Robotic-assisted proctosigmoidectomy for Hirschsprung’s disease:A multicenter prospective study

BACKGROUND Robotic surgery is a cutting-edge minimally invasive technique that overcomes many shortcomings of laparoscopic techniques,yet few studies have evaluated the use of robotic surgery to treat Hirschsprung’s disease(HSCR).AIM To analyze the feasibility and medium-term outcomes of robotic-assisted proctosigmoidectomy(RAPS)with sphincter-and nerve-sparing surgery in HSCR patients.METHODS From July 2015 to January 2022,156 rectosigmoid HSCR patients were enrolled in this multicenter prospective study.Their sphincters and nerves were spared by dissecting the rectum completely from the pelvic cavity outside the longitudinal muscle of the rectum and then performing transanal Soave pull-through procedures.Surgical outcomes and continence function were analyzed.RESULTS No conversions or intraoperative complications occurred.The median age at surgery was 9.50 months,and the length of the removed bowel was 15.50±5.23 cm.The total operation time,console time,and anal traction time were 155.22±16.77,58.01±7.71,and 45.28±8.15 min.There were 25 complications within 30 d and 48 post-30-d complications.For children aged≥4 years,the bowel function score(BFS)was 17.32±2.63,and 90.91%of patients showed moderate-to-good bowel function.The postoperative fecal continence(POFC)score was 10.95±1.04 at 4 years of age,11.48±0.72 at 5 years of age,and 11.94±0.81 at 6 years of age,showing a promising annual trend.There were no significant differences in postoperative complications,BFS,and POFC scores related to age at surgery being≤3 mo or>3 mo.CONCLUSION RAPS is a safe and effective alternative for treating HSCR in children of all ages;it offers the advantage of further minimizing damage to sphincters and perirectal nerves and thus providing better continence function.

MUTATION OF THE ENDOTHELIN-B RECEPTOR AND THE ENDOTHELIN-3 GENE IN CHINESE SPORADIC CASES OF HIRSCHSPRUNG'S DISEASE

Objective To investigate the mutation of endothelin receptor B (EDNRB) gene and endothelin 3 (EDN 3) gene in sporadic Hirschsprungs disease (HD) in Chinese population. Methods Genomic DNA was extracted from bowel tissues of 34 unrelated HD patients which were removed by surgery. Exon 3, 4, 6 of EDNRB gene and Exon 1, 2 of EDN 3 gene were amplified by polymerase chain reaction (PCR) and analyzed by single strand conformation polymorphism (SSCP).Results EDNRB mutations were detected in 2 of the 13 short segment HDs. One mutant was in the exon 3; the other one was in the exon 6. EDN 3 mutation was detected in 1 of the 13 short segment HDs and in the exon 2. Both EDNRB mutation and EDN 3 mutation were detected in one short segment HD. No mutations were detected in the ordinary or long segment HD. Conclusion The mutations of EDNRB gene and EDN 3 gene are found in the short segment HD of sporadic Hirschsprung's disease in Chinese population, which suggests that the EDNRB gene and EDN 3 gene play important roles in the pathogenesis of HD. the mutations of EDNRB and EDN 3 lead to the maldevelopment of the enteric nervous system.

Generic and disease-specific health-related quality of life in patients with Hirschsprung disease:A systematic review and meta-analysis

BACKGROUND Patients with Hirschsprung disease(HD)are at risk of persistent constipation,fecal incontinence or recurrent enterocolitis after surgical treatment,which in turn may impact physical and psychosocial functioning.Generic health-related quality of life(HRQoL)and disease-specific health-related quality of life are relevant outcome measures to assess the impact of HD on the QoL of these patients.AIM To summarize all available evidence on HRQoL of patients with HD after surgery and the impact of possible moderating factors.METHODS Pubmed,Web of Sciences,Psyc Info and Embase were searched with search terms related to’Hirschsprung disease’,’Pediatrics’and’Quality of life’.Mean and standard deviation of generic HRQoL overall and domain scores were extracted from each study,as well as data describing potential factors associated with QoL.Random effect models were used for meta-analytic aggregation of generic HRQoL scores.Meta-regression was used to assess the relationship between patient and clinical characteristics and generic HRQoL.Disease-specific HRQoL outcomes of patients with HD were systematically reviewed.RESULTS Seventeen articles were included in the systematic review(n=1137 patients)and 15 in the quantitative meta-analysis(n=1024 patients).Four studies reported disease-specific HRQoL.Patient’s age ranged between 0 and 21 years.Meta-analytic aggregation showed a nonsignificantly impaired generic HRQoL(d=-0.168[95%CI:-0.481;0.145],P=0.293,I^(2)=94.9)in patients with HD compared to healthy controls.Physical(d=-0.042[95%CI:-0.419;0.335],P=0.829,I^(2)=95.1),psychosocial(d=-0.159[95%CI:-0.458;0.141],P=0.299,I^(2)=93.6)and social HRQoL(d=-0.092[95%CI:-0.642;0.457],P=0.742,I^(2)=92.3)were also not significantly lower compared to healthy controls.There was no relation between health-related outcomes and the sex of the patients and whether generic HRQoL was measured by parental proxy or self-report.Disease-specific complaints of patients with HD impaired physical HRQoL,but not psychosocial and social HRQoL.CONCLUSION In this systematic review and meta-analysis,no evidence was found for impaired generic HRQoL in patients with HD compared to healthy controls,neither for moderating effects of sex,parental proxy or self-report.

Persistent bowel dysfunction after surgery for Hirschsprung’s disease:A neuropathological perspective

Hirschsprung’s disease(HD)is a congenital disorder,characterized by aganglionosis in the distal part of the gastrointestinal tract.Despite complete surgical resection of the aganglionic segment,both constipation and fecal incontinence persist in a considerable number of patients with limited treatment options.There is growing evidence for structural abnormalities in the ganglionic bowel proximal to the aganglionosis in both humans and animals with HD,which may play a role in persistent bowel dysfunction.These abnormalities include:(1)Histopathological abnormalities of enteric neural cells;(2)Imbalanced expression of neurotransmitters and neuroproteins;(3)Abnormal expression of enteric pacemaker cells;(4)Abnormalities of smooth muscle cells;and(5)Abnormalities within the extracellular matrix.Hence,a better understanding of these previously unrecognized neuropathological abnormalities may improve follow-up and treatment in patients with HD suffering from persistent bowel dysfunction following surgical correction.In the long term,further combination of clinical and neuropathological data will hopefully enable a translational step towards more individual treatment for HD.

Literature Review of the Outcome after One-Stage Transanal Endorectal Pull-Through Procedure for Hirschsprung’s Disease in Children

Background: Transanal endorectal one-stage pull-through (TERPT) procedure in children with Hirschsprung’s disease (HD) is frequently used worldwide. In order to give the families realistic expectations and to plan the medical care for the years after TERPT, the long term outcome is of great importance. Aim: To collect information on the long term outcome reported after one stage TERPT procedure for HD in children 0 - 15 years. Method: A literature review on the outcome of planned TERPT from 2005 through 2012 was carried out. Information was collected on the number of daily stools a few months postoperatively, incontinence and constipation and the measures taken to deal with these. Results: The reports are few and prospective studies were missing. The results show an initial high frequency of daily stools, 12% had later abnormal stool patterns, 21% had fecal incontinence and 10% had problems with constipation. Conclusion: In order to compare the long term outcome, it would be desirable to have uniform regular reports on the daily frequency of passed stools, incontinence and constipation during the first years after TERPT. Such knowledge would be of importance for the information given to the guardians of children with HD preoperatively to TERPT and in the planning of the future care. The findings can, furthermore, provide a benchmark for the outcome from a single centre.

Adult patients with allied disorders of Hirschsprung’s disease in emergency department:An 11-year retrospective study

BACKGROUND In the past years,only a few studies with a limited number of adult patients analyzed clinical features of allied disorders of Hirschsprung’s disease(ADHD),most of which were individual case reports or lacked detailed clinical information.Although many studies have reported patients presenting to the emergency department(ED)with recurrent abdominal symptoms for a number of disorders,there are few data involving ADHD.However,owing to a lack of awareness of the disease,misdiagnoses and mistreatments are common.Severe complications such as perforation,bleeding,malabsorption,and even death in ADHD had been reported by many studies.AIM To assist ED clinicians in having a more comprehensive understanding of this disease and making an early suspected diagnosis of ADHD more effectively.METHODS We enrolled 53 patients who visited the ED and were eventually diagnosed with ADHD over the past 11 years in our hospital.Their basic information,clinical manifestations,and imaging findings were analyzed.Blood indices were compared between the ADHD and irritable bowel syndrome(IBS)groups.RESULTS Adult patients with ADHD had a mean age of 48.8±14.3 years,and 77.4%had been treated before admission.The transverse colon was the most common dilated part(73.6%),and constipation(67.9%)was the most common symptom.ADHD patients can present with uncommon symptoms and false-negative imaging findings.Logistic regression analysis indicated that body mass index(BMI)[odds ratio(OR)=0.786,P=0.013],cholinesterase(per 1000 units;OR=0.693,P=0.008),and blood chlorine(OR=0.816,P=0.022)were determined to be independent related factors between the ADHD and IBS groups.The area under the receiver operating characteristics curve of these three indices combined was 0.812(P<0.001).CONCLUSION Emergency physicians should be vigilant regarding patients with chronic constipation,abdominal pain,or abdominal distension,and consider the possibility of ADHD despite its rarity.Abdominal computed tomography examination is recommended as a useful tool in the suspected diagnosis of ADHD.BMI,cholinesterase,and blood chlorine have good discriminative abilities between ADHD and IBS.The nutritional status of adult patients with ADHD is worthy of further attention.Surgical treatment for adult patients with ADHD is important and inevitable.

Very early onset perinatal constipation:Can it be cow’s milk protein allergy?

Delayed passage of meconium or constipation during the perinatal period is traditionally regarded as a signal to initiate further work up to evaluate for serious diagnoses such as Hirschsprung’s disease(HD),meconium ileus due to Cystic Fibrosis,etc.The diagnosis of HD particularly warrants invasive testing to confirm the diagnosis,such as anorectal manometry or rectal suction biopsy.What if there was another etiology of perinatal constipation,that is far lesser known?Cow’s milk protein allergy(CMPA)is often diagnosed in infants within the first few weeks of life,however,there are studies that show that the CMPA allergen can be passed from mother to an infant in-utero,therefore allowing symptoms to show as early as day one of life.The presentation is more atypical,with perinatal constipation rather than with bloody stools,diarrhea,and vomiting.The diagnosis and management would be avoidance of cow's milk protein within the diet,with results and symptom improvement in patients immediately.Therefore,we discuss whether an alternative pathway to address perinatal constipation should be further discussed and implemented to potentially avoid invasive techniques in patients.This entails first ruling out CMPA with safe,noninvasive techniques with diet modification,and if unsuccessful,then moving forward with further diagnostic modalities.

Prevalence and Clinical Characteristics of Chronic Constipation in Senegalese Children

Introduction: Constipation is the infrequent emission of hard stools. It is common, most often of functional origin, with a prevalence ranging from 0.7% to 29.6%. The aim of our study was to investigate the prevalence of constipation in children undergoing paediatric gastroenterology. Methodology: This was a bi-centric retrospective study carried out at the Albert Royer Children’s Hospital and the Dalal Jamm Hospital Pediatrics Department. Children followed in the pediatric gastroenterology consultation during the period from January 1, 2013 to February 29, 2020 were included. Results: A total of 337 children (205 boys;60.83%) were included, representing a prevalence of 25%. The median age was 3 years 6 months. The 13 - 24 months age group was the most frequent (27.6%). Rare stools were the main reason for consultation (92.8%). Rare stools were noted in 92.88% of cases. Bristol types 1 and 2 accounted for 6.53% and 54.60% respectively. The main associated signs were abdominal pain (29.4%), followed by abdominal bloating (20.96%). Abdominal pain was functional in 73.58% of cases. Under treatment, 90.19% of children had a favorable outcome. Conclusion: Constipation is common in Senegalese children with a prevalence close to that reported in Western countries. In most case, it is functional with good prognostic.

Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung’s Disease

Endogenous peptides,bioactive agents with a small molecular weight and outstanding absorbability,regulate various cellular processes and diseases.However,their role in the occurrence of Hirschsprung’s disease(HSCR)remains unclear.Here,we found that the expression of an endogenous peptide derived from YBX1(termed PDYBX1 in this study)was upregulated in the aganglionic colonic tissue of HSCR patients,whereas its precursor protein YBX1 was downregulated.As shown by Transwell and cytoskeleton staining assays,silencing YBX1 inhibited the migration of enteric neural cells,and this effect was partially reversed after treatment with PDYBX1.Moreover,immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and PDYBX1.Downregulation of YBX1 blocked the ERK1/2 pathway,but upregulation of PDYBX1 counteracted this effect by binding to ERK2,thereby promoting cell migration and proliferation.Taken together,the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural cells.PDYBX1 may be exploited to design a novel potential therapeutic agent for HSCR.

Phenotypic and functional comparison of rat enteric neural crest-derived cells during fetal and earlypostnatal stages

In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.

Diagnostic Input of Specialized Radiographic Examinations in Pediatric Setting in Ouagadougou (Burkina Faso)

Context: In spite of the development of cross-sectional medical imaging and endoscopy means, the prescription of specialized radiographic examinations is still relevant in the pediatric environment in our country. Objective: Show the contribution of specialized radiographic examinations performed in pediatric settings. Methodology: This was a retrospective descriptive study implemented over a five year-period, from June 10th, 2014 to June 10th, 2019 within the radiology department of Charles De Gaulle Pediatric Teaching Hospital in Ouagadougou. This study included the results of 192 specialized radiographic examinations collected within the concerned department. Results: The average age of the patients was 4.21 years with extremes of 8 days and 15 years. Infants (29 days to 24 months) were the predominant age group with a rate of 53.13% (n = 102 patients). Boys represented 76.51% of the sample with a sex ratio estimated at 3.25. Specialized radiographic examinations represented 0.46% of the overall imaging examinations and 0.72% of radiographic examinations performed during the study period. 67.19% of pathological examinations were reported. Colonic enema and retrograde urethrocystography (RUC) were the most performed examinations respectively accounting for 33.34% and 27.6%. The radiographic findings were consistent with the diagnostic hypotheses in 41.6% of cases. Conclusion: Specialized radiographic examinations keep their place in the exploration of several pathologies in pediatric settings.

A NEW MODIFICATION OF TRANSANAL SOAVE PULL-THROUGH PROCEDURE FOR HIRSCHSPRUNG’S DISEASE

Background One stage transanal Soave pull-through procedure （TSPP） is a recent popular operation in the treatment of Hirschsprung＇s disease （HD）. With no visible scar and a short hospital stay, it is well accepted by surgeons and mothers. In the conventional Soave procedure, a long rectal muscular cuff left for anocolic anastomosis might increase the incidence of postoperative enterocolitis and constipation. This study presents a modified transanal Soave pull-through procedure （MTSPP） which includes an oblique mucosectomy and an oblique anastomosis with a short split muscular cuff.. Methods A review of two groups of HD patients was made： 112 underwent conventional transanal Soave procedure from 1999 to 2001 （group 1） and 140 underwent modified transanal Soave procedure from 2002 to 2004 （group 2）. A comparison was made between the two groups on operative data and postoperative complications. The data included： age at the operation, operating time, blood loss, time to feeds and hospital stay, occurrence of postoperative enterocolitis or constipation, need for anal dilatation, postoperative bowel function and perianal skin problems. Results There was no significant difference between two groups with respect to age, gender, length of colon resected, operating time, blood loss and hospital stay. However occurrence of postoperative enterocolitis, constipation, anastomotic stricture and time needed for anal dilatation were evidently less in group 2 （MTSPP）. The mean operating time in group 1 was （106 ± 39） minutes with a range of 60 to 170 minutes; in group 2 was （101 ± 36） minutes with a range of 66 to 190 minutes. The average length of the bowel resected in group 1 was （24 ± 7） cm, range 15 to 58 cm; in group 2 was （26 ± 8） cm, range 15 to 70 cm. Two patients, one in each group, required laparoscopic assistance because of long aganglionic colon. Another patient in group 2 required laparotomy because of total colonic aganglionosis. Postoperative complications in group 1 included： temporary perianal excoriation in 34 patients （26 were 〈3 months of age）, enterocolitis in 21, anastomotic stricture in 11, recurrent constipation in 12, cuff abscess in 1, anastomosis leak in 1, soiling in 3 and rectal prolapse in 1. In group 2 post operative complications included： transient perianal excoriation in 37 patients （30 were 〈3 months of age）, enterocolitis in 13, anastomotic stricture in 5, recurrent constipation in 6, anastomotic leak in 1, adhesive bowel obstruction in 1 and soiling in 4. Complete bowel continence was found in 97 children （86.6%） in group 1 and in 129 children （92.1%） in group 2 at one year followup after operation. Conclusions Modified transanal Soave pull-through procedure for HD with oblique mucosectomy and anastomosis and a short split muscular cuff is a safe and feasible operation with low incidence of postoperative complication. It is an encouraging improvement of the conventional transanal Soave pull-through procedure. MTSPP is a preferable choice in the surgery of HD.

Transanal, single stage, endorectal pull through for Hirschsprung's disease in China: a collective review

In China, the first report on transanal posterior myotomy of internal sphincter for ultrashort aganglionosis was in 1997,1 while reports of the transanal, single stage, Soave for Hirschsprung＇s disease （HD） began to appear only after Torre＇s paper,2 published in 1998. The transanal endorectal pull through for HD was soon widely used by Chinese paediatric surgeons even in many provincial hospitals and local modifications frequently reported in the literature. From 2001 to 2004, 85 papers on transanal pull through for HD were published, and from 1999 to 2004, 252 patients underwent transanal endorectal operation for HD in our department. After reviewing the literature and analysing the clinical data, we discuss the present status and possible further developments of transanal, single stage,

Novel Insights into the Pathogenesis of I-lirschsprung＇s-associated Enterocolitis

Objective： To systematically summary the updated results about the pathogenesis of Hirschsprung＇s-associated enterocolitis （HAEC）. Besides, we discussed the research key and direction based on these results. Data Sources： Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords ＂Hirschsprung enterocolitis＂, ＂Hirschsprung＇s enterocolitis＂, ＂Hirschsprung＇s-associated enterocolitis＂, ＂Hirschsprung-associated enterocolitis＂, ＂HAEC＂, and ＂EC＂. Study Selection： Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. Results： Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC. Conclusions： The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung＇s disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.