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Purpose: Closure of bladder exstrophy is one of the most complex reconstructive procedures. Basic concepts of these operations, as well as their subtle nuances, require years of experience. However, the volume of these cases is low. The authors describe the experience of a junior surgeon learning the details of exstrophy closure during fellowship and her initial career., Methods: Fellows graduating in 2014 were surveyed for their exstrophy experience during fellowship and the following four years. Operative logs of the junior faculty member were reviewed during the same time. Average operative times were calculated for each year., Results: Seventeen of the 25 fellows responded to the survey. Eight surgeons did one or fewer exstrophy closures during fellowship; 14 did one or fewer closures as an attending. The junior faculty member assisted in 18 closures as a fellow and 48 exstrophy closures during the next four years. Average operative time decreased from 485 to 309 min from attendingship year one to four., Conclusions: There are subtle details inside and outside of the operating room required to ensure a successful outcome in this important step of exstrophy reconstruction. Working alongside senior colleagues is essential to allow the junior surgeon to ascend this ladder of mastering exstrophy closure., Type of Study: Diagnostic., Level of Evidence: V., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: A successful abdominal wall and bladder closure is critical in the management of cloacal exstrophy (CE). This study examines closure outcomes and practices over the last 4 decades at the authors' institution. Beginning in 1995, the authors' institution standardized CE closure and management with the Dual-Staged Pathway (DSP). The DSP consists of a staged bladder closure, a staged or concurrent osteotomy, and postoperative immobilization with external fixation. The authors hypothesize that the DSP has provided better outcomes in CE closures., Methods: A prospective database of 1332 Exstrophy-Epispadias Complex (EEC) patients was reviewed for CE patients closed between 1975 and 2015. The DSP consists of a staged osteotomy and a staged bladder closure in CE patients with a diastasis greater than 4 cm. To evaluate the DSP, outcomes of closure at the authors' institution were compared between two equal, twenty-year periods before and after its implementation. Data on timing of closure, postoperative management, surgical complications, and outcomes were collected., Results: There are 142 CE patients in the database. In this study, 49 CE patients with 50 closures met inclusion criteria. The overall success rate of closures from 1975 to 1994 was 88% (14 of 16), while the success rate of the DSP was 100% (n = 34), p = 0.098. Twenty-two (65%) primary and 12 (35%) secondary closures were performed using the DSP. Overall complication rates of the DSP remained similar to previous closures, (29% vs 19%, p = 0.508). Since incorporation of the DSP, patients referred for closure have generally had a larger preclosure diastasis (7.2 cm vs 5.1 cm, p = 0.011)., Conclusion: The standardized DSP closure has proven successful in 34 primary and reoperative cloacal closures in the past 20 years. With this approach, the authors feel that the DSP offers greater patient safety and better outcomes., Level of Evidence: Level III, retrospective comparative study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the factors affecting primary bladder closure in cloacal exstrophy (CE). A successful primary closure is important for optimizing reconstructive outcomes, and it is a critical first-step in the reconstruction of CE. The authors' hypothesize that a smaller diastasis and use of an osteotomy are independent predictors of a successful closure., Methods: A prospectively maintained database of 1332 exstrophy-epispadias complex (EEC) patients was reviewed for CE patients closed between 1975 and 2015. Univariate and multivariable analyses were performed to identify significant factors associated with CE primary bladder closure., Results: Of 143 CE patients identified, 99 patients met inclusion criteria. Median follow-up time was 8.82 [IQR 5.43-14.26] years. In the multivariable model, the odds of having a successful closure are about 4 times greater for the staged cloacal approach compared to the 1-stage approach (OR, 3.7; 95% CI 1.2-11.5; p-value = 0.023). Also, having an osteotomy increases the chance of a successful closure by almost six-fold (OR, 5.8; 95% CI 1.7-19.6; p-value = 0.004)., Conclusions: Using the staged approach with a pelvic osteotomy is paramount to a successful primary closure in CE. The authors strongly recommend using the staged approach and osteotomy as these factors independently increase the chance for a successful primary bladder closure., Study Type: Therapeutic study., Level of Evidence: Level III, Retrospective comparative study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Cloacal exstrophy is a rare and complex congenital anomaly requiring coordination among multiple pediatric subspecialties. There is currently no consensus regarding the fate and function of the hindgut, which plays an integral role in patients' long-term gastrointestinal health and genitourinary reconstruction., Methods: A retrospective chart review was performed evaluating 77 patients with cloacal exstrophy treated during the previous 44 years at our institution., Results: Seventy-seven patients with cloacal exstrophy were treated between 1965 and 2008. Sixty-five were white, 6 were African American, 3 were Asian, and 3 were Hispanic. Genotypes included 44 XY, 32 XX, and 1 XYY. Fifty-one were reared as females and 26 as males. The hindgut length was 2 to 5 cm in 11 patients, 6 to 10 cm in 18 patients, 11 to 15 cm in 6 patients, 16 to 20 cm in 7 patients, and greater than 20 cm in 2 patients. The hindgut length was unknown in 33 patients. Forty-seven patients had tubularization of the cecal plate with an end colostomy, and 30 patients had an ileostomy placed for bowel diversion purposes. Four patients had short gut syndrome. Thirty-one patients had genitourinary reconstruction, 12 using small bowel and 19 using colon. Eight patients had hindgut pull-through procedures., Conclusion: Gastrointestinal ramifications of the cloacal exstrophy complex include the occurrence of short gut syndrome and significant fluid and electrolyte derangements in patients receiving an ileostomy for initial intestinal management. This has caused a paradigm shift of initial intestinal management to tubularization of the cecal plate with end colostomy placement. This shift has eliminated the occurrence of short gut syndrome and enabled patients to be candidates for intestinal pull-through procedure if these patients are able to form solid stool, have a reasonable degree of pelvic neuromuscular development, and are able to comply with a bowel management program., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background/purpose: Hypoxia-inducible factor 1 alpha (HIF-1alpha) is an important transcriptional factor responsible for regulating expression of the angiogenic cytokine, vascular endothelial growth factor (VEGF). Little information is available regarding factors involved in the hypoxic cascade, such as HIF or VEGF in Wilms' tumor. We concomitantly evaluate the expression of HIF-1alpha and VEGF in ex vivo human Wilms' tumor specimens., Methods: Immunohistochemical analysis (IHC) utilizing a monoclonal human anti-HIF-1alpha or a polyclonal anti-VEGF antibody was performed on ex vivo specimens of Wilms' tumor (n = 18). Predominant tumor histologic subtype was divided equally between epithelial (n = 6), blastemal (n = 6), and mixed (n = 6). Specimens were scored on a predetermined scale for distribution (percent positive cells) and intensity of HIF-1alpha/VEGF expression within areas of tumor., Results: IHC analysis found that HIF-1alpha and VEGF were expressed in all Wilms' tumor specimens. Strong nuclear staining for HIF-1alpha was seen in all samples evaluated, (n = 18), mean score 2.7 (>50% cells exhibiting nuclear HIF-1alpha expression). Cytoplasmic staining for HIF-1alpha also was seen in 15 of 18 samples (83%). Distribution of VEGF was equivalent between blastemal and epthelial components, mean score 2.23 versus 2.35., Conclusions: HIF-1alpha and one of its regulatory end-products, the angiogenic cytokine VEGF, are simultaneously expressed in human Wilms' tumor. In Wilms' tumor, intratumoral hypoxia may stimulate tumor conversion to the angiogenic phenotype and incite production of VEGF. Strategies targeting the hypoxic cascade ultimately may prove efficacious against Wilms' tumor.

The outlook for children with Wilms' tumor has markedly improved with the use of multimodal therapy, and survival currently exceed 85%. Current trends have been to use less intense therapy for children whose tumors have favorable histology (FH). By decreasing the amount of therapy given to patients whose conditions have an excellent chance of responding, the need for accurate criteria to separate high-risk and low-risk groups becomes imperative. Nuclear morphometric techniques have been developed and extensively tested in the author's laboratory. Preliminary studies of FH Wilms' tumors demonstrated the applicability of this technique. Herein, the authors present a retrospective study of 108 patients with FH tumors, with a mean follow-up period of 1,994 +/- 107 days (66 months) for those whose tumors did respond to therapy, and 686 +/- 61 days (23 months) for those whose tumors did not respond. The univariate predictors were age (P = .02), the skewness of nuclear roundness factor (SNRF) (P = .009), and the mean of the lower five values for nuclear ellipticity, measured by the feret diameter method (L5EFD) (P = .01). A multivariate analysis combining all three variables better separated the two groups (P = .00016). A probability function curve was constructed to predict poor prognosis. Kaplan-Meier actuarial survival analysis was used to predict disease-free survival as clinical progression, and separated the two groups (P = .0004, Wilcoxon-Gehan statistic). These results suggest that nuclear morphometry is useful in the initial assessment of patients with Wilms' tumor.

The functional effects of bladder outlet obstruction in the developing urinary tract are well recognized in patients born with posterior urethral valves, in whom a spectrum of bladder dysfunction has been described. To better understand the changes occurring in the partially obstructed developing lower urinary tract, a fetal lamb model of partial urethral obstruction was developed. Fetal lambs at 90 days' gestation underwent surgical placement of a silver ring (ex utero) at the level of the proximal bladder neck, with concomitant ligation of the urachus. Control animals underwent urethral ligation only. The lambs were then allowed to go through normal gestation, and ewes were delivered spontaneously. The animals were studied between 2 and 7 days after birth. The postmortem examination showed that the ring was just distal to the bladder neck, around the proximal urethra. This resulted in gradual, partial occlusion of the urethra. Bladder weights, bladder wall thickness, and bladder capacity were significantly increased in the partially obstructed animals as compared with the controls. There was little or no upper tract dilatation in the obstructed group. This animal model, the first to produce gradual outflow obstruction in the fetus, provides a reproducible model of partial urethral obstruction. The model can be used to assay the biochemical and physiological changes found in the developing urinary tract of fetal lambs submitted to intravesical obstruction.

The current trend toward minimizing treatment morbidity in children with yolk sac carcinomas is laudable. As most children will present with stage I disease and be cured by radical orchiectomy alone, careful surveillance is adequate with the knowledge that effective chemotherapy is available should tumor recur. All new yolk sac carcinomas in children should be reported to the Prepubertal Testicular Tumor Registry and should ideally be treated at institutions that have experience with surveillance protocols and pediatric oncology. In this way, prospective studies on treatment options can be initiated, and management controversies may ultimately be ironed out. In particular, more information is needed on patients more than 2 years old, as the literature to date is contradictory regarding the prognosis for these patients and the need for adjuvant therapy when the older child presents with stage I disease.

The Mitrofanoff procedure (appendicovesicostomy and creation of a low-pressure urinary reservoir) is a technically innovative way of providing patients with a form of continent diversion. The principles behind the procedure are use of a narrow, supple conduit, which, when brought out to the skin as a catheterizable stoma, will provide continence by acting as a flap-valve and attachment of the conduit to a low-pressure urine storage reservoir by an antireflux mechanism. Upper-tract contamination is prevented by an antireflux mechanism at the level of the distal ureters. Strict attention to every step of the procedure is mandatory. Emptying of the reservoir is achieved by clean intermittent catheterization. Long-term results are good in a majority of patients with careful selection and education. Life-long follow-up of patients is mandatory.

Early successful closure, careful management of the incontinent interval, and a good technical bladder neck reconstruction can result in a patient with normal control and upper tracts. However, failure at any step of a staged functional reconstruction does not doom the child to failure in the eventual achievement of the above goals. Nonetheless, taking care of the exstrophy failure is still a formidable task for the reconstructive surgeon. Currently, surgical techniques exist that can salvage the vast majority of these children. Careful evaluation of the failure, waiting an appropriate interval before further reconstructive surgery is attempted, and dedication to the patient most often can produce a successful result.

The combination of biological response modifiers with cytotoxic drugs has proven to be synergistic in several tumor systems. Recombinant human tumor necrosis factor (rhTNF) has been shown to enhance the antitumor efficacy of etoposide (VP-16) in the treatment of C1300 murine neuroblastoma. However, after completion of therapy, tumor growth resumes and results in subsequent death. In an effort to assess the impact of combining surgery with rhTNF/VP-16 therapy, A/J mice bearing the C1300 murine neuroblastoma were treated within adjuvant or neoadjuvant protocols. Adjuvant-treated animals had a longer interval to disease recurrence (P = .01) and smaller average recurrent tumor volumes postexcision (P less than .05) compared with surgical controls. Histological evidence of tumor recurrence and liver metastases was seen in both adjuvant-treated and surgical control animals. Neoadjuvant-treated animals had a longer interval to disease recurrence (P = .03) and smaller average recurrent tumor volumes up to 14 days postexcision (P less than .02) compared with surgical controls. In addition, 30% of the neoadjuvant-treated animals had no microscopic evidence of disease recurrence, and only 14% had histological evidence of liver metastases. The surgical controls in the neoadjuvant experiment all had histological evidence of disease recurrence and liver metastases. Thus, the combination of surgery and rhTNF/VP-16 in the adjuvant or neoadjuvant setting appears to significantly delay the progression of C1300 murine neuroblastoma. Furthermore, administering chemoimmunotherapy prior to surgical excision in a neoadjuvant manner appears to be most beneficial as regards prevention of local disease recurrence and distant metastases.

Ureteral reimplantation is a procedure commonly performed by both urologists and pediatric surgeons. Although the vast majority are successful, there are some patients in whom technical considerations or bladder/ureteral abnormalities militate against success. We review our experience in 19 patients with multiple failed reimplants. The reasons for their failure, the investigations required to document such, and the management of these difficult problems will be discussed. In our hands, 95% of these patients ultimately became reflux-free and nonobstructed.