Kristina Suson

Gastrointestinal ramifications of the cloacal exstrophy complex: a 44-year experience

PURPOSEnCloacal 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.nnnMETHODSnA retrospective chart review was performed evaluating 77 patients with cloacal exstrophy treated during the previous 44 years at our institution.nnnRESULTSnSeventy-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.nnnCONCLUSIONnGastrointestinal 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.

Evaluation of children with urinary tract infection – Impact of the 2011 AAP guidelines on the diagnosis of vesicoureteral reflux using a historical series ☆

OBJECTIVEnTo clarify the impact of the updated American Academy of Pediatrics guidelines for the evaluation of children presenting with initial febrile urinary tract infection (UTI) on the diagnosis of vesicoureteral reflux (VUR) in children with normal renal sonograms.nnnMATERIALS AND METHODSnChildren with VUR followed between 2002 and 2004 were evaluated using criteria specified in the AAP guidelines. A total of 49 children (42 girls) who were 2-24 months of age at diagnosis of VUR made following initial febrile UTI were included.nnnRESULTSn40.8% of ultrasounds were abnormal. While children with abnormal ultrasounds were more likely to have scintigraphic evidence of renal damage than children with normal ultrasounds (50% vs 17%, p = 0.026), one third of the children with abnormal renal scans had normal RBUS. There was no statistically significant difference in diagnosis of grade 3 or higher VUR between groups (p = 0.136).nnnCONCLUSIONSnMost children in this series would not have been diagnosed with VUR after initial febrile UTI. More worrisome, 17.2% of children with normal ultrasound had renal injury identified on renal scanning, and 62.1% had grade 3 or higher VUR. These findings reinforce concerns that the new guidelines may miss or delay diagnosis of clinically significant VUR.

Bony abnormalities in classic bladder exstrophy: The urologist’s perspective

INTRODUCTIONnAs the primary practitioner managing patients with classic bladder exstrophy (CBE), it is incumbent upon the pediatric urologist to understand the associated orthopedic anomalies and their management.nnnMETHODSnA Pubmed search was performed with the keyword exstrophy. Resulting literature pertaining to orthopedics and published references were reviewed.nnnRESULTSnAnatomic changes to the bony pelvis include outward rotation, acetabular retroversion with compensatory femoral anteversion, anterior pubic shortening, and pubic diastasis. Imaging options have improved, which impacts surgical planning. Surgical approach, including type of osteotomy and method of pubic approximation, is evolving. Most centers employ immobilization after surgery, with external fixation, Bryants traction, Bucks traction, and spica casting being the most common methods. Orthopedic complications range from minor pin-site infections to neurologic and vascular compromise. Most experts agree osteotomy aids bladder closure beyond 72 h of life, but effect on continence remains controversial. Although no significant orthopedic benefit has been expounded, it may be too early to appreciate improvement in frequency or severity of osteoarthritis or hip dysplasia.nnnCONCLUSIONnWhile orthopedic surgeons remain vital to managing exstrophy patients, knowledge of the anatomy, imaging, surgical approaches, and immobilization enable effective communication with parents and other physicians, improving care for these complicated patients.

Juvenile Xanthogranuloma Presenting as a Testicular Mass in Infancy: A Clinical and Pathologic Study of Three Cases

Juvenile xanthogranulomas (JXG) is a histiocytic disorder whose most common clinical presentation is a solitary cutaneous nodule in a child under 5 years of age, but it has come to be recognized that solitary extracutaneous lesions may present in a number of sites, including the soft tissues and various organs. Involvement of the genitourinary tract has been documented in children with multifocal or systemic JXG. The current report describes our experience with 3 cases of JXG presenting as a solitary mass in the testicle of infants between 2.5 and 13 months without manifestations of JXG elsewhere. The masses were intratesticular and had an infiltrative pattern of interstitial growth by mononuclear, histiocyte-like cells with replacement of seminiferous tubules and involvement of the epididymis whose pattern resembled leukemic and lymphomatous involvement of the testis. Because extracutaneous lesions of JXG may have few or no Touton giant cells, immunohistochemistry is an important adjunct to the histopathologic diagnosis. One of the previous 2 cases in the literature of JXG of the testis recurred after partial resection without an orchiectomy. Neither of the 2 youngest patients has experienced a local recurrence of JXG elsewhere in excess of 1 year since the original orchiectomy. The oldest patient, who was treated with partial orchiectomy, remains free of recurrence after 3 months of follow-up. Though uncommon, JXG joins several other distinctive neoplasms presenting in the infantile testis.

Neuro-Orthopedic Manifestations of the Omphalocele Exstrophy Imperforate Anus Spinal Defects Complex

PURPOSEnThe omphalocele-exstrophy-imperforate anus-spinal defects complex is a severe multisystem congenital defect. To comprehensively care for these patients one must appreciate the neurological and orthopedic impact on the overall health of the child.nnnMATERIALS AND METHODSnWe retrospectively reviewed the medical records of 73 children with omphalocele-exstrophy-imperforate anus-spinal defects who were treated at our institution, identifying neurological and orthopedic anomalies, ambulatory ability and voiding status.nnnRESULTSnNo neurological data were available on 5 patients. Of the remaining 68 patients 9 had no spinal anomaly, 57 had spina bifida, 1 had hemivertebrae and 1 had coccygeal hypoplasia. We further classified the 47 spina bifida cases as spina bifida occulta in 6, meningocele/lipomeningocele in 12, myelomeningocele/lipomyelomeningocele in 24 and sacral agenesis in 6. Of the patients with spina bifida 35 had cord tethering. Commonly identified orthopedic anomalies were vertebral malformation in 59 patients, scoliosis in 25, clubfoot in 14 and limb length discrepancy in 8. Ambulatory status in 62 patients of walking age revealed that 37 ambulated fully, 15 ambulated with devices, 2 ambulated minimally with devices and 8 were wheelchair bound. Continence data were available on 61 closed cases. Of these patients 26 were incontinent, including 3 with conduit diversion, 1 with ureterostomy and 1 with vesicostomy. A total of 35 patients were socially continent, of whom 30 catheterized via a continent abdominal stoma and 5 voided/catheterized via the urethra.nnnCONCLUSIONSnEarly evaluation for neurosurgical and orthopedic anomalies is vital in these children. Despite the high incidence of spinal pathology most patients ambulate without assistance. Few children with omphalocele-exstrophy-imperforate anus-spinal defects achieve continence via the urethra. Vigilant followup is necessary to identify potentially correctable conditions.

The Fate of the Complete Female Epispadias and Exstrophy Bladder—Is There a Difference?

PURPOSEnComplete female epispadias, which occurs much more rarely than classic bladder exstrophy in females, is thought to have a more benign clinical course. We hypothesized that patients with complete female epispadias are more likely to have a larger bladder capacity and achieve voiding continence than females with classic bladder exstrophy.nnnMATERIALS AND METHODSnAfter obtaining institutional review board approval, females with complete female epispadias or classic bladder exstrophy were identified from an institutionally approved prospective database. We retrospectively reviewed the charts of 22 patients with complete female epispadias and 23 with female classic bladder exstrophy, including 3 with delayed primary closure.nnnRESULTSnPatients with complete female epispadias presented later and underwent the first reconstructive procedure at an older age than patients with classic bladder exstrophy. Patients with complete female epispadias had lower initial and final age adjusted bladder capacity than those with classic bladder exstrophy but the bladder growth rate did not differ between the groups. When patients with complete female epispadias were stratified by age at initial reconstruction, there was no difference in final age adjusted bladder capacity or the bladder growth rate. There was also no statistical difference between the groups in the number of surgeries, continence rate from initial reconstruction, bladder neck reconstruction success or need for a continent stoma.nnnCONCLUSIONSnThis study suggests that females with classic bladder exstrophy who undergo successful primary closure have higher initial and final age adjusted bladder capacity than females with complete female epispadias but with a similar growth rate. This may reflect the creation of outlet resistance at a younger age than in those with complete female epispadias. However, no difference was identified between patients with complete female epispadias who initially underwent repair before vs after age 1 year. Patients with complete female epispadias undergo procedures to achieve continence that are similar to those in patients with classic bladder exstrophy.

Transforming Growth Factor-β1 Mediates Migration in Cultured Human Control and Exstrophy Bladder Smooth Muscle Cells

PURPOSEnTransforming growth factor-β1 regulates extracellular matrix composition, and impacts function and proliferation in multiple cell types, including bladder smooth muscle cells. In this study we evaluated the response to transforming growth factor-β1 in cultured exstrophy and control bladder smooth muscle cells.nnnMATERIALS AND METHODSnPrimary bladder smooth muscle cell cultures were established from patients with bladder exstrophy or vesicoureteral reflux. Smooth muscle specific α-actin and heavy chain myosin expression was determined using immunohistochemistry. Cell migration, intracellular calcium concentration and proliferation were determined after incubation for 24 to 48 hours in basal media, with or without transforming growth factor-β1 (0.001 to 3 nM) or transforming growth factor-β1 receptor inhibitor SB 431542 (10 μM).nnnRESULTSnCultured exstrophy and control smooth muscle cells stained positive for α-actin and heavy chain myosin. Exstrophy smooth muscle cells demonstrated increased migration compared to control smooth muscle cells at baseline (38% vs 20%, p = 0.01). Transforming growth factor-β1 increased control smooth muscle cell migration while SB 431542 decreased exstrophy smooth muscle cell migration. Control cells had a higher intracellular calcium concentration, which decreased significantly when exposed to SB 431542. Transforming growth factor-β1 did not cause significant changes in intracellular calcium concentration. Inhibition of transforming growth factor-β1 receptors decreased proliferation in exstrophy and control smooth muscle cells, but exogenous transforming growth factor-β1 did not impact proliferation.nnnCONCLUSIONSnOur results suggest that there are distinct differences in bladder smooth muscle cell function between control and exstrophy cases which persist in culture. Although resting intracellular calcium concentration was higher in control cells, proliferation rates were similar in both cell types, indicating that lower intracellular calcium concentration did not impact growth potential. In contrast, enhanced migration was observed in exstrophy cells, possibly due to excess transforming growth factor-β1 signaling, but seemingly independent of increases in intracellular calcium concentration.

Initial Characterization of Exstrophy Bladder Smooth Muscle Cells in Culture

PURPOSEnPrevious studies have suggested that exstrophic bladder smooth muscle cells grown in culture show contractility similar to that of normal bladder smooth muscle cells. Despite this similar contractility, other cellular characteristics may vary between exstrophic and normal bladder smooth muscle cells.nnnMATERIALS AND METHODSnPrimary cultures of bladder smooth muscle cells were established from patients with bladder exstrophy (14) and vesicoureteral reflux as a control (10). Expression of smooth muscle specific α-actin and heavy chain myosin was determined with immunohistochemistry. Response of smooth muscle cells to high potassium Krebs solution or acetylcholine (0.1 mM) was assessed using a calcium sensitive fluorescent dye. Intracellular calcium concentration was measured after 48 hours in basal media. Cell migration in basal media during 24 hours was determined using transwell assays. Baseline proliferation and response to 10% fetal bovine serum were assessed with bromodeoxyuridine incorporation assays.nnnRESULTSnMore than 95% of exstrophy and control smooth muscle cells stained positive for actin and myosin. Functional integrity was verified in each exstrophy and control cell line by response to high potassium Krebs solution or acetylcholine. The intracellular calcium concentration was lower in exstrophy smooth muscle cells than in control smooth muscle cells (71 vs 136 nM, p <0.001). More exstrophy cells migrated than control cells (37% vs 18%, p = 0.004). There was no statistically significant difference in proliferation between exstrophy and control smooth muscle cells in basal or growth media.nnnCONCLUSIONSnCultured exstrophy smooth muscle cells demonstrate some differences in baseline characteristics compared to control cells. Differences in migration and intracellular calcium may have implications for in vivo detrusor function and tissue engineering.

Complexities of Müllerian Anatomy in 46XX Cloacal Exstrophy Patients

STUDY OBJECTIVEnTo characterize Müllerian anatomy in 46,XX cloacal exstrophy patients.nnnDESIGNnRetrospective review of prospectively maintained, institutionally approved exstrophy-epispadias-cloacal exstrophy database.nnnSETTINGnTertiary care, high-volume exstrophy center (Division of Pediatric Urology, The Johns Hopkins Hospital, Baltimore, Maryland).nnnPARTICIPANTSnWe included 31 patients who were genetically female with cloacal exstrophy for whom records included detailed evaluation of Müllerian anatomy.nnnINTERVENTIONSnNone.nnnMAIN OUTCOME MEASURESnMüllerian structures, method of evaluation, management, and sexual activity.nnnRESULTSnOf our patients, 12.9% (3/31)xa0had no identified abnormalities. Vaginal anatomy was described for 30 patients; 3/30 had vaginal agenesis, 14/30 had a single vagina, and 13/30 had vaginal duplication. Of 14 patients with 1 vagina, 5 had atresia/hypoplasia, and 1 had a lateral displacement. One patient with 2 vaginas also had distal atresia. Of the cervices evaluated, 9/14 were duplicated (2/9 with a solitary vagina), and 19/27 of the uteri were duplicated (6/22 with 1 vagina, 1/22 with no vagina). Five patients required imaging to fully characterize their anatomy, and 7 patients had studies that failed to identify Müllerian structures seen in the operating room or on physical examination. Common reconstructive surgeries included vaginoplasties, incisions of vaginal septa, colporrhaphies, and hysterectomies. Sexual activity was confirmed for 3 patients, 2 of whom had conceived.nnnCONCLUSIONnMost female cloacal exstrophy patients exhibit abnormalities of the Müllerian system. Axial imaging and ultrasound are helpful diagnostic adjuncts but do not replace careful physical examination and assessment in the operating room. Further studies of sexual activity and fertility are warranted.

MP66-16 IMMEDIATE POST-OPERATIVE COURSE FOLLOWING OPEN AND LAPAROSCOPIC ORCHIOPEXY OF ABDOMINAL TESTES: IS THERE A DIFFERENCE?

Very common, undescended testes are encountered in around 1-4.5% of full term male infants [1]. Of those, around 25% are nonpalpable, with less than 60% of nonpalpable testes found within the abdomen at exploration [2]. Nonpalpable testis may become palpable under anesthesia. Of those which do not, laparoscopy can be both diagnostic, to confi rm the presence of an abdominal testis, and therapeutic, when used to perform laparoscopic orchiopexy [3]. The 2014 update of the American Urological Association (AUA) “Evaluation and Treatment of Cryptorchidism: AUA Guideline” recommends either laparoscopic or open exploration or orchiopexy equally, as neither approach has been shown to be superior either in identifying nonpalpable testes or successfully bringing the testis to the scrotum [3].