Contemporary role of palliative cystoprostatectomy or pelvic exenteration in advanced symptomatic prostate cancer.

OBJECTIVE: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). PATIENTS AND METHODS: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien-Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. RESULTS: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15 months (range 3-41) for the entire cohort with a median survival of 15 months (95% CI 10.1-19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62-17.23, p = 0.164). CONCLUSION: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.

Kidney transplantation in Romania: two transplant centers experience.

PURPOSE: Kidney graft survival rates improved from decade to decade, but data about factors that affect patient and graft survival remain challenging and even controversial. METHODS: We analyzed retrospectively data from kidney transplanted patients followed in two Romanian transplant centers (Iasi and Bucharest)-new programmes specifically developed after 1989 to cover transplantation requirements for two-thirds of Romania. We used a composite survival outcome defined as 50% reduction in estimated glomerular filtration rate (eGFR), return to dialysis or death. Survival analysis was performed using uni- and multivariable Cox regression with baseline and time-updated covariates. RESULTS: From the entire cohort of 365 patients, 243 had the outcome of interest. In the univariable Cox survival analysis, age, hemoglobin, eGFR, cholesterol, AST and transplant center were associated with the outcome. The multivariable Cox analysis reveals that only cholesterol (HR 0.97, 95% CI 0.94-0.99 per 10 mg/dL increase) and transplant center (HR 3.64, 95% CI 2.67-4.97) remain associated. For the time-updated Cox survival analysis we found that eGFR (HR 0.91, 95% CI 0.87-0.96 per 10 ml/min/1.73 m2 increase) and cholesterol are associated with the outcome in the univariable analysis and only eGFR and transplant center in the multivariable Cox survival analysis. CONCLUSIONS: Our study reports data from two distinct transplant centers from a developing country. Our results are similar to the current literature data, but also reveal that the approach of a center to the transplantation management is an independent factor associated with graft survival.

Impact of ureteral stenting on urological complications after kidney transplantation surgery: a single-center experience.

BACKGROUND: Urological complications such as ureteral strictures and ureteral leakage can affect the outcome of kidney transplantation by increasing morbidity and mortality, including graft loss. Controversy still exists regarding the role of stents in renal transplantation. The aim of this study was to evaluate the role of ureteral stenting in kidney transplantation. METHODS: We performed a retrospective study on a series of 798 consecutive renal transplants performed in our center between January 1, 2004, and December 31, 2011. Ureteral stents were used in 152 cases (19.1%) of the total (stent group) and were removed 2 weeks postoperatively. Donor and recipient age, sex, type of ureteroneocystostomy, stent and non-stent patients, cold and warm ischemia time, and urological complications were analyzed. RESULTS: The overall incidence of urological complications was 7.8% (62 cases). Ureteral stenosis (3.1%) and ureteral leakage (2.4%) were the most common complications; 39.7% (25 cases) of complications were recorded in the first month after transplantation. Major urological complication rate was 3.3% in the stent group compared with 8.8% in the non-stent group (P = .04). However, stent use was associated with the increase of urinary tract infections rate in the stent group (51.3%) compared with the non-stent group (17.9%) (P = .03). CONCLUSIONS: In our study, the use of ureteral stents significantly decreased urological complications in kidney transplant recipients but increased the risk for development of urinary tract infections.

Comparative study of conventional urothelial carcinoma, squamous differentiation carcinoma and pure squamous carcinoma in patients with invasive bladder tumors.

PURPOSE: Treatment results evaluation (radical cystectomy and adjuvant chemo/radiotherapy) in patients with urothelial carcinoma, squamous differentiation carcinoma and pure squamous bladder carcinoma. MATERIAL AND METHODS: The study included 361 patients with invasive bladder carcinoma treated between 1990-2013. Histology showed 296 cases of urothelial carcinoma (82% - group A), 52 cases of urothelial divergent differentiation (squamous and urothelial carcinoma 14.4% - group B) and 13 cases of squamous cell carcinoma (3.6% - group C). All patients benefited from radical cystectomy. Adjuvant chemotherapy was undergone in 68 patients. RESULTS: Group A - urothelial carcinoma - had a 44% rate of patients alive with a mean survival period of 73 months. About 56% of the patients died, the mean survival period being 4 years. Group B - urothelial carcinoma with squamous differentiation - had a mean survival period of 36 months (between 1-156 months). 17 patients (33%) are alive at 50 months postoperatively. Group C - squamous carcinoma - had a mean survival period of 9.4 months. DISCUSSIONS: Locally advanced disease was diagnosed in 50% of the patients in group A, while in group B the rate was 84.6% and 70% in group C, respectively. CONCLUSIONS: Squamous pattern detected in the histopathological specimen represents a negative prognostic factor. It seems that the squamous component influences the outcome of the disease due to its biological characteristics in the evolution of squamous carcinoma, with advanced local stage disease at diagnosis - late onset of symptoms and lack of response to adjuvant treatment.

Comparative urologic complications of ureteroneocystostomy in kidney transplantation: transvesical Leadbetter-Politano versus extravesical Lich-Gregoir technique.

BACKGROUND: The incidence of urologic complications after kidney transplantation remains high despite improvements in diagnosis and operative techniques. Urinary tract reconstruction is usually done by ureteroneocystostomy (UCNS), and several techniques are available. In this study, we evaluated the outcomes of 2 different UCNS techniques performed in our department, the transvesical Leadbetter-Politano (L-P) and the extravesical Lich-Gregoire (L-G) technique. MATERIAL AND METHODS: We evaluated the outcomes of 2 different UCNS techniques, L-P versus L-G, performed in our department between July 1, 2006, and December 31, 2011. During this period, we performed 524 consecutive renal transplantations-264 cases using the L-P technique (50.3%) and 260 cases with L-G technique (49.7%). Renal grafts were obtained from cadaveric donors in 146 cases (27.86%) and from living-related donors in 378 cases (72.14%). Recipient mean age was 35.64 years and the male to female ratio was 1.63:1. RESULTS: Urologic complications after kidney transplantation occurred in 22 cases in the L-P UCNS group (8.33%). The most common complications were ureteral stenosis (3.41%) and leakage (2.65%). Other complications recorded were lymphoceles (1.89%) and hematoma with secondary ureteral obstruction (0.38%). Compared with the L-P UCNS technique, the L-G technique was associated with fewer overall complications (6.15% vs 8.33%; P = .06), a lesser rate of ureteral stenosis (2.31% vs 3.41%; P = .08), and a similar rate of leakage. However, statistical analysis revealed no differences between the 2 techniques (P = .06). In addition, we did not note any differences in graft and patient survival between the 2 groups. CONCLUSIONS: In our study, the extravesical L-G technique has a lower complication rate compared with transvesical L-P procedure, but without statistical differences. Furthermore, the L-G technique is easier and faster to perform, it avoids a separate cystotomy, and requires a shorter ureteral length. In conclusion, we recommend L-G technique as technique of choice in kidney transplantation.

Histological diagnosis and risk of renal vein thrombosis, and other thrombotic complications in primitive nephrotic syndrome.

BACKGROUND: The risk of thromboembolic events is increased in patients with nephrotic syndrome (NS) as compared with other medical conditions and is a severe complication associated with significant morbidity and mortality. We aimed to assess the risk of renal vein thrombosis, and other venous thromboembolic events (VTE) in a large cohort of patients with NS and to identify the disease-specific risk for VTE. PATIENTS AND METHODS: We performed a prospective observational study including consecutive adult patients with primitive NS admitted to our department. Clinical and biological data were obtained every six months during follow-up. Occurrence of VTE confirmed by imaging techniques was the primary study outcome. RESULTS: We enrolled 191 patients (47±15 years, 53% men) with a median follow-up of 24 [IQR:12,36] months. During follow-up, 23 VTE occurred, of which 65.2% in the first six months. The disease-specific risk of VTE during the follow-up period was different across the histological groups, with the lowest risk in minimal change disease and IgA nephropathy and the highest in membranous nephropathy and membranoproliferative glomerulonephritis patients. In the subgroup of membranous, the severity of the subepithelial electron dense deposits did not correlate with the risk for VTE (p=0.5). CONCLUSIONS: In this prospective study, the risk of VTE was higher in the first six months of follow-up in NS patients. The histological pattern seems to influence the risk of VTE in this setting.

Cytotoxic antibodies monitoring in kidney transplantation--their clinical relevance and challenges.

INTRODUCTION: The key of the successful renal transplantation is the ability to identify the best immunological match between donor and recipient considering the possibility of rejection phenomenon. The aim was to identify class I and/or class II cytotoxic antibodies in renal-transplanted patients in order to assess the immunological potential for prevention of subclinical or acute rejection episodes. PATIENTS AND METHODS: We have evaluated ninety-two patients who had kidney transplantation in 2010 in Fundeni Clinical Institute, Bucharest, Romania, concerning HLA matching and anti-HLA immunization status. For HLA genotyping were used molecular biology methods--PCR-SSP (Invitrogen, USA). For cytotoxic antibodies, the methods used were ELISA (GTI Diagnostics, USA) and Luminex (One Lambda, USA). Crossmatch tests between donor cells and recipient serum were performed by ELISA (GTI Diagnostics, USA). Rejection diagnosis was supported by renal biopsy. RESULTS: In the 20 presensitized cases, the rate of acute rejection was 30% while in the 72 unsensitized cases the rejection was 19.4%. The incidence of acute rejection was higher in anti-HLA class I presensitized patients compared with anti-HLA class II (20% and 14.3%, respectively) but there was no significant difference compared to pre-transplant unsensitized patients (19.4%). Sequential post-transplantation monitoring of anti-HLA antibodies has shown in pre-transplant sensitized patients group a constantly increasing of PRA value, while in the pre-transplant unsensitized patients group, 32% developed de novo cytotoxic antibodies. CONCLUSIONS: More sensitive and specific methods to detect anti-HLA antibodies before transplantation and sequential post-transplantation monitoring of these antibodies would be useful to identify patients who are at higher risk for allograft failure.

Prostate cancer with neuroendocrine differentiation--case report.

RATIONALE: About 95% of prostate cancers are adenocarcinoamas. Depending on the detection method used, neuroendocrine cells are found in 10% to 100% of prostate cancer specimens. OBJECTIVE: A 64-year-old patient was diagnosed in 2006 with adenocarcinoma of the prostate, PSA 4.1 ng/ml, Gleason 6, T3b, positive PSA immunohistochemistry. METHODS AND RESULTS: The patient was started on hormone therapy: orchidectomy followed by flutamide 750 mg/day for three years, and underwent radiotherapy 6400 R. The patient was asymptomatic for three years. In 2009, the patient complained of perineal and rectal pain, but the PSA remained normal. In 2010, the patient underwent TUR of the prostate for acute urinary retention. Pathological exam revealed Gleason 8 adenocarcinoma of the prostate (different pathologist suggested Gleason 9) and foci of neuroendocrine cells. Immunohistochemistry detected 15-20% positivity for Cromogranin A and 10% for synaptophysin. The patient developed multiple liver metastases in October 2010 and underwent five cycles of etoposide, carboplatin. The patient died of liver failure in March 2011. DISCUSSION: Regarding prevalence, neuroendocrine differentiation is the second phenotype after prostate adenocarcinoma, but still remains undiagnosed. It is resistant to radiation therapy and chemotherapy. Detection of the neuroendocrine differentiation is recommended during the clinical, biochemical, histopathological and immunohistochemical follow up of prostate cancer patients treated by EBRT and / or androgen deprivation.

Comparative analysis of different surgical procedures for female stress urinary incontinence. Is stem cell implantation the future?

RATIONALE: Stress urinary incontinence (SUI) represents a major public health problem and although there are many treatments available, only a few can restore the anatomical background of this disorder. Injections of stem cells into the middle urethra have the possibility of restoring the contractility of the striated muscles and rhabdosphincters. The aim of stem cell therapy is to replace, repair or enhance the biological function of damaged tissue or organs. OBJECTIVE: Assessing the latest minimally invasive procedures of intra and perisphincterian injection of autologous stem cells and to compare the urodynamic results at one year after different surgical procedures for genuine stress urinary incontinence by measuring their impact on urinary flow rate (Qmax) and bladder pressure at Qmax during micturition. METHODS AND RESULTS: On October 18, 2010, in "Fundeni" Clinic of Urology and Renal Transplantation we performed for the first time in Romania, stem cell implantation in the urethral sphincter in four patients with stress urinary incontinence and compared the results of the urodynamic investigations of female patients operated with pure SUI with other surgical techniques. The analyzed procedures were: Burch colposuspension (11 cases), TVT-like (IVS sling in 26 cases), TOT-like (CYSTO-SWING sling in 41 cases). Followed variables were: Qmax, Pves at Qmax, postvoiding residual (PVR). Clinical examination and voiding diary in six weeks after the surgery revealed a decrease of urine loss with an improvement of the patient' quality of life according to visual analogue scale. For female patients with myoblasts implant, changes in Qmax and Pves at Qmax were minimal and statistically insignificant in the context of inclusion criteria, but we noticed a trend of minimal change in these urodynamic characteristics, namely, an average decrease of Qmax with 2.1 mL/s and an average increase of Pves at Qmax with 0.6 cmH(2)O. CONCLUSIONS: The development of myoblasts implant (if they will pass the time-proof test) could represent a breakthrough in treating this condition. As the pathogenesis of SUI is better understood and the development of tissue engineering technology advances, tissue engineering will play a more important role in the treatment of patients with SUI.

Atypical primary tuberculosis mimicking an advanced penile cancer. Can we rely on preoperative assessment?

Tuberculosis of penis is a very rare clinical entity. There are isolated reports of its presentation as a subcutaneous nodule with or without superficial ulcers and can be interpreted as advanced penile cancer. We present a case of penile tuberculosis that presented in our Center with a bulky penoscrotal formation treated in other center for the suspicion of Fournier gangrene.

Morphological aspects of the kidney: can normality be predicted?

PURPOSE: Our study aimed to assess the normal parameters of renal parenchyma and upper urinary tract from a contrast enhanced computed tomography assessment in order to create a mathematical model of normal kidney. PATIENTS AND METHODS: We conducted a retrospective observation study on 520 patients with a normal abdominal contrast enhanced CT scan in our Institute during November 2008-November 2010. All CT examinations were performed using 16 slices Siemens Emotion 2007 (Siemens Medical Solutions, Malvern, PA, USA). Two experienced radiologists evaluated all the evaluations and reformatted axial sections and after excluding patients with urinary tract pathology, the images were transferred to a separate workstation (eFilm Workstation(TM) 2.2.1, Merge Healthcare, Milwaukee, USA). Parameters measured were: the number of kidneys, craniocaudal diameter (CCD) in a coronar reconstruction, transverse diameter (TD) and anteroposterior diameter (APD) as the maximum diameter of the kidneys in the axial sections, parenchymal (PW) and cortical width (CW) in axial sections, kidney pyelon width (KPW), parenchymal index (PI), kidney rotation, measured in relation to the sagittal axial plane of reference (AR) and rotation of the kidney measured in the sagittal plane in relation to the coronary reference (SR). To identify factors that can influence the variables CCD, CW and PW, multivariate regression models were performed using SPSS software (SPSS 15, SPSS Inc., Chicago, Illinois, USA). We considered p<0.05 statistically significant. RESULTS: CCD remains high until the fifth decade of life (p=0.0053 on the right side, p=0.0012 on the left, ANOVA), PW values were found to be somewhat increased (p=0.0293 on the right side, p=0.2924 on the left, ANOVA). There are linear correlations between height and CCD, CW and PW, with statistical significance (p<0.05 each, Spearman ρ between 0.13 and 0.4). In multivariate analysis, only BMI, male gender and height had statistical significance. CONCLUSIONS: There is a wide range in size kidney. Among factors that strongly influence the values of CCD, CW, and PW in adults, BMI, male gender and height are most important. Also, cranial and caudal position of the kidney influences renal size. As for the size of the renal cortex, the factor most influencing these values is the absence of a contralateral kidney.

Management of small renal masses--update 2011.

RATIONALE: The management of renal parenchymal tumors has known many changes over time, a trend that continues today, as a result of technological advances, clinical research and improved diagnostic and therapeutic tools. Unfortunately, conventional cancer treatments--chemotherapy and radiotherapy have proven ineffective and modern approaches such as immunotherapy, angiogenesis inhibitors, though they enjoyed an initial enthusiasm, subsequent studies have shown limited and controversial effects. Thus, surgery remains the gold standard therapy for this type of cancer. The options for the treatment of RCC are numerous, with options that have advantages and disadvantages, with oncological results, in most cases, positive at five years and with different impact on cancer specific survival. It is difficult to compare the results, as these are different techniques with various instruments and intraoperative steps, with more questionable inclusion criteria, selection biases and prosecution, with a tendency for preferential enrollment, different reasons to why randomized prospective studies have not been performed until today. OBJECTIVE: This article is a review of the diagnosis and methods of treatment of small renal masses 2011. CONCLUSION: At the beginning of the new millennium, kidney cancer, with all the arsenal of techniques and methods of ablative surgery, remains a potentially fatal disease for a high percentage of patients, and the decision to choose a treatment or another should be taken with responsibility, depending on currently existing medical records, the degree of expertise and not based on subjective or other non-standard parameters.

Minimally invasive treatment for female stress urinary incontinence - Romanian highlights.

RATIONALE: Stress urinary incontinence is still a "battlefield" for many minimally invasive therapies, but, unfortunately, few can restore the anatomical and functional background of this disorder. OBJECTIVE: Assessing the latest minimally invasive procedures of intra and perisphincterian injection of autologous stem cells. METHOD AND RESULT: The first stem cell implantation (myoblasts and /or mature fibroblasts grown and multiplied in the laboratory from biopsy samples taken from the pectoralis muscle) in the urethral sphincter was performed on October 18, 2010, in "Fundeni" Clinic of Urology and Renal Transplantation, in Romania. DISCUSSION: The follow-up at six weeks with the quality of life questionnaires, micturition diary and clinical examination revealed a decrease of urine loss from six pads/ day at one per day, which significantly improved the patient's quality of life according to visual analogue scale. Clinical and urodynamic evaluations will continue and will be future scientific topics.

Highlights in the minimally invasive treatment of SUI in women.

OBJECTIVE: Treatment of stress urinary incontinence consists of a wide range of options, from conservative therapies like lifestyle changes, medication, pelvic floor muscles exercises, electro-stimulation, to minimally invasive procedures--injection of collagen, suburethral slings TVT/TOT and last but not least, invasive surgical treatment reserved for recurrent and complex cases. Among the latest minimally invasive procedures reported in literature, the injection of intra-and perisphincterian of autologous stem cell (mioblasts and/or mature fibroblasts grown and multiplied in the laboratory from biopsy samples taken from the pectoralis muscles). MATERIAL AND METHOD: On October 18, 2010, in 'Fundeni' Clinical Institute of Uronephrology and Renal Transplantation was performed the first stem cell implantation procedure in the urethral sphincter, in Romania. RESULTS: Assessment at 6 weeks, the quality of life questionnaires, micturition diary and clinical examination revealed a stunning decrease of urine loss from 6 pads/day at one per day, which significantly improved the patient's quality of life. CONCLUSIONS: Stem-cell-mioblasts therapy may represent in the future an every-day intervention in the urologist's armamentarium. The effectiveness of this treatment can change the course of therapy and last but not least, the accessibility to urological evaluation of patients with stress urinary incontinence. Clinical and urodynamic evaluations will continue and will be future scientific topics.

Prognostic factors in retroperitoneal fibrosis.

UNLABELLED: The aim of this study is to evaluate effective prognostic factors in the evolution of patients with retroperitoneal fibrosis and to establish the validity of fractal analysis in determining the disease severity in these patients. MATERIAL AND METHODS: This study included 19 patients (M/F: 5/14) treated for idiopathic retroperitoneal fibrosis and bilateral obstructive renal failure between Jan 2004-Dec 2008. Patients were identified retrospectively, searching for patients diagnosed with IRF, after retroperitoneal biopsy or, in most cases the diagnosis rested on radiological findings, especially CT, with identification of a retroperitoneal mass, the absence of other demonstrable renal or ureteric disease or any other pathology that could explain the findings. CT was very useful in describing the retroperitoneal mass around the aorta and inferior vena cava, the extent of the lesion and for monitoring the response to surgical treatment during the follow-up. The data were evaluated about medical history, physical examination findings, laboratory tests (serum urea and creatinine, blood sugar, sodium, potassium, bicarbonate levels, serum pH, uric acid, haematocrit, white blood cell count), imaging methods (renal ultrasound, abdominal CT-scan, MRI). At admission all patients had active disease with obstructive renal failure and underwent bilateral ureteric stenting in order to normalize the BUN levels. After normalizing of BUN levels, ureterolysis and omental wrapping was performed. Postoperatively, ureteric stents were removed after 1 month and remission of renal disfunction was obtained in approximately 5 months (range 2-10 months). All patients were followed for at least 1 year. Patients were regularly checked every 3 months. RESULTS: Of the 19 patients, there were 5 men and 14 women. The median age at diagnosis of RF was 50 years (range 42-64 years). The most frequent presenting symptoms were back or abdominal pain, weakness, weight loss, oligoanuria, arterial hypertension and mild fever. The duration of symptoms before diagnosis ranged from 6 to 18 months. At presentation all patients had active disease, presenting renal dysfunction with a median serum creatinine of 5.18 mg/dl (range 1-15.4 mg/dl). Most of the patients had moderate bilateral hydronephrosis (2nd degree hydronephrosis). In our study, all patients had excellent prognosis, with full recovery of renal function in 78% of cases (15 patients). The fractal dimension of the fibrosis mass contour correlates with level of renal function impairment. Even more, the fractal dimension seems to slightly variate between CT evaluations (1.30 +/- 0.1), suggesting a non aggressive pattern of extension of the fibrotic mass characteristic for benign lesions. CONCLUSIONS: The imaging parameters did not predict the disease severity, except the increase in fractal dimension of fibrosis surface area. Efficacy of bilateral ureteric stenting in improving renal function is limited in most of the cases. Dispite the level of renal function impairment at admission, full recovery can be achieved after bilateral ureteric stenting/nephrostomy and ureterolisis.

Renal transplantation--substitution therapy in advanced stage uremia.

Advanced stage chronic renal failure (CRF) uremia represents one of the most severe metabolic "catastrophes" of the organism. The current therapeutic possibilities consist in: hemodialysis, peritoneal dialysis and renal transplantation. This paper presents the experience of the Urological Surgery, Dialysis and Renal Transplantation Center of the "Fundcni" Clinical Institute in renal transplantation, the single complete morphological and functional therapeutic option in CRF. During the last 10 years, renal transplantations with kidneys from brain dead donors (multiorgan harvesting) to an adult (1997), a child (1999), a diabetic recipient (1998) and an unephric child due to bilateral Wilms' tumor (2005) were performed at "Fundeni" Renal Transplantation Center as a national première. The immunosuppression protocols are complex, modern and adapted to the immunological risk. A number of 870 renal transplantations with 82% functionality rate of the grati at 10 years were performed and reported. Among these, 152 transplants were performed using kidneys harvested from brain dead donors. Owing to obtained results (60% of all transplanted and functional orgmans in Romania on December 2007) and to its achieved performances, the Fundeni Center represents a reference point on the European map of renal transplant.

New cyclosporine microemulsion randomized, cross-over bioequivalence steady-state study in renal transplanted patients.

A new microemulsion formulation of cyclosporine was compared with the marketed formulation in 18 stable renal transplanted patients. Aim of the study was not only to determine the bioequivalence between the two pharmaceutical preparations, but also to ascertain whether tested drug could maintain stable blood concentrations of cyclosporine. Renal transplanted patients under cyclosporine treatment from at least 12 months at a well individualized dosage (resulting in 90-200 ng/mL of blood level drug) have been selected. Patients received the same preceding dose of cyclosporine through both the two preparations according to a cross-over, randomized schedule during 4 weeks in two equally divided daily administrations. Serial blood samples were obtained over a 24-hour period at steady-state of each formulation. Cyclosporine concentrations were determined by a specific immunoassay method (FPIA) n whole blood taken in the last day of each cycle of treatment. Statistical comparisons of cyclosporine levels (using pharmacokinetic parameters) were cross-performed between formulations and days of blood test. Tested drug resulted bioequivalent with the reference marketed formulation. Furthermore, the study showed that tested drug maintained satisfactory stable blood concentrations of cyclosporine.