Neuroendocrine carcinomas arising in solid-organ transplant recipients: rare but aggressive malignancies.

Organ transplant recipients are at an increased risk of developing malignancies due to prolonged immunosuppression. However, the rate and clinical course of neuroendocrine tumors (NETs) following organ transplantation has not been assessed so far. We have retrospectively analyzed patients undergoing organ transplantation between 1985 and 2001 in order to assess the frequency and clinical course of NETs in organ transplant recipients. 3,190 organ transplant recipients with sufficient clinical data were identified (2,521 kidney and 669 heart transplants). In total, 161/3,190 patients (5%) developed malignancies, with 6 of them being classified as NETs (0.18%). Interestingly, all 6 patients were diagnosed with undifferentiated neuroendocrine carcinomas, while no indolent NETs were seen. Four of these patients had undergone renal, 1 patient heart and 1 patient both heart and renal transplantation. All 6 patients were given chemotherapy, but none of them responded, as all patients showed disease progression after a median of 3 cycles of chemotherapy (range 1-4) with the median survival being 4.8 months (range 2-11). The occurrence of NETs/undifferentiated neuroendocrine carcinomas following organ transplantation appears to be rare, with an incidence comparable with the normal population. Our data suggest a highly aggressive course with a dismal prognosis and unresponsiveness to chemotherapy.

Non-melanoma skin cancer and its risk factors in an Austrian population of heart transplant recipients receiving induction therapy.

BACKGROUND: Solid organ transplant recipients have a high risk of developing nonmelanoma skin cancers (NMSC). We describe the characteristics and incidence of skin tumors in an Austrian population of heart transplant recipients (HTR). METHODS: Three hundred and twenty-two HTR out of 970 who had received their organ between December 1984 and July 2003 were analyzed for NMSC. Factors associated with tumor development including the different immunosuppressive (IS) modalities were evaluated. Besides triple combination immunosuppressive therapy, all allograft recipients had received induction therapy either with antithymocyte globulin, OKT3 or monoclonal anti-IL-2 receptor antibodies. RESULTS: Median post-transplant follow-up for all patients was 74.18 months (minimum: 2.6, maximum: 224.8). The median time from transplantation until the excision of the first NMSC was 79.57 months (minimum: 2.69, maximum: 192.8). A total of 263 NMSC were excised in 73 patients. The cumulative incidence of developing a skin tumor increased from 7.3% after 5 years to 26.9% after 10 years and to 56.5% after 15 years. Older age at transplantation (P < 0.0001) and the presence of pre-cancerous skin conditions (P < 0.0001) were associated with an increased occurrence of NMSC. No significant difference in NMSC incidence was found when the different IS therapies were compared. CONCLUSIONS: The cumulative incidence of NMSC in our cohort of HTR is comparable to published data on HTR adjusted according to the geographic location. Transplant patients with clinical evidence of pre-cancerous skin conditions have a higher degree of susceptibility for the development of NMSC and require particular dermatologic care.

Novel insights into the mechanisms and treatment of intramural hematoma affecting the entire thoracic aorta.

BACKGROUND: The purpose of this study was to address a previously not described mechanism underlying intramural hematoma (IMH) of the entire thoracic aorta and to test the hypothesis whether endovascular stent graft placement in this particular mechanism could be beneficial. METHODS: Within a 5-year period, we treated 8 patients with IMH affecting the entire thoracic aorta. The presumed site of initial plaque rupture was chosen as target for endovascular stent graft placement. RESULTS: In all patients, a small atherosclerotic plaque at the free lateral wall or at the concavity of the distal aortic arch could be identified as initial site of IMH. Endovascular stent graft placement was performed successfully in all patients. By covering the suspected primary lesion, resorption of IMH especially within the ascending aorta could be achieved. Mean follow-up is 16 months (range, 1 to 25). CONCLUSIONS: Plaque rupture may be identified as the cause of IMH in a previously unrecognized subgroup of patients. If at the convexity of the distal arch, supra-aortic branches prevent retrograde extension toward the ascending aorta. If at the free lateral wall or at the concavity, IMH may affect the entire thoracic aorta, owing to the lack of the natural barrier of the supra-aortic branches. Endovascular stent graft placement of this plaque-associated IMH may be more effective and less invasive than conventional surgery to treat the entire thoracic aortic disease.

Endovascular stent-graft placement of aneurysms involving the descending aorta originating from chronic type B dissections.

BACKGROUND: The performance of endovascular stent-graft placement in patients suffering from aneurysms involving the descending aorta originating from chronic type B dissections is unclear. METHODS: Within a 2-year period, we treated 6 patients with this pathology. Four patients required extension of the proximal landing zone (autologous double transposition, n = 2; subclavian-to-carotid artery transposition, n = 2) before stent-graft placement. RESULTS: Supra-aortic rerouting procedures and endovascular stent-graft placement were performed successfully in all patients. Closure of the primary entry tear, full expansion of the stent-graft, and eventually, thrombosis of the false lumen was achieved in 5 patients. In 1 patient with a short proximal landing zone, a persisting type Ia endoleak was observed. In all patients with successful primary entry closure, a reduction in aneurysm diameter occurred. Mean follow-up is 16 months (range, 4 to 25). CONCLUSIONS: Endovascular stent-graft placement of aneurysms involving the descending aorta originating from chronic type B dissections may serve as a valuable treatment option in this complex pathology. The chronic dissection membrane can be successfully compressed against large areas of the native aortic wall. A sufficient proximal landing zone is mandatory for early and late success.

Results after endovascular stent graft placement in atherosclerotic aneurysms involving the descending aorta.

BACKGROUND: The purpose of this study was to determine durability and need for reinterventions after endovascular stent graft placement in atherosclerotic aneurysms involving the descending aorta. METHODS: We performed a prospective follow-up analysis of a consecutive series of 79 patients undergoing endovascular stent graft placement due to atherosclerotic aneurysms involving the descending aorta between 1996 and 2006. Acute aortic syndromes were excluded from this analysis. Mean follow-up was 42 months (range, 1 to 108 months). Data were collected for in-hospital mortality, occurrence of early and late endoleaks, reintervention due to early and late endoleaks, and survival. RESULTS: In-hospital mortality was 6.3% (n = 5). Two of these patients underwent emergent treatment. Early type I and III endoleaks were observed in 29% of patients (n = 23). The assisted primary endoleak rate was 11%. Late type I or III endoleaks occurred in 21% (n = 17). At 1, 3, and 5 years, overall actuarial survival was 96%, 86%, and 69%, and event-free survival was 90%, 82%, and 65%, respectively. Cox proportional hazard analysis revealed that a short proximal landing zone and a high number of stent grafts used were independent risk factors for early and late endoleak formation. Late endoleak formation was an independent predictor of survival. CONCLUSIONS: Endovascular stent graft placement in atherosclerotic aneurysms involving the descending aorta has satisfactory durability. An extensive landing zone is a prerequisite of early and late success. Further clinical investigations are warranted to evaluate long-term durability of this attractive treatment modality.

Recent trends in heart transplantation: the University of Vienna experience.

Since the beginning of the University of Vienna Cardiac Transplant Program in 1984, 1086 heart transplant procedures have been performed through the end of 2007. One- and five-year survival has increased steadily over time (82% and 76%). Ten-year survival is 65%. Over the past 10 years our program has seen dramatic changes in patient selection, accepting now patients with more risk factors (Age, diabetes, elevated pulmonary resistance,..). Developments in immunosuppression have decreased incidence of infection, rejection and graft arteriosclerosis continuously. Our program continues to pursue novel strategies to improve the survival and quality of life of our heart transplant patients.

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1.

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.

Regular physical exercise improves endothelial function in heart transplant recipients.

BACKGROUND: Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. METHODS: Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. RESULTS: Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. DISCUSSION: Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.

The University of Vienna experience in heart transplantation.

Since the University of Vienna Cardiac Transplant Program began in 1984, 892 heart transplant procedures have been performed through the end of 2001. One- and five-year survival has increased steadily over time to 80% and 75%, respectively, in the most recent cohort. Ten-year survival is 55%. Over the past 10 years our program has seen dramatic changes in patient selection, accepting now patients with more risk factors (age, diabetes, elevated pulmonary resistance,..). Developments in immunosuppression have decreased the incidence of infection, rejection and graft arteriosclerosis continuously. Our program continues to pursue novel strategies to improve the survival and quality of life of our heart transplant patients.