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Objectives At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). Materials and Methods SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). Results In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. Conclusions: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments.

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Purpose To analyze controversial clinicopathologic predictors of biochemical recurrence after surgery: age, race, tumor extent on surgical specimen, tumor extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of extraprostatic extension and positive surgical margins. Materials and Methods The needle biopsies and the correspondent surgical specimens were analyzed from 400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and risk of shorter time to recurrence using Cox univariate and multivariate analysis. Results Except for age, race, maximum percentage of cancer per core, and number of cores with cancer, all other variables studied were significantly predictive of time to biochemical recurrence using the Kaplan-Meier curves. In univariate analysis, except for focal extraprostatic extension, age, race, focal positive surgical margins, and maximum extent and percentage of cancer per core, all other variables were significantly predictive of shorter time to recurrence. On multivariate analysis, diffuse positive surgical margins and preoperative PSA were independent predictors. Conclusions Young patients and non-whites were not significantly associated with time to biochemical recurrence. The time consuming tumor extent evaluation in surgical specimens seems not to add additional information to other well established predictive findings. The higher predictive value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4 as the predominant pattern. Extent and not simply presence or absent of extraprostatic extension should be informed. Most tumor extent evaluations on needle biopsies are predictive of time to biochemical recurrence, however, maximum percentage of cancer in all cores was the strongest predictor.

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Purpose To explore the association between serum levels of Sex Hormone Binding Globulin (SHBG) and the risk of developing prostate cancer (PCa) as well as high grade disease in men undergoing prostate biopsy. Materials and Methods Between 2006 and 2012, we prospectively enrolled 740 patients with no history of PCa undergoing prostate biopsy. Before biopsy general data of the patient DRE, PSA and BMI were recorded. The risk of detecting cancer and high grade cancer was assessed as a function of SHBG using crude and adjusted logistic regressions. Results Serum levels of SHBG were not associated with an increased risk of PCa or high grade disease. Age (OR 1.027 95% CI 1.003-1.052 p = 0.027), DRE (OR 3.391 95% CI 2.258-5.092 p = 0.000) and PSA (OR 1.078 95% CI 1.037-1.120 p = 0.000) were found to be independent predictors of prostate cancer risk. Age (OR 1.051 95% CI 1.009-1.095 p = 0.016), DRE (OR 2.519 95% CI 1.384-4.584 p = 0.000), BMI (OR 1.098 95% CI 1.011-1.193 p = 0.027) and PSA (OR 1.074 95% CI 1.014-1.137 p = 0.015) were found to be independent predictors of high grade disease. Conclusions In our cohort of patients, serum levels of SHBG are not predictive of PCa or high grade disease. According to our experience SHBG should not be considered a biomarker in PCa diagnosis neither a marker for high grade disease.

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Purpose Single positive core in a prostate biopsy is usually associated with indolent prostate cancer (PCa) and is one of the active surveillance (AS) inclusion criteria. We investigated whether single positive core PCa at biopsy could define an archetype of low-risk disease. Materials and Methods A total of 1320 consecutive patients were enrolled. Among them, 249 patients with single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed. Results Out of the 249 patients, 172 (69.0%) had pathological findings ≥ pT2c and 87 (34.9%) had an undergraded Gleason Score (GS) based on the biopsy. Positive surgical margins (PSMs), extraprostatic extension (EPE) and seminal vesicle invasion (SVI) were found in 20.8%, 10.0% and 6.0% of patients, respectively. In a comparative analysis, we found that the PSA level, prostate weight and number of cores at biopsy are essential to correctly predict an indolent PCa. A total of 125 patients (67.3%) with nonpalpable tumors became high-risk tumors (pT2c-T3). Analyzing only nonpalpable tumors with a GS of 6 at biopsy (156 patients), we noted that 106 (67.9% of cT1) progressed from cT1c to pT2c-pT3. Conclusions Single core PCa have clinically significant disease in the Radical Prostatectomy specimens, with considerable rates of overgrading for the GS, pT2c-pT3, PSMs, EPE and SVI. The treatment plan must be evaluated individually for patients with single core PCa and must take into account other prognostic factors when determining whether a patient should be managed with AS.

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Objective The aim of our study was to assess short and mid-term clinical efficacy of external beam radiation therapy to achieve hemostasis in patients with bladder-cancer related gross hematuria who were unfit for surgery. We also assessed hypofractionation as a possible alternative option for more severe patients. Patients and Methods Thirty-two patients were included for hemostatic radiation therapy, with two schedules based on Eastern Cooperative Oncology Group performance status. The standard treatment was 30 Gy in 10 fractions over 2 weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5 fractions over a one week period. Clinical evaluation was performed at 2 weeks and 6 months. Results At 2 weeks, 69% of patients were hematuria-free. Subgroup analysis showed that 79% of patients undergoing hypofractionated regimen were hematuria-free. A total of 54% were hematuria-free with the standard regimen. Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of patients had relapsed, regardless of tumor stage or therapy schedules. Conclusions Hemostatic radiotherapy is an effective option for palliative-care hematuria related to bladder cancer in patients unfit for surgery. Although it appears to be rapidly effective, its effect is of limited duration. Hypofractionation also seems to be an effective option; however larger cohorts and prospective trials are needed to evaluate its efficacy compared to standard schedules.

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Objectives To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. Materials and Methods After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. Results From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with initial grade 3 renal pelvis lesions, developed metastatic disease. Conclusions Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks.

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Purpose To describe our experience in treating penile melanoma in 06 patients followed at our institution. Materials and Methods Between 2004 and 2012 six consecutive patients with penile melanoma were treated at our Institution. Stage of the disease was classified according to the 2002 AJCC pathologic system. Melanoma in situ (TIS) was diagnosed in one patient. One patient was staged as T1b, two patients as T2b and two patients as T4b. The clinical and pathological findings were evaluated. Immunohistochemical tests were performed for Melan-A, HNB-45, S-100 and C-KIT. All histological specimens were examined by the same pathologist (ABSS). The patients with Cis, stages T1b and one patient T2b underwent only local excision. One patient T2b underwent local excision and sentinel lymph node dissection. Two patients with melanoma stage T4b underwent partial penile amputation. One of these last patients had palpable inguinal lymph nodes at diagnosis and underwent bilateral inguinal lymphadenectomy and received systemic chemotherapy (dacarbazine, 30 cycles). Results Mean follow-up was 36.3 months. One patient, with stage T2b, died after 12 months due to disease recurrence with bilateral inguinal involvement. The patient who underwent chemotherapy progressed with lung metastases and died after 14 months of follow up. The disease-free survival at five years was 33.3%. Conclusion: Penile melanoma is a disease with poor prognosis in most cases. Local excision or partial penile amputation may have effective control for stages T1 and T2 lesions. Patients who have clinically proven metastases died despite surgical and adjuvant chemotherapy.

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Objective To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort. Materials and Methods Of 163 patients assessed for eligibility, 104 patients were randomly assigned to receive placebo, 2 mg of terazosin twice daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the stenting period. Prior to stenting and at stent removal, the International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the Visual Analog Scale for Pain were determined. The patients also reported their analgesic use during the stenting period. Results Ninety-four patients completed the study. We noted significant decreases in the total IPSS scores (p = 0.002), irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However, neither the obstructive subscore nor the suprapubic pain improved significantly (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS, irritative symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared with those patients receiving placebo. However, compared with placebo, terazosin monotherapy did not affect pain levels, and tolterodine monotherapy did not improve QoL, flank pain or analgesics use. Conclusions Terazosin plus tolterodine improves ureteral stent-related complications, including irritative symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but does not decrease obstructive symptoms or suprapubic pain. This trial was registered at www.clinicaltrials.gov as NCT01530243.

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Purpose The aim of this study was to assess the uroflowmetry data in a large population of asymptomatic Brazilian men submitted to a health check up program and their correlation to IPSS and prostate size. Materials and Methods Asymptomatic men underwent a health check-up program between January and December 2012. The inclusion criteria were men between 40 and 70 years, IPSS ≤ 7, without bladder, prostate, urethral surgery, neurological diseases, urinary tract infection, PSA < 4.0 ng/dL and urinary volume higher than 150 mL. Urological assessment consisted of clinical history, IPSS, digital rectal examination (DRE), prostate specific antigen (PSA), urinalysis, ultrasonography and uroflowmetry. Results A total of 1041 asymptomatic men were included in this study. The average age was 49 years and average maximum flow rate was 17.4 mL/s. In spite of IPSS and prostate size increase with aging, they had a weak correlation with Qmax cutoffs (10 mL/s and 15 mL/s). A total of 85 men (8.3%) had more than 60 years, and even in this group, Qmax was higher than 15 mL/s. Out of 1041 men, 117 had IPSS less than 8 and Qmax less than 10 mL/s. Conclusions In asymptomatic men there is a weak correlation between IPSS, prostate size and uroflowmetric data. The establishment of different normal cutoffs seems to be complicated and uroflowmetry data should be interpreted with caution in order to avoid misdiagnosis.

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Objective The aim of this study was to assess pelvic floor muscle (PFM) strength in different body positions in nulliparous healthy women and its correlation with sexual activity. Materials and Methods Fifty healthy nulliparous women with mean age of 23 years were prospectively studied. Subjective evaluation of PFM was assessed by transvaginal digital palpation (TDP) of anterior and posterior areas regarding the vaginal introitus. A perineometer with inflatable vaginal probe was used to assess the PFM strength in four different positions: supine with extended lower limbs (P1); bent-knee supine (P2); sitting (P3); standing (P4). Results Physical activity, 3 times per week, was reported by 58% of volunteers. Sexual activity was observed in 80% of women and 82% of them presented orgasm. The average body mass index (BMI) was 21.76 kg/m2, considered as normal according World Health Organization (WHO). We observed that 68% of volunteers were conscious about the PFM contraction. TDP showed concordance of 76% when anterior and posterior areas were compared (p = 0.00014). There was not correlation between PFM strength and orgasm in subjective evaluation. The PFM strength was significantly higher in standing position when compared with the other positions (p < 0.000). No statistical difference was observed between orgasm and PFM strength when objective evaluations were performed. Conclusions There was concordance between anterior and posterior areas in 76% of cases when subjective PFM strength was assessed. In objective evaluation, higher PFM strength was observed when volunteers were standing. No statistical correlation was observed between PFM strength and orgasm in nulliparous healthy women.

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Purpose The objective of this paper is to analyze the structure of the ureter in normal and anencephalic human fetuses. Materials and Methods We studied 16 ureters from 8 human fetuses without congenital anomalies aged 16 to 27 weeks post-conception (WPC) and 14 ureters from 7 anencephalic fetuses aged 19 to 33 WPC. The ureters were dissected and embedded in paraffin, from which 5 µm thick sections were obtained and stained with Masson trichrome, to quantify smooth muscle cells (SMC) and to determine the ureteral lumen area, thickness and ureteral diameter. The samples were also stained with Weigert Resorcin Fucsin (to study elastic fibers) and Picro-Sirius Red with polarization and immunohistochemistry analysis of the collagen type III fibers to study collagen. Stereological analysis of collagen, elastic system fibers and SMC were performed on the sections. Data were expressed as volumetric density (Vv-%). The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done using the Image Pro and Image J programs. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p < 0.05). Results The ureteral epithelium was well preserved in the anencephalic and control groups. We did not observe differences in the transitional epithelium in the anencephalic and control groups. There was no difference in elastic fibers and total collagen distribution in normal and anencephalic fetuses. SMC concentration did not differ significantly (p = 0.1215) in the anencephalic and control group. The ureteral lumen area (p = 0.0047), diameter (p = 0.0024) and thickness (p = 0.0144) were significantly smaller in anencephalic fetuses. Conclusions Fetuses with anencephaly showed smaller diameter, area and thickness. These differences could indicate that anencephalic fetal ureters tend to have significant structural alterations, probably due to cerebral lesions with consequent brain control damage of ureter nerves.

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Objective To investigate the relationship between urinary symptoms and quality of life of patients infected with HTLV-1. Materials and Methods This is a cross-sectional study that enrolled individuals with HTLV-1 positive serology from February 2010 to March 2011. Participants were HTLV-1 infected subjects followed in the HTLV-1 clinic of the University Hospital in Salvador, Bahia, Brazil. Patients with HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP), who had evidence of other neurological diseases, diabetes mellitus or were pregnant were excluded from the study. The questionnaire SF-36 was used to evaluate quality of life and the questionnaire OAB-V8 was used to evaluate urinary symptoms. Results From the 118 individuals evaluated, 50 (42.4%) complained of urinary symptoms and 68 (57.6%) did not. Most participants were females. There was no difference between the groups regarding demographic variables. The group with symptoms showed significantly lower scores in all domains of the SF-36 questionnaire. The domains with greatest differences were vitality and general health state. Conclusions Urinary symptoms negatively influence the quality of life of individuals infected with HTLV-1.

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Purpose To assess the prevalence of LUTS, urinary tract and urodynamics changes in patients with Friedreich's Ataxia (FA), the most common form of hereditary ataxia. Materials and Methods This study evaluated 258 patients with genetically confirmed diagnoses of FA. Of the patients, 158 responded to a questionnaire which assessed their urinary symptoms. Patients with clinical changes underwent renal function examinations, ultrasound, and urodynamic studies (UDS). Results The sample analyzed showed that 82% of the patients complained of LUTS, although only 22% related the symptoms with quality of life impairment. Twenty eight (18%) of them agreed to undergo urodynamic evaluation. Urgency was the most common symptom. The exam was normal in 4 (14%) and detrusor underactivity was the most common finding. 14% (4 patients) presented with dilatation of the upper urinary tract at ultrasound scans. None of them had creatinine alterations. Conclusions LUTS was found in a large percentage of patients with FA, but only a few related it to their quality of life impairment. Although creatinine levels was normal in this sample, some patients may show upper urinary tract abnormalities, with deserves close observation and proper care.

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Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway.

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Purpose To compare the histological characteristics of keratinized versus non-keratinized onlay island flaps in an experimental rabbit model. Materials and Methods Sixteen male rabbits were randomly allocated into two experimental groups: keratinized and non-keratinized onlay island flaps. A defect was created in the ventral aspect of the penile urethra. In the keratinized group, a longitudinal island flap was harvested from the external prepuce and rotated to cover the urethral defect. In the non-keratinized group a transverse island flap was harvested from the inner prepuce. The animals were sacrificed after 2, 4, 8 and 12 weeks. Results The flaps were viable in all animals, and no deaths were associated with the procedure. Two urethrocutaneous fistulas were identified, one in each experimental group. A similar pattern of fibrosis was identified in both groups. The keratinized epithelium of the external prepuce kept its histological aspect and keratin production. Both keratinized and non-keratinized groups presented a slight decrease on the epithelial thickness, however without a statistically significant difference between groups. Conclusions In this short-term rabbit model, we observed that the stratified squamous keratinized epithelium from the external prepuce kept its keratin production. There was no statistical influence of the flap type on the mean epithelial thickness.

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Introduction Open inguinal lymphadenectomy is the gold standard for the treatment of inguinal metastasis in patients with penile cancer (PC). Recently the Video Endoscopic Inguinal Lymphadenectomy (VEIL) was proposed as an option to reduce the morbidity of the procedure in patients without palpable inguinal lymph nodes (PILN), however the oncological equivalency in patients with PILN remains poorly studied. The aims of this video are the demonstration of VEIL in patients with PILN and present the preliminary experience comparing patients with and without PILN. Materials and Methods The video illustrates the procedure performed in two cases that were previously underwent partial penectomy for PC with PILN. Data from the series of 15 patients (22 limbs operated) with PILN underwent VEIL were compared with our series of VEIL in 25 clinically N0 patients (35 limbs operated). Results The comparison between the groups with and without PILN found, respectively, these outcomes: age 52,45 × 53,2 years, operative time 126,8 × 95,5 minutes, hospital stay 5. × 3.1 days, drainage time 6.7 × 5.7 days, 9 resected lymph nodes on average in both groups, global complications 32% × 26%, cellulitis 4.5% × 0%, lymphocele 23% in both groups, skin necrosis 0% × 3%, myocutaneous necrosis 4.5% × 0%, pN+ 33% × 32%, cancer specific mortality 7% × 5% and mean follow-up 17.3 × 35.3 months. None of the variables presented p < 0.05. Conclusions VEIL is a safe complementary procedure for treatment of PC, even in patients with PILN. Oncological results in patients with PILN seem to be appropriate but are still very premature. Prospective multicenter studies with larger samples and long-term follow-up should be conducted to determine the oncological equivalence of VEIL compared with open surgery in patients with PILN.

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Since the first laparoendoscopic single-site (LESS) surgery report in urology in 2007 (1) (Rane A e Cadeddu JA), the few reports of LESS extraperitoneal access in the literature were mainly described for less complex cases. The aim of this video is to demonstrate the feasibility of LESS extraperitoneal access in a morbid obese patient presenting a malignant tumor in the renal pelvis. The patient is positioned in 90-degree lateral decubitus. An incision is made below the abdominal skin crease on the left side of the patient and the anterior rectus fascia is vertically incised with manual dissection of the extra/retroperitoneal space. We use an Alexis® retractor to retract the skin maximizing the incision orifice. Three trocars (12, 10 and 5 mm) are inserted through a sigle-port. The pedicle was controlled “en bloc” with a vascular stapler and the bladder cuff treated by the conventional open approach through the same incision. Operative time was 126 minutes with minimal blood loss. The pathology reported high grade papillary urothelial carcinoma in the pelvis (pT3N0M0) and in the ureter (pTa). LESS extraperitoneal nephroureterectomy is feasible and safe, even in more complex cases. It is a good alternative for morbid obese patients and for patients with synchronous distal ureteral tumors for whom an open approach to the bladder cuff is proposed to avoid incisions in two compartments of the abdominal wall.

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Introduction Cloacal exstrophy is a rare occurrence with an incidence of 1:200,000 to 1:400,000 live births. It represents one of the most challenging reconstructive endeavors faced by pediatric surgeons and urologists. Aside from the genitourinary defects, there are other associated anomalies of the gastrointestinal, musculoskeletal and neurological systems that require a multidisciplinary approach when counseling anxious parents. Material and Methods We present a video of a patient with cloacal exstrophy treated with 21 days of life. Surgery consisted of separation and tubularization of the cecal plate from the exstrophied bladder halves and colostomy construction. The bladder was closed primarily and umbilical scar reconstructed and used for ureteral and cistostomy drainage. A urethral catheter was used to guide bladder neck tubularization. A final epispadic penis was obtained and planned for further repair in a second step. Results The patient had an initial uneventful postoperative course and immediate outcome was excellent. The bladder healed nicely but patient presented with abdominal distension in the 5th day of postoperative setting requiring parenteral nutrition. The distal colon persisted with lower diameter although non obstructive, but causing difficulty for fecal progression. Continuous colostomy dilatation and irrigation were required. Conclusions Approximating the bladder halves in the midline at birth and primary bladder closure is a viable option, intestinal transit may be a issue of concern in the early postoperative follow-up.