Hepatocytes derived from adult stem cells.

UNLABELLED: We characterized the functional properties of mesenchymal stem cells from various human tissues for their potential to differentiate into hepatocyte-like cells in vitro. METHODS: Mesenchymal stem cells were isolated from human bone marrow (hBM-MSC) and peritoneal and subcutaneous adipose tissues (hpAT-MSC and hsAT-MSC) based on their capacity to adhere to plastic culture surfaces. Cells were analyzed by reverse transcriptase polymerase chain reaction and for urea as well as glycogen synthesis. Their potential for multiple differentiation pathways was investigated by incubation in culture media triggering osteogenic, adipogenic, or hepatogenic features. Global gene expression patterns were analyzed in hepatocyte differentiated hBM-MSC compared with undifferentiated MSC and adult and fetal human liver. RESULTS: Applying osteogenic or adipogenic differentiation conditions, the cells from each tissue under investigation differentiated appropriately. Treatment of the cells with hepatogenic medium induced mRNA transcripts typical for hepatocytes, as well as the onset of urea synthesis and glycogen storage. Analysis of global gene expression patterns revealed that hepatocytes differentiated from hBM-MSC were clearly distinct from undifferentiated MSC. These cells had acquired features of adult as well as fetal human hepatocytes. CONCLUSION: In vitro, MSC from human bone marrow and adipose tissue differentiated to hepatocyte-like cells closely related to adult elements on the molecular and functional levels.

Improved regional left ventricular performance in mitral valve replacement with orthotopic refixation of the anterior mitral leaflet.

BACKGROUND AND AIMS OF THE STUDY: To investigate the influence of different surgical techniques of chordal preservation in mitral valve replacement (MVR) on left ventricular size and function, we studied a series of 244 patients who underwent mitral valve replacement either with (n = 161) or without (n = 83) preservation of the subvalvular structures. RESULTS: Preoperatively there were no differences between the two patient groups. Three months postoperatively, echocardiography demonstrated that chordal preservation in MVR resulted in smaller left ventricular end-systolic diameter (LVESD) and end-diastolic diameter (LVEDD): preservation versus resection, LVESD: 43.4 +/- 7.8 mm versus 48.8 +/- 9.2 mm (p < 0.05), LVEDD: 57.3 +/- 7.8 mm versus 62.9 +/- 10.5 mm (p < 0.05) and a significantly decreased LV-L (long axis) (87.1 +/- 4.2 mm versus 97.5 +/- 5.7 mm; p < 0.05). There was no significant difference in cardiac dimensions between the three patient subgroups in whom chordal preservation was possible. In addition, left ventricular ejection fraction in the preservation groups was significantly improved compared with the resection group (54.2 +/- 11.2% versus 48.1 +/- 12.4%, p < 0.05); there were no differences between the preservation subgroups. Regional wall motion analysis revealed significantly improved segmental myocardial performance in all segments if both leaflets were preserved or the anterior mitral leaflet was reattached to the anterior mitral annulus.

Dissection of an aneurysmic ascending aorta in a child with atresia of the aortic isthmus.

A boy with atresia of the aortic isthmus suffered dissection of the aneurysmatic ascending aorta. It is assumed that he had coarctation as a newborn and survived the subsequently developed atresia because of extensive collateralization.

Postoperative assessment of chordal preservation and changes in cardiac geometry following mitral valve replacement.

Mitral valve replacement (MVR) is still associated with a relatively high mortality. To investigate the influence of chordal preservation in MVR on left ventricular size and function, we studied a series of 82 patients who underwent MVR either with (group A n = 50) or without (group B n = 32) preservation of the subvalvular structures and compared the two groups. Echocardiography was performed preoperatively, and 7 days and 3 months postoperatively. Echocardiographic investigations included left atrial and ventricular diameters, right ventricular diameters and left ventricular length. Preoperatively there were no difference between the two groups of patients. Intraoperative and postoperative management was similar in the groups. Three months postoperatively echocardiographic examinations demonstrated that chordal preservation in MVR resulted in smaller left ventricular systolic and diastolic diameters (LVESD: gr. A 43.4 +/- 7.8 mm vs gr. B 48.8 +/- 9.2 mm P < 0.05, LVEDD: 57.3 +/- 7.8 mm vs 62.9 +/- 10.5 mm P < 0.05) and a significantly decreased left ventricular length (87.1 +/- 4.2 mm in gr. A vs 97.5 +/- 5.7 mm in gr. B P < 0.05). In addition, left ventricular ejection fraction in group A was significantly improved compared to group B (54.2 +/- 11.2% vs 48.1 +/- 12.4%, P < 0.05). We conclude that chordal preservation in MVR improves left ventricular function and reduces left ventricular diameters and volumes compared to resection of the mitral subvalvular appartus and that these beneficial effects can be maintained in the postoperative course.

Pulmonary carcinosarcoma: diagnostic problems and determinants of the prognosis.

OBJECTIVE: Bronchopulmonary carcinosarcoma is a very rare tumor and the prognosis of patients with carcinosarcoma is assessed as unfavourable. The problems concerning diagnosis, therapy, and prognosis after resection treatment are discussed with reference to our seven cases and with consideration of the pertinent literature. METHODS: The retrospective data of seven patients with pulmonary carcinosarcoma were analysed. All were staged postoperatively according to the international TNM staging system. The diagnosis was verified by immunohistochemical investigation. The prognosis of the patients with carcinosarcoma was compared with the prognosis of patients with non-small cell carcinoma of the lung. RESULTS: Whether lung resection is the treatment of choice for these patients is of no relevance, because in most cases the preoperative diagnosis is incomplete, as only one component of the tumor, namely the epithelial one, is found in the biopsy specimen. The complete and correct diagnosis in five of the seven cases was not made before the resection had been performed and in the remaining two patients it was only made when tumor recurrence or metastases occurred. The prognosis of patients with carcinosarcoma of the lung is assessed to be comparable to that of patients with other pulmonary carcinoma: in this study survival times ranged from only 3 months (T2N3) to 4 years 6 months (T3N1). The causes of death of the patients with carcinosarcoma were local recurrence in four patients and metastases at distant sites in two. Two recurrent tumors as well as the metastases consisted only of the sarcoma component of the primary tumor histologically. CONCLUSION: One may suggest that the prognosis of carcinosarcoma might be determined by the sarcoma component of the tumor. Therefore the generally accepted therapies of soft tissue sarcomas should be adopted for the follow-up treatment of patients with pulmonary carcinosarcoma.

Pulmonary embolism: a frequent cause of acute fatality after lung resection.

Between 1975 and 1993, lung resections were performed in 1735 patients because of malignancies, with an early postoperative mortality of 7.2% (125 patients). Early postoperatively acute cardiorespiratory failure was experienced by 32 patients (1.85%), of whom 26 died despite immediate resuscitation measures. In 20/26 patients autopsy was performed revealing central pulmonary embolism as the cause of death in 19 of them. In one patient a rupture of the free posterior left ventricular wall following transmural myocardial infarction was found. Two patients who could be resuscitated successfully were operated on with extracorporeal circulation after pulmonary angiography had been performed to confirm the diagnosis; however they died 2 days later of right heart failure. Of the survivors three cases had myocardial infarctions, one patient had arrhythmias of unknown etiology. Immediate embolectomy with the use of extracorporeal circulation was performed in two patients, only on the ground of suspected pulmonary embolism and without further diagnostic measures. Both patients survived. Of the 23 cases, with proven pulmonary embolism 17 were still under postoperative prophylaxis with heparin. Six patients were already fully mobilized. We conclude that massive pulmonary embolism is a frequent early postoperative fatal complication after lung resections, which cannot be safely prevented by postoperative heparinization. The only successful life-saving measure in the case of central pulmonary embolism is immediate pulmonary embolectomy, if necessary without further diagnostic measures.

Effects of high-dose aprotinin on renal function in aortocoronary bypass grafting.

BACKGROUND: To reduce blood consumption in cardiac surgery, aprotinin has been widely used for years. Because aprotinin is metabolized in the kidney, damage of the renal system has been discussed. METHODS: To study these possibly unfavorable effects of aprotinin, a prospective, randomized, placebo-controlled study of 20 patients undergoing aortocoronary bypass operations was performed. A placebo group P was compared with group A, in which patients received high-dose aprotinin according to the "Hammersmith" regimen. Renal function was assessed for 5 postoperative days using sodium dodecyl sulfate gel electrophoresis and quantitative protein analysis of the urine. RESULTS: During and after the operation, temporary renal dysfunction was found in all patients, with a substantial increase of all investigated indices. The alpha 1-microglobulin level in the urine was significantly increased in the aprotinin group for 5 days in comparison with the placebo group, with a maximum on the third postoperative day (64.8 +/- 13.7 versus 21.0 +/- 6.5 mg/L; p < 0.05). Similarly, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the bands of proteins filtrated in the renal tubular system were almost tripled in the aprotinin group 5 days postoperatively (5.0 +/- 0.8 versus 2.1 +/- 0.2; p < 0.05). Although urine production was significantly increased in group A (4789 +/- 580 versus 3653 +/- 492 mL/24 h postoperatively; p < 0.05), no relevant changes in serum or urine creatinine levels could be observed in either group. CONCLUSIONS: Patients undergoing aortocoronary bypass operations demonstrate a temporary renal dysfunction. Aprotinin impairs renal function in addition by overloading the tubular reabsorption mechanisms. Patients with normal renal function preoperatively--as were included in this study--are able to compensate for both the perioperative renal dysfunction caused by the extracorporeal circulation and the additional tubular damage due to aprotinin.

Preservation of the mitral subvalvular apparatus in multiple valve procedures.

The advantages of chordal preservation in mitral valve replacement have been demonstrated, but there is no detailed information available on the effect of chordal preservation in patients undergoing multiple valve operations. We assessed therefore a series of 61 patients who underwent multiple valvular procedures either with (Group A, n = 42) or without (Group B, n = 19) preservation of the subvalvular structures. Echocardiographic examinations were performed preoperatively, seven days and three months postoperatively. In addition clinical and electrocardiographic examinations were performed. Echocardiographic investigations included left atrial, left and right ventricular diameters and left ventricular length. Preoperatively there were no differences between the two groups. Intra- and postoperative management was similar in the two groups. Postoperative clinical and echocardiographic examinations demonstrated that, although beneficial effects were evident in both groups, improvement of left ventricular function and decrease in left ventricular size were more pronounced in patients in whom chordal preservation was possible.

Celite and kaolin produce differing activated clotting times during cardiopulmonary bypass under aprotinin therapy.

Since the introduction of the proteinase inhibitor aprotinin in cardiac surgery, a strong increase of the activated clotting time (ACT) during the extracorporeal circulation phase (ECC) was reported in many clinical studies, but with a lack of correlation between ACT and heparin concentration. In searching for a cause of this inconsistency we investigated different surface activators of the ACT in a clinical study. During ECC ACT was measured in parallel, using a Hemochron device and corresponding tubes (nominally 12 mg celite activator) for celite ACT, and a HemoTec device with corresponding double tubes (nominally 0.1 ml kaolin activator) for kaolin ACT. Under the conditions of ECC, the kaolin ACT values (482 +/- 145 sec) were significantly lower than the celite ACT values (985 +/- 267 sec). These results were confirmed in ex-vivo experiments using an activated partial thromboplastin time (aPTT) model. With heparin alone, aPTT activated with celite and kaolin were similar. Including aprotinin in this model, the celite aPTT showed no correlation to the heparin concentration, whereas the kaolin aPTT remained well correlated to the heparin concentration and similar to the values without aprotinin. With aprotinin alone there were no changes of the aPTT times, whereas the celite ACT times were without any correlation. Our results indicate that using kaolin instead of celite the ACT measurements under aprotinin therapy stay in the same ranges as without application of aprotinin: aprotinin has no detectable influence on kaolin-activated ACT. In our opinion, kaolin should be used as the surface activator for ACT measurements under the conditions of ECC, heparinization, and aprotinin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve replacement with preservation of the subvalvular structures where possible: an echocardiographic and clinical comparison with cases where preservation was not possible. Surgical technique and early postoperative course.

Mitral valve replacement (MVR) is still associated with a relatively high mortality. To prove the benefits of chordal preservation at mitral valve replacement, we investigated its effects in a series of 65 consecutive MVR patients. Of those patients, in 42 preservation of the mitral subvalvular structures was possible whereas in the other 23 they had to be excised. Both groups showed no differences in age, sex, preoperative NYHA class, and valve pathology. Intra- and postoperative management was similar in both groups. The surgical techniques employed are described and the early postoperative course of both groups are analysed. Clinical, electrocardiographic and echocardiographic investigations, measuring left-atrial and -ventricular diameters, right-ventricular diameters and left-ventricular length, demonstrated that whereas beneficial effects were evident in both groups, the amount of benefits was higher in patients with chordal preservation. Chordal preservation also provided less arrhythmias than chordal resection.

The pectoral muscle flaps in the treatment of bronchial stump fistula following pneumonectomy.

Between 1975 and June 1992, pneumonectomy was performed in 594 patients, of whom 33 (5.6%) developed bronchopleural fistulae postoperatively. Until 1989 25 cases were reoperated: 5 patients were treated by thoracoplasty primarily, 20 by repair of the stump with sutures and by covering the stump with pericardial tissue or intercostal muscle, of whom 10 suffered from empyema. In 5/20 patients (25%) chronic fistulae developed making further interventions necessary. Since 1989 seven patients with bronchial stump fistulae have been reoperated with a delay of less than 12 h after diagnosis. Surgery consisted of reclosure of the stump with sutures in five patients. In addition, every patient was treated with the intrathoracic transposition of a petiolated ipsilateral pectoral muscle graft, which was the only treatment in two patients. Neither recurrence of the bronchopleural fistula nor empyema was seen in this group of patients (0%). We conclude that bronchial stump fistulae in patients after pneumonectomy can be treated successfully by the use of pectoral muscle flaps either combined with a closure of the leak using sutures or as the only measure. The method proved to be simple, safe and without major impairment of the patient. In combination with early reintervention, postpneumonectomy empyema including a disfiguring thoracoplasty can thereby often be avoided.

Is there a phase of hypercoagulability when aprotinin is used in cardiac surgery?

To determine a possible phase of hypercoagulability after the use of high-dose aprotinin, a prospective randomized double-blind study was performed. Twenty patients undergoing aortocoronary bypass surgery were investigated, a placebo group P (n = 10) was compared to an aprotinin group A (n = 10). Examining parameters of thrombin activation and fibrinolysis, we found during extracorporeal circulation--under continuous aprotinin infusion--a significant inhibition of thrombin activation and fibrinolysis in the aprotinin group (thrombin-antithrombin-III-complexes: 95 +/- 23 micrograms/l, d-dimers: 448 +/- 60 ng/ml, plasminogen activity: 33 +/- 3%, plasminogen activator inhibitor: 98 +/- 14 U/ml) compared to the placebo group (thrombin-antithrombin-III-complexes: 143 +/- 13 micrograms/l, d-dimers: 2755 +/- 430 ng/ml, plasminogen activity: 125 +/- 15%, plasminogen activator inhibitor: 10 +/- 4 U/ml). In contrast, after stopping the aprotinin infusion--from the end of extracorporeal circulation until the morning of the first postoperative day--strong thrombin activation took place in the aprotinin group (d-dimers increased from 472 +/- 90 to 1607 +/- 140 ng/ml), while in the placebo group a decrease could be registered. At this time, the fibrinolysis was still reduced in the aprotinin group (plasminogen activity: 48 +/- 6% vs 85 +/- 16% in the placebo group). In conclusion, interference with the thrombohemorrhagic balance induces hypercoagulability after the use of high-dose aprotinin, with elevated levels of thrombin-antithrombin-III-complexes, d-dimers, and plasminogen and a decreased level of plasminogen activator inhibitor. In our opinion, it is necessary to prevent this counter-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Activated clotting time, anticoagulation, use of heparin, and thrombin activation during extracorporeal circulation: changes under aprotinin therapy.

In a prospective randomized double-blind study, the activated clotting time (ACT), heparin use, parameters of anticoagulation, and thrombin activation during extracorporeal circulation were studied in 20 patients who underwent aortocoronary bypass operations. The patients were divided into two groups: Group A was given a placebo, while Group B was given aprotinin according to the high-dosage Trasylol scheme. During ACT-controlled heparinization (ACT > 460 s) there was a significant heparin reduction in Group B (22,100 USP-E) in comparison to Group A (35,200 USP-E). Despite this lower quantity of total heparin, the ACT in Group B was significantly extended (Group B = 837 s, Group A = 492 s). The ACT did not correlate thereby with the heparin concentration or the total quantity of heparin in either group. In contrast to the control group, there was no increased thrombin generation in the aprotinin group. The thrombin-antithrombin III complexes (Group A = 143 micrograms/L, Group B = 102 micrograms/L) as well as the specific dimers (Group A = 2755 ng/ml, Group B = 448 ng/ml) were significantly lower under the use of aprotinin. The connection between the ACT, the heparin concentration, and the aprotinin concentration was further investigated in an ex-vivo model. The ACT samples were diluted with the aim of eliminating the influence of aprotinin. Under these conditions it was shown that for heparin concentrations between 2-4 U/ml there was a parallel shift of the ACT/heparinconcentration curve with the addition of aprotinin in a defined concentration range of 200-300 KIU.(ABSTRACT TRUNCATED AT 250 WORDS)

Squamous cell carcinoma of the lung: prognostic factors affecting the long-term outcome after surgical resection.

From 1976 to 1989, 638 patients with squamous cell carcinoma were operated on. Reliable information concerning survival could be obtained in 540 of these cases via follow-up examinations. All tumors were retrospectively classified according to the TNM system of the fourth edition of UICC classification. The average survival time after potentially curative operation was 7.32 years in patients with stage I tumors, the 5-year survival rate was 55.3%. The corresponding values were 2.42 years and 29.1% respectively in patients with stage II tumors, compared to 1.22 years and 12.0% respectively in those with stage III a tumors. The differences between tumor stages are statistically significant. Analyzing the influence of the T and N factors on the prognosis following potentially curative surgery, the classification in the various tumor stages was largely verified. Stage III a is inhomogeneous in terms of prognosis. T and N factors showed prognostic value in this group. In the group with T3 tumors there was a significant difference in the mean survival times, independently of the lymph node status, when the patients were divided into those with T3 tumors close to the main carina (16 months) and those who had infiltrated adjacent structures (7.5 months). When differentiating the N1 location, a significant difference was found between the group of patients with T2 tumors and true lymph node metastases and the group with T2 and direct tumor infiltration of the lymph node (mean survival time 27.5 vs 42.3 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma of the lung: a contribution on prognosis after potentially curative resection.

From 1976 to 1989, 166 patients were operated on for primary adenocarcinoma of the lung. For better comparison, all the tumors were categorized retrospectively according to the TNM system of the UICC 4th edition of 1987. One hundred and thirty-eight patients could be potentially curatively operated. The average survival time following incomplete resection was 5 months and after potentially curative resection it was 65 months for stage I, 22 months for stage II and 6.5 months for stage IIIa. The 5-year survival rate was 53.7% for stage I, 18.5% for II and 0% for IIIa. The differences between the tumor stages are statistically significant. At the time of writing a large number of the patients have already died due to either recurrence of the tumor or, as in most cases, secondary metastases distant from the primary growth CI: 32%, II: 66%, IIIa: 79%). Comparison of the results of potentially curative operations in patients with adenocarcinoma and those with squamous cell carcinoma show a better prognosis in the equivalent stages for cases of squamous cell carcinoma. In seven cases there was the situation of ipsilateral pulmonary metastasis which could be subjected to potentially curative resection together with the primary tumor (5 bronchioloalveolar, 2 other adenocarcinomas). The prognosis of these patients was just as good, following resection, as for cases of T2N0 tumors without such metastases.

The role of protein C as an inhibitor of blood clotting during extracorporeal circulation.

The plasma levels of protein C, AT III, the perioperative administration of fresh frozen plasma (FFP) and AT III concentrate were compared under the use of various drugs in a randomized, prospective double-blind study in 40 patients in whom an aortocoronary bypass operation was carried out. We formed four groups of ten patients: group A served as a control group, group B received a prostacyclin (PGI2) infusion of 10 or 20 ng/kg/min, group C high-dose aprotinin substitution, and group D was treated with a combination of prostacyclin and aprotinin. After an initial short-term rise in the inhibitors protein C and AT III, there was a fall in all groups in the further course of extracorporeal circulation. The initial preoperative values were reached again on the morning of the first postoperative day. This indicates a raised turnover and in association with this a raised rate of elimination of these factors caused by an increased thrombin activation during the extracorporeal circulation which cannot be prevented by the usual heparinization. Whereas prostacyclin had no effect on our results mediated by thrombocytic mechanisms, use of aprotinin led to a significant saving in the requirement for perioperative fresh frozen plasma and AT III substitution therapy. A clinical advantage of prostacyclin and aprotinin combination was not observed. In view of our results (individual analyses were mainly in the normal range), we consider that AT III and fresh frozen plasma should not be substituted routinely during or after extracorporeal circulation.

[Cardiac metastasis as cause of therapy-resistant heart failure]. / Herzmetastase als Ursache einer therapierefraktären Herzinsuffizienz.

Ultrasonography revealed a renal tumour (4 x 4 cm) in a 67-year-old man with right-sided lumbar pain and macrohematuria. In addition he had marked nocturnal dyspnoea with dry cough. He had lost about 10 kg in weight. On admission he had atrial fibrillation with an irregular ventricular rate (140 beats/min) and engorgement of the neck veins. Two-dimensional echocardiography, undertaken because of signs of increasing heart failure and a fall of systolic blood pressure to below 100 mm Hg, demonstrated a space-occupying lesion in the right ventricle, 4 x 2 x 1 cm, indicating an intracardiac thrombus or solid tumour. The heart failure continued to worsen, despite treatment with cardiac glycosides, verapamil and diuretics. Hence an exploratory thoracotomy was performed. This revealed an intracardiac tumour which had markedly displaced the right ventricular inflow tract and infiltrated the entire myocardium, but not the tricuspid valve. As much of the tumour as possible was resected, but the patient died postoperatively of heart failure. The intracardiac tumour proved to be a metastasis from the papillary carcinoma of the kidney. This had infiltrated the renal capsule and pelvis and invaded the branches of the right renal vein.

Large cell carcinoma of the lung: a contribution on prognosis after potentially curative resection.

Between 1976 and 1989, 53 out of 60 patients with large cell carcinoma of the lung underwent potentially curative surgery, i.e. macroscopically and microscopically complete resection. For better comparison, all tumors were classified according to the TNM staging system of the UICC 4th edition of 1987. Following potentially curative surgery, in stage I the mean survival time was 19 months and the five-year survival rate 30.1%, in stage II 8 months and 10%, and in stage IIIa 6.5 months and 0%, respectively. The differences in the long term prognosis between the tumor stages are significant. No significant differences could be demonstrated between II and IIIa in terms of the mean survival times. The prognosis for patients with potentially curatively resected squamous cell carcinoma is significantly better than that for patients with large cell carcinoma.

[Tension chylothorax following left-sided lung surgery]. / Spannungschylothorax nach linksseitigen Lungenoperationen.

This is a report on 3 patients who presented with chylothoraces (chylopleurae) with haemodynamic effect subsequent to left-side lung surgery. This complication occurred twice after pneumonectomy and once after atypical resection with extirpation of a mediastinal lymph node. Clinical signs and symptoms appeared with all the patients between the 5th and 8th postoperative day, as a result of the haemodynamic effect of the chylothorax in the sense of volume loss combined with heart tamponade. In one patient there was additionally the pattern of signs and symptoms of an acute abdomen, which could be explained by a descended diaphragm with compression of the abdominal organs in case of an additionally present phrenicoparesis. One patient was at first treated conservatively after application of thoracic drainage, feeding being exclusively parenteral, and was finally operated on after 10 days, whereas the other two patients were primarily subjected to surgery. The surgical methods employed consisted of right side ductal ligature after Lampson, ductal ligature from the left thoracic side and direct closure of the chyle leakage.

[Third replacement of the tricuspid valve in combined aortic-tricuspid defect]. / Trikuspidalklappen-Drittersatz bei kombiniertem Aorten-Trikuspidal-Vitium.

The implantation of valvular prostheses in tricuspid position is problematic due to the slow blood flow in the low-pressure system with the risk of valvular thromboses. Today there are prostheses with supportable low transvalvular gradients; nevertheless, the risk of valvular thromboses is, in spite of anticoagulation, increased by using mechanical prostheses in tricuspid position. We report on a 51-year-old woman in whom a dysfunction of the Starr Edwards ball prosthesis 15 years after its implantation in the tricuspid position was diagnosed. The prosthesis, which was unable to function due to connective tissue proliferation, was replaced by a St. Jude Medical prosthetic valve, which also presented a disturbed function a few days after the implantation. Because of a suspected valve thrombosis the patient was treated with rt-PA-lysis which proved to be ineffective. Thus it was inevitable to implant a third tricuspid valve; this time a bioprosthesis was used.