Neoplastic heart disease -- the Muenster experience with 108 patients.

BACKGROUND: Tumours of the heart are rare. Different histological subtypes are known. The most common tumour entity is benign cardiac myxoma. Malignant heart tumours are less common. Tumours originating in other organs such as the kidney may also affect the heart by tumour progression via the inferior caval vein. A large experience with surgical treatment of different types of heart tumours is presented. METHODS: Between January 1989 and April 2004, 108 patients with a heart tumour were included in a database. All patients underwent radical surgical resection, except for 2 patients who had malignant lymphoma of the heart. RESULTS: Histological findings included 78 myxomas (72.2 %), and 6 other benign cardiac tumours in 5.6 % of the patients. Primary malignant heart tumours were seen in 10 (9.2 %) and renal cell carcinoma with cardiac involvement in 6 (5.6 %) patients. Eight patients presented with tumour metastases inside the heart (7.4 %). Mean overall survival was 12.7 years for myxoma patients and 5.6 years for patients with other benign heart tumours. Patients with primary malignant heart tumours survived 5.5 years on average. CONCLUSIONS: Heart tumours are rare, but usually life-threatening. Radical surgical resection is the therapy of choice and may offer excellent long-term survival, even in cases with malignant heart tumours.

Radical resection of cardiac sarcoma.

We report on our experience with six patients with malignant sarcoma of the heart and show that long-term survival is possible after radical resection. At presentation, the 6 patients (3 male, 3 female) were 45.8 +/- 20 years old. Three patients are alive without evidence of metastases since 29.6 +/- 36.8 months, three patients died after 38 +/- 50.2 months due to distant metastases. Precise preoperative localization of the tumor by means of imaging techniques is very important. In some cases, radical surgery requires an ex situ procedure (autotransplantation). If necessary, the right heart can be resected almost completely, and reconstructed in the form of a Fontan-type circulation. A heart transplantation, as suggested by others, is not justified from our point of view, since prognosis is not better and donor organs are too rare. The results of radical resection are promising, but new concepts for treatment--in particular chemotherapy concepts--for these mostly middle-aged or young patients are required.

TSH-receptor expression and human thyroid disease: relation to clinical, endocrine, and molecular thyroid parameters.

Thyrotropin receptor (TSH-R) gene expression can be positively or negatively regulated by TSH and stimulating TSH-R antibodies (TSAbs) in immortalized thyroid cell lines such as rat FRTL-5 cells. However, regulation is less clear in other mammalian cells including cultures of human thyroid cells. Additionally, it has been suggested, based on FRTL-5 cell data, that TSH-R gene negative regulation by TSH or TSAbs might be lost in Graves' disease. The present study evaluated TSH-R gene transcript levels in thyroids from patients with Graves' disease to correlate in vivo data with in vitro observations or hypotheses. TSH-R mRNA levels were characterized in a total of 66 human thyroid glands with particular concern to levels in Graves' patients. Results were related to clinical parameters, transcript levels of thyroglobulin (TG), and thyroid peroxidase (TPO), as well as transcript levels of thyroid transcription factor 1 (TTF-1) which regulates the expression of all three genes and paired box-gene 8 (Pax-8) which regulates TG and TPO gene expression. Northern blot analyses showed that TSH-R expression was significantly increased, 2.2-fold, in Graves' thyroids (p = 0.0098, n = 35) by comparison to normals (n = 6). TSH-R mRNA levels were decreased to 30% and 7% of normal levels in Hashimoto's thyroids (p = 0.0281, n = 5) and anaplastic carcinomas (p = 0.0033, n = 6), respectively. No significant changes were seen in endemic goiters (n = 8) and in thyroid autonomy (n = 6). TSH-R RNA levels were higher, 3.6-fold, in thyroids of a subgroup of Graves' patients that had not been pretreated with iodide before surgery (n = 10) by comparison to thyroids from those that had been treated before surgery, 1.7-fold (n = 25). TSH-R antibodies exhibited a nonsignificant tendency toward a negative correlation. All other clinical or endocrine parameters showed no clear relation to TSH-R mRNA levels. Pax-8 and TTF-1 transcripts were detectable in normal thyroids; however, Pax-8 expression was increased in Graves' thyroids (3.8-fold), whereas TTF-1 expression was only minimally changed in all thyroids investigated. Changes of the two did not correlate. Pax-8 expression correlated with TG and TPO expression (in all cases, p = 0.0001); TTF-1, despite its minimal change, still correlated with TG (p = 0.0471) but not with TPO expression (p = 0.0984). TTF-1, again despite its minimal changes, correlated positively with TSH-R gene expression (p = 0.0251); however, surprisingly, Pax-8, which does not regulate TSH-R gene expression, correlated even better with TSH-R transcript levels (p = 0.0001). We conclude that augmentation of TSH-R expression levels, and thus potential ligand binding sites, may indicate an important regulatory principle in the pathogenesis of autoimmune hyperthyroidism in vivo: the responsiveness of the TSH-R to TSH and TSAb induced negative regulation is lost. This increase of TSH-R expression levels is not due to an ongoing transcriptional activation of the TTF-1 gene. Pax-8, though positively correlated with TSH-R RNA levels, cannot be the factor either, because Pax-8 does not upregulate TSH-R expression. This predicts that other factors involved in TSH-R induced negative regulation are abnormal and must be searched for and evaluated.