Skin cancers are the most common tumors in patients who have received organ transplants. This review discusses the epidemiology, pathogenesis, and management of squamous-cell and basal-cell carcinomas, cancers of the anogenital region, Kaposi's sarcoma, melanoma, neuroendocrine skin carcinoma, and cutaneous manifestations of lymphoma in transplant recipients.

Skin cancers after organ transplantation.

Epidemiology of cardiovascular disease in chronic renal disease

In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

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Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis

Background Merkel cell carcinoma (MCC) is an aggressive skin cancer with a mortality of 33%. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. No systematic analysis has been published to define the clinical features that are characteristic of MCC. Objective We sought to define the clinical characteristics present at diagnosis to identify features that may aid clinicians in recognizing MCC. Methods We conducted a cohort study of 195 patients given the diagnosis of MCC between 1980 and 2007. Data were collected prospectively in the majority of cases, and medical records were reviewed. Results An important finding was that 88% of MCCs were asymptomatic (nontender) despite rapid growth in the prior 3 months (63% of lesions) and being red or pink (56%). A majority of MCC lesions (56%) were presumed at biopsy to be benign, with a cyst/acneiform lesion being the single most common diagnosis (32%) given. The median delay from lesion appearance to biopsy was 3 months (range 1-54 months), and median tumor diameter was 1.8 cm. Similar to earlier studies, 81% of primary MCCs occurred on ultraviolet-exposed sites, and our cohort was elderly (90% >50 years), predominantly white (98%), and often profoundly immune suppressed (7.8%). An additional novel finding was that chronic lymphocytic leukemia was more than 30-fold overrepresented among patients with MCC. Limitations The study was limited to patients seen at a tertiary care center. Complete clinical data could not be obtained on all patients. This study could not assess the specificity of the clinical characteristics of MCC. Conclusions To our knowledge, this study is the first to define clinical features that may serve as clues in the diagnosis of MCC. The most significant features can be summarized in an acronym: AEIOU ( a symptomatic/lack of tenderness, e xpanding rapidly, i mmune suppression, o lder than 50 years, and u ltraviolet-exposed site on a person with fair skin). In our series, 89% of primary MCCs had 3 or more of these findings. Although MCC is uncommon, when present in combination, these features may indicate a concerning process that would warrant biopsy. In particular, a lesion that is red and expanding rapidly yet asymptomatic should be of concern.

Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features

http://www.coaching-for-health.net/eisenzentrum/studien/studie13.pdf

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

Background. The pathogenesis of haemodialysisinduced hypotension is multifactorial and may include autonomic nervous system dysfunction. The present study was undertaken to (i) determine heart rate variability (HRV) in chronic haemodialysis patients without and with haemodynamic instability (hypotensionprone) during ultrafiltration and (ii) identify patients at risk and the predictors of dialysis-related hypotension. Methods. HRV was evaluated in 56 chronic haemodialysis patients without (stable; n ¼ 27) and with symptomatic hypotension episodes (unstable; n ¼ 29) during daytime, haemodialysis and night-time periods. Logistic regression analysis was performed in a model that included clinical and biochemical data and HRV measurements. Results. HRV was significantly reduced in haemodynamically unstable as compared with the stable patients. LF/HF ratio, an index representative of sympathovagal balance, was significantly lower in unstable patients, especially in those with ischaemic heart disease and diabetes mellitus. In a logistic regression model including clinical data and HRV measurements, ischaemic heart disease and left ventricular systolic dysfunction were found to be the main predictors of haemodynamic instability. Conclusions. These data suggest that haemodynamic instability is strongly associated with a decreased HRV and an impaired sympathovagal balance, suggesting disturbed autonomic control in uraemic patients with cardiac damage. Patients with ischaemic heart disease, reduced left ventricular systolic function and decreased HRV may be at the highest risk to be haemodynamically unstable during haemodialysis. The role of early detection and treatment of ischaemic heart disease in preventing symptomatic hypotensive episodes in these patients remains to be determined.

Predictors of haemodynamic instability and heart rate variability during haemodialysis

Adequate sympathetic nervous system activation is essential for the compensatory mechanisms of blood pressure maintenance during the hemodialysis (HD) procedure. Chronic sympathetic nervous system overactivity, however, may lead to the development of hypertension and cardiovascular disease in HD patients. The present review focuses on recent findings on the sympathetic nervous system activity in these patients. Sympathetic overactivity has been demonstrated directly by muscle sympathetic nerve activity recordings (MSNA) in chronic renal disease, but only rarely in HD patients. In the latter, sympathetic activity has mostly been assessed using indirect methodology. Decreased heart rate variability, increased blood pressure variability (BPV), and suppressed baroreflex function are believed to represent chronic sympathetic overactivity in HD patients. The HD procedure and ultrafiltration are associated with enhanced sympathetic activity and baroreflex activation. During most episodes of intradialytic hypotension, the baroreflex is adequately activated; sympathetic withdrawal with bradycardia, however, has been reported during excessive hypovolemia. Sympathetic overactivity is also believed to be a mechanism associated with intradialytic hypertensive episodes and refractory hypertension. While successful renal transplantation is associated with improvement of heart rate variability (HRV), improvement and restoration of baroreflex function, persistent sympathetic overactivity has been documented in transplanted patients using MSNA recordings. Decreased HRV and baroreflex function have been reported to be associated with increased mortality and morbidity in HD patients. The predictive value of sympathetic outflow assessed by MSNA has yet to be determined. Optimization of HD treatment, pharmacological interventions, and renal sympathetic denervation are several approaches targeting sympathetic overactivity to improve cardiovascular morbidity and mortality.

Sympathetic Nervous System Function and Dysfunction in Chronic Hemodialysis Patients

A 46-year-old male received two preemptive living-donor kidney transplants in 1989 and in 1998 and was treated with prednisone, cyclosporine (CsA), and azathioprine. Pulse methylprednisolone and ATG therapy were given in 1992 for acute cellular rejection. In September 1999, a cervical swelling was removed and recurred 3 months later. Histology of the removed tissue showed Merkel cell carcinoma (MCC) (sheets of closely packed small cells with round nuclei containing finely dispersed chromatin, scant cytoplasm, and mitotic figures and immunohistochemistry showing scattered staining with chromogranin and prominent paranuclear dot-like staining with cytokeratin, epithelial membrane antigen moderately to intensely positive and negative for leukocyte common antigen, desmin and S-100). Azathioprine therapy was stopped. Five courses of cyclophosphamide, adriamycin, vincristine, and etoposide had no effect on the neck swelling, which increased in size during therapy. Local radiotherapy to a total dose of 50 Gy caused reduction in the swelling. Oral prednisone 7.5 mg and CsA 100 mg twice daily were continued. The patient remained in good general condition without local tumor recurrence for over 6 months. In October 2000 the patient returned with recent onset of anorexia, weight loss, and diffuse bone pains that were unresponsive to analgesics. He was unable to walk. There was a painful swelling in his neck at the site of the previously resected tumor. Multiple new growths protruding from his skull had appeared. One of these was excised and confirmed the metastatic spread of the MCC. Immunohistochemistry performed on this biopsy material showed positive staining for transforming growth factor (TGF)(Fig. 1). Tc-99 M-MDP bone scan showed multiple areas of increased uptake including in the skull, right acromion, several ribs, and left sacroiliac joint. Biochemistry showed normal renal function and no change in mildly elevated liver enzymes (chronic biopsy verified hepatitis C). The patient received further palliative radiotherapy to his left shoulder region and to his sacrum. CsA was stopped and only 5 mg of prednisone was continued. Carboplatin therapy was advised but the patient opted not to receive this because, soon after stopping CsA, he became free of pain. All visible signs of his MCC metastases disappeared, he was freely mobile, and gained weight. External examination of his cranium revealed no signs of the previous multiple metastatic growths. His kidney function was excellent. The whole blood-specific CsA levels before cessation of therapy were 96–130 ng/ml. The patient remained in excellent condition for 8 months after withdrawal of CsA therapy. In May 2001 sudden paraparesis occurred. CT scan showed thoracic spinal compression by a soft tissue lesion and several hypodense liver lesions. Palliative radiotherapy did not prevent total paraplegia and the patient died at home 1 month later. His renal function remained normal until his death. MCC is a rare skin cancer arising from cells of neuroendocrine origin and seems to be especially aggressive after organ transplantation (1). The value of reduction in immunosuppressive therapy, especially cessation of azathioprine, has been shown mostly in tumors associated with oncogenic viruses such as Kaposi’s sarcoma and posttransplantation lymphoproliferative disease (2, 3), but there are very few reports of regression of solid tumors. CsA therapy has been associated with more rapid growth of hepatic tumors (4) and stimulates tissue expression of TGF(5). A nonimmunologic mechanism whereby CsA promoted phenotypic changes in several types of malignant cells in vitro and increased tumor growth and metastatic spread of malignant cells in vivo has recently been described (6). Treatment with anti-TGFmonoclonal antibodies prevented these effects of CsA. The MCC metastases in our patient showed positive staining for TGF, and it is thus possible that the dramatic regression of the MCC metastases in our patient were via such a CsA-induced TGFmechanism. Withdrawal of CsA therapy enabled a terminally ill patient to return to good health for an 8-month period until a new spinal metastasis caused a rapid fatal outcome.

Temporary regression of Merkel cell carcinoma metastases after cessation of cyclosporine.

The present study was undertaken to compare heart rate variability (HRV) values in patients on maintenance hemodialysis with no evidence of ischemic or hypertensive heart diseases to those of age- and gender-matched healthy individuals and those of patients after renal transplantation. To assess the effects of a common confounding factor, HRV values were also determined in patients with systemic amyloidosis, in chronic hemodialysis, and after successful renal transplantation. Spectral analyses of RR intervals from continuous electrocardiogram recordings were performed to quantify ultra low frequency, very low frequency, low frequency, and high frequency powers. HRV determinations were all significantly reduced in uremic patients undergoing hemodialysis compared with the healthy control subjects, especially in those with systemic amyloidosis. Renal transplantation normalized HRV in most patients; HRV, however, remained reduced in isolated amyloidosis patients with cardiac or adrenal involvement. HRV circadian day/night differences were preserved in hemodialysis patients and after renal transplantation in those without amyloidosis but not in those with amyloidosis. These data suggest that reduced HRV in chronic hemodialysis patients may precede other manifestations of cardiovascular disease. In uremic patients with amyloidosis, a more severe form of autonomic failure may occur. Successful transplantation corrects HRV abnormalities in most patients, suggesting that the autonomic dysfunction of uremia is caused by humoral factors reversed by the normalization of the renal function.

Heart Rate Variability during Chronic Hemodialysis and after Renal Transplantation: Studies in Patients without and with Systemic Amyloidosis

bedside TenckhoV; CAPD; heart failure; tion of CHF; (ii) number and duration of hospitaliza-life quality; mild renal failure; treatment tion; (iii) number of drugs taken by the patients; (iv)complications related to CAPD, and (v) survival.Nine patients suVering from CHF NYHA class IVwere enrolled. All patients had signiﬁcant residual

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Dvora Rubinger

Papers

Predictors of haemodynamic instability and heart rate variability during haemodialysis

Sympathetic Nervous System Function and Dysfunction in Chronic Hemodialysis Patients

Temporary regression of Merkel cell carcinoma metastases after cessation of cyclosporine.

Heart Rate Variability during Chronic Hemodialysis and after Renal Transplantation: Studies in Patients without and with Systemic Amyloidosis

CAPD to improve quality of life in patients with refractory heart failure.