Molecular Characterization of Microrna Interference and Aristolochic Acid Intoxication Found in Upper Tract Urothelial Carcinoma in Patients with Balkan Endemic Nephropathy: A Systematic Review of the Current Literature.

The term "aristolochic acid nephropathy" (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) or by the environmental contaminants in food such as in Balkan endemic nephropathy (BEN). Aristolochic acid (AA) intoxication is strongly associated with the development of upper tract urothelial carcinoma (UTUC); however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNA) regulate several biological processes, including cell proliferation, differentiation, and metabolism, acting as oncogenes or tumor suppressors. A unique miRNA expression profile suggested that miRNAs could function as regulators in UTUC developmental processes. This review aimed to summarize data available in the literature about underlying molecular mechanisms leading to the expression of miRNAs in AA-UTUC patients with BEN. Strong correlation in AA-UTUC has a distinctive gene alteration pattern, AL-DNA adducts, and a unique tumor protein (TP53) mutational spectrum AAG to TAG (A: T→T: A) transversion in codon 139 (Lys → Stop) of exon 5 activates the p53 tumor suppressor protein. Further, p53 protein is responsible not only for the expression of miRNAs but also acts as a target molecule for miRNAs and plays a crucial function in the AA-UTUC pathogenicity through activation of cyclin-dependent kinase (CyclinD1) and cyclin protein kinase 6(CDK6) to support cell cycle arrest. This study, proposed a molecular mechanism that represented a possible unique relationship between AA intoxication, miRNAs expression, and the progression of UTUC in patients with BEN.

Identificación endoscópica de la composición de los cálculos urinarios: un estudio del Southeastern Group for Lithiasis Research (SEGUR 2) / Endoscopic identification of urinary stone composition: A study of South Eastern Group for Urolithiasis Research (SEGUR 2)

INTRODUCCIÓN Y OBJETIVOS: Evaluar la capacidad del endourólogo para evaluar la composición del cálculo mediante la observación de imágenes endoscópicas. MATERIALES Y MÉTODOS: Una serie de 20 videoclips de tratamientos endoscópicos de cálculos urinarios que también estaba disponible el resultado de la espectroscopia infrarroja se cargó en un sitio de YouTube accesible solo a miembros del South Eastern Group for Urolithiasis Research (SEGUR), a quienes se les preguntó para identificar la composición de los cálculos. RESULTADOS: Un total de 32 endourólogos de 9 países diferentes participaron en el estudio. El número promedio de detecciones correctas de participantes fue de 7,81 ± 2,68 (1-12). La precisión general fue del 39% (250 de 640 predicciones). Cálculos de dihidrato de oxalato de calcio se han detectado correctamente en el 69,8%, monohidrato de oxalato de calcio en el 41,8%, ácido úrico en el 33,3%, oxalato de calcio/ácido úrico en el 34,3% y cistina en el 78,1%. Las tasas de precisión para estruvita (15,6%), fosfato de calcio (0%) y oxalato de calcio/fosfato de calcio (9,3%) fueron bastante bajas. CONCLUSIONES: La observación del cálculo durante el procedimiento endoscópico no fue confiable para identificar la composición de la mayoría de los cálculos, aunque los cálculos de oxalato de calcio dihidrato y cistina pueden identificarse con buena precisión. Sin embargo, se debe alentar la presentación de fotos o videos de cálculo intacto y su estructura interna para implementar los resultados del análisis de cálculo después de la cirugía. Los endourólogos deben mejorar su capacidad de identificación visual de los diferentes tipos de cálculos

INTRODUCTION AND OBJECTIVES: To assess the surgeon's ability to evaluate the composition of the stone by observation of endoscopic images. MATERIALS AND METHODS: A series of 20 video clips of endoscopic treatments of urinary stones of which was also available the result of infrared spectroscopy was uploaded to a YouTube site accessible only to members of the South Eastern Group for Urolithiasis Research (SEGUR) who were asked to identify the composition of the stones. RESULTS: A total of 32 clinicians from 9 different countries participated in the study. The average number of correct detections of participants was 7.81 ± 2.68 (range 1-12). Overall accuracy was 39% (250 out of 640 predictions). Calcium oxalate dihydrate stones have been correctly detected in 69.8%, calcium oxalate monohydrate in 41.8%, uric acid in 33.3%, calcium oxalate/uric acid in 34.3% and cystine in 78.1%. Precision rates for struvite (15.6%), calcium phosphate (0%) and mixed calcium oxalate/calcium phosphate (9.3%) were quite low. CONCLUSIONS: Observation of the stone during the endoscopic procedure was not reliable to identify the composition of most stones although it gave some information allowing to identify with a good sensitivity calcium oxalate dihydrate and cystine stones. Nevertheless, photo or video reporting of the intact stone and its internal structure could should be encouraged to implement results of still mandatory post-operative stone analysis. Endourologists should improve their ability of visual identification of the different types of stones

Endoscopic identification of urinary stone composition: A study of South Eastern Group for Urolithiasis Research (SEGUR 2). / Identificación endoscópica de la composición de los cálculos urinarios: un estudio del Southeastern Group for Lithiasis Research (SEGUR 2).

INTRODUCTION AND OBJECTIVES: To assess the surgeon's ability to evaluate the composition of the stone by observation of endoscopic images. MATERIALS AND METHODS: A series of 20 video clips of endoscopic treatments of urinary stones of which was also available the result of infrared spectroscopy was uploaded to a YouTube site accessible only to members of the South Eastern Group for Urolithiasis Research (SEGUR) who were asked to identify the composition of the stones. RESULTS: A total of 32 clinicians from 9 different countries participated in the study. The average number of correct detections of participants was 7.81 ± 2.68 (range 1-12). Overall accuracy was 39% (250 out of 640 predictions). Calcium oxalate dihydrate stones have been correctly detected in 69.8%, calcium oxalate monohydrate in 41.8%, uric acid in 33.3%, calcium oxalate/uric acid in 34.3% and cystine in 78.1%. Precision rates for struvite (15.6%), calcium phosphate (0%) and mixed calcium oxalate/calcium phosphate (9.3%) were quite low. CONCLUSIONS: Observation of the stone during the endoscopic procedure was not reliable to identify the composition of most stones although it gave some information allowing to identify with a good sensitivity calcium oxalate dihydrate and cystine stones. Nevertheless, photo or video reporting of the intact stone and its internal structure could should be encouraged to implement results of still mandatory post-operative stone analysis. Endourologists should improve their ability of visual identification of the different types of stones.

Increased aquaporin 1 expression in the tunica albuginea of Peyronie's disease patients: an in vivo pilot study.

Peyronie's disease (PD) is a localized disorder of the connective tissue of the tunica albuginea (TA) whose etiology has not been elucidated. Although several studies have implicated genetic susceptibility and/or mechanical trauma as triggering events for PD, the underlying molecular mechanisms remain largely unknown. Aquaporin 1 (AQP1) is a water channel protein potentially implicated in connective tissue resistance to mechanical stress, acting primarily by increasing tension within the collagen network. Although it represents a potentially attractive molecular target in PD, to date no studies had ever addressed whether AQP1 is detectable and/or differentially expressed in the TA of these patients. Herein the present study, through immunohistochemical and biochemical approaches, we were able to detect AQP1 expression in the TA of control and PD affected patients. We demonstrated that AQP1-like immunoreactivity and expression are significantly increased in plaques of PD patients Vs controls, implying that AQP1 overexpression might be the consequence of a localized maladaptive response of the connective tissue to repeated mechanical trauma. In summary, these data support the idea that AQP1 might represent a potentially useful biomarker of mechanical injury in the TA and a promising target for the treatment of PD.

Context-dependent responses to novelty in Rainbow trout (Oncorhynchus mykiss), selected for high and low post-stress cortisol responsiveness.

Previous studies in a rainbow trout model, selectively bred for high (HR) and low (LR) post stress plasma cortisol levels, have yielded data that are indicative of contrasting stress coping styles. Fish from the HR line have been suggested to display a more diverse behavioral repertoire in challenging situations than the LR counterpart. The present study addressed whether such variation in behavioral flexibility traits was evident in different experimental settings using these selection lines. The fish were subjected to three sets of challenges (novel object test, resident-intruder test and confinement stressor test), all which were repeated a week later. Introducing a novel object evoked a divergent behavioral response in association with feeding: fish from the LR line displayed consistently suppressed feed intake while the HR fish remained unaffected. This observation was found to be repeatable along with attack latency and movement activity from the resident-intruder and confinement stressor tests. These results indicate that the behavioral responses in this animal model are context-dependent and shed new light on the expression of behavioral flexibility.

Aggression in rainbow trout is inhibited by both MR and GR antagonists.

The present study has investigated the effect of exogenous cortisol on aggression in juvenile rainbow trout, along with the involvement of mineralocorticoid (MR) and glucocorticoid receptors (GR) mediating the effects of cortisol. Fish were fed pellets supplemented with cortisol, the GR antagonist mifepristone (RU486) in combination with cortisol, the MR antagonist spironolactone (SA) in combination with cortisol or both antagonists in combination with cortisol. Aggressive behaviour was then assessed 1h subsequent to feeding. Our results showed that the attack latency was increased by exogenous cortisol, an effect that was not abolished by the antagonists. The intensity of aggression was not changed by exogenous cortisol. However, the intensity of aggression was significantly reduced by both antagonists. These results are discussed with regard to cortisol affecting aggressive behaviour through genomic and non-genomic pathways. Our results have demonstrated the involvement of both MR and GR in regulating behavioural responses during social interactions in teleost fish. The intensity of aggression seen in control and cortisol treated fish is probably mediated by the basal levels of cortisol through the intracellular MRs and GRs. We conclude that the initiative to engage in social confrontations is mediated through a non-genomic pathway, which could involve extracellular corticoid receptors. Further, the majority of arguments lean towards the MR and GR antagonists blocking the effect of cortisol on aggressive intensity through intracellular receptors. If this is the case, then it is probable that these two aspects of aggressive behaviour are based on different neuronal mechanisms.

Multiple cutaneous metastases of advanced prostate cancer: case report and a review of the literature.

Between 2% and 9% of malignant tumours are metastasizing to the skin. Cutaneous metastases from carcinoma of the prostate occur infrequently. Their presence is associated with poor prognosis. We report the case of a 65-year-old man with carcinoma of the prostate, presenting multiple metastases in the scrotal skin region.

[Retrocaval ureter based on a series of 16 cases]. / Uretère rétrocave: à propos de 16 cas.

INTRODUCTION AND OBJECTIVES: To analyse the postoperative results of surgical treatment for retrocaval ureter. MATERIAL AND METHODS: The authors report a retrospective clinical study of a series of 16 patients (six women and 10 men) with a mean age of 38 years (range: 15-45 years) with retrocaval ureter treated between 1975 and 2005. The mean follow-up was 18 months (range: 12 to 34 months). All patients were evaluated by the standard diagnostic protocol for the time and were treated by one of the following surgical techniques: resection of the ureter and renal pelvis to renal pelvis anastomosis; resection of the ureter and pyelo-ureteric anastomosis; resection of the ureter and oblique end-to-end uretero-ureteric anastomosis; nephrectomy. RESULTS: The mean operating time was 95 min. Late postoperative follow-up revealed two cases (13%) of ureteric stenosis at the site of the oblique end-to-end uretero-ureteric anastomosis. Surgical revision was performed in one patient with resection of the ureter and reanastomosis, while anterograde dilatation of the stenosis was performed in the other patient. The postoperative course was uneventful in both patients. All patients were reviewed at six months with a satisfactory result, corresponding to reduction of hydronephrosis and improvement of renal function. CONCLUSION: Over the last 30 years, the diagnosis of retrocaval ureter has become more reliable and less invasive. Satisfactory results can be obtained with conventional surgical management.

Treatment of emergency surgical complications of kidney transplantations.

Surgical complications subsequent to the kidney transplantation are not infrequent and they are characterized by the high percentage of graft loss (596-18% in standard surgical procedures and up to 37% in atypically performed transplantations). The study included 311 transplanted patients (206 (66.2%) living donors and 105 (33.8%) cadaver donors). Surgical complications developing during the immediate posttransplantation period as well as during the late period (after a year and a half) were classified as: I urinary complications; II vascular complications; III other complications. In majority of the cases urinary complications (urinary fistulas, ureteral obstructions, vesico-ureteral reflux) as well as other complications (cholecystopancreatitis and lymphocele) did not necessitate urgent treatment, unlike most of the vascular complications. All the vascular complications (29/311) developed during the immediate postoperative period, except for occurrence of arterial stenoses which ensued later on, while the development of symptoms was rapid. Severity of both symptoms and clinical picture necessitated urgent surgical re-intervention in order to preserve the graft and patient's life. Vascular complications were classified as: true vascular complications, hemorrhages and kidney ruptures in order to distinguish technical and other factors contributing to development of the complications. Onset of the true vascular complications related to the graft and recipient blood vessel changes was evidenced in 20 patients (69%/29 patients) while the incidence of hemorrhages and ruptures was considerably lower (14%/29 patients and 17%/29 patients). As for the true vascular complications, vascular stem thrombosis subsequent to cadaveric transplantations was the most frequent, and transplantectomy was performed in all the cases in absence of any lethal outcomes. Two cases with iliac artery rupture resulted in graft loss subsequent to urgen exploration. In all cases with hemorrhages the applied therapy resulted in positive responses, except in one case in which massive gastrointestinal hemorrhage led to lethal outcome. The response to the urgent surgical treatment of spontaneous kidney graft ruptures was positive in 60% of the cases, while in the remaining 40% transplantectomy was necessitated due to the extensiveness of the lesion in order to preserve patient's life.

The history of urinary diversion.

The earliest attempt to divert urine flow from the ureters to the intestine, was performed in 1851 by John Simon. In the absence of antibiotics, ureterosigmoidostomy and its modifications during the 19th and early 20th century have been associated with high rate of surgical and metabolic complications. In 1910, Robert Coffey demonstrated a new method for ureterointestinal anastomosis, which renovated primary enthusiasm in ureterosigmoidostomy and it gained broad popularity during the next forty years. In 1950, Ferris and Odel reported 80% incidence of hyperchloremic metabolic acidosis following ureterosigmoidostomy. Based on further investigations by Lapides in 1951, Parsons, Powel and Pyrah in 1952, and Stamey in 1956, which clearly demonstrated that hyperchloremic metabolic acidosis is inevitable complication of ureterosigmoidostomy, this urinary diversion lost its popularity. In 1950's ileal conduit, popularized by Bricker, became the gold standard for the subsequent 35 years. Early attempts for continent urinary diversion occurred form 1888, by Guido Tizzoni and Alfonso Poggi, while the first reservoir-type ileal loop urinary diversion was performed by Cuneo in 1911. By better understanding of principles of detubularization, based on works of Kock and principles of clean intermittent catheterization, established by Lapides, interest in continent urinary diversion has increased. Up to date, various continent cutaneous stomal reservoirs, sigmoidorectal pouches and orthotopic bladder substitutes have been described. Regarding encouraging improvements in biocompatible materials, alloplastic bladder replacement could be the next step for the future in bladder replacement surgery.

Modified Mainz pouch II (Sigma Rectum pouch) urinary diversion: 12 years experience.

OBJECTIVE: To analyze the outcome of Mainz Pouch II urinary diversion related to complications and life quality. PATIENTS AND METHODS: From 1995 to 2006, a total of 67 patients (60 male and 7 female, mean age 58.4 years, range 48 to 70) who underwent modified ureterosigmoidostomy (Mainz Pouch II) procedure have been retrospectively analyzed. The mean follow-up was 18 (1 - 72) months and it was available for 56 patients (84%). Early and late postoperative complications as well as quality of life after surgery were analyzed. An clinical questionairre has been used for examination specific urinary diversion items. RESULTS: Early postoperative complications (<30 days) we-re detected in 9 patients (13%) and late complications (>30 days) in 19 patients (28%). Early complications consisted of urine leakage of moderate degree in 5 (7%) and ileus requiring surgical revision in 4 (6%) patients. The late complications included acute pyelonephritis in 12 patients (18%) and uretero-sigmoidal anastomotic site stenosis in 7 (11%). Ureterosigmoidal anastomotic site stenosis was detected in 7 patients with 7 renoureteric units (RU). In 4 RU, metal Strecker stent was successfully applied. In 3 RU, permanent nephrostomy catheter was applied. Oral alkalizing agents were applied in 22 patients (33%) due to metabolic acidosis. Two patients died due to severe acidosis. Continent rate was 96%. The mean voiding frequency during the day and night was 5.2+/-1.8 and 2.7+/-0.5, respectively. Global life quality was bad for 3 (8%), acceptable for 15 (38%) and good for 22 (54%) patients. CONCLUSION: The Mainz Pouch II urinary diversion is simple and safe procedure regarding complications rate, continence and quality of life. It is good alternative to other forms of continent urinary diversion. Patient selection and compliance following by meticulous follow-up are of utmost importance for successful operative outcome.

[Selection and perioperative management of patients undergoing an orthotopic ileal bladder substitution].

Orthotopic ileal bladder substitution (Studer pouch) has gained much popularity during the last decade, offering the best form of urinary diversion in appropriately selected patients. The superiority of this procedure is well known, with a low complication and high success rate. In the present study the most important details in patient selection, surgical technique, perioperative management with short- and long-term postoperative follow-up are described. Adequate preoperative assessment results in a proper indication for surgery and appropriate patient selection. The cystectomy should be performed with atraumatic dissection and preservation of the urethral autonomic innervation and sphincter apparatus. The bladder substitute is constructed from a terminal ileal segment of proper length formed into a spherical shape. Implantation of the ureters into the reservoir should not be performed using an anti- reflux technique to avoid a high stricture rate. Anastomosis of the bladder substitute to the urethra must be flat and wide open, avoiding a funnel-shaped outlet. In the immediate postoperative period, careful monitoring is necessary to minimize metabolic complications of acidosis and salt loss. To achieve successful voiding rehabilitation, with complete reservoir emptying, good functional reservoir capacity and satisfactory continence, it is necessary to educate the patients as to the physiological functioning of the bladder substitute. Careful lifelong follow up is essential for the successful outcome. Respecting strict patient selection criteria and proper surgical technique are of utmost importance for the successful outcome of the procedure, but only if combined with regular follow-up.

Radical retropubic prostatectomy--results in 127 surgically treated patients.

Radical prostatectomy represents an optimal therapeutic method in treatment of the localized prostatic carcinoma. It may be performed using retropubic, perineal, transcoccygeal or laparoscopic approach. In a multicenter study, the authors have analyzed 127 patients surgically treated in the period 1992 - 2003. All the patients were preoperatively diagnosed with the localized prostatic carcinoma. The patients were operated at the Clinic of Urology in Belgrade (92 patients) and other departments of urology in Serbia (35 patients). The youngest patient was 49 while the oldest one was 75 (mean age 64 years). The surgical procedure duration ranged between 60 and 120 minutes. Over the last five years, the need for blood transfusion was below 50%. All the patients underwent retropubic radical prostatectomy.

Clinical and urodynamic outcomes of tension-free vaginal tape procedure.

The tension--free vaginal tape procedure (TVT) has been regarded as a safe, minimally invasive method for the treatment of female stress urinary incontinence. In a prospective multicenter study we evaluated safety and efficacy of TVT procedure for the treatment of female stress incontinence. From 1998. to 2003, a total of 42 patients, mean age 60 years (range 34-76) with urodynamically verified stress urinary incontinence underwent the TVT procedure. The mean follow-up period was 28 months (range 14 to 32). Intra- and postoperative complications were few, including bladder perforations (4.7%), vaginal hematoma (2.4%), complete urinary retention (2.4%), transient urinary retention (19%) and urinary tract infection (7.1%). Postoperatively, voiding time and functional urethral length significant increased. The subjective and objective cure rates were 85.7% and 90.5%, respectively. We conclude that the TVT procedure is associated with high cure rate and low morbidity.

Renal allograft implantation in respect of atypical vascular procedures.

In minority of renal transplants it is unevitable to perform atypical vascular procedures of renal allograft implantation, which increases the risk of vascular complications, graft loss and lethality. In the presenting study, we retrospectively evaluated kinds of atypical vascular procedures in renal allograft implantation by donor type and the transplants outcome related to these procedures. From 1980 to 1998, a total of 463 patients (mean age 36.2+/-10.3), underwent renal transplantation (319 from living donor and 144 from cadaveric donor) at the Institute of Urology & Nephrology in Belgrade. Atypical vascular procedures of renal allograft implantation were representative for the some of the following cohorts: bypass grafting, endarterectomy, end to side both arterial and venous anastomotic site. A total of 45 patients (9.72%) underwent some of atypical vascular procedures (41 from living donor and 4 from cadaveric donor) (p<0.01). Among analyzed procedures, bypass grafting was performed in majority of cases (n=38). A total of 101 patients underwent endarterectomy. End to side both arterial and venous anastomotic site was done in two patients. Severe direct postoperative vascular complications following by lethal outcome appeared in 2 patients. Related to standardized, atypical vascular procedures had been of increased risk for appearance of severe vascular complication.

A comparison of five clock scoring methods using ROC (receiver operating characteristic) curve analysis.

OBJECTIVE: To compare the accuracy of five clock scoring methods for detecting dementia in English-speaking patients. DESIGN: A prospective cohort study. SETTING: A general geriatric outpatient clinic in southwest Sydney, Australia. PARTICIPANTS: A total of 127 consecutive new referrals to the clinic, of mean age 78.2 years. MEASUREMENTS: The clock drawing test was conducted at the beginning of each clinic appointment by a blinded observer. Each patient was then assessed by a geriatrician, who collected demographic data, administered the modified Barthel index, the geriatric depression scale, and the Folstein Mini-Mental State Examination, and categorised each patient as demented or not demented, according to DSM-4 criteria. Each clock was scored according to the methods of Mendez, Shulman, Sunderland, Watson and Wolf-Klein, and evaluated for reliability, and predictive accuracy, using receiver operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve was largest for the Shulman (0.79, 95% CI 0.70-0.85) and Mendez (0.78, 95% CI 0.70-0.85) methods. Both predicted dementia more accurately than the Sunderland (area = 0.71) and Watson (area = 0.65) methods (p < 0.05). The inter-rater (0.81-0.93) and intra-rater (0.87-0.96) correlation coefficients were high for all five methods. CONCLUSIONS: While substantial differences among the clock scoring methods were evident in our sample, the accuracy of each was modest at best. Unless further studies in relevant settings suggest otherwise, we caution on the use of clock drawing alone to screen for dementia.

Microencapsulation and transplantation of genetically engineered cells: a new approach to somatic gene therapy.

In order to develop a model for gene therapy which avoids dependence on an autologous source of target cells and immunosuppressive therapy, mouse Ltk fibroblasts transfected with a human growth hormone (hGH) fusion gene were encapsulated in a semipermeable alginate-poly-L-lysine-alginate (APA) membrane. The encapsulated cells were cultured in vitro or transplanted intraperitoneally into mice to monitor cell viability, cell growth, and hGH secretion. The effect of Zn2+ ions on vector expression was also monitored in vitro and in vivo. Results indicate that: (1) the capsule environment is compatible with cell viability and cell growth; (2) the capsule limits cell growth; (3) the capsule membrane is permeable to the exit of hGH; (4) gene product expression may be stimulated by external means; (5) the novel gene product is delivered in vivo; and (6) encapsulated cells recovered from transplant recipients continue to secrete hGH in vitro. The results suggest therapeutic potential of this approach to somatic gene therapy.