RESUMEN
We report the case of a 57-year-old man who underwent successful simultaneous surgery involving mitral valve replacement for acute endocarditis and orthotopic liver transplantation for end-stage liver disease.
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Endocarditis Bacteriana/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Cirrosis Hepática/cirugía , Trasplante de Hígado , Válvula Mitral/cirugía , Enfermedad Aguda , Resultado Fatal , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
PURPOSE: Previous studies have shown high sensitivity of positron emission tomography (PET) with 11C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of 11C-methionine PET and 99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of 11C-methionine in those patients with inconclusive or negative conventional imaging. METHODS: Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with 99mTc-MIBI and PET with 11C-methionine. SUV(parathyroid)/SUV(cervical soft tissue) (target-to-background) and SUV(parathyroid tissue)/SUV(thyroid tissue) (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one. RESULTS: In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with 11C-methionine PET and 17 (47%) with 99mTc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. 99mTc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with 99mTc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non-diagnostic scintigraphy/SPECT, hyperfunctional parathyroid tissue was identified with 11C-methionine PET. The highest SUV(parathyroid)/SUV(cervical soft tissue) ratio was found 10 min, and the highest SUV(parathyroid tissue)/SUV(thyroid tissue) ratio 40 min post injection. In three patients clear delineation of hyperfunctional tissue was only achieved after 40 min post injection. CONCLUSION: 11C-methionine PET is a clinically useful method in highly pre-selected patients with recurrent primary HPT as well as in secondary and tertiary HPT if ultrasound and 99mTc-MIBI SPECT are inconclusive or negative. PET imaging of atypical PTA localisations is more accurate than conventional scintigraphy. In order to achieve optimal contrast of parathyroid glands versus thyroid tissue and adjacent soft tissue, imaging at both 10 min and 40 min is recommended.
Asunto(s)
Hiperparatiroidismo/diagnóstico por imagen , Hiperparatiroidismo/cirugía , Metionina , Tomografía de Emisión de Positrones/métodos , Cuidados Preoperatorios/métodos , Tiroidectomía/métodos , Adulto , Anciano , Femenino , Humanos , Hiperparatiroidismo/diagnóstico , Hiperparatiroidismo Secundario/diagnóstico , Hiperparatiroidismo Secundario/diagnóstico por imagen , Hiperparatiroidismo Secundario/cirugía , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The fibrolamellar karzinoma of the liver (FLC) as an uncommon variant of the hepatocellular karzinoma (HCC) is an indolent growing tumor. In its prior manifestation the FLC occurs at the adolescence and young adult stage. Early stage diagnosis and aggressive surgical treatment achieve better long-term results than usual resection of the HCC. Usually the FLC is, caused by its inconspicuous clinical appearance, diagnosed at a stage too advanced for effective surgical treatment. Especially the young patient's age and the remaining therapeutic options for palliative or curative treatment postulate a difficult decision for the surgeon. When a subtotal hepatectomy cannot be performed, total hepatectomy with liver transplantation is a valuable option. Palliative treatment protocols include systemic chemotherapy, ethanol instillation and chemoembolisation. We report the case of a 21-year-old male patient who presented with a recurrent intrahepatic FLC, peritoneal karzinomatosis confined to the right lower abdomen including gastric, splenic, diaphragmatic and colon transversum metastasis 14 months after primary surgery. We selected this patient as a reasonable candidate for an extended resection in trying to offer the optimal therapeutic modality. Thus we performed a right hemihepatectomy, near complete resection of the right diaphragm, total gastrectomy with lymphadenectomy including en bloc resection of spleen, colon transversum, omentum majus and peritonectomy of the paravesical region. Furthermore hyperthermic intraperitoneal chemotherapy was carried out the next day. The patient's postoperative course remained uncomplicated with fast recovery. Presently, 6 months after surgery, the patient has no evidence of recurrence.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Cisplatino/administración & dosificación , Hipertermia Inducida , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Adulto , Colectomía , Neoplasias del Colon/secundario , Neoplasias del Colon/cirugía , Terapia Combinada , Estudios de Seguimiento , Gastrectomía , Hepatectomía , Humanos , Infusiones Parenterales , Escisión del Ganglio Linfático , Masculino , Epiplón/cirugía , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Peritoneo/cirugía , Cuidados Posoperatorios , Esplenectomía , Neoplasias del Bazo/secundario , Neoplasias del Bazo/cirugía , Neoplasias Gástricas/secundario , Neoplasias Gástricas/cirugía , Factores de TiempoRESUMEN
BACKGROUND: The expression of RET/PTC chimeras was demonstrated in 10% to 20% of sporadic papillary thyroid carcinomas (PTCs), whereas rearrangements of NTRK1 were detected less frequently. Some investigators have hypothesized that RET/PTC activation is preferentially associated with slow-growing tumors of low malignancy in elderly patients; other studies support the contrary. METHODS: Expression analysis of RET and NTRK1 was performed by duplex reverse transcription-polymerase chain reaction in tumor tissues from 119 patients with PTC. Samples with suspected rearrangements were further analyzed for the expression of the hybrid messenger RNAs RET/PTC 1 to RET/PTC 7 and for known NTRK1 chimeras, respectively. RESULTS: Seventeen of 119 tumors (14.3%) revealed somatic rearrangements of RET; NTRK1-derived hybrids were demonstrated in 15 cases (12.6%). In patients with RET/PTC chimeras, a statistically not significant tendency towards younger age, lower recurrence rate, and improved survival was observed, despite increased incidence of lymph node metastasis. Cumulative survival analysis of NTRK1 rearrangement-positive individuals demonstrated a worse outcome when compared with patients with expression of RET hybrids (P =.055). CONCLUSIONS: The high incidence of yet uncharacterized NTRK1 hybrid mRNAs in our patient cohort leads to the speculation that activating chromosomal rearrangements of several tyrosine kinase receptors may be a common feature of PTCs and that the expression of distinct chimeras may potentially be of prognostic significance.
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Carcinoma Papilar/genética , Proteínas de Drosophila , Reordenamiento Génico , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Receptor trkA/genética , Neoplasias de la Tiroides/genética , Carcinoma Papilar/mortalidad , Femenino , Humanos , Masculino , Pronóstico , Proteínas Proto-Oncogénicas c-ret , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Tiroides/mortalidadRESUMEN
BACKGROUND: Hormone substitution for the treatment of adrenocortical insufficiency (Addison's disease) does not adequately substitute the hormone peaks required in stress situations. Therefore, allogeneic transplantation of adrenal cortex could offer an intriguing alternative. METHODS: Major histocompatibility complex (MHC) class I transgenic mice were used for the implementation of an animal model of adrenocortical cell transplantation in adrenalectomized mice. K(b)-transgenic cells and allogeneic adrenocortical cells were cocultured in mixed lymphocyte cultures to examine the alloimmune response. Lymphocytes from T-cell receptor transgenic mice and normal allogeneic mice served as responder cells. The effect of corticosteroids secreted by adrenocortical cells was antagonized by the steroid receptor antagonist mifepristone (RU486). RESULTS: In vitro coculture experiments showed that MHC class I disparate adrenocortical cells failed to activate B10.BR and T-cell receptor transgenic lymph node cells. In the presence of mifepristone this inhibitory effect was antagonized, resulting in strong lymphocyte proliferation. Activation of B10.BR lymphocytes by K(b)-disparate spleen cells was also abolished in the presence of adrenocortical cells. This effect, however, could not be reversed by mifepristone. CONCLUSIONS: In vitro, the presence of adrenocortical cells potently suppressed allogeneic immune responses. This effect was only in part due to the secretion of corticosteroids, pointing to an additional immunomodulatory property of adrenocortical cells.
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Enfermedad de Addison/terapia , Corteza Suprarrenal/citología , Trasplante de Células , Corticoesteroides/fisiología , Animales , Células Cultivadas , Técnicas de Cocultivo , Antígenos de Histocompatibilidad Clase I/análisis , Humanos , Prueba de Cultivo Mixto de Linfocitos , Ratones , Ratones Transgénicos , Mifepristona/farmacología , Linfocitos T/inmunología , Trasplante HomólogoRESUMEN
The aim of this study was determination of the significance of the arterial stimulation test with venous sampling (ASVS) in the preoperative localization of insulinoma. Eleven patients with endogenous hyperinsulinism underwent preoperative transabdominal US, spiral computer tomography (spiral CT), MRI, endoscopic ultrasound (EUS) as well as angiography (DSA) combined with ASVS. The results were compared with intraoperative findings, intraoperative ultrasound (IOUS) and histopathology. There were no complications related to the ASVS test. In 11 patients the tumor could be localized with the various modalities as follows: US 1 of 11 (9%), MRI 3 of 10 (30%), spiral CT 4 of 11 (36%), EUS 5 of 10 (50%), DSA 8 of 11 (73%), and ASVS 10 of 11 (91%). In 2 patients the tumors were intraoperatively neither palpable nor detectable by IOUS, and consequently the intraoperative management was governed by information provided by DSA combined with the ASVS test. Ten patients had solitary benign insulinomas and 1 patient with multiple endocrine neoplasia I had two tumors adjacent to each other in the pancreatic tail. Arterial stimulation test with venous sampling was the most sensitive preoperative test for regionalizing the insulinoma in our set of patients. It can be performed safely in the course of a regular DSA examination and may affect intra-operative management in patients in whom the tumors are not detectable by palpation or IOUS.
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Gluconato de Calcio , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Cuidados Preoperatorios/métodos , Adolescente , Adulto , Anciano , Glucemia/metabolismo , Gluconato de Calcio/administración & dosificación , Cateterismo Periférico , Niño , Diagnóstico Diferencial , Femenino , Arteria Hepática , Humanos , Inyecciones Intraarteriales , Insulina/sangre , Insulinoma/sangre , Insulinoma/cirugía , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estimulación QuímicaRESUMEN
UNLABELLED: Syngeneic transplantation of adrenocytes was investigated in Lewis rats in regard to differentiated hormone secretion and cortex regeneration after bilateral adrenalectomy as an alternative to steroid substitution. METHODS: Purified cell suspensions of glomerulosa (density 1.061 +/- 0.001 g/ml) and fasciculata (density 1.034 +/- 0.003 g/ml) cells were obtained by density gradient separation and were transplanted under the kidney capsule either immediately or after a 29-day culture period. Animals were killed after transplantation of cultured glomerulosa (CG-Tx) or cultured fasciculata cells (CF-Tx), noncultured glomerulosa cells (G-Tx) or non-cultured fasciculata cells (F-Tx), or both cell types (GF-Tx) for morphological studies after 30, 120, and 360 days. Plasma samples were drawn for measurement of corticosterone and aldosterone as well as 24 hr-urine for sodium and potassium levels at day 3, 30, 120, and 360 after transplantation. RESULTS: In primary culture fasciculata cell number remained stationary although glomerulosa cell number increased to almost 10-fold. Vital cortex cells were demonstrated in each explanted graft by histochemistry but only group G-Tx, CG-Tx, and GF-Tx (purified cell suspensions of zona glomerulosa and fasciculata) showed neocortex-like structures. We found plasma (urine) corticosterone to decrease from preoperatively 256-304 ng/ml (226-239 ng/day) in untreated animals to levels about half as high 3 days after transplantation, increasing to normal values in all study groups 30 days after treatment (data given as range). Plasma aldosterone concentrations, 150-180 pg/ml in untreated rats, decreased to nondetectable levels for 1 week after bilateral adrenalectomy. At day 30 group GF-Tx, G-Tx, and CG-Tx showed comparable aldosterone plasma concentrations (104-122 pg/ml); however, levels in F-Tx and CF-Tx were 19-49 pg/ml, and did not increase significantly within the observation period. CONCLUSIONS: Cells derived from the zona glomerulosa maintain viability, produce both aldosterone and corticosterone, and regenerate a neocortex with cells that histologically resemble both zona glomerulosa and fasciculata cells. They are therefore suitable for adrenocortical transplantation. In contrast, cells derived from the zona fasciculata maintain viability, but do not regenerate zona glomerulosa and do not produce aldosterone. These results suggest that the cell migration model, in which zona glomerulosa cells can acquire the phenotype of zona fasciculata cells as they can migrate centripetally, is more likely the correct explanation of adrenocortical zonation.
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Corticoesteroides/metabolismo , Corteza Suprarrenal/citología , Adrenalectomía , Corteza Suprarrenal/química , Corteza Suprarrenal/fisiología , Hormona Adrenocorticotrópica/farmacología , Aldosterona/metabolismo , Animales , Recuento de Células , Trasplante de Células/patología , Células Cultivadas , Corticosterona/sangre , Corticosterona/metabolismo , Corticosterona/orina , Masculino , Ratas , Ratas Endogámicas Lew , RegeneraciónRESUMEN
BACKGROUND: A new model of cellular adrenocortical transplantation after bilateral adrenalectomy in the mouse was established. This model was used to study the effects of the expression of the transgenic MHC class I molecule H-2K(b) (Kb) on graft survival and morphologic features, corticosterone secretion, and the possibility of tolerance induction in the recipient. METHOD: A single cell suspension of purified adrenocortical cells was grafted under the kidney capsule of B10.Br (H-2k) mice having adrenalectomies. Syngeneic, fully MHC-mismatched, and MHC class I-incompatible Kb-transgenic mice served as donor strains. To analyze graft function, urinary excretion and serum levels of corticosterone were monitored over 100 days. Tolerance induction in the graft recipients of Kb-transgenic and third party skin grafts was tested on day 50 after adrenocortical transplantation. Histological sections of the adrenocortical grafts were obtained on day 100. RESULTS: Recipients of syngeneic and Kb-transgenic grafts displayed pretransplant corticosterone levels on days 20, 50, and 100 and ACTH-stimulated serum corticosterone levels similar to those of controls on day 100 after adrenocortical transplantation. In contrast, in recipients of fully MHC-mismatched grafts, corticosterone excretion was significantly reduced. In this group, 4 of 7 mice did not survive. Syngeneic skin grafts survived indefinitely in recipients of syngeneic and Kb-transgenic adrenocortical grafts, whereas Kb-transgenic and fully MHC-mismatched skin grafts were acutely rejected. Tissue sections of the adrenocortical grafts revealed vascularized cell conglomerates in syngeneic and Kb-transgenic grafts without infiltrations of mononuclear cells. Furthermore, a differentiation similar to adrenocortical organization was partly found. CONCLUSION: In conclusion, a model of cellular adrenocortical transplantation was established. The results show that syngeneic transplantation resulted in physiological corticosterone levels early after transplantation, whereas fully MHC-incompatible grafts were rejected. Recipients of Kb-transgenic grafts showed unimpaired adrenocortical function, but did not tolerize toward Kb-transgenic skin grafts. Possible mechanisms include a local immunomodulatory effect of glucocorticoids secreted by the graft and a low immunogenicity of the relatively small numbers of transplanted cells.
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Corteza Suprarrenal/citología , Corteza Suprarrenal/inmunología , Adrenalectomía , Trasplante de Células , Antígenos H-2/fisiología , Trasplante Heterotópico , Animales , Corticosterona/sangre , Corticosterona/orina , Femenino , Supervivencia de Injerto/fisiología , Antígenos H-2/genética , Histocompatibilidad , Tolerancia Inmunológica , Ratones , Ratones Endogámicos , Ratones Transgénicos/genética , Trasplante de Piel/inmunología , Trasplante IsogénicoRESUMEN
Pleuropulmonary blastoma (PPB) is a rare dysontogenetic tumor that usually develops in the first decade of life and has been recognized as a distinct clinico-pathological entity different from the ordinary pulmonary blastoma of adulthood. Since the tumor grows aggressively and tends to metastasize early, physicians have to be aware of late onset of symptoms and uncommon manifestations. We report a case of PPB in a young adult and its recurrence in the pancreas after primary surgical treatment and adjuvant chemotherapy. Keeping in mind the moderate prognosis of PPB in children, accurate assessment and treatment of PPB require a team approach of oncology, radiology and surgery to establish new therapeutic guidelines in the future.
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Neoplasias Pulmonares/patología , Neoplasias Pancreáticas/secundario , Blastoma Pulmonar/secundario , Adolescente , Quimioterapia Adyuvante , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Pronóstico , Blastoma Pulmonar/tratamiento farmacológico , Blastoma Pulmonar/cirugía , RecurrenciaRESUMEN
BACKGROUND: Although differentiated carcinoma of the thyroid gland is a relatively benign tumor, up to 20% of patients are endangered by potentially fatal complications resulting from infiltrating tumor growth into the upper aerodigestive tract. METHODS: This study included 33 patients who underwent 34 tracheal or laryngotracheal procedures for invasive differentiated thyroid carcinoma under the direction of a single surgeon (G.F.W.S.). From 1990 to 1994, radical tumor extirpation was performed by "window" resection, and from 1995 to 1998, radical surgery consisted of either circumferential sleeve resection or laryngotracheal "step" resection--a novel method of reconstruction in cases of unilateral tumor infiltration into the larynx and trachea. Resection was limited to laminar ablation in 17 cases. The mean follow-up of 16 patients who survived was 42.5 months (range, 2 months to 8.9 years). RESULTS: Procedures resulting in primary end-to-end anastomosis of the upper airways were associated with lower perioperative morbidity and improved recurrence-free survival when compared with "window" resections with muscle flap reconstruction. In cases of superficial tracheal tumor infiltration, laminar ablations were sufficient for local tumor control. CONCLUSIONS: Radical eradication of differentiated thyroid carcinoma infiltrating the upper airways followed by radioiodine application should be considered the treatment of choice. Laryngotracheal "step" resection allows tumor extirpation with preservation of neural and muscular structures of the larynx.
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Carcinoma/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Neoplasias de la Tráquea/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Carcinoma/secundario , Femenino , Estudios de Seguimiento , Humanos , Laringe/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias/mortalidad , Nervio Laríngeo Recurrente , Estudios Retrospectivos , Neoplasias de la Tiroides/patología , Tráquea/irrigación sanguínea , Tráquea/cirugía , Neoplasias de la Tráquea/secundario , Resultado del TratamientoRESUMEN
BACKGROUND: Metastatic neuroendocrine pancreatic tumors have a poor prognosis. We have studied retrospectively the efficacy of liver transplantation as ultimate therapy of otherwise untreatable symptomatic neuroendocrine hepatic metastases originating in the pancreas. METHODS: We reviewed our experience of liver transplantation (LTx) for hepatic metastases of neuroendocrine pancreatic tumors in ten patients. The indication for liver grafting was seen in cases of irresectable metastases and when patients were suffering from otherwise untreatable tumor-associated symptoms due to massive hormonal release or large intra-abdominal tumor bulk. RESULTS: In four patients, the primary tumors had been removed before LTx, in five patients simultaneously with LTx and in one case 46 months after grafting. There was no operative mortality. After hepatectomy and LTx, all patients had complete relief of symptoms and all preoperatively increased hormonal levels returned to normal. In nine of ten patients, the transplant procedure had the potential for cure, whereas, in one patient, the primary tumor had remained in situ at LTx and was removed 46 months later by an R2-resection. At present, nine patients are alive with a median follow-up of 33 months (range 13.5 months to 117 months). The one patient in whom the primary tumor was removed after transplantation died due to massive intra-abdominal tumor spread 68 months after LTx. Currently, two patients are without evidence of disease, but one of them after re-operation because of lymph-node metastases 8 months after transplantation. The longest disease-free survival is now more than 7 years. In seven of nine patients, tumor recurred between 1.5 months and 48 months after transplantation. CONCLUSIONS: Patients with otherwise untreatable symptomatic neuroendocrine hepatic metastases of pancreatic origin may benefit from total hepatectomy and liver transplantation with regard to symptomatic relief and long-term survival, despite frequent recurrence of disease. In some patients, liver transplantation may even offer the chance for cure.
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Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Tumores Neuroendocrinos/secundario , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tumores Neuroendocrinos/mortalidad , Pronóstico , Factores de TiempoRESUMEN
Full text is available as a scanned copy of the original print version.
RESUMEN
103 patients from a group of 115 patients with catecholamine secreting tumours were reinvestigated 7.0 +/- 4.9 years following surgery. Throughout the follow-up period 15 patients had died. In four of them death was definitively, in seven subjects possibly associated to the primary endocrine disorder. Following surgery improvement of general well-being was documented in 85% of the patients. Hypertension was corrected in 61 %, but 26% of the patients remained hypertensive and symptoms of hypotension like orthostasis developed in 24%. A significant increase in weight (> 5 kg) was observed in 26% of the subjects throughout the follow-up period, but did not result in a higher prevalence of diabetes mellitus which had to be treated in 16% of the patients before and only 14% following surgery. However, palpitations, increased sweating and headache persisted in 16%, 17% and 12% of the patients, respectively. Symptoms of cardiac insufficiency developed in 32%. Persistent discomfort related to the scar was reported by 55% of the patients following lumbar surgery and by 30% of the subjects that were operated on via a transabdominal approach. Hence we conclude that surgery of catecholamine-secreting tumours results in an improvement of health and well-being in most subjects according to objective criteria as well as to the judgement of the patients themselves.
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Catecolaminas/metabolismo , Neoplasias de las Glándulas Endocrinas/metabolismo , Adolescente , Adulto , Anciano , Neoplasias de las Glándulas Endocrinas/fisiopatología , Neoplasias de las Glándulas Endocrinas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A growing number of reports describing the association of certain deletions within exon 11 of the RET proto-oncogene with aggressive courses of medullary thyroid carcinoma, point to a potential prognostic relevance of molecular features in the sporadic tumor, analogous to the hereditary variant.
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Carcinoma Medular/genética , Deleción Cromosómica , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de la Tiroides/genética , Sustitución de Aminoácidos/genética , Emparejamiento Base/genética , Carcinoma Medular/patología , Codón , Análisis Mutacional de ADN , Exones , Humanos , Invasividad Neoplásica/genética , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-ret , Neoplasias de la Tiroides/patologíaRESUMEN
A retrospective immunohistochemical analysis of the adhesion molecule E-cadherin (E-CD) was performed in 112 differentiated thyroid carcinomas and 38 synchronous and 20 relapse metastases primarily from operations performed at the Medical School Hanover between 1982 and 1992. E-CD-specific antibody 5H9 was applied to paraffin-embedded tissues. All patients were clinically followed for a maximal period of 12 years. Lack of E-CD expression i.e., <5% of tumor cells positive) occurred in 18 of 112 (16.1%) cases, whereas the majority showed either low (24.1%), medium (35.7%), or high (24.1%) positivity. No difference was found between papillary (n = 88) and follicular (n = 24) carcinomas. Univariate statistical analysis for survival (Kaplan-Meier) showed that lack of E-CD expression (P < 0.024) is an adverse prognostic factor for differentiated thyroid carcinomas. The highest significance was seen among patients without lymph node involvement at first presentation (pN(0); P = 0.0068) and among females (P = 0.0033). Multivariate analysis (Cox model) indicated that E-CD staining is an independent prognostic factor (corrected risk factor, 3.7; P < 0.03) in addition to distant metastasis (pM1) and tumor size. A comparison of E-CD stainings between primary tumors and their metastatic lesions showed similar results in both synchronous and relapse metastases after therapy. In conclusion, E-CD immunostaining is an independent prognostic indicator for differentiated thyroid carcinomas. It may help to uncover the small group of patients with differentiated thyroid carcinomas carrying a high risk of suffering an unfavorable clinical outcome.
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Cadherinas/análisis , Neoplasias de la Tiroides/química , Neoplasias de la Tiroides/diagnóstico , Biopsia , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia , Neoplasias de la Tiroides/patologíaRESUMEN
Despite recent advances in the understanding of the role of the RET proto-oncogene in the development of familial and approximately 30% of sporadic medullary thyroid carcinomas (MTC), little is known about other genetic events that modify the course and outcome of the disease. We compared the expression of genes in intrathyroidal MTCs to autologous local lymph node metastases by means of mRNA differential display (DDRT-PCR). This is the first report of differential display using surgical specimens of a primary cancer and its metastases. Total RNA was extracted from tumor tissue of two patients with MTC associated with multiple endocrine neoplasia (MEN 2B) and sporadic MTC, respectively. Following reverse transcription (RT), the products were PCR-amplified and separated on a denaturating polyacrylamide gel. RT-PCR products demonstrating differential expression were reamplified and used as probes for Northern blot analysis. Six fragments for which differential expression was confirmed were cloned and sequenced. Resultant sequences were tested for homology to sequences in public data bases, and two novel MTC-derived fragments (MDF-1, MDF-2) were identified. Sensitivity of the method was confirmed by identification of a sequence encoding the calcitonin precursor flanking peptide which is expressed almost exclusively in MTC and normal thyroid C cells. Overexpression of the ribosomal genes S3a and P0 was found in the metastases. Recent reports suggest that components of the translational apparatus act as regulatory mediators of growth, proliferation, and neoplastic change. The altered expression of ribosomal proteins and gene products encoded by MDF-1 or MDF-2 may play an important role in the progression and metastatic spread of MTC.
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Carcinoma Medular/genética , Carcinoma Medular/secundario , Metástasis Linfática/genética , Reacción en Cadena de la Polimerasa/métodos , Neoplasias de la Tiroides/genética , Transcripción Genética , Northern Blotting , Clonación Molecular , ADN Complementario/genética , Humanos , Masculino , Proteínas de Neoplasias/genética , Fragmentos de Péptidos/genética , Proto-Oncogenes Mas , ARN Mensajero/genética , ARN Neoplásico/genéticaRESUMEN
OBJECTIVE: This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA: Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS: In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS: Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS: In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective.
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Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Tumores Neuroendocrinos/secundario , Tumores Neuroendocrinos/cirugía , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
While autoantibodies against thyroid peroxidase (TPO) are known to produce cytotoxicity in vitro, their in vivo effects are still obscure. In addition, the mechanism of TPO autoantibody creation needs to be disclosed because the localization of TPO on thyrocytes is considered to be restricted to the apical membrane, which is not in contact with immunocompetent cells. In order to study these crucial processes in the pathogenesis of thyroid autoimmunity, the ultrastructural localization of TPO and IgG was determined and quantified in thyrocytes of normal thyroid gland and thyroid tissue of patients suffering from Graves' disease. This was done by using ultrathin frozen sections and the immunogold method. IgGs were detected in the follicular lumen, close to the apical membrane, in transport vesicles, the endoplasmic reticulum, and the Golgi apparatus of thyrocytes from patients with Graves' disease. The labeling of TPO in the basolateral membrane was distinctly lower than that of the apical membrane, but was significant in comparison to the plasma membrane labeling of fibroblasts present in the same sections. These data indicate that thyroid autoantibodies may perform their cytotoxic function in intracellular compartments besides the plasma membrane. TPO molecules on the basolateral membrane of HLA class II antigen-positive thyrocytes may initiate antigen presentation of TPO as well as the formation and uptake of TPO autoantibodies.
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Inmunoglobulina G/metabolismo , Yoduro Peroxidasa/inmunología , Yoduro Peroxidasa/metabolismo , Glándula Tiroides/patología , Tiroiditis Autoinmune/patología , Autoantígenos/inmunología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Enfermedad de Graves/inmunología , Enfermedad de Graves/metabolismo , Enfermedad de Graves/patología , Humanos , Inmunohistoquímica , Glándula Tiroides/metabolismo , Glándula Tiroides/ultraestructura , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/metabolismoRESUMEN
OBJECTIVE: To evaluate the prognostic factors that influence survival and recurrence after "completion" thyroidectomy (removal of the total thyroid remnant after diagnosis of carcinoma has been made in a specimen that was incompletely excised for a benign condition). DESIGN: Open study. SETTING: Teaching hospital, Germany. SUBJECTS: 131 Patients (65 with papillary and 66 with follicular thyroid cancer) who underwent completion thyroidectomy after primary subtotal resection. INTERVENTIONS: Indications for further operation were: tumour stage worse than pT1 ( n = 116), tumour stage pT1 and the suspicion of persistence of the tumour (n = 13), and incompletely resected tumour (n = 2). Multivariate analysis by Cox's proportional hazards model. MAIN OUTCOME MEASURES: Recurrence, development of metastases, and length of survival. RESULTS: Patients who underwent their completion thyroidectomies within six months of the primary operation had significantly fewer recurrences, fewer lymph node metastases, fewer haematogenous metastases and survived significantly longer than those in whom the second operation was delayed for longer than six months. The age at the time of diagnosis and the stage of the tumour influenced survival, whereas sex and type of tumour did not. CONCLUSION: Completion thyroidectomy as soon as possible after incomplete resection of the tumour may improve prognosis in differentiated thyroid cancers the stage of which is worse than pT1 or in patients whose recurrent tumour is diagnosed at follow-up.