Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma.

OBJECTIVE: • To analyse the safety and efficacy of simultaneous standard anti-angiogenic therapy and stereotactic radiosurgery (SRS) in patients with spinal and cerebral metastases from renal cell carcinoma. PATIENTS AND METHODS: • In all, 106 patients with spinal (n= 55) or cerebral (n= 51) metastatic lesions and an Eastern Cooperative Oncology Group status of 0 or 1 were treated with sorafenib or sunitinib and simultaneous SRS. • The primary endpoint was local control. • Secondary endpoints were toxicity and overall survival. RESULTS: • Median follow up was 14.7 months (range 1-42 months). Forty-five patients were treated with sunitinb and 61 patients with sorafenib. Two patients had asymptomatic tumour haemorrhage after SRS. • No skin toxicity, neurotoxicity or myelopathy occurred after SRS, and SRS did not alter the adverse effects of anti-angiogenic therapy. • Local tumour control 15 months after SRS was 98% (95% confidence interval 89-99%). The median pain score before SRS was 5 (range 1-8) and was lowered to 0 (range 0-2, P < 0.01) after SRS. There were no treatment-related deaths or late complications after SRS. • Overall survival was 17.4 months in patients with spinal lesions and 11.1 month in patients with cerebral lesions (P= 0.038). CONCLUSIONS: • Simultaneous systemic anti-angiogenic therapy and SRS for selected patients with renal cell carcinoma who have spinal and cerebral metastases is safe and effective. • Single-fraction delivery allows for efficacious integration of focal radiation treatment into oncological treatment concepts without additional toxicity. • Further studies are needed to determine the limits of SRS for renal cell carcinoma metastases outside the brain and spine.

Sorafenib in advanced clear-cell renal-cell carcinoma.

BACKGROUND: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. METHODS: From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo. Consequently, crossover was permitted from placebo to sorafenib, beginning in May 2005. RESULTS: At the January 2005 cutoff, the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P=0.02), although this benefit was not statistically significant according to the O'Brien-Fleming threshold. Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo (P<0.001). Diarrhea, rash, fatigue, and hand-foot skin reactions were the most common adverse events associated with sorafenib. Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo. CONCLUSIONS: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects. (ClinicalTrials.gov number, NCT00073307 [ClinicalTrials.gov].).

Carcinoma of the collecting ducts of Bellini of the kidney: adjuvant chemotherapy followed by multikinase inhibition with sunitinib.

BACKGROUND: Carcinoma of the collecting ducts (CDC) of Bellini of the kidney is very rare but is among the most aggressive urologic entities. PATIENTS AND METHODS: Radical nephrectomy revealed CDC in stage pT3a pN2 M0 G3 in 2 male patients. Four courses of adjuvant chemotherapy with cisplatin and gemcitabine were given. RESULTS: Subsequent restaging revealed local recurrence and lymph node metastases. Both patients were operated on again, and metastatic CDC was found. Second-line therapy with sunitinib was administered. After 2 cycles, multiple liver, lung, and bone metastases and mediastinal lymphopathy occurred. Eight weeks later, the patients died, with a survival of 8 months from initial diagnosis. CONCLUSION: Nephrectomy, adjuvant gemcitabine/cisplatin, and sunitinib therapy did not alter the course of disease in these patients. Gross resection of disease was rapidly followed by local recurrence and, subsequently, widespread dissemination of disease. Clinical trial investigation is urgently needed because of the aggressive and refractory nature of CDC.

Repeated gamma knife surgery for multiple brain metastases from renal cell carcinoma.

OBJECT: The aim of this study was to evaluate the therapeutic profile of repeated gamma knife surgery (GKS) for renal cell carcinoma that has metastasized to the brain on multiple occasions. METHODS: Data from this study were culled from a single institution and cover a 6-year period of outpatient radiosurgery. A standard protocol for indication, dose planning, and follow up was established. In cases of distant or local recurrences, radiosurgery was undertaken repeatedly (up to six times in one individual). Seventy-five patients harboring 350 cerebral metastases were treated. Relief from pretreatment neurological symptoms occurred in 72% of patients within a few days or a few weeks after the procedure. The actuarial local tumor control rate after the initial GKS was 95%. In patients free from relapse of intracranial metastases after repeated radiosurgery, long-term survival was 91% after 4 years; median survival was 11.1+/-3.2 months after radiosurgery and 4.5+/-1.1 years after diagnosis of the primary kidney cancer. Survival following radiosurgery was independent of patient age and sex, side of the renal cell carcinoma, pretreatment of the cerebrum by using radiotherapy or surgery, number of brain metastases and their synchronization with the primary renal cell carcinoma, and the frequency of radiosurgical procedures. In contrast, survival was dependent on the patient's clinical performance score and the extracranial tumor status. Tumor bleeding was observed in seven patients (9%) and late radiation toxicity (LRT) in 15 patients (20%). Treatment-related morbidity was moderate and mostly transient. Late radiation toxicity was encountered predominantly in long-term survivors. CONCLUSIONS: Outpatient repeated radiosurgery is an effective and only minimally invasive treatment for multiple brain metastases from renal cell cancer and is recommended as being the method of choice to control intracranial disease, especially in selected patients with limited extracranial disease. Physicians dealing with such patients should be aware of the characteristic aspects of LRT.

Interstitial laser coagulation combined with minimal transurethral resection of the prostate for the treatment of benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) represents the gold standard in the surgical treatment of benign prostatic hyperplasia (BPH). However, this method still has significant morbidity mainly associated with irrigation fluid absorption and blood loss. PATIENTS AND METHODS: A combination of interstitial laser coagulation (ILC) with limited TURP was established to reduce specific risks of transurethral resection and was applied in 41 patients with bladder outlet obstruction caused by BPH. In these patients, a subtotal resection of the prostate was not possible because of anesthesiologic risk factors. After insertion of a suprapubic catheter, ILC was performed under visual control using an Nd:YAG laser followed by resection of the bladder neck or the median lobe. Isotonic carbohydrate solution with 1% ethanol was used for irrigation, and irrigation fluid uptake was quantified by measurements of the ethanol concentration in the patients' exhaled breath. Additional measures such as blood loss, need for blood transfusions, and operative time were evaluated. RESULTS: The operations were performed without major complications with a mean operative time of 35 +/- 11 minutes for the entire procedure. An irrigation fluid uptake of 9 +/- 32 mL and no TUR syndrome were observed. The mean blood loss was minimal with a change in the hemoglobin of -1.3 +/- 1.1 g/dL and no need for blood transfusions. CONCLUSION: These results demonstrate that ILC with subsequent minimal TURP is an applicable method in the surgical treatment of BPH with reduction of blood loss and of the risk of TUR syndrome. This procedure may help to reduce the morbidity of TURP, especially in high-risk patients.

Treatment algorithm for metastatic renal cell carcinoma--recommendations based on evidence and clinical practice.

Until a few years ago, the treatment options for metastatic renal cell cancer (mRCC) were very limited. The growing understanding of the molecular pathomechanisms underlying RCC allowed the development of new treatment approaches. Meanwhile, several approved target-oriented substances from different drug classes are available for mRCC. The mechanism of action of vascular endothelial growth factor (VEGF) and VEGF receptor or mTOR inhibition is well documented by phase III trials and reflected in the current guidelines. However, no predictive biomarkers have been identified in mRCC so far to demonstrate a benefit by a specific compound in an individual patient. Meanwhile, the sequential use of 'targeted therapies' in mRCC has been established as standard treatment. The optimal sequence of available agents is still unclear. A German RCC expert panel discussed and developed an algorithm for the choices of first- and second-line treatment in mRCC based on established clinical criteria.

Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention.

BACKGROUND: Former systemic therapy for metastatic renal cell cancer (mRCC) based on immunomodulation could achieve complete remissions (CR) in only some patients. Angiogenic therapy with sunitinib, sorafenib, and temsirolimus changed the paradigm of treating mRCC based on a doubled progression-free survival (PFS) and 10% to 30% of patients achieving partial remission (PR). Unfortunately, CR is rarely seen. Within our patients we could achieve some CR, which we are presenting in this study. PATIENTS AND METHODS: We assessed 194 consecutive patients of an institutional database that were treated for mRCC with either sorafenib or sunitinib between 05/2006 and 12/2007. Restaging with repeated high-resolution computed tomography (CT) of thorax and abdomen was performed in an 8 to 10 weeks interval. Five patients who achieved CR in repeated CT under therapy are included in this analysis. RESULTS: Of the patients in whom we achieved CR, two were female and three were male. Median age was 63.2 years (range 52-70). All patients had clear cell histology. In three of the five patients, CR was achieved by surgery after partial remission, and in two patients it was achieved by sole medical therapy. All patients remained in CR until now with a median duration of CR of 24 months (range 24-29 months). One patient still is on therapy, while four patients do not receive any systemic treatment. CONCLUSIONS: We proof long-term confirmed CR in mRCC achieved by anti-angiogenic therapy alone or in combination with surgery. Combining surgery and anti-angiogenic therapy based on sorafenib and sunitinib could render patients free of disease even after repeated cycles of systemic treatment.

Renal cell carcinoma in patients with a solitary kidney after nephrectomy treated with radiofrequency ablation: mid term results.

This retrospective study aimed to evaluate the feasibility and effectiveness of radiofrequency ablation (RFA) in patients with solitary kidney for the treatment of renal cell carcinoma (RCC). Within 2 years 10 patients (seven males, three females; age 65+/-8 years) were treated. All patients had a history of nephrectomy of the contralateral kidney. The indications for RFA were inoperability or high probability of complete renal failure after surgical enucleation of the tumor. 13 tumors with a size between 1.9 and 4.2 cm (average 2.7 cm) were treated. In patients with a tumor diameter larger than 2.5 cm a transarterial embolization was performed prior to RFA to reduce heat sink effect and risk of bleeding. Therapeutical success was defined as a lack of contrast enhancement in follow up examinations and shrinking of the treated area. Furthermore all patients' renal function was monitored. RFA of renal tumors under CT-fluoroscopy was feasible in all patients. Within the follow up (3 and 24 months) no tumor recurrence or major complication was detected. One patient developed another RCC and was successfully treated with a second RF-ablation. None of the patients developed renal failure with the need of hemodialysis. In one of the patients a hemorrhage into the surrounding tissue was noticed, which stopped spontaneously. RFA is a valuable and effective therapeutical option in patients with solitary kidney suffering from inoperable renal cell carcinoma. The complication rate is small and an excellent tumor control can be achieved without deterioration of the renal function.

The role of surgery in clinical management of patients with metastatic papillary renal cell carcinoma.

OBJECTIVES: Patients with metastatic papillary renal cell carcinoma (RCC) show special clinical behavior compared to patients with other histologic subtypes of RCC. This study aimed to assess the relevance of surgical and systemic options used in treatment of these patients prior to the recent era of targeted therapies. METHODS: Retrospectively, we assessed clinical data of 61 patients with metastatic papillary RCC who were treated at eight centers in Germany. RESULTS: Median follow-up was 20 (range 1-114) months and median age at time of diagnosis was 62 (range 24-85) years. Men were affected predominantly (50/61; 82%). Twenty-one patients (34%) showed metastases at time of diagnosis. In the remaining 40 patients, median time to development of metastases was 30.4 (range 3-143; mean 16.5) months. Sites of metastases were lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%), and local recurrence (17; 28%). Others sites of disease were brain metastases (6 patients/10%), peritoneal carcinosis (5 patients/8%), and others. A surgical approach with potentially curative intention was performed primarily in 11 patients (18%). 31 patients received an immuno- (interferon-alpha +/- interleukin-2) or immunochemotherapy as first line treatment for metastatic disease. Overall, 42/61 patients (69%) received systemic therapy. Supportive care only was performed in 12 patients (20%) because of poor performance status. Median overall survival after diagnosis of metastatic disease was longer than 48 months in patients with tumor resection (n = 11) compared to 13.0 +/- 4.3 months 95% CI 4.5-21.5 (n = 42) months in patients without surgical approach. CONCLUSIONS: Complete resection of metastases represents a valid option in management of patients with relapsing or metastatic papillary RCC.

Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma.

Preclinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase 1 vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of the HLA-A*0201 allotype, with at least one metastatic lesion, were included. Irradiated vaccine cells were applied in increasing doses of 2.5, 10, and 40 x 10(6) cells over 22 weeks. Primary study parameters included safety and toxicity. Sequential blood samples were analyzed by interferon-gamma enzyme-linked immunospot assays to detect tumor antigen-associated (TAA) effector cells. The vaccine was well tolerated and the designated vaccination course was completed in 9 of 15 patients. Neither vaccine-induced autoimmunity nor systemic side effects were observed. Delayed-type hypersensitivity skin reactions were detected in 11 of 12 evaluated patients and were particularly strong in patients with prolonged survival. In parallel, vaccine-induced immune responses against vaccine or overexpressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria; however, median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. We conclude that vaccine use was safe and feasible in mRCC. Clinical benefits were limited in these patients with advanced disease; however, immune monitoring revealed vaccine-induced responses against multiple TAAs in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.

Treatment of brain metastases in renal cell carcinoma: radiotherapy, radiosurgery, or surgery?

Metastases from renal cell carcinoma raise specific therapeutic problems because they are relatively unresponsive to whole brain radiation therapy and tend to bleed. Recently, stereotactically guided high-precision irradiation as a single dose application (radiosurgery) showed promising treatment results for selected patients with brain metastases from renal cell carcinoma. Radiosurgery appears attractive due to its low risk and minimal invasiveness. Multiple lesions can be treated at the same time and retreatments can be performed for local or distant recurrences.

Immunotherapy in metastatic renal cell carcinoma.

Metastatic renal cell carcinoma has a poor prognosis. Conventional therapies such as chemotherapy, radiation or hormonal treatment have hardly any effect on the progression of this disease. As renal cell carcinoma seems to be an immunogenic tumor, several immunotherapeutic approaches with different response rates have been developed since the early 1990s. We present an overview of various immunotherapeutic approaches such as cytokine-based regimes, with and without different cytotoxic chemotherapy, of metastatic renal cell carcinoma. In addition, local therapies (e.g. inhalation of interleukin-2) are reviewed.

High power (80 W) potassium-titanyl-phosphate laser vaporization of the prostate in 66 high risk patients.

PURPOSE: Men with lower urinary tract symptoms secondary to benign prostatic hyperplasia who are at high cardiopulmonary risk or on oral anticoagulation are often denied surgical treatment. Potassium-titanyl-phosphate (KTP) laser vaporization at 80 W is a novel, rapidly emerging technique that promises instant hemostatic tissue ablation. We evaluated the merits of this procedure in patients at high risk and those on long-term anticoagulation. MATERIALS AND METHODS: The prospective study included 66 patients with severe lower urinary tract symptoms who underwent 80 W KTP laser vaporization of the prostate. All patients were at high cardiopulmonary risk, having presented with an American Society of Anesthesiology score of 3 or greater. Additionally, 29 patients were being treated with ongoing oral anticoagulant therapy (26) or had a severe bleeding disorder (3). RESULTS: In all 66 patients KTP laser vaporization was performed successfully. Mean preoperative prostate volume +/- SD was 49 +/- 30 ml and mean operative time was 49 +/- 19 minutes. No major complication occurred intraoperatively or postoperatively and no blood transfusion was required. Postoperatively 48 of 62 catheterized patients (77%) did not require irrigation. Average catheterization time was 1.8 +/- 1.4 days. Two patients required reoperation due to recurrent urinary retention. At 1, 3, 6 and 12 months mean urinary peak flow increased from 6.7 +/- 2 ml per second preoperatively to 18.5 +/- 9, 18.9 +/- 10, 19.2 +/- 8 and 21.6 +/- 7 ml per second, respectively. Mean International Prostate Symptom Score decreased from 20.2 +/- 6 to 11.7 +/- 7, 7.9 +/- 7, 6.9 +/- 5 and 6.5 +/- 4, respectively. CONCLUSIONS: Our initial experience indicates that 80 W KTP laser vaporization is a virtually bloodless and, hence, safe but effective treatment option in seriously ill patients or those on oral anticoagulants.

Diagnosis of urothelial carcinoma of the bladder using fluorescence endoscopy.

Bladder cancer is a frequent disease and represents the second most common genitourinary neoplasm. Although many aspects of the management of superficial bladder cancer are now well established, significant challenges remain, which influences patient outcome. Early detection and treatment of recurrent disease is required to optimize bladder preservation, reduce patient morbidity, and increase quality of life and survival. Fluorescence endoscopy, often referred to as 'photodynamic diagnosis' (PDD), with intravesical application of photosensitizing agents, has been developed to enhance the early detection of bladder cancer. There is growing evidence that PDD using 5-aminolaevulinic acid (ALA), hexyl-ALA ester or hypericin enhances the detection of bladder cancer, particularly of high-grade flat lesions. Furthermore, transurethral resection of bladder tumour under fluorescence guidance reduces the risk of recurrent tumours. However, the impact on the progression of disease remains unclear and must be investigated in prospective randomized trials.

Retroperitoneoscopy-assisted cryoablation of renal tumors using multiple 1.5 mm ultrathin cryoprobes: a preliminary report.

OBJECTIVES: Laparoscopic cryoablation has recently been proposed as a minimally invasive nephron-sparing treatment for selected patients. We report on our experience with a retroperitoneoscopic technique using multiple ultrathin cryoprobes. METHODS: Seven patients underwent retroperitoneoscopic renal cryoablation for solid renal masses. Mean tumor size on the CT scan was 2.6 (1.5-3.5) cm. A double freeze-thaw cycle of renal cryoablation was performed under real-time ultrasound monitoring using a total of six 1.5-mm cryoprobes simultaneously. RESULTS: Cryoablation was technically successful in all patients without any need for conversion. Mean duration of surgery was 161 (130-195) minutes and mean blood loss was 107 (50-250) ml. Perioperative biopsy of the tumor confirmed renal cell carcinoma in four patients and angiomyolipoma in two patients; it was inconclusive in one case. Mean follow-up for 13.6 (4-22) months showed no evidence of residual tumor or recurrence. CONCLUSIONS: Retroperitoneoscopy-assisted cryosurgical ablation using multiple ultrathin 1.5-mm cryoprobes is a minimally invasive treatment that is suitable to treat small renal tumors.

Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells.

Initial vaccine developments for renal cell carcinoma (RCC) have concentrated on cell-based approaches in which tumor cells themselves provide mixtures of unknown tumor-associated antigens as immunizing agents. Antigens derived from autologous tumors can direct responses to molecular composites characteristic of individual tumors, whereas antigens derived from allogeneic tumor cells must be commonly shared by RCC. Three types of cell-based vaccine for RCC have been investigated: isolated tumor cell suspensions, gene modified tumor cells and dendritic cells (DCs) expressing RCC-associated antigens. Approaches using genetic modification of autologous RCC have included ex vivo modification of tumor cells or modification of tumors in vivo. We have used gene-modification of allogeneic tumor cell lines to create generic RCC vaccines. More recently, emphasis has shifted to the use of DCs as cell-based vaccines for RCC. DCs have moved to a position of central interest because of their excellent stimulatory capacity, combined with their ability to process and present antigens to both naive CD4 and CD8 cells. The long impasse in identifying molecular targets for specific immunotherapy of RCC is now rapidly being overcome through the use of tools and information emerging from human genome research. Identification of candidate molecules expressed by RCC using cDNA arrays, combined with protein arrays and identification of peptides presented by MHC molecules, allow specific vaccines to be tailored to the antigenic profile of individual tumors, providing the basis for development of patient-specific vaccines.

Autofluorescence and 5-aminolevulinic acid induced fluorescence diagnosis of penile carcinoma -- new techniques to monitor Nd:YAG laser therapy.

Nd:YAG laser coagulation is possible for superficial tumors of the penis. The value of photodynamic diagnosis (PDD) and autofluorescence imaging (AF) in detecting malignant lesions on the penis was evaluated. Twelve patients with biopsy-confirmed squamous cell cancer (SCC) of the penis were examined with PDD and AF. For the PDD and AF the penis was illuminated with the blue excitation light from a xenon arch lamp. Biopsies were taken from suspicious lesions detected by PDD or AF and then treated with Nd:YAG laser coagulation. Neoplastic lesions presented with a positive red fluorescence under PDD or a diminished appearance under AF. The HPV-analysis was positive in eight of the 12 lesions. Fluorescence diagnosis is used for the detection of neoplastic lesions. It assists the urologist in detecting neoplastic and preneoplastic lesions, ensuring a more reliable destruction of all tumor material in penile sparing surgery.

Argon plasma coagulation (APC) for endo-urological procedures: ex-vivo evaluations of hemostatic properties.

OBJECTIVES: Argon plasma coagulation (APC) is an innovative therapeutic modality of non-contact electrocoagulation, which applies high-frequency current via ionized argon plasma. After several years of successful use in open surgery, endoscopic techniques have been established in various surgical fields. The aim of this study was to evaluate the hemostatic properties of this technique in a fluid medium with regard to endourological procedures. METHODS: Isolated blood-perfused porcine kidneys were used to determine hemostatic efficacy of APC following TURP-like tissue ablation with a conventional loop electrode, compared to standard electrocoagulation with a ball electrode after tissue resection. Blood loss was quantified, specimens were evaluated histologically for coagulation zones. RESULTS: APC following tissue resection significantly (p<0.001) reduced bleeding compared to conventional contact electrocoagulation subsequent to tissue resection for an ablation volume of 4 cm(3) of perfused kidney tissue (2.1 ml/min vs. 5.6 ml/min). The depths of the coagulation zones were significantly larger (2.4 mm vs. 0.8 mm) and remarkably uniform for the groups treated with APC following tissue resection. CONCLUSIONS: APC performed in a fluid medium is feasible. APC following conventional TURP-like tissue resection creates significantly better hemostasis compared to standard contact coagulation after tissue resection. These findings justify further investigations to elucidate the value of APC in endourological procedures.

Risks and complications in 160 living kidney donors who underwent nephroureterectomy.

BACKGROUND: The rate of living donor renal transplantations has increased. However, in view of the possible complications, the question as to whether the condition of the recipient justifies operation of the donor still remains unanswered. The present retrospective study evaluates the perioperative and post-operative risks and complications for the donor at a single major transplantation centre. METHODS: From 1994 to 2001, 160 live donor nephroureterectomies were performed. The median age of living donors was 51 years (range 21-77 years); 19 patients were older than 61 years. After confirming blood group compatibility and negative cross-match, donors underwent an extensive medical and psychological examination. Comorbidities and anatomical features of the donor were evaluated and the impact they may have on the outcome was determined. The nephroureterectomies were performed transperitoneally, with the right kidney being preferred. Pre-operative, intraoperative and post-operative complications were documented. Serum creatinine levels as well as new-onset proteinuria or hypertension were used as criteria for assessing long-term renal function. RESULTS: Complications were observed in 41 donors: 35 were minor and six were major (splenectomy; revisions due to liver bleeding, incarcerated umbilical hernia or infected pancreatic pseudocyst; pneumothorax; and acute renal failure). No patient died. Multiple arteries (14 patients), significant renal artery stenosis (two patients) and additional risk factors (e.g. increased age and previous operations) did not affect the complication rate. In the post-operative follow-up period of 0.5-62 months (mean: 38 months), renal function remained stable in all donors. CONCLUSIONS: Living donor nephrectomy appears to be a safe intervention in specialized centres, where it entails a low morbidity for the donor. Even in high-risk donors, long-term complications were not observed.