose of 5 mg/kg/body weight in a 500 ml 5% Dextrose +0.9% saline solution 1 hour before surgery. All adenomas (10 patients), hyperplastic parathyroid glands (12 patients) and 45 of 52 suppressed glands (82%) were stained. In patients with thyroid carcinoma (7) and thyrotoxicosis (5), 42 of 48 normal parathyroid glands (87%) were stained. There were no maneuver-related complications. Thallium technetium scan (TT) accurately identified 10 of 10 (100%) parathyroid adenomas and 13 of 26 (50%) hyperplastic parathyroid glands. US successfully localized 10 of 10 (100%) adenomas and 18 of 26 (66%) hyperplastic glands. Neither technique was successful in identifying normal glands. The intraoperative identification of the parathyroid glands with methylene blue was found to be an effective, safe and cost-effective technique which helps the surgeon in the dissection and shows abnormal parathyroid glands more accurately than preoperative imaging techniques.

Adult

Localization procedures in patients with persistent or recurrent hyperparathyroidism.

OBJECTIVE: To determine the accuracy of noninvasive and invasive localization studies in patients with persistent or recurrent hyperparathyroidism (HPT). DESIGN AND SETTING: Reoperations based on patients who were treated surgically for recurrent or persistent HPT at the University of California-San Francisco Hospitals from 1982 to 1993. PATIENTS: This study evaluated 174 localization studies performed in 152 patients before reoperation (110 women and 42 men). MAIN OUTCOME MEASURES: The accuracy of localization studies, including ultrasonography, thallous chloride T1 201-technetium Tc 99m pertechnetate scanning, technetium Tc 99m sestamibi scanning, magnetic resonance imaging, computed tomography, and selective venous catheterization, were evaluated, as were the results of parathyroid reoperations. RESULTS: A total of 174 consecutive reoperations were performed in 152 patients with HPT (persistent, 113; recurrent, 39; mean age, 54 years; range, 21 to 88 years). One hundred thirty-three patients had primary HPT, 15 had secondary HPT, and four had tertiary HPT. Overall, 141 (93%) became normocalcemic, two (1%) became hypocalcemic, and nine (6%) remained hypercalcemic. Abnormal parathyroid glands at reoperation were situated in a normal location in 77 cases (44%), in the mediastinum in 37 cases (22%), in a deep cervical location in 34 cases (19%), or in an intrathyroidal location in 14 cases (8%), or were undescended in four cases (2%); supernumerary glands were found in 26 cases (15%). Some patients had more than one remaining abnormal gland. Selective venous catheterization with a parathyroid hormone assay was done in cases in which the results of noninvasive localization studies were equivocal or negative, and it frequently converted an equivocal result of a localization study to a definitely positive result. There were no complications from the localization studies. At reoperation, permanent hypoparathyroidism that required parathyroid autotransplantation of cryopreserved tissue developed in two patients and two patients had recurrent laryngeal nerve palsies. CONCLUSION: We currently recommend using ultrasonography and technetium Tc99m sestamibi scanning and magnetic resonance imaging for patients with recurrent or persistent HPT. Selective venous catheterization with a parathyroid hormone assay is done selectively. Localization tests decrease morbidity and improve overall results in these patients.

Adult

Desensitization of adenylate cyclase in Chinese hamster ovary cells transfected with human thyroid-stimulating hormone receptor.

Desensitization or decreased response to the same (homologous) or other stimuli (heterologous) is a well known process. Homologous desensitization to TSH has been demonstrated in normal thyroid tissue. Chinese hamster ovary cells (CHO) transfected with normal human TSH receptor (hTSHR) DNA, in contrast, have been reported not to desensitize. The purpose of our investigation was to determine whether CHO cells transfected with hTSHR desensitize in response to TSH and postreceptor stimulation. CHO cells were stably transfected with plasmid DNA containing hTSHR; nontransfected CHO cells served as the control. TSH (10 mU/ml), 5'-beta,gamma-imido-triphosphate [Gpp(NH)p; 0.1 mM], sodium fluoride (NaF; 10 mM), forskolin (10 microM), and (Bu)2cAMP (100 microM) were used to determine whether homologous or postreceptor heterologous desensitization of adenylate cyclase activity occurred in CHO-transfected cells. Intracellular cAMP accumulation was determined by RIA. Cells were incubated with TSH (to stimulate TSH receptor), Gpp(NH)p, NaF (to stimulate G-protein), forskolin (to stimulate adenylate cyclase activity), and (Bu)2cAMP (nonmetabolized cAMP analog). A second incubation was carried out with TSH (10 mU/ml). Maximal desensitization to either TSH or postreceptor stimulation was observed at 2 h. When transfected CHO cells were preexposed to TSH (10 mU/ml) for 4 h, even the smallest dose of TSH (0.001 mU/ml) caused desensitization. All substances that increased the intracellular cAMP concentration, such as TSH, Gpp(NH)p, NaF, forskolin, and (Bu)2cAMP, caused desensitization. The decrease in the cAMP response to TSH added in the second incubation was 63% less than the initial response to TSH or to postreceptor stimulation (P = 0.0001). In conclusion, desensitization of hTSHR-transfected CHO cells occurs in response to both receptor and postreceptor stimulation that increase cAMP levels. Because hTSHR transfected CHO cells desensitize, no specific thyroid factor(s) other than increased levels of cAMP is required.

Adenylyl Cyclases

Thyrotropin stimulates invasion and growth of follicular thyroid cancer cells via PKC- rather than PKA-activation.

The signal transduction of TSH in invasion and growth of FTC 133, a human follicular thyroid cancer cell line, was investigated. TSH (0.01-1 mIU/ml) stimulated invasion of FTC 133 by 21% and growth by 20% of basal. Cyclic AMP-stimulators and inhibitors had no effect at any concentration. The PKC-agonist TPA enhanced invasion and growth by 15%, whereas staurosporine, a PKC-antagonist, inhibited them by 32% and 60%, respectively. The latter also reversed TSH stimulation. EGF enhanced invasion (42%) and growth of FTC 133 (25%). Staurosporine did not reverse EGF stimulation. The tyrosine kinase antagonist genistein reversed EGF, but not TSH stimulation. Pertussis toxin inhibited invasion (18%) and growth (22%). Cholera toxin was less inhibitive. We demonstrated for the first time, that TSH stimulates invasion and growth of human thyroid cancer cells in vitro by PKC- rather than PKA-stimulation.

Alkaloids

Tumoral calcinosis. Controversies in the etiology and alternatives in the treatment.

OBJECTIVE: To examine our experience and review the literature concerning the diagnosis, origin, and treatment of tumoral calcinosis (TC). DESIGN/SETTING: Case series based on patients with TC treated in University of California-San Francisco hospitals from 1981 to 1992 and the review of the patients described in the English-language literature. PATIENTS: The study included a total of 17 patients: 10 women and seven men. MAIN OUTCOME MEASURES: Sex, age, origin, symptoms, localization, treatment, and morbidity. RESULTS: Seven men and six women, from 32 to 62 years of age, had known disorders of calcium metabolism, and four women, from 37 to 84 years of age, did not. The main causes of the calcium metabolic disorder were secondary hyperparathyroidism in 11 patients (85%) and primary hyperparathyroidism in two patients. In three patients there was a history of trauma at the involved site and in one patient the origin was unknown. Swelling and pain are the most common presenting complaints. Generalized pruritus was observed in 54% of the patients with metabolic disorders (P < .001) but not in patients without metabolic disorders. Among our patients with metabolic disorders, TC occurred most frequently at the shoulder (46%) and elbow (31%). Eleven patients with secondary hyperparathyroidism had received calcium carbonate to bind phosphate, a high level of calcium in the dialysate, and calcitriol (1,25-vitamin D) either orally, intravenously, or both, and three received epoetin alfa (Epogen). Following parathyroidectomy, the patients with hyperparathyroidism improved symptomatically, although calcifications did not change in size. One patient had the calcifications resected and did well, whereas another was treated by subtotal resection and had a recurrence 3 years later. All four of our patients without a metabolic disorder had complete resection of TC with no recurrence. CONCLUSION: We believe TC is becoming more common in uremic patients with secondary hyperparathyroidism because of recent changes in the medical treatment of these patients. The increased use of calcium carbonate to bind phosphate as well as calcitriol and calcium to suppress parathyroid function and possibly epoetin alfa are causing more patients to develop TC.

Adult

Concurrent hyperthyroidism and thyroid carcinoma.

Between 1986 and 1991, thyroidectomy was performed on 138 patients with hyperthyroidism. Thyroid carcinoma was found in eight patients (5.8 per cent). Eighty (58.0 per cent) of the 138 patients had toxic nodular goitre, 33 (23.9 per cent) toxic diffuse goitre and 25 (18.1 per cent) toxic adenoma. Concurrent carcinoma was more frequent in patients with toxic adenoma (8 per cent) than in those with Graves' disease (6 per cent) and toxic nodular goitre (5 per cent). Papillary carcinoma was found in seven patients and follicular carcinoma in one. Three papillary carcinomas were occult with a diameter less than 1.5 cm. Five patients received 100 mCi 131I after operation. There was no morbidity. During follow-up of 10-45 months, there was neither death nor recurrence.

Adenocarcinoma, Follicular

Double parathyroid adenomas. Clinical and biochemical characteristics before and after parathyroidectomy.

OBJECTIVE: There is considerable debate about whether double parathyroid adenomas are a discrete entity or represent hyperplasia with parathyroid glands of varying sizes. This distinction is important because it impacts on the extent of parathyroid resection and the success of the parathyroid operation. SUMMARY BACKGROUND DATA: Double parathyroid adenomas have been reported to occur in 1.7% to 9% of patients with primary hyperparathyroidism (HPT). It is important for surgeons to differentiate between double adenoma and hyperplasia with glands of varying sizes using gross examination during the initial procedure because microscopic findings of a small biopsy specimen at frozen-section examination may not be diagnostic. METHODS: From 1982 to 1992, 416 unselected patients (309 women and 107 men) with primary HPT without familial HPT or multiple endocrine neoplasia (MEN) were treated by one surgeon at the University of California at San Francisco. Double adenoma occurred in 49 patients, solitary adenoma in 309 patients, and hyperplasia in 58 patients. The authors analyzed the clinical manifestations, the preoperative and postoperative serum levels of calcium, phosphate, and parathyroid hormone (PTH), and the success rate and outcome after parathyroidectomy and compared their results in 49 patients with double adenomas to the results for patients with solitary adenomas or hyperplasia. RESULTS: Ten of the patients with double adenomas (20.4%) were referred for persistent HPT after removal of one abnormal parathyroid gland. The ages of the patients with double adenoma, single adenoma, and hyperplasia were 61 +/- 14, 56 +/- 15, and 58 +/- 7 years, respectively. Fatigue, muscle weakness, and bone pain were common in patients with double adenomas, whereas nephrolithiasis occurred more frequently in patients with solitary adenoma (p = 0.0001). Serum calcium and PTH levels (per cent of upper limit of normal) fell from 11.5 +/- 1.2 mg/dL and 487% to 9.5 +/- 0.8 mg/dL and 61% for patients with double adenomas; from 11.9 +/- 0.9 mg/dL and 378% to 9.3 +/- 1.4 mg/dL and 101% for patients with single adenoma; and from 10.9 +/- 0.5 mg/dL and 418% to 9.1 +/- 0.7 mg/dL and 94% for patients with hyperplasia, respectively. There was no recurrence in the patients with double adenomas with a mean follow-up time of 5.8 years. CONCLUSIONS: Double adenomas are a discrete entity and occur more often in older patients. Patients with double adenomas can be successfully treated by removal of the two abnormal glands.

Adenoma

Thyroid-stimulating hormone activates phospholipase C in normal and neoplastic thyroid tissue.

BACKGROUND: Thyroid-stimulating hormone (TSH) stimulates thyroid growth through two signal transduction pathways: the G protein-adenylate cyclase system and the G protein-phospholipase C (PLC) system. The adenylate cyclase system has been studied extensively, but there is little information available concerning PLC activity in thyroid neoplasms. METHODS: Human thyroid membranes were incubated for 30 minutes at 37 degrees C in the presence or absence of bovine TSH (300 mU/ml). PLC activity was assayed by liberation of inositol phosphates from the enzymatic hydrolysis of tritiated phosphatidylinositol bisphosphate. Fifty-six tissues were assayed (normal, 23; multinodular goiter, 5; follicular adenoma, 9; and differentiated thyroid cancer, 19 [9 low risk and 10 high risk]). RESULTS: TSH significantly increased PLC activity in normal, benign, and most malignant thyroid neoplasms. Although there were no differences in basal or TSH-stimulated PLC activity between the groups of normal thyroid, multinodular goiter, follicular adenoma, or the cancers, one half of the high-risk cancers had an aberrant PLC response. CONCLUSIONS: This is the first demonstration that TSH stimulates PLC activity in normal and neoplastic human thyroid tissue. Aberrant TSH-stimulated PLC activity was present in half of the aggressive thyroid neoplasms.

Enzyme Activation

Transhiatal oesophagectomy for oesophageal carcinoma.

Between 1979 and 1990 transhiatal oesophagectomy and reconstruction with stomach was performed in 148 patients with carcinoma of the oesophagus. Ninety-seven patients were men and 51 were women; ages ranged from 21 to 88 years with a mean of 57.4 years. Dysphagia and weight loss were the usual clinical symptoms. The mean duration of symptoms was 14 weeks. Squamous cell carcinoma was present in 129 patients (87.2 per cent), 18 patients (12.2 per cent) had adenocarcinoma, and one had lymphoma (0.7 per cent). In two-thirds of the patients tumours were located in the middle thoracic (50 of 148 patients) or distal thoracic oesophagus (59 of 148 patients). Three-quarters of the patients had tumours determined as stage III. The mean length of hospital stay after operation was 12.8 days. Anastomotic leakage occurred in 15 cases (10.1 per cent). Pulmonary complications other than pneumothorax were observed in 36 cases (24.3 per cent). The 30-day postoperative mortality rate was 8.1 per cent (12 of 148 patients). Respiratory insufficiency was observed as the major cause of death (six of 12 patients). Mediastinitis due to necrosis of the transposed stomach in the mediastinum was the cause of death in three cases. Two-year actuarial survival rates in patients with cervical, upper, middle and lower thoracic tumours were 20, 22, 26 and 30 per cent respectively. Transhiatal oesophagectomy is safe and offers limited morbidity and mortality, although pulmonary complications and anastomotic leakage in the early postoperative period still pose a significant risk, especially for elderly patients in poor condition.

Adult

Radioiodine-associated thyroid cancers.

Numerous investigations document that exposure to low dose external therapeutic radiation leads to the development of benign and malignant thyroid neoplasms. There is considerable controversy, however, concerning whether radioactive iodine (131I) causes thyroid cancer. The aim of this investigation was to examine our experience and that in the literature related to this problem. From 1982 to March 1993 seven of 373 patients (1.9%) with thyroid cancer who were treated by one surgeon had a history of treatment with radioactive iodine for Graves' disease and toxic nodular goiter. Sixty-five patients have previously been reported in the literature from 1957 to present. Our patients (five women, two men) ranged in age from 26 to 80 years (mean 57 years). The interval between the exposure to the internal radiation and development of cancer ranged from 3 to 29 years (mean 11.4 years), and the mean age at the time of 131I treatment was 45 years (18-76 years). The therapeutic dose of 131I was 5 to 100 mCi (mean 25.3 mCi) in our patients. Two of our patients received 131I twice. The age of patients reported in the literature at the time of 131I treatment ranged from 7 to 74 years (mean 48 years). The mean therapeutic dose of 131I was 20.6 mCi (1.25-180.0 mCi) and the latent period was documented for a mean 8.7 years (0.25-28.0 years) in these patients. Three of 29 patients in the literature received 131I twice. Fine-needle aspiration cytology of thyroid nodules was positive for cancer in six of our patients (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular