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Following publication of the original article [1], the authors reported that the affiliation of author Annalisa Orenti was omitted.

Background: An increase in naturally-occurring porphyrins has been described in the blood of subjects bearing different kinds of tumors, including colorectal, and this is probably related to a systemic alteration of heme metabolism induced by tumor cells. The aim of our study was to develop an artificial neural network (ANN) classifier for early detection of colorectal adenocarcinoma based on plasma porphyrin accumulation and risk factors., Methods: We measured the endogenous fluorescence of blood plasma in 100 colorectal adenocarcinoma patients and 112 controls using a conventional spectrofluorometer. Height, weight, personal and family medical history, use of alcohol, red meat, vegetables and tobacco were all recorded. An ANN model was built up from demographic data and from the integral of the fluorescence emission peak in the range 610-650 nm. We used the Receiver Operating Characteristic (ROC) curve to assess performance in distinguishing colorectal adenocarcinoma patients and controls. A liquid chromatography-high resolution mass spectrometry (LC-HRMS) analytical method was employed to identify the agents responsible for native fluorescence., Results: The fluorescence analysis indicated that the integral of the fluorescence emission peak in the range 610-650 nm was significantly higher in colorectal adenocarcinoma patients than controls (p < 0.0001) and was weakly correlated with the TNM staging (Spearman's rho = 0.224, p = 0.011). LC-HRMS measurements showed that the agents responsible for the fluorescence emission were mainly protoporphyrin-IX (PpIX) and coproporphyrin-I (CpI). The overall accuracy of our ANN model was 88% (87% sensitivity and 90% specificity) with an area under the ROC curve of 0.83., Conclusions: These results confirm that tumor cells accumulate a diagnostic level of endogenous porphyrin compounds and suggest that plasma porphyrin concentrations, indirectly measured through fluorescence analysis, may be useful, together with risk factors, as a clinical decision support tool for the early detection of colorectal adenocarcinoma. Our future efforts will be aimed at examining how plasma porphyrin accumulation correlates with survival and response to therapy.

Background: Despite the clear endocrine-metabolic relationship between androgenic activity and adiposity, the role of androgens in breast cancer prognosis according to patient's adiposity is scarcely explored. Here, we aimed at investigating the prognostic value of circulating testosterone in association with patient's body mass index (BMI)., Methods: Circulating testosterone and BMI were evaluated at breast cancer diagnosis in 460 estrogen receptor (ER)-positive postmenopausal patients. Local relapse, distant metastasi(e)s and contralateral breast cancer were considered recurrence events. The Kruskal-Wallis test was performed to evaluate if testosterone levels differed within subgroups of categorical tumour characteristics. The Cox proportional hazard regression model was fitted to estimate the impact of standard prognostic factors on relapse-specific hazard ratio (HR). After backward selection, a model including continuous testosterone level, BMI categories (< 25, normal-weight; =25-30, overweight; ≥30 kg/m 2 , obese), tumour size and lymph nodes number was fitted. Furthermore, Cox models provided the relapse-specific HRs for median, third quartile and 95th percentile compared to the first quartile of testosterone levels, stratified by BMI categories., Results: During a median follow up of 6.3 years, 45 patients relapsed. Testosterone levels significantly increased across BMI categories (p = 0.001). Both circulating testosterone and BMI were positively associated with disease free survival (p = 0.005 and p = 0.021, respectively). A significant interaction was found between testosterone and BMI (p = 0.006). For normal-weight women, testosterone concentration around median (0.403 ng/mL) or third quartile (0.532 ng/mL) showed a high significant HR of relapse (5.52; 95% CI:1.65-18.49 and 4.55; 95% CI:1.09-18.98, respectively). Overweight patients showed increased HR at increasing testosterone levels, reaching a significant high HR (4.68; 95% CI:1.39-15.70) for testosterone values of 0.782 ng/mL (95th percentile). For obese patients HR decreased (not significantly) at increased testosterone concentrations, explaining the interaction between testosterone levels and BMI categories., Conclusions: In ER-positive postmenopausal breast cancer patients, high testosterone levels are associated with worse prognosis in normal-weight and overweight women, whereas in obese seems to be associated with a better outcome. Although the results require further validation, they suggest that assessment of circulating testosterone and BMI could help to identify postmenopausal ER-positive patients at higher risk of relapse and potentially open new therapeutic strategies.

Introduction and Objective: Urethral duplication is a rare congenital anomaly, with roughly 200 cases reported in the literature (1). It is more frequent in males, with few cases reported in females. The clinical presentation differs according to the anatomical variant present. The duplication most commonly occurs in the sagittal plane with one urethra located ventrally and the other dorsally (2). Usually the ventral urethra is the more functional of both. Duplications occurring in the coronal plane are quite rare and they are usually associated with bladder duplication (3). The purpose of this paper was to present a video of a boy with an unusual urethral duplication form., Materials and Methods: Patient was born premature due to oligohydramnios at 7 months-gestational age and he has initial diagnosis of hypospadia. Since then, he presented at least 7 febrile UTI and mother complained of difficult micturition and a presence of a mass at lower abdomen. Patient was referred to our institution and we identified urethral duplication with a glandar and scrotal meatus, palpable bladder and left penile-hemiscrotum transposition. US and CT-scan showed left kidney agenesis and overdistended bladder. VCUG and retrograde urethrography showed duplication, presence of contrast in the seminal vesicles and complete catheterizing of both urethras was not possible., Results: The topic urethra was dysplastic and not patent to a 4Fr plastic tube so we were unable to access it endoscopically. We performed initially a Mitrofanoff procedure to allow CIC and treat chronic retention. Six months later, we assessed both urethras surgically and concluded that dorsal urethra was dysplastic after 3cm still in the penile area and scrotal urethra was not possible to be catheterized. We excised the ventral urethra because of dribbling complaints up to bulbar area and reconstructed the scrotal transposition, keeping the topic urethra for cosmetic issues. Patient had excellent outcome, performs CIC every 4 hours and has not presented further UTI episodes., Discussion and Conclusion: The urethral duplication is an anomaly that has multiple anatomical presentations. There are several theories about the etiology, but none can explain all types of presentations. There is also more than one rating available, and the Effmann classification is the most detailed. The case exemplifies this varied spectrum of anatomic urethral duplication. It resembles the urethral duplication type IIa-Y, however, ventral urethra meatus was located in penoscrotal area and both urethras were at least partially hypoplastic/dysplastic associated with obstruction and bladder retention. In determining how to best manage a patient with Y-type urethral duplication, the caliber and quality of the orthotopic urethra must first be assessed. Published reports suggest that best outcomes are those using the ventral duplicated urethra for the reconstruction (4). In this case, none of urethras were functional and a supravesical outlet channel had to be provided. The treatment of this condition requires an individualized planning and a vast technical knowledge of reconstructive surgery., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Introduction: Y-type urethral duplication describes the condition in which a functional urethra is implanted in the rectum, and there is also a dysplastic topic urethra which produces mostly urinary dribbling. These patients are at risk of urinary tract complications and UTI. We aimed to present the surgical steps of a case treated by ASTRA approach in which we separated the urethra from the rectum and created a perineal urethrostomy., Material and Methods: We treated a 5-month-old boy with Y-type (IIA-2) urethral duplication, in whom the orthotopic urethra was patent just in the penile segment. The patient had urinary flow per anus and minimal dribbling through the orthotopic urethra. We performed a combined cystoscopy with retrograde urethrogram and managed to catheterize the dysplastic urethra with a guide-wire that showed ectopic implantation in the prostatic urethra, below the bladder neck. We performed an ASTRA procedure to separate the urethra from the rectum. The urethral stump was further mobilized to the perineum and anastomosed to a perineal skin flap to create a stoma and minimize the risk of stricture., Results: The patient was followed at 2 month-intervals, and at 6 months follow-up had an excellent outcome., Conclusion: The ASTRA approach proved to be an excellent alternative for Y-type urethral duplication with functional urethra implanted in the rectum. We believe that further efforts to reconstruct the urethra should be avoided, with a better and simpler option being to create a definitive perineal urethrostomy., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Tobacco use and the Western diet are two of the most important and investigated topics in relation to adolescents' health. In addition, air pollution is a crucial subject for future generations. School is a key social environment that should promote healthy behaviors in children and adolescents. In this field many different programs have been conducted, with mixed results and effectiveness. Research data suggest that comprehensive and multicomponent approaches may have a greater effect on tobacco use and diet, especially when integrated into a community-wide approach., Methods: The present work describes a multi-area pilot study called "La Scuola della Salute" (the School of Health) with a focus on the methodological aspects of the intervention. In our study we assessed different web-based and practical experiences related to adolescents' smoking and dietary behaviors and awareness of smoke-related air pollution. Furthermore, to make adolescents more conscious of smoking and dietary behaviors, we conducted experiential workshops that addressed smoking and environmental pollution, food education, and lifestyle. Teachers and school administrators were involved in the project., Results: At baseline we investigated dietary habits, tobacco use, and individual and social characteristics by means of lifestyle questionnaires. In addition, we collected anthropometric parameters and performance indicators such as exhaled carbon monoxide and urinary fructose to assess smoking and nutrition habits. At the end of the intervention lifestyle questionnaire and biological markers were collected again: knowledge about these topics was significantly improved, and the urinary fructose was able to estimate the levels of obesity in the classes., Conclusions: The integrated approach, combined with the use of biological markers, could be an innovative approach to the promotion of healthy lifestyles among adolescents, but further research is needed.

Trehalose is a nonreducing disaccharide that has recently attracted much attention because of its ability to inhibit protein aggregation, induce autophagy, and protect against dissections and strokes. In vertebrates, the biosynthesis of trehalose was long considered absent due to the lack of annotated genes involved in this process. In contrast, trehalase (TreH), which is an enzyme required for the cleavage of trehalose, is known to be conserved and expressed. Here, we show that trehalose is present as an endogenous metabolite in the rodent hippocampus. We found that primary astrocytes were able to synthesize trehalose and release it into the extracellular space. Notably, the TreH enzyme was observed only in the soma of neurons, which are the exclusive users of this substrate. A statistical analysis of the metabolome during different stages of maturation indicated that this metabolite is implicated in neuronal maturation. A morphological analysis of primary neurons confirmed that trehalose is required for neuronal arborization.

Clinical and epidemiological data show that biological sex is one of the major determinants for the development and progression of cardiovascular disease (CVD). Impaired endothelial function, characterized by an imbalance in endothelial Nitric Oxide Synthase (eNOS) activity, precedes and accelerates the development of CVD. However, whether there is any sexual dimorphism in eNOS activity and function in endothelial cells (ECs) is still unknown. Here, by independently studying human male and female ECs, we found that female ECs expressed higher eNOS mRNA and protein levels both in vitro and ex vivo. The increased eNOS expression was associated to higher enzymatic activity and nitric oxide production. Pharmacological and genetic inhibition of eNOS affected migratory properties only in female ECs. In vitro angiogenesis experiments confirmed that sprouting mostly relied on eNOS-dependent migration in female ECs. At variance, capillary outgrowth from male ECs was independent of eNOS activity but required cell proliferation. In this study, we found sex-specific differences in the EC expression, activity, and function of eNOS. This intrinsic sexual dimorphism of ECs should be further evaluated to achieve more effective and precise strategies for the prevention and therapy of diseases associated to an impaired endothelial function such as CVD and pathological angiogenesis.

Purpose: Premature delivery is a major complication of in utero myelomeningocele repair. The prematurity rate in MOMS (Management of Myelomeningocele Study) was 79%, with a mean gestational age at birth of 34 weeks. We speculated that prematurity could also influence urological outcome in patients operated on prenatally for myelomeningocele., Materials and Methods: Beginning in November 2011, we prospectively followed a population of patients with myelomeningocele who had undergone in utero repair., Results: We compared patients based on gestational age at birth, ie younger than 34 weeks (group 1, 42 patients) and 34 weeks or older (group 2, 37 patients). Mean gestational age at birth was 28.3 weeks (range 25 to 33) in group 1 and 35.2 weeks (34 to 38) in group 2. Of the cases 47.5% in group 1 were classified as high risk, 35% as incontinent, 10% as hypocontractile and 7.5% as normal. By comparison, 54.5% of cases in group 2 were classified as high risk, 33.3% as incontinent and 12.1% as normal. Differences between the groups were not statistically significant. Mean followup was 27.9 months in group 1 and 24.3 months in group 2., Conclusions: Our results show that gestational age at birth has little impact on bladder pattern. These data reinforce the need to follow this population closely., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: We evaluated the long-term results with a left antegrade continence enema (LACE) approach: "Macedo-Malone (MM) procedure" to define parameters such as clinical durability of the technique and patients' compliance with the method., Methods: We reviewed the medical records of all patients that underwent the MM procedure in our institution since 2001 and conducted a telephonic interview to investigate the use of the enema and satisfaction with the procedure., Results: Thirty-five MM procedures were performed, but eight patients lost to follow-up were excluded. Fifteen patients (55%) were female. Myelomeningocele was the clinical diagnoses in 25 (93%). Mean age at surgery was 9 years (3-27 years) and mean follow-up was 75 months (median: 56 months). The indication for LACE was clinically intractable constipation with fecal leakage. Most patients still used the stoma regularly to do the enema (74%). Mean washout time was 27 min (2-90 min). The revision rate due to stenosis was 22.2% (6/27) and all underwent suprafascial revision. We performed one classical MACE by infrafascial approach as a salvage procedure. Overall reoperation rate was 25.8% and fecal continence was 89%. There were no reports of leakage through the stoma. Among patients who still used the stoma, 74% were satisfied with surgery and would strongly recommend the procedure to another patient., Conclusions: The MM procedure is a straightforward procedure, which can be performed in 15-20 min, avoids additional entero-entero anastomosis, precludes the use of the appendix, and has shown comparable results to either "classical" MACE or other LACE variants. Neurourol. Urodynam. 36:111-115, 2017. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: One-carbon metabolism-important for DNA stability and integrity-may play a role in breast carcinogenesis. However, epidemiologic studies addressing this issue have yielded inconsistent results., Objective: We prospectively investigated associations between breast cancer and plasma folate, riboflavin, vitamin B-6, vitamin B-12, and homocysteine in women recruited to the Varese (Italy) cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition) study., Methods: We performed a nested case-control study on women aged 35-65 y at recruitment with a median body mass index of 25.3 kg/m(2) who gave blood samples in 1987-1992 and again in 1993-1998. Breast cancer cases identified by 31 December 2009 were individually matched to controls. RRs of breast cancer (and subtypes defined by hormone receptor status) with 95% CIs were estimated by unconditional logistic regression, controlling for matching factors and breast cancer risk factors., Results: After a median of 14.9 y, 276 breast cancer cases were identified and matched to 276 controls. Increasing plasma vitamin B-6 was associated with decreased risk of overall (RR: 0.78; 95% CI: 0.63, 0.96 for 1-SD increase), premenopausal (RR: 0.66; 95% CI: 0.48, 0.92 for 1-SD increase), estrogen receptor-positive (RR: 0.79; 95% CI: 0.63, 1.00 for 1-SD increase), and progesterone receptor-positive (RR: 0.72; 95% CI: 0.55, 0.95 for 1-SD increase) breast cancers. Increased plasma vitamin B-6 was also associated with decreased breast cancer risk in alcohol consumers (≥7 g/d) compared with consumption of <7 g/d or nonconsumption (RR: 0.71; 95% CI: 0.51, 0.99). High plasma riboflavin was associated with significantly lower risk in premenopausal women (RR: 0.45; 95% CI: 0.21, 0.94; highest compared with the lowest quartile, P trend = 0.021). Plasma homocysteine, folate, and vitamin B-12 were not associated with breast cancer risk., Conclusions: High plasma vitamin B-6 and riboflavin may lower breast cancer risk, especially in premenopausal women. Additional research is necessary to further explore these associations., (© 2016 American Society for Nutrition.)

Objective: Aphallia is a rare penile congenital abnormality. The aim of this systematic review was to assess all available literature on neophalloplasty in infancy with an interest in technical alternatives and clinical outcome., Materials and Methods: We performed a Pubmed search using the terms: neophalloplasty, neophallus, and phalloplasty, and selected articles that presented technical alternatives for penile construction in cases of penile dysgenesis, especially aphallia in children and/or adolescents., Results: A total of 319 articles were identified in the initial search. Among the different techniques presented in 19 papers collected, we categorized reconstructive procedures into two groups: microsurgical and non-microsurgical techniques. Among the microsurgical techniques, procedures such as the osteocutaneous fibular flap (n = 18), the myocutaneous latissimus dorsi flap (n = 24), and the radial forearm free flap (n = 293) were reported. Among the non-microsurgical techniques, we found a wider range of technical options (6 in total). Most were based on groin, abdominal, and scrotal flaps. Long-term reports on the functionability of the neophallus and psychological aspects of the patients are lacking., Conclusion: In assessing recent literature, it seems rational that neophalloplasty should be regarded as the preferred strategy for boys born with aphallia, in opposition to female gender assignment., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Neurons have a very high energy requirement, and their metabolism is tightly regulated to ensure delivery of adequate substrate to sustain neuronal activity and neuroplastic changes. The mechanisms underlying the regulation of neuronal metabolism, however, are not completely clear., Objective: The objective of this study was to investigate the central carbon metabolism in neurons, in order to identify the regulatory pathways governing neuronal anabolism and catabolism., Methods: Here we first have applied MS-based endometabolomics to elucidate the metabolic dynamics in cultured hippocampal primary neurons. Using nanoLC-ESI-LTQ Orbitrap MS approach followed by statistical analysis, we measure the dynamics of uniformly labeled 13 C-glucose entering neurons. We adapted the method by coupling offline patch-clamp setup with MS to confirm findings in vivo., Results: According to non-parametric statistical analysis of metabolic dynamics, in cultured hippocampal neurons, the glycerol phosphate shuttle is active and correlates with the metabolic flux in the pentose phosphate pathway. In the hippocampus, glycerol-3-phosphate biosynthesis was activated in response to long-term potentiation together with the upregulation of glycolysis and the TCA cycle, but was inactive or silenced in basal conditions., Conclusions: We identified the biosynthesis of glycerol-3-phosphate as a key regulator in mechanisms implicated in learning and memory. Notably, defects in enzymes linked with the glycerol phosphate shuttle have been implicated in neurological disorders and intellectual disability . These results could improve our understanding of the general mechanisms of learning and memory and facilitate the development of novel therapies for metabolic disorders linked with intellectual disability.

Objective: Aphallia is a rare congenital abnormality with an incidence of 1 in 30 million births. In this video, we demonstrate implantation of a penile prosthesis in a neophallus performed 10 years previously in a patient aged 21., Methods: Through a midline perineal incision aiming to reach the inferior surface of the pubic arch, we created a 16-cm tunnel for prosthesis insertion into the neophallus. We dressed the prosthesis with a polypropylene mesh to give stability to the component and avoid its extrusion. We anchored the lateral mesh to the inferior aspect of the pubic arch with 2.0 vicryl sutures in both sides., Results: The patient had an excellent initial outcome, without any complaints of pain or other inflammatory findings., Conclusion: We acknowledge limited clinical experience with this technique. Further psychological evaluation will confirm if patients can have pleasant sexual experiences., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Primary congenital bladder diverticulum (PCBD) is related to a deficient detrusor layer allowing out-pouching of the bladder mucosa through the inadequate muscularis wall. We aimed to review our experience with symptomatic PCBD in order to correlate clinical findings with anatomical aspects and to present late outcome., Materials and Methods: We reviewed all patients operated in our institution since 2004. We evaluated the charts for complaints, radiological exams, method of treatment, complications and length of follow-up., Results: We treated 10 cases (11 renal units - [RU]), predominantly males (9/10), mean age at surgery of 5.3 years. All patients had significant urological complaints presenting either with antenatal hydronephrosis (4) or febrile urinary tract infection (5) and urinary retention in one. The ureter was found implanted inside the diverticulum in 8/11 RU. An extravesical psoas-hitch ureteroneocystostomy and diverticulum resection was performed in 10/11 cases, whereas 1 case was treated intravesically based on surgeon's preference without performing cystoscopy. Mean follow-up was 34.1 months (1-120) without complications., Conclusions: PCBD is an uncommon diagnosis and has a high probability of drainage inside the diverticulum (72.7%). We recommend the extravesical approach associated with diverticulectomy and ureteroneocystostomy as the preferred technique to treat this abnormality.

Purpose: We categorized bladder patterns and principles of treatment applied to patients who underwent myelomeningocele repair during gestation in a prospective urological assessment., Materials and Methods: We performed urinary tract ultrasound, voiding cystourethrogram and urodynamic evaluation. We then categorized patients into 4 patterns, including normal, high risk (overactive bladder with detrusor leak point pressure greater than 40 cm H2O and high filling pressure also greater than 40 cm H2O), incontinent and underactive bladder., Results: A total of 51 patients were enrolled in study at the first medical appointment. Urodynamic evaluation was done in 48 of these patients as the initial investigation, enabling attribution of a bladder pattern. The high risk pattern was found in 27 patients (56.2%), 18 were incontinent and 1 had an underactive bladder. Only 2 patients (4.2%) in this series had a normal bladder., Conclusions: Of patients who underwent myelomeningocele closure during gestation 93.7% had significant lower urinary tract dysfunction consisting of high bladder pressure or incontinence. These data reinforce the absolute need to follow these patients closely. The potential benefits of fetal surgery in the urinary tract remain to be proved., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Complete female epispadia (CFE) is a rare congenital anomaly occurring in 1 of 500,000 live births. The goals of CFE management include achieving continence, while protecting the kidneys, and creating functional, cosmetic external genitalia., Patient and Methods: We demonstrate in this video the steps of the surgery and present midterm follow-up of a 6-year-old child with CFE., Results and Discussion: The patient had an excellent cosmetic result, and reported continence of 3 h period with mild leakage. The perineal infrapubic approach offers the possibility of restoring cosmesis and providing resistance in one surgery precluding the need for abdominal bladder neck surgery., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

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.

Objective: To demonstrate ventral corporoplasty, with tunica vaginalis flap to reconstruct the corpora cavernosa, in a two-stage strategy for proximal hypospadias surgery., Methods: Assessment of residual curvature after complete urethral plate division and transverse superficial cuts in albuginea. Ventral incision of tunica albuginea to elongate the ventral surface of the penis and use of a tunica vaginalis flap to reconstruct the defect in corpora cavernosa. Dorsal preputial island flap was used to cover the penile ventral surface, to be tubularized in a second stage, together with the original urethral plate., Results: Patient had an uneventful follow-up. Penile aspect was very satisfactory with no residual curvature., Conclusion: Tunica vaginalis is an attractive alternative for ventral corporoplasty in hypospadia repair and has the advantages of prompt disposability, autologous use, and does not represent an extra cost for treatment., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate long-term efficacy of an original technique of catheterizable ileal reservoir designed for bladder augmentation and/or substitution, precluding the need to use a Yang-Monti channel or appendix., Materials and Methods: Our series comprised 19 patients, operated in 1998-2000, with a mean age of 10.1 years (1.6-30). Two were excluded from analysis because lost to follow-up after 1.5 and 7 years of surveillance. The primary disease was posterior urethral valves (9), myelomeningocele (4), anorectal malformation (1), rhabdomyosarcoma (1), medullary astrocytoma (1) and urethral stricture (1). Surgery consisted of creating a continent catheterizable ileum-based reservoir from a 35-cm ileum segment., Results: Mean follow-up was 11.2 years (10-12.4). All 16 patients eligible for final evaluation of the procedure were continent, excluding two lost of follow-up and one that underwent undiversion. Complications noted were: stomal stenosis (3), leakage associated with false passage (1) and false passage (1). One patient underwent a Bricker undiversion procedure, an appendicovesicostomy was performed in 2, and 1 patient received a Monti channel to replace the outlet conduit. The overall complication rate was 29.4% (5/17)., Conclusion: We have confirmed the long-term efficacy of the technique. The results are comparable to other 'gold standard' treatments, with the advantage of being simpler, faster and sparing the appendix for other uses (Malone antegrade continent enema), as well as precluding the need to create a Monti channel., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: We investigated continence outcomes for patients undergoing primary or redo reconstruction of a urinary catheterizable reservoir involving the Yachia technique of intersecting two rectus abdominis strips over the outlet channel., Materials and Methods: A retrospective evaluation of 22 consecutive patients operated from March 2009 to August 2010 was performed, consisting of 16 primary reconstructions (Macedo catheterizable ileal reservoirs) and 6 rescue cases for leaking stomas. Our data comprised 18 spina bifida patients, 1 sacral agenesis, 1 posterior urethral valves and 1 genitourinary tuberculosis. Mean age at surgery was 8.5 years (3-21 years). We evaluated continence at 3, 6, 12 months, and at the last follow-up based on data from urinary charts., Results: Mean follow-up was 21.1 months (12-29 months). Overall continence was 100% for the primary cases and 66% for the redos (2/6 failed). Three patients had initial difficulty in performing clean intermittent catheterization but this resolved with time and experience., Conclusion: Using Yachia's technique has improved the continence rate of our catheterizable reservoirs and was partially successful for suprafascial revision of incontinent conduits., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

3-hydroxy-3-methylglutaric aciduria (OMIM 246450) is a rare autosomal recessive inborn of metabolism due to the deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase, an enzyme involved both in the ketogenic pathway and leucine catabolism. Acute decompensations present with lethargy, cianosis, hypotonia, vomiting and metabolic acidosis with hypoketotic hypoglycemia. We report the case of a 3 days male with sudden hypoglycemic crisis initially misdiagnosed as a sepsis. HMG-CoA lyase deficiency was achieved through acyl-carnitines profile (showing a typical increasing of 3-hydroxy-isovaleryl and 3-methylgluraryl carnitines) and urinary organic acids analysis (disclosing elevation of 3-hydroxy-3-methylglutaric, 3-methyl-glutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids). This case underlines the need of suspecting such inborn metabolic disorder in cases with hypoglycemia and metabolic acidosis. Acyl-carnitine and urinary organic acids profiles are essential to achieve a prompt diagnosis of treatable metabolic disorders in order to prevent their acute crisis with serious or even fatal consequences.

Objective: To use anthropometric measurements to compare nutritional status in children with neurogenic bladder dysfunction secondary to meningomyelocele who underwent enterocystoplasty and those who did not undergo surgery., Methods: A case-control study was conducted in 20 children, divided into two groups: those who had enterocystoplasty (Group A) and those who did not undergo surgery (Group B), matched for genre and age. Weight, height, arm circumference, and triceps skinfold thickness were the parameters used. Nutritional assessment was determined by calculating the indexes, based on age and genre. Classification was based on the percentile and the results were compared with the reference values., Results: The mean age was 6.41 years in Group A and 6.35 years in Group B. The interval between surgery and evaluation was 11 months. The following measures were found for Group A: 80% of children were eutrophic, a percentage 30% greater than that in Group B; arm muscle circumference was adequate in 40% of patients, a percentage 20% greater than that in Group B; arm muscle area was adequate in 90%, a percentage 30% greater than that in Group B. Values in Group B were as follows: for triceps skinfold thickness, 60% of patients had values above the mean, a percentage 20% greater than that in Group A; for arm fat index, 60% of patients were above the mean value, 40% greater than in Group A., Conclusion: Patients who had undergone enterocystoplasty showed better nutritional status, while the control group presented higher fat indexes in anthropometric measures. However, the differences between groups were not statistically significant.

Introduction: Urethral duplication is a rare congenital anomaly affecting mainly boys. Generally, the duplication develops on the sagittal plane; the accessory urethra may run dorsally or ventrally to the orthotopic one. We present a patient with urethral duplication in which the orthotopic urethra was patent in the penile segment but atresic in the bulbar and prostatic segment. The patient had urinary flow from the rectum and the ectopic urethra could be well identified by anal examination., Materials and Methods: Age at surgery was 13 months. The procedure consisted of an ASTRA (anterior sagittal trans-ano-rectal) approach for dividing the urethra and rectum and was successful to move the urethra up to the perineal area. The rectum was reconstructed and the patient placed into a lithotomy position. A urethral catheter inserted in the penile urethra oriented us were the atresic urethra in bulbar area started. The scrotum was opened in the middle and the distance between the two urethral stumps proximal and distal defined the extension of no urethral tissue that consisted of 5 cm. We opened the right scrotal space and a tunica vaginalis flap was obtained and attached to the bulbar tissue for a two-stage urethroplasty strategy., Results: Patient had a nice healing and the tunica vaginalis was nicely incorporated to the adjacent tissue, having the two urethral stumps well delineated., Conclusions: ASTRA approach in combination with a two-stage urethroplasty with tunica vaginalis dorsal flap proved to be an excellent combination for a rare case of urethral Y duplication having the main urethra into the rectum.

Objective: The Mitrofanoff principle is a well established strategy in pediatric urology, with the appendix and Yang-Monti tube being the most used channels. The search for an alternative tube with less morbidity is justified. Hence, we present a patient treated via an alternative approach in which the channel was constructed from two lower abdominal transverse skin flaps (the RPM technique)., Methods: A 17-year-old patient with posterior urethral valves, hypocontractile bladder and experiencing pain on urethral clean intermittent catheterization was selected. The procedure consisted of defining two rectangular transverse skin flaps of 5 × 1 cm opposite to each other. The flaps were rotated 90° and anastomosed to create a tube. A small extraperitoneal bladder wall incision was performed and the tube was connected to the bladder. Two rectal abdomen muscle strips were crossed in the midline as a neosphincter., Results: The patient had an uneventful postoperative course and remains continent for intervals of 4 h. The stoma and incision have a good cosmetic aspect at 16 months follow-up., Conclusion: The RPM technique is an alternative approach for a minimal invasive strategy according to the Mitrofanoff principle. Long-term follow-up is necessary to confirm the excellent initial results., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: Complex primary hypospadias repair that warrants urethral plate division is treated mostly in two steps, not necessarily in two surgeries. Our aim was to review long-term results with a one-stage strategy based on reconstruction of the urethral plate with buccal mucosa graft and onlay transverse preputial flap anastomosis protected by a tunica vaginalis flap (the three-in-one concept)., Material and Methods: We were able to report on 35 patients operated for primary scrotal, penoscrotal and perineal hypospadias between March 2002 and June 2008. We reviewed all charts and had phone interviews with patients not seen for the last 24 months. We investigated parameters such as UTI occurrence, fistula, residual curvature, meatal stenosis, urethral diverticula, dehiscence, orchitis and parental perception., Results: Surgical complications occurred in 13 patients (37%): 4 meatal stenosis, 4 diverticula, 5 fistulae and 2 residual penile curvatures (total 42%). Meatal dilatation was successful in 2 cases, reflected in fistula resolution. The reoperation rate was 31.5% consisting mostly of simple procedures like fistula closure, meatotomy and penile curvature release, and complex diverticula repair in 4 cases. Parental perception was excellent for 57% (20 patients) and good or acceptable for the remaining. Mean follow-up was 4.6 years., Conclusions: The one-step strategy is associated with 68.5% success in a single operation, whereas 31.5% will need a second repair. We recognize that meatal problems are mostly associated with fistulae and diverticula; therefore, we recommend a final acceptable proximal glandar opening that will not compromise the neourethra., (Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: Complex hypospadia repair can be performed according to different strategies, mostly in one or two stages. We present a detailed video of one patient operated according to the three-in-one technique, which combines dorsal buccal mucosa grafting for reconstruction of the incised urethral plate and a preputial flap onlay urethroplasty covered by a tunica vaginalis graft., Method: After sectioning of the urethral plate to correct ventral curvature, the original plate is anchored to the proximal penile shaft. Buccal mucosa is harvested from the lower lip and sutured to the ventral penile shaft area. A transverse preputial flap is obtained and anastomosed 'onlay' to the reconstructed neouretha. The scrotal fascia is opened at the site opposite to the placement of the pedicle of the preputial flap and a careful dissection of the tunica vaginalis and cremasteric tissue is performed. This second flap is used to cover the neourethra and is fixed to the corpora by angular interrupted 6-0 PDS sutures., Results: Our series of 35 patients resulted in 68.5% success after a single operation, whereas 31.5% needed a second repair., Conclusion: The technique gives excellent results and can be considered an alternative to one-stage repair in primary cases., (Copyright © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: The multimodal approach to treatment of genitourinary rhabdomyosarcoma (RMS) has improved survival rates, but there is now a focus on the effect on quality of life. Our aim was to evaluate erectile function in children with rhabdomyosarcoma (RMS) who underwent chemotherapy, radiotherapy, cystectomy and continent urinary diversion., Material and Methods: We evaluated four eligible patients (age > 14 years) from our genitourinary RMS database. In two patients the reservoir was constructed at the same time of the cystectomy and in two after undiversion of an ileal conduit. All patients were treated with chemotherapy and radiation therapy before cystectomy. We used a questionnaire to estimate erectile function in adolescents and young adults. There were four questions, each one to be scored 1-5, assessing capability to masturbate., Results: Mean follow up after cystectomy was 9.75 years. We considered that two patients had erections of good quality (scores 18 and 20) and two of moderate quality (scores 8 and 10). One patient had a good response to sildenafil administration., Conclusion: Our data demonstrate that it is possible to keep erectile function during masturbation in children with RMS who have undergone chemotherapy, radiotherapy, cystectomy and continent urinary diversion., (Copyright © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the role of elective appendicovesicostomy in association with Monfort abdominoplasty to avoid urinary tract infection (UTI) and renal damage in the post-operative follow-up of patients with prune belly syndrome., Materials and Methods: We followed 4 patients operated in our institution (UNIFESP) (Monfort, orchidopexy and Mitrofanoff) and compared them to 2 patients treated similarly, but without an appendicovesicostomy, in a second institution (UFBA). We evaluated postoperative clinical complications, UTI and preservation of renal parenchyma. Patients were followed as outpatients with urinalysis, ultrasonography (US) and occasionally with renal scintigraphy., Results: Mean follow-up was 23.5 months. Immediate post-operative course was uneventful. We observed that only one patient with the Mitrofanoff channel persisted with UTI, while the 2 patients used as controls persisted with recurrent pyelonephritis (> 2 UTI year)., Conclusion: Our data suggest that no morbidity was added by the appendicovesicostomy to immediate postoperative surgical recovery and that this procedure may have a beneficial effect in reducing postoperative UTI events and their consequences by reducing the postvoid residuals in the early abdominoplasty follow-up. However, we recognize that the series is small and only a longer follow-up with a larger number of patients will allow us to confirm our suppositions. We could not make any statistically significant assumptions regarding differences in renal preservation due to the same limitations.

Purpose: The treatment of bladder-prostate rhabdomyosarcoma has evolved into multimodal therapy, including chemotherapy, radiotherapy and organ sparing surgery with bladder preservation. We investigated bladder function in children who underwent multimodal therapy at our institution and retained the original bladder for at least 6 months after treatment ended., Materials and Methods: We evaluated 8 children with bladder-prostate rhabdomyosarcoma treated at our institution between 1999 and 2003 according to inclusion criteria. All patients underwent history, physical examination and urodynamic study at least 6 months after completion of treatment (range 6 to 39 months)., Results: All patients were treated following the same chemotherapy and radiotherapy scheme. Three patients (37.5%) were asymptomatic and had normal urodynamic studies, and 1 had only dysuria (this patient later underwent continent urinary diversion with transverse colon). The 4 remaining patients had urological complaints, and the urodynamic findings were reduced bladder capacity in 4, overactivity plus sensory urgency in 2, sensory urgency only in 1 and suprapubic pain during filling in 1., Conclusions: Among 8 patients 3 had normal urinary function and 4 had minor tolerable alterations. Cystectomy and urinary diversion were later necessary in only 1 patient due to disabling dysuria. The fact that the original functioning bladder was preserved in 7 of 8 patients suggests the feasibility of multimodal therapy. Long-term followup will still be necessary for definite conclusions, since we recognize that the deleterious effects, mainly of radiotherapy, may take longer to become evident.

Purpose: The successful treatment of fecal incontinence can dramatically improve the quality of life of affected children. The introduction of the Malone antegrade continence enema provides the opportunity to manage previously resistant cases. However, using the to create this catheterizable channel is not always possible, and the duration of these antegrade enemas is a source of concern for the patients. We describe a new approach to create left continent colonic access to shorten the duration of these enemas, and report the experience gained from the first 9 cases managed at our institution., Materials and Methods: During a 5-year period 9 patients underwent a Macedo-Malone antegrade continence enema at our institution. Incontinence was associated with myelomeningocele in 7 patients and anorectal malformation in 2. The antegrade continence enema procedure is begun by isolating a 2 cm flap in a tenia on the left colon (spleen flexure). A 12Fr silicone Foley catheter is placed on the mucosal surface of the flap to allow tubularization of the plate with interrupted polyglycolic acid 3-zero transverse sutures, creating an efferent tubular conduit. Antegrade colonic washouts were started 2 weeks after surgery with saline solution or tap water in all patients., Results: Followup of our 9 cases ranged from 8 to 33 months (average 20.7). Enema volume varied from 250 to 800 ml, with administration taking from 45 to 60 minutes, and colonic evacuation occurred within 30 to 60 minutes of enema administration. Of the 9 patients 8 were completely continent and 1 was partially continent. Four patients experienced difficulty with catheterization initially because of stenosis of the stomal track. The affected stomas were dilated, which was successful in 1 case. Three patients subsequently required stomal revision., Conclusions: The Macedo-Malone procedure is a relatively straightforward operative approach providing an effective washout technique that is acceptable to parents and children.

Because recent research reports indicated clinical and biological differences in major depression with and without comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) panic disorder, and as altered immune measures were reported in selected subgroups of depressive patients, we investigated 51 pairs of major depressive episode (MDE) subjects, and gender- and age-matched healthy controls in order to determine if T lymphocytes number and function abnormalities were associated with Panic Disorder comorbidty. We found that those MDE subjects with DSM-III-R panic disorder (PD) had greater numbers of T cells (p less than 0.05) and PHA mitogen (p less than 0.05) responses than depressive patients without PD, as well as increased phytohemagglutinin (PHA) (p less than 0.05) concanavalin A (ConA) (p less than 0.02) mitogen responses compared to their controls. These data suggest that panic disorder comorbidity significantly contributes to the variance of immunologic parameters in major depression and has to be carefully assessed within psychoimmunological studies of psychiatric patients with affective disorders.

A steady-state model is here developed as a framework for the analysis of blood concentrations of clomipramine, obtained during routine drug monitoring. A model is proposed to account for its major metabolic pathways, hydroxylation and demethylation, including first-pass effect. Impaired hydroxylation capacity is shown to lead to a dramatic increase in the concentration of demethyl-clomipramine, with a concomitant moderate increase in that of the parent drug. Deficient demethylation capacity is associated with a reduced ratio of demethyl metabolite to parent drug. A nomogram is provided to allow easy determination of hydroxylation and demethylation capacities from routinely measured blood concentrations. Data from 150 patients are analysed in order to identify interindividual variability factors. Average pseudo-clearances, calculated from trough blood concentrations at steady-state, are 17 L/h for hydroxylation, 23 L/h for demethylation and 40 L/h for elimination of hydroxylated metabolites. Maximum to minimum ratios are 8, 27 and 11, respectively. The metabolising capacity through either process significantly decreases with increasing age, clearance estimates being 40 to 50% lower for patients 75 years or older than for those 40 years or younger. Tobacco smoking and chronic alcohol consumption induce and reduce the demethylation clearance, respectively. Inhibition of hydroxylation in the presence of phenothiazine comedication is also shown. Finally, small but significant differences according to sex are observed. Potential implications of the proposed model-based approach include adaptation of the dosage regimen to individual characteristics at the very beginning of antidepressant therapy, and early detection of patients with impaired metabolising capacities.

The psychological and environmental factors involved in cardiovascular psychosomatic disorders are reviewed. Attention to these factors makes it possible not only to suggest preventive measures, but also to supplement the usual treatment with educational, dietetic and hygienic measures which will help to facilitate rehabilitation.

In the light of present knowledge the author examines the courses which psychiatry of the future could follow. In the fields concerning secondary or tertiary prevention it seems probable that psychiatry of the future is situated in a line of continuity in relation to psychiatry of the present, while affirming and complementing it. On the other hand, primary prevention still requires to be found, the operational models of the past and present being manifestly inadequate.

This is a preliminary study focusing on a 2 years follow-up of 78 patients addressed to psychiatric hospitalization and psychodynamically oriented crisis intervention. Relationship between psychopathological, clinical and interactional profile at first medical interview and clinical/social assessment at 1 and 2 years follow-up were studied, indicating different predictors for long-term treatment (DSM III R diagnosis and psychotic symptoms scores) and global improvement (age and sex) as well as poorer outcome for social functioning than for symptomatic measures. Comment is also provided on the observed high concordance between clinical predictions at crisis treatment completion and research staff assessments at 1 and 2 years follow-up. The evaluated crisis intervention model was found to provide a valuable setting to structure acute psychiatric episode treatment and long-term care, even though transition from clinical recovery to effective social-interpersonal reinvestments was observed to raise problems in the addressed psychiatric population.

A multitude of psychotherapic methods are proposed to the patients and their demand for psychotherapy is steadily increasing. The reasons of this phenomena are analyzed by the authors. On the basis of their different conceptual background and their ends, the psychotherapies are divided in six groups. The criteria by which the choice of a method is made as well as this of different possible associations are discussed. The assessment of efficacy is considered. The social implications and future of the different psychotherapic methods are screened.

The problems encountered during the longterm treatment of psychotic patients with neuroleptics are illustrated by six typical case reports. A group of patients who had had a new acute episode despite seemingly adequate treatment were selected. In these six cases it was demonstrated that the neuroleptics dosage was inappropriate, being either too high or too low as judged from the plasma concentrations. Ways of improving the adequacy of the treatment of psychotic patients with neuroleptics are discussed.

The concept of crisis is defined from the point of view of the actual practice and is compared with the concepts of illness, of acute states and emergency psychiatry. The crisis intervention means of the psychiatric sector in Geneva are described as well as their place in the general organisation of the psychiatric care.

In carcinoid syndrome, calcitonin administration proved to have an effective action in reducing symptomatology. During the perioperative period, treatment with somatostatin, thanks to the ease of administration of the drug and the reductive action of gastroenteric secretion, demonstrated its usefulness in countering the action of serotonin. In the present case, the data reported in the most recent literature on the use of the two drugs in the carcinoid syndrome are confirmed.

For more than two decades, a number of experimental findings are raising an increasing interest and evidence of S.N.C. regulatory function in immune response modulation. By this paper, we provide a large review of major recent studies aimed to investigate immune response, depression and stress conditions relationships. Assessment methods and study design issues are also discussed by special reference to the major psychiatric and psychosomatic interest of the demonstrated psychoneuroendocrine pathways of T-Lymphocytes response modulation.

The clinical classification of depressive states has undergone considerable modification in the past few years. More particularly, the various clinical forms described earlier in relation to age or dubious etiological hypotheses have been reorganized within the framework of general categories of depression established according to clinical criteria. This development has been largely due to the work accomplished by the American Psychiatric Association Task Force and its Diagnostic and Statistical Manual of Mental Disorders, which has become a standard reference work worldwide. With its precise criteria, this classification enables clinicians to adjust therapeutic indications more readily to each particular case. Monotherapy is the rule of thumb for the pharmacological treatment of depression, particularly in the elderly. Combination of medications in the treatment of agitated or melancholic depressive states must be limited to situations in which it is absolutely necessary, and in such cases it is even more important to monitor blood levels than in monotherapy. When there is a significant psychotic component to major depression (hallucinations, delusions), it is advisable to undertake specific antipsychotic treatment before initiating antidepressant medication. In the majority of cases it is possible to treat depressive states in the elderly by appropriate selection of both medication and dosage, and by careful clinical attention to the patients' physical and psychological well-being.