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The treatment of Hirschsprung disease (HSCR) is surgical resection of aganglionic bowel and subsequent pull-through of ganglionated bowel. Despite many advances since the initial description of the disease and its surgical management more than half a century ago, there remain considerable controversies regarding the history of the surgical technique, the optimal timing of the primary and multistage pull-through, the best treatment for patients with a delayed diagnosis of HSCR, and the management of post pull-through complications such as soiling due to sphincter incompetence, the presence of a transition zone, and the prevention of enterocolitis. The following review will explore each of these controversies.

The conventional approach to managing a newborn with cloacal exstrophy typically includes separating the cecal plate from between the two hemibladders, tubularizing it to be included in the fecal stream, creating an end colostomy, and bringing the two bladder halves together. This study introduces an alternative approach wherein the cecal plate is retained in its original position and designated for future use as an autoaugment of the bladder. Four cases of cloacal exstrophy cases managed between November 2019 and February 2024 are described, with surgical approach and postoperative outcomes reported. Two patients who underwent traditional reconstruction experienced bacterial overgrowth attributed to stasis in the cecal plate, which manifested in increased ostomy output and feeding intolerance. Treatment in these two cases was to remove the cecum from the fecal stream and use it instead for a bladder augment. Learning from these cases, the third and fourth newborn's approach involved retaining the cecum in situ for autoaugmentation of the bladder and performing an ileal to hindgut anastomosis. No postoperative acidosis occurred in these patients. The alternative approach to the newborn management of cloacal exstrophy whereby the cecal plate is left in situ can decrease stasis and postoperative bacterial overgrowth. It allows for an autoaugmentation of the bladder and is technically easier than the traditional rescue of the cecal plate from within the two hemibladders.

Aim: Most patients with functional constipation (FC) improve with medical treatment. For those with refractory symptoms, we propose a comprehensive and multidisciplinary work-up and decision-making approach to therapy. Methods: We retrospectively reviewed patients referred to our center between 2019-2022 with suspected FC who had failed medical management. All patients underwent a contrast enema, anorectal manometry, examination under anesthesia, rectal biopsy (if needed), and botulinum toxin injection (as indicated). Results: 54 patients were evaluated using our algorithm. One was found to have anal stenosis on exam. The rectoanal inhibitory reflex (RAIR) was normal in 41(76%) patients and unable to be elicited in 12(22%). Two (17%) patients without a RAIR had Hirschsprung Disease (HD) and underwent a pull-through. 10(83%) with no RAIR had normal biopsies and were managed successfully with laxatives. Of the 41 patients with a normal RAIR, 14(34%) had high resting pressures (external sphincters) or non-relaxing (internal) sphincters and received botulinum toxin. 8(57%) of them were emptying well after one month. 24 patients failed laxatives (with or without botulinum toxin injections) and then underwent a Malone procedure. 23(96%) of these patients improved with antegrade flushes. One patient (1/21, 4.1%) did not undergo Malone and instead underwent colonic manometry and a sigmoid resection, after which he emptied well. Conclusion: We propose a systematic multidisciplinary approach for constipated patients who failed medical management starting with assessment of anal sphincters. This allows for targeted adjustment of laxative regimen, use of botulinum toxin to the internal and/or external anal sphincter and antegrade flushes via a Malone. Level of evidence level: IV

We present a rare case of a 2-year-old male patient referred for primary evaluation of constipation and ultimately treatment of Hirschsprung disease (HSCR) whose preoperative workup incidentally revealed a posterior paraspinal mass. Following the biopsy of the mass, the patient exhibited hypoventilation and hypoxia requiring a delayed extubation, raising suspicion for congenital central hypoventilation syndrome (CCHS). We focus on the known history of associations between HSCR and CCHS, in addition to recently found genetic mutations in paired-like homeobox 2B that link HSCR, CCHS, and neuroblastoma.

We present a case of a rare complication in a 10-month-old female referred to our institution for an anal stricture after primary cloacal repair as an infant. Multimodal imaging, careful physical exam, and endoscopic evaluation revealed her vagina had been pulled through to the location of her anal sphincter muscle complex. We describe the correction of this problem, including identification of her rectum.

Cloaca is a rare, complex malformation encompassing the genitourinary and anorectal tract of the female in which these tracts fail to separate in utero, resulting in a single perineal orifice. Prenatal sonography detects a few cases with findings such as renal and urinary tract malformations, intraluminal calcifications, dilated bowel, ambiguous genitalia, a cystic pelvic mass, or identification of other associated anomalies prompting further imaging. Multi-disciplinary collaboration between neonatology, pediatric surgery, urology, and gynecology is paramount to achieving safe outcomes. Perinatal evaluation and management may include treatment of cardiopulmonary and renal anomalies, administration of prophylactic antibiotics, ensuring egress of urine and evaluation of hydronephrosis, drainage of a hydrocolpos, and creation of a colostomy for stool diversion. Additional imaging of the spinal cord and sacrum are obtained to plan possible neurosurgical intervention as well as prognostication of future bladder and bowel control. Endoscopic evaluation and cloacagram, followed by primary reconstruction, are performed by a multidisciplinary team outside of the neonatal period. Long-term multidisciplinary follow-up is essential given the increased rates of renal disease, neuropathic bladder, tethered cord syndrome, and stooling issues. Patients and families will also require support through the functional and psychosocial changes in puberty, adolescence, and young adulthood.

The serine/threonine phosphatase 2A (PP2A) has been implicated in the pathogenesis of Alzheimer's disease (AD) due to its important role in regulating dephosphorylation of the microtubule-associated protein tau and mitogen-activated protein (MAP) kinase. In the present study, we show that PP2A was responsible for dephosphorylation of the extracellular signal-regulated kinase 1/2 (Erk1/2) following its activation by BK stimulation. Abnormal gene and protein expressions of PP2A, as well as its activity, were found to contribute to the abnormally prolonged Erk1/2 phosphorylation in the AD fibroblasts. Inhibition of PP2A with okadiac acid produced enhanced and more lasting Erk1/2 phosphorylation after BK stimulation, whereas FK506, an inhibitor of PP2B and FK-binding protein, inhibited the BK-stimulated Erk1/2 phosphorylation. Furthermore, while the phosphorylated Erk1/2 was concentrated in the nucleus of AC cells, it was mainly distributed in the extranuclear compartments of AD cells. These results suggest that the delayed dephosphorylation of Erk1/2 in AD cells following its BK-stimulated activation may be due to deficits of PP2A activity and impaired nuclear translocation of phosphorylated Erk1/2.