Santiago Vallasciani

Transitional cell carcinoma of the bladder in children and adolescents: Six-case series and review of the literature *

OBJECTIVE Lower urinary tract tumours are uncommon in paediatrics. Transitional cell carcinoma of the bladder (TCCB) is rarely found in the first two decades of life and is exceptional under 10 years of age. The present series aimed to expand the number of reported cases in the literature. PATIENTS AND METHODS In 1984-2007, six patients (four male, two female), aged 6, 9, 12, 13, 14 and 17 years, were treated at our centre. Clinical presentation was macroscopic haematuria in five and pyelonephritis in one. Physical examination, laboratory analysis, ultrasound and cystoscopy were performed before surgical treatment in all patients. Follow up was by clinical and ultrasound assessment. RESULTS Neither physical examination nor laboratory analysis revealed any significant abnormalities, but ultrasound showed exophytic intravesical lesions. Surgical resection was performed endoscopically. Histological studies showed grade I TCCB in all cases. The immediate postoperative period was uneventful and long-term follow up did not reveal recurrence. CONCLUSION Despite its low incidence in children, TCCB must be suspected in the event of macroscopic haematuria. Ultrasound followed by cystoscopy are the ideal diagnostic tools for visualization of these tumours. Endoscopic resection proved effective in all the present cases. Follow up must be clinical with periodic ultrasound evaluation. Urine cytologic examination is ineffective. Periodic cystoscopy is indicated only in cases of clinical or ultrasonographic suspicion of recurrence.

Failed hypospadias in paediatric patients

Failed hypospadias refers to any hypospadias repair that leads to complications or causes patient dissatisfaction. The complication rate after hypospadias repairs ranges from 5–70%, but the actual incidence of failed hypospadias is unknown as complications can become apparent many years after surgery and series with lifelong follow-up data do not exist. Moreover, little is known about uncomplicated repairs that fail in terms of patient satisfaction. Risk factors for complications include factors related to the hypospadias (severity of the condition and characteristics of the urethral plate), the patient (age at surgery, endocrine environment, and wound healing impairment), the surgeon (technique selection and surgeon expertise), and the procedure (technical details and postoperative management). The most important factors for preventing complications are surgeon expertise (number of cases treated per year), interposition of a barrier layer between the urethroplasty and the skin, and postoperative urinary drainage. Major complications associated with failed hypospadias include residual curvature, healing complications (preputial dehiscence, glans dehiscence, fistula formation, and urethral breakdown), urethral obstruction (meatal stenosis, urethral stricture, and functional obstruction), urethral diverticula, hairy urethra, and penile skin deficiency.

Snodgrass urethroplasty: grafting the incised plate--10 years later.

PURPOSE We report our retrospective, nonrandomized, single center experience with modified tubularized incised urethral plate repair, consisting of grafting the incised urethral plate before tubularization, as first introduced 10 years ago. Indications, technical points and results are described. MATERIALS AND METHODS From 1997 to 2007 at our unit 1,095 cases of hypospadias were treated, including 75% primary and 25% repeat cases. Of primary cases 18 (8%) of those suitable for tubularized incised urethral plate were instead selected for a grafted tubularized incised urethral plate. All 18 patients were characterized anatomically by a small glans, a flat urethral groove and a long spongiosum defect. Of repeat cases 83 were suitable for a tubularized incised urethral plate, of which 44 (53%) were selected for the modified procedure. Grafted tubularized incised urethral plate surgery consisted of an extended longitudinal incision of the urethral plate distal beyond the neomeatal line associated with scar excision in repeat cases. The resulting urethral plate defect was then lined with a graft. RESULTS Mean followup was 36 months (range 4 to 122). Complications were noted in 8 repeat cases (13% overall), representing 18% of this subgroup. CONCLUSIONS Case selection is a crucial factor that influences the quality of tubularized incised urethral plate results. However, in most repeat cases scarring may lead to an increased complication rate after tubularized incised urethral plate surgery. The grafted modification has the advantage of extending indications for the tubularized incised urethral plate to cases in which another surgical procedure would be necessary. To our knowledge we present the first series of primary and repeat cases.

A New Suture Material for Hypospadias Surgery: A Comparative Study

PURPOSE We compared the results of hypospadias repair using polyglytone versus polydioxanone to evaluate the potential benefit of using a suture with a rapid absorption time. MATERIALS AND METHODS A total of 100 patients 8 to 24 months old affected by distal isolated penile hypospadias were considered for this study. Patients were randomized and assigned to 2 different groups according to the suture material used during the surgical procedure (tubularized incised plate repair with or without preputial reconstruction). Polyglytone was used in group A and polydioxanone was used in group B. All patients were evaluated at 4 intervals (1 week, 1 month, 6 months and 2 years postoperatively). Persistence of sutures on penile skin, urethral fistulas, skin dehiscence, infection and skin tracks were recorded. Statistical analysis was performed using chi-square test. RESULTS Followup data documented the absence of significant differences in terms of urethral fistula rate, skin dehiscence and acute skin infection. Persistence of sutures and multiple skin tracks at long-term followup were significantly greater in patients in group B. CONCLUSIONS Both sutures are adequate for hypospadias surgery in small children. The use of a rapid absorption monofilament may allow much more rapid disappearance of the skin sutures. In the long term this outcome means almost complete absence of suture tracks. No statistically significant difference in terms of urethrocutaneous fistula was observed, suggesting that the tensile strength of polyglytone is adequate.

Environmental, parental and gestational factors that influence the occurrence of hypospadias in male patients

OBJECTIVE Hypospadias is a congenital defect, which affects normal development of the male urogenital external tract. In this malformation, the urethral orifice of the penis is positioned ventrally, thus interfering with normal urination and creating, in some adults, problems during sexual intercourse. Heritability of hypospadias has been shown in some reports, and the abnormality has been associated with the presence of mutations in one of the genes involved in urogenital development. However, even for patients who were born in families with a higher incidence rate of this defect, no evident genetic alteration could be identified in known genes, indicating that the list of loci involved is still incomplete. To further complicate matters, recent reports also underline that epigenetic changes, without any identifiable gene sequence mutation, may be involved in gene function impairment. Therefore, the inheritance of most hypospadias cases is not evident, suggesting that the genetic background is not the only cause of this malformation; indeed, the majority of hypospadias cases are classified as sporadic and idiopathic. MATERIALS AND METHODS Evidence has accumulated highlighting the role of the environment and of its relationships with the genome in the etiology of this abnormality. In particular, the interaction between some chemicals, which are able to mimic endogenous molecules such as sexual hormones--for this reason called endocrine disrupting compounds (EDC)--and specific receptors has been extensively investigated during the pregnancy. Additionally, several articles have shown that parental and gestational factors play a significant role too. Indeed, physiological alterations, such as body weight of the mother and/or of the newborn, mothers diabetes, impaired father fertility, and exposure of one parent to job-related pollutants, show in many cases a direct correlation with hypospadias incidence. The overall prevalence of this condition has been studied in many countries, suggesting that at least in some periods and/or in specific populations there are detectable fluctuations, probably mirroring the different natural environments. However, many articles present data that do not agree with these findings and, consequently, most causes of hypospadias are still highly debated. RESULTS In this review, we summarize the developmental steps involved in urogenital tract formation, with a particular emphasis on the genes that most frequently are associated with this condition, or that are subject to environmental stress, or that may be the targets of hormone-like, exogenous molecules. Then, we make an overview of the identified factors able to impair the function of important genes, even in the absence of their mutations, including those for which contradictory reports have been published. Finally, we propose an explanation of sporadic cases of hypospadias that reconciles these contradictions and suggest some steps for moving forward in the research focused on this condition. CONCLUSION We hypothesize that most patients develop hypospadias because of gene-environment interactions acting on polymorphic genes that, in the absence of environmental stimuli, would otherwise cause no developmental anomaly during urogenital development.

Observational retrospective study on acquired megalourethra after primary proximal hypospadias repair and its recurrence after tapering.

INTRODUCTION Acquired megalourethra (AMU) after repair of proximal hypospadias can be a serious complication. An observational retrospective study of its incidence among different types of repair was performed. MATERIALS AND METHODS Clinical charts of patients operated on for proximal hypospadias were reviewed. INCLUSION CRITERIA all primary hypospadias operated in 1991-2004, with the meatus positioned in proximal penile, scrotal or perineal position. RESULTS Of 770 hypospadias cases treated, 130 (16%) were proximal. Seventy-two patients (55%) were treated using preputial flaps: 36 with a tubularized preputial island flap (TIF) and 36 an onlay island flap (OIF). Fifty-eight patients (45%) underwent staged repairs: Belt-Fuquà (BF) in 18 and Bracka procedure in 40 cases. After a mean follow up of 16 years (range 6-19) the overall incidence of complications for each technique was: TIF 36%; OIF 33%; BF 25%; two-stage Bracka 7.5%. The most common complication encountered was neo-urethral fistula. AMU occurred in only 5 cases, none with associated distal urethral stenosis, all in the TIF and OIF groups, and all successfully treated by reduction re-do urethroplasty. CONCLUSION A very small number of the patients operated using preputial island flaps techniques developed AMU. None of the staged repairs developed AMU, and this is the preferred choice in proximal hypospadias when the urethral plate requires division and/or substitution. All cases of AMU resolved after urethral tapering.

Simplifying the surgical approach to glanular and coronal hypospadias: Longitudinal urethral incision and glanuloplasty

OBJECTIVE Meatal advancement with glanuloplasty incorporated (MAGPI) is an appropriate approach for most glanular and coronal hypospadias. The very low incidence of complications with this technique (i.e., fistulas, meatal regression and stenosis) makes MAGPI very competitive if compared with other approaches proposed for similar anatomical defects. In certain cases, however, the MAGPI approach has led to an unsatisfactory neo meatus; instead of a natural slit-like appearance, the meatus can look too rounded and puckered. METHODS The last 84 patients referred to our unit with indications suitable for MAGPI (mean age 39 months) were operated on using a novel approach: the glanuloplasty was associated with a simple deep urethral plate incision, extending along the urethral channel, and left unsutured. RESULTS At minimum follow up of 12 months two meatal regressions to mid glans were recorded. No meatal stenosis was seen in this series. CONCLUSION This approach allowed us to achieve a conical glans with a natural looking meatus, avoiding urethral sutures.

Comment on “Complete Androgen Insensitivity Syndrome: Optimizing Diagnosis and Management”

We read with interest the paper of Pizzo et al. [1], confirming that adolescence is a key period for the diagnosis of 46,XY disorders of sex development (DSD) [2]. However, in our opinion, some points should be better addressed. Among these, we have the following. The authors stated that the reported girl showed “normal intellectual function,” but this information had little relevance because mental function is not impaired in females with 46,XY DSD, reaching adolescence without any clinical suspicions. Indeed, this statement might be stigmatizing for these persons. The statement that this adolescent was affected by hypergonadotropic hypogonadism (HH) is correct, according to the high LH and FSH values shown in Table 1 [1]. Very low levels of both 17β-estradiol and testosterone were also shown [1]. This endocrine pattern is not typical of late adolescent and young adult females with complete androgen insensitivity syndrome (CAIS) and intact testes. On the contrary, these persons show high/normal levels of both 17β-estradiol (for a person with a 46,XY karyotype) and testosterone [3–5]. In addition, adolescent/young adult women with CAIS did not show HH: LH is in high normal range or slightly elevated (due to the androgen resistance at central level), but FSH is in normal range (due to unaffected inhibin secretion from Sertoli cells) [3–5]. In addition, SHBG was reported within adult male range by Pizzo et al. [1], suggesting a normal sensitivity to the low levels of androgens in this girl [6]. Indeed, SHBG is within normal female range in women with CAIS, due to peripheral androgen resistance [5]. All these findings show poor agreement with the affirmed diagnosis of CAIS [1]. The clinical phenotype of the reported girl did not match with the phenotype of adolescents with CAIS; in fact, the latter shows normal breast development related to the relatively high normal estrogen levels and unopposed androgen action [3, 4, 7] and does not show hypotrophic breasts [1]. It is quite surprising that hormonal replacement therapy was started before any diagnosis was established. Histological findings do not completely agree with the diagnosis of CAIS, in particular the absence of Leydig cells, which are abundant in adolescent females with CAIS and sometimes formed aggregates up to 2 mm in diameter [8, 9]. 46,XY karyotype, female phenotype, and absence of mullerian derivatives may be present in several 46,XY DSD; they should be excluded before diagnosis of CAIS by optimal clinical, endocrine, and genetic investigations [10]. For example, the testosterone/Δ4-androstenedione ratio in the adolescent reported by Pizzo et al. [1] is very low (0.13; normal values >0.8 [11]). Thus, diagnoses of 17β-hydroxysteroid-dehydrogenase deficiency type 3 or 46,XY gonadal dysgenesis [11, 12] must be considered in the diagnostic process. Risk of gonadal cancer largely varies among 46,XY DSD. For example, in CAIS is very low at least during the first two decades of life [13–15]. Thus, delayed gonadal removal can be recommended to permit both full sexual development [15] and better bone health [16]. If diagnosis of CAIS is certain, surgery can be postponed—at least until the legal age at which the propositus can participate in decision making [1, 15, 17–19]. We are concerned and in complete disagreement with the decision to perform gonadectomy without full disclosure and assent of the adolescent [17–19]. In conclusion, some findings are poorly consistent with a diagnosis of CAIS, which should be confirmed by molecular analysis of androgen receptor gene [2, 7]. In our experience, more than 25% of the females referred to our departments with clinical/endocrine diagnosis of CAIS did not have this diagnosis confirmed by genetic analysis [20]. Clinical approach should be changed according to the new guidelines for management of persons with 46,XY DSD and directly involving the girl in the decision process [2, 18, 21]. We also stress that multidisciplinary team evaluation in tertiary centers with documented experience in this field must be guaranteed to each person with 46,XY DSD for optimal holistic management [21], especially before performing irreversible surgical procedures.

Scafoid megalourethra-a reliable surgical approach

Congenital megalourethra is a very rare malformation, which has 2 anatomical variants, scafoid and fusiform. The etiology of this malformation is still a matter of discussion. A surgical approach is proposed here, which has been successfully used in the case of a boy affected by scafoid megalourethra.

Hypospadias repair: The ongoing challenge

Hypospadias surgery has had a continuous evolution along time. The wide spectrum of hypospadias anomalies and the many options available for hypospadias reconstruction continue to challenge the urological, pediatric surgical, and plastic surgical skills of the pediatric urologist. In the preoperative assessment, the use of hormone adjuvant therapy and the timing for surgery are analyzed. Although new information from evidence-based outcomes has made us look more critically at our decision-making process for choice of repairs, controversies in nearly every aspect of hypospadias management still exist. It is the aim of this chapter to review the areas of ongoing controversy, to provide a simple and reliable algorithm for choice of procedure that we have found useful, and to create a keener awareness about the need to base the choice of technique on intraoperative anatomical findings rather than on the preoperative location of the meatus. Finally, the need of long-term follow-up into the postadolescent years and the importance of outcomes studies from the patient’s point of view are emphasized.