High prevalence of same-sex twins in patients with cloacal exstrophy: Support for embryological association with monozygotic twinning.

PURPOSE: Previous studies have hypothesized that cloacal exstrophy may be caused by errors early in embryological development related to monozygotic twinning. This study reports the prevalence of twins in a large cohort of patients with cloacal exstrophy. METHODS: Patients with cloacal exstrophy treated 1974-2015 were reviewed for reports of multiple gestation or conjoined twinning. The genetic sex of the patient and their twin, and any mention of anomaly in the twin were recorded. Neither placental exam nor genetic testing results were available to definitively determine zygosity. RESULTS: Of 71 patients, 10 had a live born twin (14%), all of whom were of the same genetic sex as the affected patient. One additional patient's twin suffered intrauterine fetal demise, and another patient had a conjoined heteropagus twin. None of the twins were affected by exstrophy-epispadias complex. The rate of twin birth in this cohort was 4.4-7.7 higher than that reported by the Centers for Disease Control in the general population time period (P<0.001), with a striking preponderance of same-sex pairs. CONCLUSIONS: The highly significant prevalence of same-sex twin pairs within this cohort supports the hypothesis that the embryogenesis of cloacal exstrophy may be related to errors in monozygotic twinning. LEVEL OF EVIDENCE: 2b.

The 1951 Harvard student uprising against the intern match.

In the fall of 1951, a group of Harvard medical students led by W. Hardy Hendren, III organized a national movement against the newly instituted match that would assign graduating seniors to hospital internship programs. Before then, hospitals with intern positions to fill rushed to secure commitments from students, who in turn accepted the first decent offer that came their way. Knowing that students could not risk waiting for a better offer, hospitals pushed them into making early commitments. When some students began getting offers in their junior and sophomore years, medical schools, professional groups, and hospitals organized the National Inter-association Committee on Internships to deal with the issue. The intern match was thus organized and scheduled to take place in 1952. When the plan was announced in mid-October 1951, Hendren recognized that the proposed algorithm placed students at a disadvantage if they did not get their first choice of hospitals. Facing resistance at every step from the National Inter-association Committee on Internships and putting his standing at Harvard Medical School at risk, Hendren led a nationwide movement of medical students to change the procedure to one that favored students' choices. Their success <1 month later established in the inaugural match the fundamental ethic of today's National Resident Matching Program to favor students' preferences at every step of the process.

Growth morbidity in patients with cloacal exstrophy: a 42-year experience.

PURPOSE: Cloacal exstrophy is associated with multiple comorbidities that affect growth. This report describes long-term growth outcomes in a large cohort of patients with cloacal exstrophy and explores associated comorbidities. METHODS: Records of 71 patients with cloacal exstrophy who were treated between 1974 and 2015 were reviewed, and 62 patients with growth data from 2 to 20years of age were included. Genetic sex, gender of rearing, and all heights, weights, and comorbidities were noted for each patient. Height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, and BMIZ) were determined using US Centers for Disease Control 2000 growth data, and average patient z-scores were calculated. RESULTS: There were 904 height and 1301 weight measurements available for 62 patients. 31 were genetically 46,XY, 21 of whom underwent gonadectomy in infancy and were raised female. 46,XX patients, 46,XY male patients, and 46,XY female patients all had median HAZ and WAZ substantially lower than the general population, with median HAZ less than -2, while maintaining normal BMIZ. Short bowel syndrome and enterocystoplasty with intestine were associated with lower z-scores for all parameters. CONCLUSIONS: Patients with cloacal exstrophy have significant multifactorial long-term growth failure. These benchmark data can be used to further optimize management. LEVEL OF EVIDENCE: 2b.

"A thrill of extreme magnety": Robert E. Gross and the beginnings of cardiac surgery.

Seventy-five years ago, a 7-year-old girl underwent the first successful ligation of a patent ductus arteriosus. This procedure transformed her health and was a milestone in the development of cardiac surgery. The operation was performed by Dr. Robert E. Gross, then the surgical chief resident at Boston Children's Hospital, who went on to have a distinguished career in pediatric surgery. The patient is now a great-grandmother and the oldest known survivor of cardiac surgery.

Bladder neck reconstruction is often necessary after complete primary repair of exstrophy.

PURPOSE: A major goal of bladder exstrophy management is urinary continence, often using bladder neck reconstruction. We report our experience with bladder neck reconstruction after complete primary repair of exstrophy. MATERIALS AND METHODS: Patient history, ultrasound, voiding cystourethrogram, examination using anesthesia and urodynamics were performed during a prospective evaluation. Continence was assessed using the International Children's Continence Society classification and the dry interval. Bladder capacity was measured by examination using anesthesia, voiding cystourethrogram and/or urodynamics. Urodynamics were also done to assess bladder compliance and detrusor muscle function. RESULTS: From 1994 to 2010 we treated 31 male and 15 female patients with bladder exstrophy after complete primary repair of exstrophy. Of patients 5 years old or older bladder neck reconstruction was performed after complete primary repair in 9 of 21 males (43%) and in 3 of 11 females (27%) at a mean age of 6.3 and 8.1 years, respectively. By the International Children's Continence Society classification 6 of 12 patients (50%) were continent less than 1.5 years after bladder neck reconstruction and 2 of 9 (23%) were evaluable 1.5 years or greater after reconstruction. Median bladder capacity was 100 ml before, 50 ml less than 1.5 years after and 123 ml 1.5 years or greater after bladder neck reconstruction. Three males and 2 females emptied via an appendicovesicostomy. Two boys underwent augmentation. CONCLUSIONS: In our experience most patients with bladder exstrophy require bladder neck reconstruction after complete primary repair of exstrophy. The need for reconstruction is more common in males. Our rates of bladder neck reconstruction after complete primary repair of exstrophy and of continence after bladder neck reconstruction are similar to those in other reports.

Prospective followup in patients after complete primary repair of bladder exstrophy.

PURPOSE: The new technique of complete primary repair of bladder exstrophy has offered the promise of improved bladder functional outcomes and yet longitudinal followup in patients with exstrophy who have undergone this form of closure is sparse. We present our median 5-year data on patients who have undergone complete primary repair of bladder exstrophy. MATERIALS AND METHODS: The records of patients who underwent complete primary repair of bladder exstrophy were analyzed retrospectively. Patients were followed prospectively using case report forms, radiological and clinical data, and semistructured parental and patient interviews. We reviewed parameters including clinical events, scarring on renal scan, vesicoureteral reflux, surgical procedures, urodynamic studies, urinary and fecal continence status, and episodes of urinary tract infection. RESULTS: From 1994 to 2007 complete primary repair of bladder exstrophy was performed in 32 patients. Of these patients 28 underwent closure within 72 hours of life, including 20 males and 8 females, and 4 underwent it after 72 hours at ages 7 days to 12 months. One patient underwent complete primary repair of bladder exstrophy elsewhere. Median followup was 5 years (range 1 to 13). In 32 patients a total of 193 surgical procedures were done, of which 40% were minor endoscopic cases. Six of 23 males (26%) underwent bladder neck reconstruction at a median age of 4.5 years (range 4 to 10). Two boys and 1 girl received Deflux injection to the bladder neck at ages 3 to 5 years. To date no patient has undergone bladder augmentation. Nine patients (28%) had 1 to 4 episodes of pyelonephritis and 6 had cortical defects on renal scan. A total of 30 patients were voiding or incontinent via the urethra. One patient performed clean intermittent catheterization via the urethra and 1 performed it via appendicovesicostomy. All 4 children who were at least 6 months from bladder neck reconstruction after complete primary repair of bladder exstrophy had urinary continence periods of 2 to 3 hours or greater. Parents did not report any fecal incontinence or soiling in children older than 4 years. Relative to males the females had better urinary continence and a decreased need for bladder neck reconstruction. CONCLUSIONS: Complete primary repair of bladder exstrophy has been shown to be safe and efficacious. Prospective followup in this small number of evaluable patients reveals that continence periods of more than 2 hours are possible in patients after bladder neck reconstruction. Long-term followup in patients after complete primary repair of bladder exstrophy continues to be necessary to establish the long-term effects of this procedure.

Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach.

PURPOSE: We assessed bladder growth and dynamics following complete primary repair of bladder exstrophy (CPRE) compared to the staged approach. MATERIALS AND METHODS: We reviewed the records of 16 boys and 7 girls who underwent CPRE within 3 days of life from 1996 to 2004 and compared them to the records of 8 boys and 6 girls treated with a staged repair from 1979 to 1996. Screening methods included voiding cystourethrogram, radionuclide cystogram and urodynamic study. We estimated growth curves for bladder capacity following repair in each group, and compared percent predicted bladder capacity (PPBC), compliance and detrusor overactivity between the CPRE and staged repair groups following bladder neck reconstruction. RESULTS: Bladder capacity in the staged repair group was 69.8 ml (95% CI 46.7-104.4) immediately after bladder neck reconstruction and increased by 15.0% per year thereafter (95% CI 6.2-24.5, p = 0.002). In the CPRE group bladder capacity was 29.0 ml (95% CI 21.3-39.5) initially and increased by 28.9% per year thereafter (95% CI 17.4-41.5, p <0.001). PPBC started at 45.6% (95% CI 35.7-55.5) and increased 1.2% per year (95% CI -1.1-3.5, p = 0.29) following repair for all genders and surgery groups. Compliance was 124.4% (95% CI 22.6-310.7, p = 0.01) greater in the CPRE group at all times following repair. Detrusor overactivity was present in 0 of 19 patients in the CPRE group and 6 of 13 (46%) in the staged group (exact p = 0.002). CONCLUSIONS: Within the CPRE group bladder stability was universal, and sphincter electromyography was normal suggesting no neuromuscular compromise of the pelvic floor. At early followup, our results suggest that PPBC is equivalent irrespective of gender or management. Further objective evaluation is needed in both groups.

Early outcome following complete primary repair of bladder exstrophy in the newborn.

PURPOSE: Complete primary repair of bladder exstrophy (CPRE) represents a paradigm shift from the staged approach for surgical management. We present early clinical outcomes in our patients following CPRE. MATERIALS AND METHODS: From 1996 to 2004 all newborns with bladder exstrophy were treated with CPRE within 48 hours of birth. We reviewed parameters including transfusions (packed red blood cells), urethral meatal position, complications, findings on renal ultrasound and renal scan, and post-CPRE procedures and infections. RESULTS: A total of 16 boys and 7 girls were treated with CPRE. Followup ranged from 8 to 96 months. Twelve boys (75%) and 2 girls (29%) received packed red blood cells at CPRE (p = 0.066). The tubularized urethral plate could not be brought to the penile tip, resulting in hypospadias in 9 of 11 boys (82%) with the running suture technique and only 1 of 5 boys (20%) with the interrupted technique (p = 0.036). Of the 23 patients 6 had a total of 8 complications after CPRE. Vesicoureteral reflux was present in 17 of 23 patients. After CPRE a total of 93 endoscopic/surgical procedures (median 4, range 0 to 16 per patient) were performed. Five patients had 1 to 4 episodes of pyelonephritis, 16 of 23 had 1 or more episodes of asymptomatic bacteriuria and 5 had cortical defects on renal scan. CONCLUSIONS: We recommend that urethral closure during CPRE be performed with interrupted suture technique to prevent hypospadias. An aggressive approach should be taken toward reflux in the setting of urinary infection. Consideration should be given for repair of all aspects of the defect during CPRE, including bilateral ureteral reimplantation.

Congenital adrenal hyperplasia: surgical considerations required to repair a 46,XX patient raised as a boy.

21-hydroxylase deficiency (P450 CYP21) accounts for 90% of cases of congenital adrenal hyperplasia (CAH), which is associated with abnormally low cortisol and high production of androgen precursors and is the most common cause of ambiguous genitalia. Increased androgen causes in utero virilization of the fetus, consisting of clitoral enlargement, an urogenital sinus, and labioscrotal enlargement and fusion. This is the first case in an experience covering more than 30 years, of a 46,XX patient raised as a boy. The authors report a case of a Pakistani patient born of a consanguineous union, who came to medical attention at age 3 because of severe genital ambiguity; genetic analyses showed that the child was a compound heterozygote for CAH. The surgical management of this patient consisted of (1) staged hypospadias repairs preceded by testosterone therapy, (2) creation of a bladder graft neourethra, (3) removal of müllerian structures, (4) correction of bifid prepenile scrotum, and (5) insertion of testicular prostheses. The commitment to raise a 46,XX child as a boy is a very rare event. With a series of staged complex surgical procedures and careful steroid replacement, normal secondary sexual characteristics can be achieved in these children.

Fibroepithelial polyps causing ureteropelvic junction obstruction in children.

PURPOSE: Fibroepithelial polyps are benign mucosal projections that can be found throughout the urinary system. We review our experience with fibroepithelial polyps of the ureteropelvic junction in children to define more clearly this entity and its outcome following treatment. METHODS: We reviewed the records of all children with fibroepithelial polyps causing ureteropelvic junction obstruction treated at our institution between December 1967 and February 2002. RESULTS: Nine patients 6 weeks to 9 years old had 11 ureteropelvic junction obstructions secondary to fibroepithelial polyps, representing a 0.5% incidence of all ureteropelvic junction obstructions seen during that period. The majority of the patients were male (89%) and had obstruction on the left side (78%). Only 22% of the patients had a diagnosis of obstructing polyps suggested preoperatively. All patients underwent dismembered pyeloplasty but 1 required subsequent nephrectomy due to progressive loss of renal function. All lesions were characterized microscopically by polypoid projections of fibrous tissue covered by epithelium and demonstrating varying degrees of inflammation. No recurrences were seen during a mean followup of 44 months. CONCLUSIONS: Fibroepithelial polyps are rare lesions that cause ureteropelvic junction obstruction in children, primarily in males and on the left side. Filling defects were diagnosed preoperatively in 22% of the patients in this series. Excision and dismembered pyeloplasty were curative, and recurrences were not observed. The etiology of this disease remains obscure.

Triplets after cloacal malformation repair.

BACKGROUND: Patients with cloacal malformations at birth usually require multiple surgical procedures to correct their anatomic defects. In addition, many also have associated Müllerian anomalies. Those who conceive after repairs invariably are considered "high-risk" pregnancies and are considered poor candidates for maintaining multiple gestations. Further, because of the nature of their defects and their repairs, following such patients with multiple gestation presents unique challenges. CASE: A 29-year-old multipara conceived triplets and delivered at 30 weeks with a good maternal and neonatal outcome. CONCLUSIONS: Patients with repaired cloacal abnormalities present unique challenges and risks compared to the general population with regard to the risks of multiple pregnancies.