Could living unrelated renal transplantation ameliorate the actual shortage of organs in the Balkan region?

BACKGROUND: Despite the efforts for more transplants performed with organs from deceased donors, the living renal transplantation is still the predominant transplant activity in the Balkan region. In order to adress the severe organ shortage, we started accepting unrelated (emotionally related) living donors (LURD). Here we present our 10-year experience with living unrelated renal transplantation (LURT). METHODS: Twenty four LURT were performed in our center in the last 10 years. The mean recipients and donors age was 41.7 and 47.2 years, respectively. As LURD spouses (n=17) and extended family members (n=7) were accepted predominantly. All donors went through careful psychological evaluation in order to confirm emotional relationship. The final decision was taken after both the recipient and the donor signed a consent in front of a judge. A quadruple sequential immunosuppressive protocol was used in all recipients. The 5-year Kaplan Meier graft survival rate, HLA mismatch, rejection episodes, delayed graft function, serum creatinine and Glomerular filtration rate-Modification of the diet in renal disease (GFR-MDRD) were analyzed. The results were compared with 30 living related renal transplants (LRT) performed during the same time with mean recipients and donors age of 35.9 and 58.5 years, respectively. RESULTS: The mean follow up for LURT and LRT recipients were 81.4 and 79.6 months, respectively. There was a significant difference regarding recipients and donors age, HLA mismatch (5.07 and 2.9) and rejection episodes (16% vs. 11%) in LURT and LRT recipients. The 5 years graft survival rate was excellent in both groups (83 and 81%, respectively). There was no significant difference in 5 years serum creatinine (129.3 vs 121.1 µmol/lit) and 5 years GFR-MDRD (56.6 and 58.6 ml/min). CONCLUSION: The authors present an excellent 5-year graft survival rate in both LURT and LRT recipients. Therefore, LURT could ameliorate the severe organ shortage in the region and could be recommended as a valuable source of organs in the countries with developed and underdeveloped deceased donor donation.

Evaluation of the value of p53 protein expression in the extra-capsular extension of prostate cancer.

INTRODUCTION AND OBJECTIVES: The objective of this study is to identify the nuclear expression of the p53 protein in prostate cancer and to determine its relationship with clinico-pathological variables. MATERIAL AND METHODS: The research included 83 patients, 43 of whom are patients with prostate cancer who underwent radical prostatectomy and a control group of 40 patients with benign hyperplasia of the prostate in whom a transurethral resection or a transvesical prostatectomy was undertaken. In all cases the nuclear expression of p53 protein was evaluated. A hystopatological evaluation of the tumour characteristics and the data of the local progression of the cancer were undertaken in the research group. RESULTS: The results show that the expression of the p53 protein does not have an important correlation with the preoperative PSA, but that it is in direct correlation with the malign potential of the cancer (Gleason score, Gleason sum, primary tumour) and with the features of the disease (metastatic lymph nodes, stage of the disease). CONCLUSION: p53 protein could be used as a valid biomarker in determining the malignant potential of the tumour and the prognosis of the disease. There is no practical use in predicting the extraprostatic extension.

Screening for prostate cancer: a controversy or fact.

BACKGROUND: Adenocarcinoma of the prostate is the most frequent malignancy in men and the second leading cause of death in the male population worldwide. The screening for prostate cancer allows early diagnosis of prostate malignancy before the individual presents with symptoms. The early stage of the disease is easier to manage by different therapeutic modalities. AIM: The aim of this review is to evaluate the reasons and facts for enthusiasm and positive approach towards the clinical decision about whether to screen or not male patients for early detection of prostate cancer. METHODS: We performed a computerized MEDLINE search followed by a manual bibliographic review of cross-references. These reports were analyzed and the important findings were summarized. We analyzed the methods and schedule of screening, as well as advantages and disadvantages of the prostate cancer screening. RESULTS: There were more than a hundred studies on prostate cancer screening performed but only a few are eligible for a decisive conclusion concerning the prostate cancer screening issue. We reviewed the screening methods, the schedule of screening, the advantages and disadvantages of prostate cancer screening. CONCLUSION: The role for prostate cancer screening is not established yet. Definite proof of screening should be assumed as a decrease in the death rate of that cancer due to screening activity.

Does prostate specific antigen density correlates with aggressiveness of the prostate cancer?

BACKGROUND: As already documented, a high prostate specific antigen in men with normal size of prostate gland is more likely to be associated with an aggressive cancer as compared to others with the same prostate specific antigen and a large gland size. In this retrospective study we tested the association between Prostate Specific Antigen Density (PSAD) and tumor aggressiveness in patients with clinically localized Prostate Cancer (PCa) surgically treated by radical prostatectomy. METHODS: We evaluated data from patients records in a cohort of 72 patients who underwent radical prostatectomy between January 2000 and June 2007. PSAD was calculated as ratio between the preoperative total prostatic specific antigen (PSA) in nanograms per milliliter with the prostate weight (PW) of prostatectomized specimen in grams or prostate volume measured with ultrasound (US). The patients were stratified into four PSAD categories: 0.1-0.15, 0.16- 0.20, 0.21-0.5 and greater than 0.51 ng/ml/gr. Parameters that were included into analysis were: PSA, measurement of the prostate volume by ultrasound (preoperatively) and prostate weight, pathological tumor stage, Gleason sum, Gleason grade, metastatic lymph nodes, seminal vesicle involvement and organ confine disease (postoperatively). Worsening of the clinicopathological properties was defined as aggressiveness. RESULTS: There was a significant correlation between US-PSAD and PW-PSAD (p<0.001). In US-PSAD categories the statistic tests found significant correlation with the primary tumor (R=0.303, p<0.01), metastatic lymph nodes (R=0.331, p<0.01), and the organ confine disease (R=0.296, p<0.05). The PW-PSAD categories correlated significantly with the pathologic findings from other parameters. Hence, a statistically significant correlation was found with Gleason sum (R=0.246, p<0.05), Gleason grade (R=0.234, p<0.05), primary tumor (R=0.285, p<0.05), metastatic lymph node (R=0.287, p<0.05) and organ confine disease (R=0.303, p<0.01). CONCLUSIONS: Prostate specific antigen density measurement is useful tool for the assessment of the degree of aggressiveness in clinically localized prostate cancer, and further investigation regarding its possible use as a prediction marker is justified.

Urinary diversion: 30 years experience of a single centre in Republic of Macedonia.

OBJECTIVES: The aim of this report is to present our 30 years experience with various types of urinary diversions, in particular the Bricker and Studer techniques for the management of muscle invasive bladder cancer at our institution. Perioperative, early and late complications are also evaluated. MATERIAL AND METHODS: Between 1977 and 2007, 186 male and 15 female patients underwent combined radical cystectomy, pelvic lymphadenectomy and urinary diversion. In two subgroups of patients we evaluated the complications, divided as early and late, and subdivided as those related or unrelated to the neobladder. Mean follow up time was 28 months (range 12-60 months). RESULTS: Two main types of urinary diversion were performed: the ileal conduit diversion using a technique previously described by Bricker and the ileal neobladder diversion using a technique previously described by a Studer. The ages at surgery ranged from 40 to 82 years with a mean age of 60 years. Histopathologically, transitional cell carcinoma was the most common tumor cell type (93,7%), followed by difuse papilomatosis (5.5%) and adenocarcinoma (0.7%). The pathological tumor stage was pT1 (4.7%), pT2 (31.4%), pT3 (50.3 %) and pT4a (13,3%). Histological evidence of regional lymph node involvement was seen in 25% of the cases. From 52 patients from the Studer subgroup perioperative complications were found in 16 patients (30.7%). Specific early complications directly related to the neobladder occurred in 14 (26.9%) patients. Prolonged ileus in 2 patient (3.8%), ureteral leakage in 9 patients (17.3%), mucous buildup within the diversion in 3 patients (5.7%). Late complications occurred in 10 patients (19.2%): retention of the urine in 4 patients (7.6%) (stricture of the urethra-pouch anastomosis in one 1 patient) and to big reservoir in 3 patients. One patient (1.9%) developed prolonged metabolic acidosis. Stone formation was observed in one patient, two years postoperatively. Unilateral hydroureteronephrosis was observed in 2 patients whereas bilateral hydroureteronephrosis was observed in one patients at one year postoperatively. Perioperative and late complications were similar in the 32 patients from the Bricker subgroup. CONCLUSION: We show that our results with urinary diversion are promising in patients requiring radical cystoprostatectomy. The two methods preferred in our institution offer a sufficient protection of the upper urinary tract with a low complication rate, good voiding function and continence.

Radical retropubic prostatectomy for prostate carcinoma; first results of the Clinic of Urology in Skopje.

OBJECTIVES: The aim of this retrospective study is to present our experience and results in the management of prostate carcinoma, with radical retropubic prostatectomy, for a period of seven years. MATERIAL AND METHODS: From December 1997 to April 2005, 61 radical retropubic prostatectomies for prostate carcinoma were performed at the Clinic of Urology in Skopje. Mean age of the treated patients was 66.4 years. Mean serum PSA level was 32.75 ng/ml. None of the patients had distant or bone metastases. Mean operative time was 160 minutes and from 2 to 4 units of blood were transfused intra and postoperatively. Mean follow up time was 39 months. RESULTS: In all of 61 patients, the RRP was performed for adenocarcinoma of the prostate. The pathological findings postoperatively showed the following pTNM grade: pT2a in 8, pT2b in 10, pT3a in 10, pT3b in 27and pT4 in 6 patients. Positive lymph nodes were found in 14 cases. Intraoperative complications occurred in 6 patients. Early postoperative complications were seen in 12 patients. Urine leakage was seen in 2 patients, incontinence (day and night) in 8 and pulmonary embolia in 2 patients. Late postoperative complications occurred in 11 patients. Stenosis of the vesicourethral anasthomosis was seen in 3 patients and incontinence (during the night only) in 8 patients. The rate of potency was not evaluated but in the last 30 cases we insisted on preservation of the neurovascular bundles in the cases that it was possible. CONCLUSION: Radical retropubic prostatectomy is the method of choice and the golden standard for treatment of organ confined prostate carcinoma in patients with long life expectancy, no neither local nor distant metastases and good overall status. With this technique complication rates are minimal, the cure rate is very big and the patients have high quality of life. The experience of the surgeon is very important since the learning curve is crucial for diminishing operative time, postoperative complications and blood transfusions.

[Postoperative complications following kidney transplantation]. / Complications chirurgicales après la transplantation rénale.

Despite the remarkable development of kidney transplantation techniques, surgical complications are still a very important factor affecting the final outcome of kidney transplantation. After 92 kidney transplantations (22 from cadaver donors and 70 from living donors) performed at Skopje hospital (Macedonia), we observed the following complications: nine (10%) urinary fistula, five (5%) graft ruptures, seven (8%) lymphoceles, two (2%) urinary calculosis, two (2%) intestinal perforations, four (4%) renal artery stenoses, one (1%) renal artery thrombosis, and seven (8%) early complications following surgical incision. Complications were detected by either ultrasonography, intravenous pyelography, percutaneous nephrostomy with anterograde pyelography, computerized tomography, and intravenous digital angiography. They were subsequently treated by application of modern surgical procedures: use of the ureter (termino-terminal or uretero-pyelic anastomosis) for treatment of urinary fistulas; conservative surgery using tissue glue and external compression with polyglactin 910 (Vicryl) mesh for graft ruptures; drainage and application of sclerosants under ultrasound control and intraperitoneal marsupialization for the clinically relevant lymphoceles; transluminal angioplasty with balloon dilatation in case of significant arterial stenosis; extracorporeal shock wave lithotripsy and surgery for urinary calculi. Intestinal perforations and problems relating to parietal tissue were quickly solved using standard surgical techniques. On total, rejection of the graft occurred in four (4%) cases following surgical complications, while one death was encountered due to septic peritonitis. We consider the percentage of surgical complications acceptable, as this work consists of a pioneering effort in this Balkan region.

[Mono- and oligoclonal immunoglobulin anomalies in kidney transplant patients]. / Les anomalies immunoglobulinémiques mono- et oligoclonales chez les transplantés rénaux.

Serum from 115 HIV negative renal transplant recipients having more than 6 months follow-up was tested for the presence of mono- or oligoclonal immunoglobulins (moIg) by immunoelectrophoresis or immunofixation. Mono/oligoclonal gammapathy was detected in 16 patients (13.9%). Eight of these patients had only one monoclonal band, whereas the other eight had two or more bands. Thirteen of the 16 patients (81.3%) were IgG kappa positive, nine (56.3%) were IgG lambda positive, four (25.0%) were IgM lambda positive and only one (6.3%) was IgM kappa positive. Six monoclonal patients (37.5%) were IgG kappa positive and two monoclonal patients (12.5%) were IgG lambda positive. The oligoclonal combination IgG kappa lambda was present in three patients (18.8%), the combination IgG lambda + IgM lambda was present in two patients (12.5%) and IgG lambda + IgM lambda was present in one patient. The triple combination IgM kappa lambda + IgG kappa lambda and IgM lambda + IgG kappa lambda was found in two patients (12.5%). Ninety percent of these moIg did not exceed 2 g/L. MoIg appeared between 1 and 28 months after the kidney transplantation (mean value: 8.5 5.9 months) but were often transient, disappearing within 1 to 19 months in 13 patients (81.3%). Nine of the 16 cases (56.3%) disappeared before the end of the first year after detection. Risk factors for the appearance of these immunoglobulins have been identified as: the patient's age, the duration of haemodialysis, the occurrence of prior (anti-cytomegalovirus [CMV]) infection, and therapy with cyclosporin A (CsA). The persistence of monoclonal gammapathy was associated with acute or reactivated Epstein-Barr virus (EBV) infection and inability to convert IgM to IgG CMV antibodies. Furthermore, no association was established with previous hepatitis B or C infection or the number of rejection episodes. Kaposi's sarcoma was found in one patient (6.3%) but had no correlation with the presence of moIg. We recommend careful follow up of renal transplant patients in whom moIg have been discovered.