BALKAN ENDEMIC NEPHROPATHY AND MALIGNANT UROTHELIAL TUMORS

One of the features of Balcan endemic nephropathy (BEN) is higher frequency of urothelium malignant tumors, primarily of pyelon (Mtp) and urether (Mtu). Jablanica region is known for the presence of endemic, hypoendemic and non-endemic areas with BEN. The aim of our research was to analyze the appearance of MTUi n endemic settlements of Jablanica region with BEN and to see what the relation of tumor frequency between endemic and non-endemic settlements is. The appearance of MTU was analyzed on the basis of operative protocol data of Urology department, The Health Center in Leskovac and Urology Clinic of The Clinical Center in Nis for the period from 1978 to 2002. We collected data about our patiens regarding their sex, age, the place of living and the place of birth. In order to make classification of settlements we used data of the Institute for Nephrology and hemodialysis (INH) in Nis. Data on total number of population living in these settlements were obtained from the official registration data published in 1981 and 1991. The incidence rate was calculated in the sample of 100,000 people.The average annual incidence rate (AAIR) of MTU in endemic settlements for the considered period is 37.82 (tumors of urether and pyelon - 17.56; malignant tumors of urinary bladder (MTUB 20.26); in hypoendemic settlements the rate is 13.28 (MTp and Mtu - 5.06; MTUB - 8.22); and in non-endemic urban settlements it is 7.35 (Mtu and MTp - 1.04, MTUB - 6.31).AAIR of MTU in endemic areas is 2.85 times higher when compared to hypoendemic areas; it is 6.75 times higher than in non-endemic urban areas, and 5.15 times higher than the rate of non-endemic rural areas. Mtu and MTp are 18.68 times more frequent in endemic settlements than in non-endemic urban areas and 3.47 times more frequent when compared to hypoendemic settlements. The linear trend of the diseased from MTp and MTu in endemic areas of Jablanica region for 25-year period was slowly decreasing according to statistics (y= -0.0054x + 0.59; r2=0.0031.High frequency of Mtu, primarily of Mtu and MTp in areas with BEN, probably points to the common nephropathogenic and cancerogenic etiologic factor, confirming thus the existence of positive correlation between BEN and malignant tumors of upper urothelium (MTUU)

Assessment of cryopreserved human tunica albuginea for the surgical treatment of penile defects

Peyronie’s disease, a connective tissue disorder of penile tunica albuginea (TA) associated with penile deformity, curvature, pain and erectile dysfunction, is best managed surgically, but suitable graft biomaterials are not available. To establish whether cryopreservation affects human TA in view of its use in allotransplants. The effects on TA samples of the two most widely used tissue cryopreservation methods were investigated using an ad hoc panel of histochemical, immunohistochemical and ultrastructural tests. Apoptotic cells were evaluated using the TUNEL assay. Assessment of tissue integrity and arrangement of collagen and elastic fibers in thawed TA. Both cryofixation methods provided TA tissue suitable for use as graft material. Significant ultrastructural changes, namely a greater diameter of collagen fibrils, were detected in sections preserved in liquid nitrogen; nonetheless, such increase never exceeded the normal range. The comprehensive panel of assays used proved suitable to characterize the thawed tissue. Human TA is suitable for cryopreservation; freezing at -80 °C provides better results than preservation in liquid nitrogen

The role of intrinsic pathway in apoptosis activation and progression in Peyronie’s disease

Peyronie’s disease (PD) is a connective tissue disorder where formation of fibrous plaques in tunica albuginea (TA) and erectile tissue can result in penile deformity, pain, and erectile dysfunction. Fibrosis, its major pathological manifestation, arises from fibroblast proliferation and accumulation of extracellular matrix; PD progresses with formation of plaques or even ectopic calcification having the appearance of scar tissue, which prevent TA expansion during erections. The mechanisms underpinning PD are unclear, and relatively little is known about the disease itself. To date corrective surgery is the sole effective treatment. A greater understanding of PD pathophysiology at the molecular level has the potential to help develop novel medical therapeutic approaches. The aim of this study was to investigate the activation of the apoptotic intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD and control patients were assessed for the expression of bax, bcl-2, caspase 9 and 3 using immunohistochemistry, and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplasic bone tissue, in fibroblasts and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplasic bone tissue. Apoptotic cell death occurs in stabilized PD plaques and is partly induced by the intrinsic mitochondrial pathway. The present findings can have clinical implications and may help devise improved treatment strategies. A therapeutic approach aimed at enhancing apoptosis-inducing molecules would at least help delay the progression of PD. Identification of target molecules for gene construct or biological or chemical reagent delivery to target sites could contribute to induce PD plaque stabilization

Results of the modification of antireflux subserosal and submucosal implantation of the ureter into the rectosigmoid urinary reservoir after total cystectomy

Introduction. Uretero-intestinal anastomisis has a large influence on derivation quality. Objective. The aim of the study was to present the modified serous lined extramural Abol-Enein method of implantation of low quality ureter into the sigma-rectum pouch and comparison of the results with Le Duc implantation. Methods. From 1995 to 2009, 62 dilated ureter units were implanted in the detubularized rectosigmoid urinary reservoir. In 28 units Le Duc, and in 34 Abol-Enein method was done. Urinary fistula and ileus were considered as early complications, while late complications included stenosis and reflux pyelonephritis. Frequency of urination was considered as a parameter of functionality. Results. Transitory urine fistulae occurred only in the ureters implanted according to Le Duc technique in 4/28 (14.2%); the difference between the examined groups was close but still below the level of statistical significance (p=0.07). Ileus occurred with nearly equal frequency in both groups. Stenosis on the ureteral implantation place was significantly more frequent (p=0.04) in the Le Duc group 5/28 (21.7%) than in the Abol-Enein group 0/34 (0%). Refluxive pyelonephritis occurred in 3/34 (8.8%) of the Abol-Enein group, and in 5/28 (21.7%) of patients in the Le Duc group. Concerning the daily frequency, there was no difference between the examined groups. Conclusion. Uretero-intestinal anastomisis of dilated ureters through a serous-lined extramural tunnel decreases the risk of reflux in a considerable number of patients, with an acceptable level of complications. There are several advantages in comparison with Le Duc method

[90] Self-created transobturator tape (TOT) vs standard industrially created TOT in the treatment of stress urinary incontinence: Should we change the concept?

Objective: To compare the benefit and cost of tension-free self-created transobturator tape (SCTOT) with the standard industrially created TOT (ICTOT) in the treatment of stress urinary incontinence (SUI). Methods: A prospective study of the treatment of SUI with SCTOT (98 patients) and ICTOT (77 patients) was performed. Two types of industrially created slings were used: the ‘T sling’ (Herniamesh, Torino, Italy), and the ‘TVT obturator’ (Johnson & Johnson, Somerville, NJ, USA). SCTOT (15 × 1 cm) was created from a polypropylene rectangular 30 × 30 cm macroporous polypropylene monofilament mesh weighing 48 g/m2 (Pelvimesh®, Herniamesh) and monofilament sutures. Sutures (polydioxanone [PDS] 2–0) were passed through both ends of the mesh stripe to make a ‘composite’ sling consisting of monofilament suture-sling-monofilament suture (Video). The Urogenital Distress Inventory (UDI-6), the Incontinence Impact questionnaire (IIC-7) and the International Continence Impact questionnaire short form (ICIQ5-SF) were used to evaluate symptoms before and after surgery. The Overactive Bladder Symptom Score (OABSS >8) was used to identify patients with mixed UI (MUI). Results: The follow-up period was 12 months. There was no statistically significant difference (P > 0.05) in objective cure between patients in the SCTOT group 84/98 (85.7%) and the ICTOT group 68/77 (88.3%). According to the IIC-7, UDI-6, ICIQ5-SF and OABSS symptom scores, significant improvement occurred in both groups, but it was better in the group with pure SUI than in the group with MUI, although it was not statistically significant. Symptom scores are shown in Tables 1 and 2. In all, 12 SCTOT were made from one polypropylene rectangular mesh priced at €60/piece. Compared to the price of the ICTOT (€400–700/piece) the SCTOT price is about 100-fold less. Conclusion: The results of the treatment with SCTOT are not inferior to the results of the treatment with ICTOT but are less expensive

A martius flap in the treatment of iatrogenic distal urogenital fistula

ABSTRACT Introduction: Distal urogenital fistulas (DUF) are usually iatrogenic and are uncommon in Europe. They occur in the urethra or near the bladder neck, and can be caused by vaginal hysterectomy, para-urethral cyst surgery, or erosion of the bladder or urethra from tension-free slings or meshes. The psychological and physical health consequences of DUF are devastating because most patients consider themselves “healthy” before surgery. Incontinence can appear after successful DUF closure due to previously occult incontinence or urethral incompetence. Additional surgery for incontinence is sometimes necessary to achieve satisfactory outcome. Materials and Methods: A Martius flap was used in 23 patients between 2000 and 2015. Patient age range was 38-75 years (mean, 58.7). DUF was due to gynecologic surgery for benign disease (15 / 23; 65.2%), mesh / sling erosion (2 / 23; 8.7%), and malignancy (6 / 23; 26.1%). The follow-up period was one year. Results: DUF was closed in 22 patients (95.6%). Satisfaction and complete dryness was achieved in 16 patients (69.6%) after the first procedure. Postoperative complications were: postoperative hematoma in 1 (4.4%), primary failure in 1 (4.4%), overactive bladder (OAB) syndrome in 3 (13.2%) and postoperative incontinence in 6 (26.4%) patients. A fascial sling was placed in patients with incontinence. All patients were dry after the secondary surgery. Anticholinergics were used for the treatment of OAB syndrome. Discomfort at the flap harvesting site was of minor importance. Finally, 22 out of 23 patients (95.6%) were satisfied. Conclusion: A Martius flap and additional fascial sling could be successfully used to optimize DUF treatment

Resection of the Urethral Plate and Augmented Ventral Buccal Graft in Patients with Long Obliterative Urethral Strictures

The treatment of long urethral strictures is based on the use of buccal mucosa graft (BMG). Postoperative failures commonly occur in patients with the obliterative strictures, and the long augmented part of the urethra which is prone to fibrotic changes. Combined approach with the resection of the obliterative part of the urethral plate located in the bulbar urethra, together with the ventral placement of BMG was performed in 36 patients. Etiology of the stricture was: idiopathic in 19/36 (52.7%), iatrogenic in 14/36 (38.8%), and other causes in 3/36 (8.3%). Mean length of the stricture was 7.2±1.6 cm, and the length of the augmented graft 4.5±1.2 cm (due to resected urethral plate) so, the single BMG was enough in 25/36 (69.4%) patients. The medium postoperative follow up was 24 months (20–28 months) months. Success of the surgery was defined as no need for additional surgery neither dilatation. Cystoscopy was performed 4–6 months after the surgery and additional follow up with IPSS and uroflowmetry. Overall success was achieved in 31/36 (86.1%) patients. Mean postoperative IPSS was 9.5±2.1 in these patients. Complications were according to Clavien Dindo scale: grade II in 11/36 (30.5%-infection, orchialgia, scrotal pain), grade III in 4/36 (11.1%-fistula) and grade IV in 5/36 (14.5% - restenosis). Postoperative Qmax= 13.2±1.2 ml/s. Bell shaped curve was present in 14/36(38.8%). Our results suggest that overall success rate is similar to the expected values for BMG surgery, and the number of the grafts used is lower due to reduced stricture length

Predictive Markers for Malignant Urothelial Transformation in Balkan Endemic Nephropathy: A Case–Control Study

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease frequently accompanied by urothelial carcinoma (UC). In light of the increased UC incidence and the markers observed in BEN patients with developed UC, the aim of the current case–control study is to assess survivin, p53 protein, growth factors and receptors (VEGF, VEGFR1, IGF I, IGF-1R and IGFBP5), tumor marker (TF)/CD142, circulating soluble Fas receptor and neopterin, as potentially predictive markers for UC in patients with BEN (52 patients), compared to healthy, age-matched subjects (40). A threefold increase was registered in both circulating and urinary survivin level in BEN patients. Especially noticeable was the ratio of U survivin/U Cr level five times the ratio of BEN patients associated with standard renal markers in multivariate regression models. The concentrations of VEGF, VEGFR1, (TF)/CD142, (sFas) were not significantly different in BEN patients, while urinary/plasma level demonstrated a significant decrease for VEGF. The levels of IGF I, IGFBP5 and IGF-1R were significantly reduced in the urine of BEN patients. Plasma concentration of neopterin was significantly higher, while urinary neopterin value was significantly lower in BEN patients compared to healthy controls, which reflected a significantly lower urine/plasma ratio and low local predictive value. As BEN is a slow-progressing chronic kidney disease, early detection of survivin may be proposed as potential predictor for malignant alteration and screening tool in BEN patients without the diagnosis of UC