Routine use of Circumferential 'Doughnut' Biopsy in Pull through Surgery for Hirschsprung's Disease: Advantages and Limitations.

AIMS: The aim of this study was to review the use of the on-table "doughnut" biopsy for frozen section assessment of bowel in the operative management of Hirschsprung's disease (HD). METHODS: This was a single-center retrospective review of doughnut histopathology reports, operation notes, and slides from 2010 to 2017. Data were assessed for the presence of transition zone (TZ) features and the subsequent decision as to the level of pull-through. RESULTS: Fifty-five patients had a doughnut biopsy taken as part of their intraoperative frozen section histopathology for pull-through for HD during the study period. Forty-eight required a single doughnut, six required a second more proximal doughnut, and one required a third doughnut. Of the 55 first doughnuts, 37 were identified as normal bowel, 17 were TZ, and not defined in the report in one case. Of the 17 TZ doughnuts, 8 were accepted for pull-through and 7 underwent second doughnuts (normal = 4 and TZ = 3). The third doughnut (one case) was normal. TZ was accepted for pull-through in 10/54 (18.5%) patients despite the use of a doughnut. However, TZ was avoided in six (11.1%), where the single-point biopsy was "normal." CONCLUSIONS: The doughnut allows the entire circumference of pull-through level to be assessed, enabling TZ identification that can be missed by single seromuscular biopsies. This allows identification and avoidance of TZ pull-through, although sometimes, it is accepted for other reasons.

Human and Doll's Hair in a Gastric Trichobezoar, Endoscopic Retrieval Hazards.

Trichobezoars are masses of ingested hair, usually the individual's own hair, that accumulate in the gastrointestinal tract, most commonly in the stomach. When extending into the small intestine, this is termed "Rapunzel syndrome." Removal has traditionally been by laparotomy; however, successful endoscopic removal has also been described. We report the case of a 9-year-old-girl with undiagnosed coeliac disease and Rapunzel syndrome who underwent endoscopic removal of a large trichobezoar, which was followed by unexpected multiple perforations of the small bowel and stomach. Argon plasma coagulation (APC) and snare electrocautery were employed during endoscopy to remove the trichobezoar piecemeal, and approximately 70% was removed without any clear signs of damage to the mucosa. It was discovered subsequently that about 20 of her dolls were found without hair. On investigating the composition of a specific doll hair from the manufacturer, it was discovered that it could be hazardous if burned. It was, therefore, hypothesized that a constellation of factors had conspired to lead to perforation, that is, the potentially hazardous gas produced from the electrical energy applied to the synthetic hair and possible mucosal damage by the physical abrasion of this hair. A review of the literature on endoscopic attempts to remove trichobezoars irrespective of the result reveals a success rate of 30.7%.

Management of large primary spontaneous pneumothorax in children: radiological guidance, surgical intervention and proposed guideline.

PURPOSE: Primary spontaneous pneumothorax (PSP) is managed in accordance with the adult British Thoracic Society (BTS) guidelines due to lack of paediatric evidence and consensus. We aim to highlight the differences and provide a best practice surgical management strategy for PSP based on experience of two major paediatric surgical centres. METHODS: Retrospective review of PSP management and outcomes from two UK Tertiary Paediatric hospitals between 2004 and 2015. RESULTS: Fifty children with 55 PSP (5 bilateral) were referred to our Thoracic Surgical Services after initial management: 53% of the needle aspirations failed. Nine children (20%) were associated with visible bullae on the initial chest X-ray. Forty-nine children were assessed with computed tomography scan (CT). Apical emphysematous-like changes (ELC) were identified in 37 children (75%). Ten children had also bullae in the asymptomatic contralateral lungs (20%). In two children (4%), CT demonstrated other lung lesions: a tumour of the left main bronchus in one child; a multi-cystic lesion of the right middle lobe in keeping with a congenital lung malformation in another child. Contralateral asymptomatic ELC were detected in 20% of the children: of those 40% developed pneumothorax within 6 months. Best surgical management was thoracoscopic staple bullectomy and pleurectomy with 11% risk of recurrence. Histology confirmed ELC in 100% of the apical lung wedge resections even in those apexes apparently normal at the time of thoracoscopy. CONCLUSION: Our experience suggests that adult BTS guidelines are not applicable to children with large PSP. Needle aspiration is ineffective. We advocate early referral to a Paediatric Thoracic Service. We suggest early chest CT scan to identify ELC, for counselling regarding contralateral asymptomatic ELC and to rule out secondary pathological conditions causing pneumothorax. In rare instance if bulla is visible on presenting chest X-ray, thoracoscopy could be offered as primary option.

The role of stomas in the initial and long-term management of Hirschsprung disease.

AIM: To review the role of stomas in the initial and long-term management of Hirschsprung disease (HD). METHODS: Patients treated for HD at our institution between January 2004 and August 2021 were identified. Data were collected regarding: demographics, indication/bowel location/type of stomas performed and outcomes, pull-through (PT) procedure, and follow-up duration. RESULTS: Ninety-five patients (78 male) were identified including one early unrelated death. Forty-four of 94 (47%) required a stoma before PT procedure. Of these 44, 38 (86%) had ileostomies and the remaining six (14%) colostomies; one ileostomy remains long-term. The commonest indication for initial stomas was washout failure (41%). Ninety-one patients had undergone primary PT or secondary PT with stoma closure at the time of the study. A further new stoma was required after primary PT or three-stage management in 20/91 (22%). The commonest indications were constipation/soiling (25%) and anastomotic leak (20%). Seven out of 20 (35%) were performed within 30 days of a previous procedure and all were closed; three patients required further long-term stomas. Thirteen (65%) required a stoma >30 days, nine remain long-term. Surgical revision of stomas was required in 14/56 (25%) - prolapse and retraction being the commonest indications. Overall, 56/94 (60%) patients required stomas (pre- and/or post-PT) to manage their condition and 13/94 (14%) have a long-term stoma in place. Mean follow-up was 7.8 years (0.5 - 17.6). CONCLUSIONS: Stomas remain an integral part of HD management both initially (47%) and long-term (14%); they carry a considerable associated morbidity. Ileostomy is preferred for initial management. LEVEL OF EVIDENCE: Level III.

Celiac Plexus Block to Treat Refractory Feed Induced Dystonia in Children with Severe Neurodisability: A Single Center Case Series.

This observational study describes the procedure technique, safety outcomes, and patient responses to celiac plexus blockade (CPB) in children with severe neurodisability with refractory feed intolerance, feed induced pain or feed induced dystonia (FID). Method: A review of the pathophysiological response to feeding in children with significant neurodisability and the effect on the neuroenteric system. A 2-stage CT-guided temporary celiac plexus blockade followed by neurolysis technique is described. We compile a case series of 5 patients with life limiting conditions and significant disability undergoing CPB in a single tertiary pediatric hospital. Results: A total of 10 separate procedures in 5 children were completed. A positive outcome was observed in 3 out of 4 cases of pediatric FID. Two of the three patients on parenteral nutrition had improved feed tolerance postprocedure. All children tolerated the procedure well, no postprocedure complications were documented. Conclusions: In selected cases, children with life-threatening feed induced dystonia or effective intestinal failure can be safely treated with celiac plexus blockade when other therapies have failed.

Functional outcome, quality of life, and 'failures' following pull-through surgery for hirschsprung's disease: A review of practice at a single-center.

AIMS: The purpose of this study was to assess bowel function and quality of life (QoL) in patients with Hirschsprung's disease (HD) and identify patients who have 'failed' treatment. METHODS: A review of a single-center HD cohort treated with pull-through surgery from 2004 to 2017 was completed. Bowel function of patients five years and above and QoL of all patients were assessed using validated questionnaires. Patients who 'failed' treatment were defined as above five years with one or more of: a) long-term stoma, b) needing an antegrade continence enema or transanal irrigation, c) severe soiling, or d) severe constipation. Statistical analysis was performed with P < 0.05 deemed significant. Data are given as mean [range]. RESULTS: Seventy-one patients presented with HD within the study period. Mean follow-up was 5.4 years [0.7-13.3]. Of 38 eligible patients, bowel function was assessed in 24 patients (nine had a stoma, five lost to follow-up). The mean incontinence score was 17 [0-28)], and the mean constipation score was 17 [5-25]. Incontinence and constipation scores were worse than healthy controls (P < 0.001 and P = 0.001, respectively) and did not improve with age. Fifty-six patients had QoL assessed with no difference between our cohort (81 [25-100]) and healthy controls (81 [unknown]); (P = 0.85). Thirty-three patients were assessed for 'failure' (bowel function score n = 24; stoma n = 9). Thirty of 33 (91%) children older than five years can be considered to have 'failed' treatment. CONCLUSIONS: Patients have worse bowel function than healthy children, which does not improve with age. QoL is comparable to healthy controls. A significant proportion of patients have poor outcomes and have 'failed' treatment. LEVEL OF EVIDENCE: Level III.

Human and mouse enteric nervous system neurosphere transplants regulate the function of aganglionic embryonic distal colon.

BACKGROUND & AIMS: Recent advances have raised the possibility of treating enteric nervous system (ENS) disorders with transplanted progenitor cells (ENSPC). Although these cells have been shown to migrate and differentiate after transplantation, no functional effects have been demonstrated. We therefore aimed to investigate whether embryonic mouse and neonatal human ENSPC can regulate the contractility of aganglionic bowel. METHODS: Embryonic mouse and neonatal human ENSPC were grown as neurospheres before transplantation into aganglionic embryonic mouse hindgut explants and culture for 8-12 days. Engraftment and neural differentiation were confirmed using immunofluorescence and transmission electron microscopy. The contraction frequency of transplanted bowel was measured and compared with that of embryonic day 11.5 embryonic ganglionic and aganglionic bowel cultured for the same period. Calcium movement was measured at spatially defined points in bowel wall smooth muscle. Neural modulation of bowel contractility was assessed using tetrodotoxin. RESULTS: Both mouse and human ENSPC migrated and differentiated after neurosphere transplantation. Transmission electron microscopy demonstrated the existence of synapses. Transplantation restored the high contraction frequency of aganglionic bowel to the lower rate of ganglionic bowel. Calcium imaging demonstrated that neurosphere transplantation coordinates intracellular free calcium levels. Both these effects were reversed by the addition of tetrodotoxin, indicating the functional effect of neurosphere-derived neurons. CONCLUSIONS: Neonatal human gut is a source of ENSPC that can be transplanted to restore the contractile properties of aganglionic bowel by a neurally mediated mechanism. This may aid development of a stem cell-based treatment for Hirschsprung's disease.

Idiopathic small bowel diaphragm disease identified by laparoscopic-assisted double-balloon enteroscopy in a child: an integrated successful definitive therapeutic method.

In adults, small bowel diaphragm disease is a rare complication of small bowel enteropathy secondary to the use of nonsteroidal antiinflammatory drugs. The main clinical manifestations are gastrointestinal bleeding and subacute obstruction, and management can be challenging. We present a case of a 5-year-old girl with small bowel diaphragm disease. To our knowledge, this is the first idiopathic case (no history of nonsteroidal antiinflammatory drug use) in the pediatric age group. This report describes an integrated successful definitive therapeutic method of double-balloon enteroscopy and minimal invasive bowel surgery for small bowel pathology.

Properties of secondary and tertiary human enteric nervous system neurospheres.

UNLABELLED: Advances in enteric nervous system (ENS) stem cell biology have raised the possibility of treating Hirschsprung's disease with ENS stem/progenitor cell (ENSPC) transplantation. This study aimed to expand ENSPC numbers by the growth and redissociation of neurospheres and assess their differential potential. METHODS: Human ENS neurospheres were cultured as previously described and redissociated to generate secondary and tertiary neurospheres. Neurospheres were assessed for the presence of neuronal (PGP9.5), glial (S100), and stem cell (p75, nestin markers). The degree of immunofluorescence was quantified using the ImageJ program. Secondary/tertiary neurospheres were transplanted into mouse distal colon grown in tissue culture. RESULTS: Secondary/tertiary neurospheres could be generated with exponentially increasing numbers. Tertiary neurospheres showed a significant increase in the proportion of p75 staining but a significant decrease in the proportion of S100 staining. After transplantation, secondary/tertiary neurosphere-derived cells positive for PGP9.5 and S100 could be identified. CONCLUSIONS: It is possible to exponentially expand neurosphere and therefore ENSPC numbers by repeated dissociation and culture. There is a loss of S100-positive cells in secondary/tertiary neurospheres, but the ENSPCs remain capable of differentiating into neurons and glia when transplanted into an embryonic gut environment.

Characterisation and transplantation of enteric nervous system progenitor cells.

AIMS: Enteric nervous system (ENS) progenitor cells have been postulated to be an appropriate source of cells for the treatment of Hirschsprung's disease. In order for this to be successful, the techniques previously used for the isolation of rodent ENS progenitor cells need to be adapted for postnatal human tissue. In this paper, we describe a method suitable for the preparation of both mouse and human postnatal ENS progenitor cells and assess their transplantation potential. METHOD: Single cell suspensions were isolated from 11.5 days post-coitum embryonic mouse caecum and postnatal human myenteric plexus. These cells were cultured under non-adherent conditions to generate neurospheres which were implanted into aganglionic embryonic mouse hindgut explants. Cell proliferation, migration and differentiation were observed using immunofluorescence microscopy. RESULTS: Neurospheres generated from both mouse and human tissues contained proliferating neural crest-derived cells that could be expanded in tissue culture to generate both glial cells and neurons. When implanted into aganglionic murine gut, cells migrated from the neurospheres using pathways appropriate for cells derived from the neural crest, and differentiated to become glia and neurons expressing neuronal phenotypic markers characteristic of the ENS including nitric oxide synthase and vasoactive intestinal polypeptide. CONCLUSION: We have developed a technique for the isolation and expansion of ENS progenitor cells from human neonates. These cells have the ability to differentiate into neurons and glia when transplanted into aganglionic gut, this demonstration being a necessary first step for their autologous transplantation in the treatment of Hirschsprung's disease.

Delays in the diagnosis of anorectal malformations are common and significantly increase serious early complications.

AIM: To clarify the extent of delayed diagnosis of anorectal malformations and the consequences of delaying this diagnosis. METHODS: We performed a retrospective case review of all neonatal admissions with an anorectal malformation to a tertiary paediatric surgery unit. A delayed diagnosis was considered to be one made 24 h or more after birth. RESULTS: 75 patients were included in the study group: 31 (42%) had a delay in the diagnosis; 44 (58%) had no delay in the diagnosis. The time of diagnosis where a delay had occurred ranged from 2-16 (median 2) d. A delay in diagnosis could not be accounted for by differences in age, sex, birthweight, gestational age, the severity or visibility of the lesion, the need for neonatal special or intensive care, or the presence of other anomalies. There were significantly more complications (including one death) amongst the group of children who had a delay in the diagnosis of an anorectal malformation. There was no significant difference in long-term functional outcome. CONCLUSION: Delays in the diagnosis of anorectal malformations are much more common than previously thought. A delay in diagnosis significantly increases the risk of serious early complications and death.