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1.
J Intern Med ; 258(1): 55-66, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15953133

RESUMO

OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997. PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment. SETTING: One referral centre for all patients from the western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra- or post-operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre- and post-operative hypertension did not influence the risk for death versus controls. CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Feocromocitoma/cirurgia , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Medula Suprarrenal/patologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hiperplasia , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Paraganglioma/mortalidade , Paraganglioma/patologia , Paraganglioma/cirurgia , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Período Pós-Operatório , Cuidados Pré-Operatórios/métodos , Receptores Adrenérgicos alfa/administração & dosagem , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
2.
Br J Surg ; 91(6): 713-8, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15164440

RESUMO

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.


Assuntos
Cromossomos Humanos Par 10/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Mutação/genética , Proteínas Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Fenótipo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret
3.
Br J Cancer ; 89(11): 2093-7, 2003 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-14647143

RESUMO

Our objective was to examine the usefulness of the Ki67 proliferation index as a prognostic marker in patients with medullary thyroid carcinoma (MTC). It is difficult to predict the prognosis of MTC by using conventional prognostic factors. Immunocytochemical analysis of tumour proliferation has been used as a prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from 36 patients were investigated, by using a semiautomatic image analysis programme. On average 10,000 nuclear profiles were counted per tumour, and the percentage of tumour cells expressing the proliferation marker, Ki67, was calculated. Primary tumours that had metastasised had higher Ki67 indices than primary tumours that had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices than the primary tumours. By using a Poisson model, it was possible to estimate the median survival time for individual patients if the Ki67 index for the primary tumour and the age at surgery were known. The higher the Ki67 index and the age at operation were, the shorter was the survival. Estimating the median survival of individual patients will be of help for planning the patients' life and postoperative follow-up and treatment.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Medular/diagnóstico , Antígeno Ki-67/análise , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Feminino , Humanos , Imuno-Histoquímica , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Prognóstico , Tireoidectomia , Proteína Supressora de Tumor p53/análise
4.
Eur J Surg ; 167(8): 587-91, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11716444

RESUMO

OBJECTIVE: To find out whether preoperative parathyroid localisation studies are cost-effective in patients with persistent hyperparathyroidism (HPT). DESIGN: Retrospective study. SETTING: University hospital, Sweden. PATIENTS: 29 consecutive patients with persistent HPT who were reoperated on with or without localisation studies. 15 other patients had initial operations for HPT without localisation studies. INTERVENTIONS: Initial or repeat operation for HPT, localisation studies with 99mTc sestamibi scintigraphy, and catheterisation of large cervical and mediastinal veins with measurements of serum concentrations of parathyroid hormone. MAIN OUTCOME MEASURES: Operative time. Cost of operations, frozen section biopsy and localisation studies. RESULTS: The mean durations of reoperation with localisation studies and for the initial operation without them, were 124 and 135 minutes, respectively, while it was 269 minutes for reoperation without studies. For patients who had localisation studies the mean total cost of the investigations, operating time, and frozen section biopsy was 28% less than for patients who were reoperated on without such studies. CONCLUSION: Preoperative localisation studies before repeat operations for HPT were cost-effective. Even if it has not been shown in this series, the reduction in operating time and the extent of dissection by localisation studies has the potential to decrease morbidity.


Assuntos
Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/economia , Paratireoidectomia/economia , Cuidados Pré-Operatórios/economia , Biópsia/economia , Cateterismo Venoso Central/economia , Análise Custo-Benefício , Feminino , Humanos , Hiperparatireoidismo/diagnóstico por imagem , Hiperparatireoidismo/cirurgia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Radiografia Intervencionista/economia , Cintilografia , Compostos Radiofarmacêuticos , Recidiva , Reoperação , Estudos Retrospectivos , Tecnécio Tc 99m Sestamibi
5.
Lakartidningen ; 98(35): 3690-1, 3694-5, 2001 Aug 29.
Artigo em Sueco | MEDLINE | ID: mdl-11577645

RESUMO

A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of this specific RET mutation in a large Swedish family. The family was mapped back to the 18th century. Since 1971 the family has been included in a biochemical screening program, and since 1994 has undergone genetic screening. Twenty-seven individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were detected by screening. The incidence of pheochromocytoma (4%) and hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none had been included in the screening program. One patient underwent prophylactic thyroidectomy after positive genetic screening. MTC tumor aggressivity differed markedly between gene carriers. The screening program shows that the clinical aggressivity of MTC can be mitigated by early and adequate surgical intervention.


Assuntos
Regulação da Expressão Gênica , Neoplasia Endócrina Múltipla Tipo 2a/genética , Mutação de Sentido Incorreto , Fenótipo , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/genética , Hiperparatireoidismo/cirurgia , Masculino , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Linhagem , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/cirurgia , Proto-Oncogene Mas , Suécia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
6.
Ann Surg ; 233(1): 60-4, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11141226

RESUMO

OBJECTIVE: To evaluate randomly the effect of thyrostatic treatment (tiamazole) versus selective (metoprolol) and nonselective beta-blockade (propranolol) on whole-body energy metabolism in women with hyperthyroidism. SUMMARY BACKGROUND DATA: beta-blockade is used as an alternative to thyrostatic drugs in the preoperative treatment of patients with hyperthyroidism. beta-blockers have well-established symptomatic effects, but in contrast to antithyroid drugs beta-blockade is thought to lack direct effects on the increased metabolism in hyperthyroidism. METHODS: Whole-body oxygen consumption and carbon dioxide production was measured in a semiopen canopy system with paramagnetic O2 and infrared CO2 sensors. A constant flow generator and the gas-dilution method for calculation of gas flow were used. Anabolic parameters were body weight, triceps skinfold, and arm muscle circumference. RESULTS: Tiamazole normalized oxygen consumption and induced signs of anabolism with improved nutritional state. Metroprolol did not affect oxygen consumption. Propranolol reduced elevated oxygen consumption by 54%. Body weight and other anthropometric assessments were stable after specific and nonspecific beta-blockade, which also led to symptomatic relief in approximately 90% of the patients. CONCLUSION: Tiamazole was the most effective drug to oppose the adverse effects of hyperthyroidism. Therefore, thyrostatic agents are recommended for preoperative treatments of patients with severe catabolic hyperthyroidism. Whenever beta-blockers are chosen for treatment of hyperthyroidism, propranolol (beta 1 + beta 2) has an advantage because it reduces the metabolic rate, whereas selective beta 1-blockade seemed to provide only symptomatic relief, related to the normalization of heart rate.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antitireóideos/uso terapêutico , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/metabolismo , Metimazol/uso terapêutico , Metoprolol/uso terapêutico , Consumo de Oxigênio/efeitos dos fármacos , Propranolol/uso terapêutico , Adulto , Idoso , Análise de Variância , Dióxido de Carbono/metabolismo , Feminino , Humanos , Hipertireoidismo/cirurgia , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Prospectivos , Resultado do Tratamento
7.
J Nucl Med ; 41(4): 636-42, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10768564

RESUMO

UNLABELLED: The purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide. METHODS: Concentrations of 111In activity in human thyroid tumors and normal thyroid tissue and blood samples were determined 1-15 d after intravenous injection of 111In-diethylenetriaminepentaacetic acid-Phe1-octreotide. The results were compared with SS receptor (sstr subtype profile (by Northern blot analysis) and the relative expression of the second subtype, sstr2 (by ribonuclease protection assay, RPA). The true tumor volumes in lymph node metastases from 1 patient were estimated. In total, tissues from 68 patients were included in the study. RESULTS: The highest tumor-to-blood ratio (T/B) for medullary thyroid carcinoma (MTC) was 360; for follicular adenoma (FA), 190; for Hurthle cell adenoma (HCA), 140; and for Hurthle cell carcinoma (HCC) and papillary carcinoma (PC), 70. The corresponding value was 7-18 for normal thyroid tissue, with higher values for colloid goiter (8-48) and thyroiditis (7-120). A high T/B was related to a large fraction of tumor cells in lymph node metastases. T/Bs were higher for the tumor samples with expression of sstr2 at Northern blot analysis than for those without. All thyroid tumor types regularly expressed sstr1, sstr3, sstr4, and sstr5. sstr2 was expressed in most MTC tumors but was not detected in FA or PC and was irregularly expressed in HCA and HCC. However, RPA analysis detected sstr2 in all tumors studied. CONCLUSION: Despite the lack of sstr2 at Northern blot analysis in most of the thyroid tumors studied, high T/Bs were in general found when compared with corresponding values for normal thyroid tissue. The sometimes extremely high ratios are promising and indicate a possibility of using radiolabeled octreotide for radiation therapy of sstr-positive tumors in the future.


Assuntos
Radioisótopos de Índio/uso terapêutico , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Receptores de Somatostatina/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Northern Blotting , Humanos , Metástase Linfática , Octreotida/farmacocinética , Octreotida/uso terapêutico , Ácido Pentético/farmacocinética , Ácido Pentético/uso terapêutico , RNA Mensageiro/genética , Compostos Radiofarmacêuticos/uso terapêutico , Receptores de Somatostatina/classificação , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo
8.
Eur J Surg ; 165(7): 628-31, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10452255

RESUMO

OBJECTIVE: To characterise the cholecystokinin (CCK) receptor subtypes in medullary thyroid cancer by measuring the expression of CCK-A and CCK-B/gastrin receptor mRNA. DESIGN: Open study. SETTING: Teaching hospital, Sweden. SUBJECTS: 6 patients with medullary thyroid cancer. INTERVENTION: Pentagastrin stimulation test and measurement of calcitonin concentration. Biopsy specimens were analysed using reverse transcription polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE: Presence of CCK-A and CCK-B/gastrin receptors. RESULTS: All 6 patients with medullary thyroid cancer had positive pentagastrin tests preoperatively. CCK-B/gastrin receptors but not CCK-A receptors were detected by RT-PCR in all six biopsy specimens. By contrast, no CCK receptors were found in normal thyroid tissues or in other thyroid tumours (follicular adenoma, papillary carcinoma, or anaplastic carcinoma). CONCLUSION: The presence of CCK-B/gastrin receptors in medullary thyroid tumours may have important clinical implications.


Assuntos
Carcinoma Medular/química , Regulação Neoplásica da Expressão Gênica/fisiologia , Receptores da Colecistocinina/análise , Neoplasias da Glândula Tireoide/química , Adulto , Idoso , Sequência de Bases , Biópsia , Carcinoma Medular/genética , Carcinoma Medular/patologia , Primers do DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores da Colecistocinina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
9.
Br J Cancer ; 80(8): 1259-61, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10376980

RESUMO

The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated.


Assuntos
Tumor Carcinoide/patologia , Neoplasias Intestinais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
11.
Br J Cancer ; 79(9-10): 1579-82, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10188909

RESUMO

Ten consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood (111)In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of (111)In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.


Assuntos
Adenoma Oxífilo/metabolismo , Proteínas de Neoplasias/metabolismo , Ácido Pentético/análogos & derivados , Receptores de Somatostatina/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adenoma Oxífilo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Northern Blotting , Feminino , Humanos , Radioisótopos de Índio/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Octreotida/análogos & derivados , RNA Mensageiro/metabolismo , Cintilografia , Receptores de Somatostatina/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem
13.
J Intern Med ; 243(6): 521-6, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9681853

RESUMO

Residual or recurrent medullary thyroid carcinoma (MTC), manifested by elevated calcitonin levels, occurs commonly following primary treatment of MTC. Re-operation in appropriately selected patients is the only treatment modality which consistently and reliably reduces stimulated calcitonin levels, and results in excellent local disease control. We report improved results of surgical management of recurrent MTC in two consecutive series of patients. In our most recent series (1992-96), 38% of patients (17 out of 45) had normal postoperative stimulated calcitonin levels, compared to 28% (nine of 32) in our first series (1990-92). In the most recent series, only 13% (six of 45) of patients had no decrease in calcitonin levels following re-operation, compared to 31% (10 of 32) in our first series (P = 0.07, Fisher's exact test). This improvement has mainly occurred through better preoperative selection of patients, and the institution of routine laparoscopic liver examination preoperatively, which identified metastases in 10 patients, nine of whom had normal CT or MRI imaging.


Assuntos
Carcinoma Medular/cirurgia , Neoplasia Endócrina Múltipla/complicações , Neoplasias da Glândula Tireoide/cirurgia , Adolescente , Adulto , Carcinoma Medular/genética , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Neoplasias da Glândula Tireoide/genética , Resultado do Tratamento
14.
World J Surg ; 22(7): 679-83, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9606281

RESUMO

Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.


Assuntos
Hormônios/uso terapêutico , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/uso terapêutico , Receptores de Somatostatina/análise , Adenocarcinoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Medular/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Neoplasias da Glândula Tireoide/diagnóstico por imagem
15.
World J Surg ; 22(6): 605-11; discussion 611-2, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9597936

RESUMO

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. It has been difficult to establish a strict treatment program for ACC, and better treatment alternatives and diagnostic tools must be sought. Even though surgery is the treatment of choice, the role of surgery in advanced disease has been questioned. Eighteen consecutive patients were treated at our unit over a 22-year period (1975-1997). All patients underwent surgery and were followed by our protocol, which includes urinary steroid profiles, clinical examinations, analysis of steroid hormones, and radiologic investigations. Twelve patients received mitotane with drug concentration measurements to deliver an effective, nontoxic dose. The median duration of mitotane treatment was 12 months. Few side effects were observed. Four patients with low-stage tumors underwent second-look operations with no pathologic findings. Five patients were subjected to repeat operations, and the mean duration of the disease-free interval before repeat surgery for these patients was 59 months. There was a significant positive correlation between the disease-free interval and the observed survival after repeat surgery. Eleven patients with intentionally curative surgery had their urinary steroid profiles tested several times postoperatively. For five patients preoperative urine samples were also available. Steroid profiles indicated recurrent disease despite normal radiologic findings in two of these five patients. The follow-up ranged from 6 weeks to 24 years. The predicted 5-year survival was 58% according to the Kaplan-Meier method. We conclude that monitoring serum concentrations of mitotane makes long-term treatment possible with few side effects; steroid profile analysis can be used for early detection of tumor recurrence; and repeat surgery for recurrence is of value for patients with long disease-free intervals.


Assuntos
Neoplasias do Córtex Suprarrenal/terapia , Antineoplásicos Hormonais/uso terapêutico , Mitotano/uso terapêutico , 17-Hidroxicorticosteroides/urina , 17-Cetosteroides/urina , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/urina , Adulto , Idoso , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/urina , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitotano/administração & dosagem
16.
Br J Surg ; 84(4): 543-7, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9112914

RESUMO

BACKGROUND: 111In-radiolabelled (DTPA-D-Phe1)-octreotide scintigraphy can be used to localize neuroendocrine tumours expressing somatostatin receptors (SSTRs). The aim of this paper was to analyse the importance of tumour volume and growth for the visualization by SSTR scintigraphy of metastases from medullary thyroid carcinoma (MTC). METHODS: Serum calcitonin concentrations were used to estimate volume and growth rate of MTC. Twenty-two patients who had persistent hypercalcitoninaemia after total thyroidectomy for MTC, indicating the presence of metastases, were studied. RESULTS: SSTR scintigraphy visualized 15 tumours in 11 patients. Patients with scintigraphically visualized tumours had higher serum calcitonin and carcinoembryonic antigen concentrations and larger tumours, and the serum calcitonin concentration increased more rapidly with time. Tumour-associated symptoms and death from MTC occurred only in patients with scintigraphically visualized tumours. CONCLUSION: Scintigraphically visualized tumours grow more rapidly and are more aggressive than nonvisualized lesions. SSTR scintigraphy can be helpful in the planning of palliative surgery for MTC and for diagnosing distant metastases, but cannot localize microscopic metastases.


Assuntos
Receptores de Somatostatina/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Northern Blotting , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/complicações , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Cintilografia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
17.
Lakartidningen ; 94(10): 829-30, 835-8, 1997 Mar 05.
Artigo em Sueco | MEDLINE | ID: mdl-9102509

RESUMO

Verification of the presence of somatostatin receptors on neuroendocrine tumour cells opened up unique diagnostic and therapeutic possibilities. Long-acting somatostatin analogues are currently used to alleviate symptoms of excessive hormone synthesis in patients with such tumours. Radiolabelled somatostatin analogues can be used both for high specificity and high sensitivity scintigraphic localisation of such tumours and for intraoperative scintillation detection. Detailed studies in patients and in tumour cells in vitro have shown 111In-octreotide uptake to be high and retention times long in tumour tissue, and have yielded evidence of intracellular localisation of the radionuclide. These findings thus showed somatostatin receptor-mediated radiotherapy to be a possible treatment alternative after close characterisation of the individual tumour. In the future, it may be possible to use other peptide receptors (e g, growth factor receptors) according to the same principles as applied in the case of somatostatin receptors.


Assuntos
Tumores Neuroendócrinos , Receptores de Somatostatina , Autorradiografia , Terapia Combinada , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/terapia , Cintilografia , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo
18.
Yale J Biol Med ; 70(5-6): 523-33, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9825479

RESUMO

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).


Assuntos
Radioisótopos de Índio , Receptores de Somatostatina/análise , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Adenoma Oxífilo/diagnóstico por imagem , Adulto , Idoso , Northern Blotting , Carcinoma Medular , Carcinoma Papilar/diagnóstico por imagem , Feminino , Humanos , Radioisótopos de Índio/análise , Radioisótopos de Índio/sangue , Metástase Linfática/diagnóstico , Masculino , Octreotida , Cintilografia , Receptores de Somatostatina/genética
19.
Eur J Endocrinol ; 135(4): 469-80, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8921831

RESUMO

Epithelial properties of thyrocytes are difficult to maintain in conventional cell culture systems. We used bicameral chambers (Transwell) in attempts to establish a functional epithelium of thyrocytes of human origin. Thyroid follicle segments were isolated by collagenase digestion of paradenomatous tissue obtained at surgery for follicular adenoma and of tissue from glands with Graves' disease. After careful separation from connective tissue and single cells by centrifugation, the follicles were plated at high density on the collagen-coated filter of the chambers and cultured in Eagle's essential medium (EMEM) containing 10% fetal calf serum (FCS) or Coon's modified Hams medium enriched with five or six factors (5H, 6H); the latter media contained 5% FCS without (5H) or with (6H) thyrotropin (TSH). The follicles were converted into a confluent cell layer, which had similar DNA content irrespective of type of medium, after 4-6 days. Cells grown in EMEM or 5H established a transepithelial electrical resistance (R) of 200-500 omega.cm2 and was impermeable to [3H]inulin, indicating the formation of epithelial junctions. Addition of 6H to confluent cells initially cultured in EMEM or 5H caused a further increase of R, maximally to 1500 omega.cm2, along with a rise of the transepithelial potential difference; 6H promoted the monolayer formation of cells, increased the number of apical microvilli and reinforced the junctional distribution of actin, cadherin and ZO-1; 6H also enhanced the polarized secretion of [3H]leucine-labeled thyroglobulin into the apical medium. Cells from Graves' thyroid tissue established an epithelium on the filter with similar characteristics to that of normal thyrocytes; some platings contained in addition large numbers of HLA-DR positive cells with a dendritic shape. HLA-DR expression was generally absent in EMEM-or 5H-grown thyrocytes, but appeared in limited areas of the cell layer after 6H and was expressed by all epithelial cells after interferon-gamma stimulation for 48 h. We conclude that human thyrocytes form a tight and polarized epithelium when cultured on permeable filters. The polarized structure and function of the cells are positively regulated by TSH. The culture system may be useful in studies addressing the role of the epithelial phenotype (cell polarity and tight barrier) in normal thyroid function as well as in pathological processes in the thyroid, such as autoimmunity, cell transformation and tumor progression.


Assuntos
Técnicas Citológicas/instrumentação , Glândula Tireoide/citologia , Tireotropina/farmacologia , Polaridade Celular , Células Cultivadas , Epitélio/metabolismo , Doença de Graves/imunologia , Doença de Graves/patologia , Antígenos HLA-DR/análise , Humanos , Proteínas de Membrana/metabolismo , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo
20.
World J Surg ; 20(7): 854-9, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8678962

RESUMO

A total of 195 patients had surgery for papillary thyroid cancer. The mean age at operation was 50 years. A microdissection technique was used for total thyroidectomy and lymph node clearance. Postoperative radioiodine tests showed no uptake or an uptake close to the background activity in 77% of the examined patients. By counting the lymph nodes removed at surgery we were able to check on the quality of the lymph node dissection. Men had a higher incidence (70%) of lymph node metastases than women (45%). Only 4% of the patients had radioiodine ablation of the thyroid remnant. The median follow-up time was 13 years. None of the patients below 45 years of age at surgery died of thyroid cancer. In the older age group eight patients died of thyroid cancer at a mean age of 75 years. Five of those who died of a thyroid carcinoma had distant metastases at diagnosis. Among patients with resectable disease, three (1.6%) died of thyroid cancer, all of whom had lived for more than 17 years after surgery. Hence longer follow-up is needed before we know the final mortality in our series. The results suggest that surgical technique and strategy can positively influence the survival of patients with papillary thyroid cancer.


Assuntos
Carcinoma Papilar/cirurgia , Microcirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/secundário , Causas de Morte , Criança , Intervalo Livre de Doença , Dissecação , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Fatores Sexuais , Taxa de Sobrevida
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