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.

Botulinum toxin injections after surgery for Hirschsprung disease:Systematic review and meta-analysis

BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.

The development of colon innervation in trisomy 16 mice and Hirschsprung’s disease

AIM To study the colon innervation of trisomy 16 mouse, an animal model for Downs syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprungs disease (HD). METHODS Trisomy 16 mouse breeding; cytogenetic analysis of trisomy 16 mice; and PGP 9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was revealed in the stenosed segment of HD colon. CONCLUSION Trisomy 16 mice could serve as an animal model for Hirschsprung s disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency.

Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype

AIM:To investigate the role of IKBKAP(inhibitor of kappa light polypeptide gene enhancer in B-cells,kinase complexassociated protein)in the development of enteric nervous system(ENS)and Hirschsprung disease(HSCR).METHODS:In this study,we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos.The phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker Hu C/D followed by enteric neuron counting.The mean numbers of enteric neurons were compared between the morphant and the control.We also studied the expressions of ret and phox2bb,which are involved in ENS development,in the ikbkap morpholino injected embryos by quantitative reverse transcriptase polymerase chain reaction and compared them with the control.RESULTS:We observed aganglionosis(χ2,P<0.01)and a reduced number of enteric neurons(38.8±9.9 vs50.2±17.3,P<0.05)in the zebrafish embryos injected with ikbkap translation-blocking morpholino(morphant)when compared with the control embryos.Specificity of the morpholino was confirmed by similar results obtained using a second non-overlapping morpholino that blocked the translation of ikbkap.We further studied the morphant by analysing the expression levels of genes involved in ENS development such as ret,phox2bb and sox10,and found that phox2bb,the ortholog of human PHOX2B,was significantly down-regulated(0.51±0.15 vs 1.00±0,P<0.05).Although we also observed a reduction in theexpression of ret,the difference was not significant.CONCLUSION:Loss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos.

Genetic interactions and modifi er genes in Hirschsprung's disease

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

Megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood

Hirschsprung＇s disease （HD） is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel, However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of lid in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient＇s bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify lid patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage. 2005 The WJG Press and Elsevier Inc. All rights reserved

Genetic polymorphism of UL144 open reading frame of human cytomegalovirus DNA detected in colon samples from infants with Hirschsprung's disease

AIM： To explore the genetic diversities of UL144 open reading frame （ORF） of cytomegalovirus DNA detected in colon tissue from infants with Hirschsprung＇s disease （HD） by sequencing UL144 DNA in 23 aganglionic colon tissue and 4 urine samples from 25 HD infants. METHODS： Nest PCR was performed for amplification of the UL144 gene. The UL144 gene was analyzed with soffwares, such as DNAclub, BioEdit, PROSITE database, and DNAstar. RESULTS： The strains from HD patients were distributed among three genotypes of UL144： group 1A （64%）, group 2 （24%）, and group 3 （12%）. The UL144 genotypes between strains from HD and control group were compared by chi square test （x^2 = 1.870, P = 0.393）. Strains from the colon were sporadically distributed in UL144 genotypes. CONCLUSION： There are genetic diversities of UL144 ORF in colon tissue of infants with HD. However, cytomegalovirus UL144 genotypes are not associated with clinical manifestations of HD.

Hirschsprung's disease:Is there a relationship between mast cells and nerve fibers?

AIM:To define the topography of mast cells and their numbers in cases of Hirschsprung's disease(HD)and non-HD,assess neural hypertrophy using imaging software and to study the relationship between mast cells and nerve fibers.METHODS:HE stained sections of 32 cases of chronic constipation in the age group of 0-14 years were reviewed for ganglion cells.AChE staining was performed on frozen sections of colonic and rectal biopsies.Based on their findings cases were divided into HD and non-HD and mast cells stained by toluidine blue were evaluated.Image analysis by computerized software was applied to S-100 stained sections for assessment of neural hypertrophy.RESULTS:Difference between number of mast cells in HD group(mean=36.44)and in non-HD group(mean =14.79)was statistically significant.Image analysis morphometry on S-100 stained sections served as a useful adjunct.The difference between number,size,and perimeter of the nerve fibers between HD and non-HD group was statistically significant.CONCLUSION:Mast cells are significantly increased in HD and their base line values are much higher in Indian children than that reported in Western literature.Their role in HD needs further research.Morphometry of S-100 stained nerve fibers is a useful adjunct to conventional methods for diagnosis of HD.

Clinical outcomes and ergonomics analysis of three laparoscopic techniques for Hirschsprung's disease

AIM: To report the clinical outcomes and ergonomics analysis of three laparoscopic approaches in the management of Hirschsprung's disease(HD).METHODS: There were 90 pediatric patients(63 boys, 27 girls; mean age: 3.6 ± 2.7 mo; range: 1.0-90.2 mo) who underwent laparoscopic endorectal pull-through Soave procedures for short- and long-segment HD in our hospital. Three laparoscopic approaches were used: conventional laparoscopic pull-through(CLP) in 30 patients between 2009 and 2013, single-incision laparoscopic pull-through(SILP) in 28 patients between 2010 and 2013, and hybrid single-incision laparoscopic pull-through(H-SILP) in 32 patients between 2011 and 2013. We applied the hybrid version of the single-incision approach in 2011 to preserve the cosmetic advantage of SILP and the ergonomic advantage of CLP. We retrospectively analyzed the clinical data, cosmetic results, and ergonomics of these three approaches to have a better understanding of the selection of one approach over another. RESULTS: The CLP, SILP, and H-SILP groups were similar in regard to age, sex, transition zone, blood loss, hospital stay, and intraoperative complications. Early and late postoperative results were not different, with equal daily defecation frequency and postoperative complications. No conversion to open technique was needed and none of the patients had recurrent constipation. With proper training, the ergonomics challenges were overcome and similar operative times were registered for the general operative time in the patients < 1 year of age and the short-segment HD patients. However, significantly shorter operative times were registered compared to SILP for patients > 1 year of age(CLP and H-SILP: 120 ± 15 min and 119 ± 12 min, respectively, vs 140 ± 7 min; P < 0.05) and for long-segment HD patients(152 ± 3.5 min and 154 ± 3.6 min, respectively, vs 176 ± 2.3 min; P < 0.05). The best cosmetic result was registered with the SILP(scarless), followed by the H-SILP(near scarless appearance) and the CLP(visible scars) procedures. CONCLUSION: Based on the results, we believed that the laparoscopic approach should be selected according to the age, transition zone, and desired cosmetic result.

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.

Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

AIM: To investigate whether the expression of platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells is altered in Hirschsprung’s disease (HD).METHODS: HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of PDGFRα+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

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.

Transumbilical enterostomy for Hirschsprung’s disease with a two-stage laparoscopy-assisted pull-through procedure

BACKGROUND A one-stage laparoscopic operation has recently been considered a favorable option for the management of patients with Hirschsprung's disease(HD)due to its superior cosmetic results.One-stage transanal endorectal pull-through for the treatment of rectosigmoid HD has been widely used in newborns without complications.However,enterostomy is required in some HD cases for enterocolitis and dilated colon.Our transumbilical enterostomy(TUE)and twostage laparoscopy-assisted anorectoplasty were effective and achieved a similar cosmetic effect to one-stage laparoscopy on the abdominal wall in patients with anorectal malformation,but the effect in patients with HD is unclear.AIM To evaluate the safety,efficacy and cosmetic results of TUE in two-stage laparoscopy-assisted pull-through for HD.METHODS From June 2013 to June 2018,53 patients(40 boys,13 girls;mean age at enterostomy:5.5±2.2 mo)who underwent enterostomy and two-stage laparoscopy-assisted pull-through for HD with stoma closure were reviewed at our institution.Two enterostomy approaches were used:TUE in 24 patients,and conventional abdominal enterostomy(CAE)in 29 patients.Eleven patients with rectosigmoid HD had severe preoperative enterocolitis or a dilated colon.26 patients had long-segment HD,and 16 patients had total colonic aganglionosis(TCA).The patients with left-sided HD underwent the two-stage laparoscopic Soave procedure,and the patients with right-sided HD and TCA underwent the laparoscopic Duhamel procedure.Demographics,enterostomy operative time,complications and cosmetic results were respectively evaluated.RESULTS There were no differences between the groups with respect to gender,age at enterostomy,weight and clinical type(P>0.05).No conversion to open technique was required.Two patients experienced episodes of stomal mucosal prolapse in the TUE group and 1 patient in the CAE group(8.33%vs 3.45%,P>0.05).No parastomal hernia was observed in either of the two groups.Wound infection at the stoma was seen in 1 case in the TUE group,and 2 cases in the CAE group(4.17%vs 6.90%,P>0.05).No obstruction was noted in any of the patients in the TUE group,whereas obstruction was found in 1 patient in the CAE group.Enterocolitis was observed in 3 and 5 patients in the TUE and CAE group,respectively(12.50%vs 17.24%,P>0.05).There was no significant difference between the TUE group and CAE group in terms of the incidence of soiling and constipation(P>0.05).The cosmetic result using the scar score in the TUE group was better than that in the CAE group(6.83±0.96 vs 13.32±1.57,P<0.05).CONCLUSION TUE is a safe and feasible method for the treatment of HD,and the staged enterostomy and two-stage laparoscopy-assisted pull-through achieved a similar cosmetic effect to the one-stage laparoscopic procedure.

Abundance and significance of neuroligin-1 and glutamate in Hirschsprung's disease

AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate(Glu) in Hirschsprung's disease(HSCR).METHODS: Ninety children with HSCR and 50 children without HSCR matched for similar nutritional status, age and basal metabolic index were studied. The expression and localization of neuroligin-1 and Glu were assessed using double-labeling immunofluorescence staining of longitudinal muscles with adherent myenteric plexus from the surgically excised colon of children with HSCR. Western blot analysis, quantitative real-time PCR(q RT-PCR) and immunohistochemistry were performed to evaluate the abundance of neuroligin-1 and Glu in different HSCR-affected segments(ganglionic, transitional, and aganglionic segments). Enzyme-linked immunosorbent assay(ELISA) was used to detect and compare serum Glu levels in the long-segment HSCR, short-segment HSCR and non-HSCR samples.RESULTS: Neuroligin-1 and Glu were co-expressed highest to lowest in the ganglionic, transi tional and aganglionic segments based on Western blot(neuroligin-1: 0.177 ± 0.008 vs 0.101 ± 0.006, 0.177 ± 0.008 vs 0.035 ± 0.005, and 0.101 ± 0.006 vs 0.035 ±0.005, P < 0.005; Glu: 0.198 ± 0.006 vs 0.115 ± 0.008, 0.198 ± 0.006 vs 0.040 ± 0.003, and 0.115 ± 0.008 vs 0.040 ± 0.003, P < 0.005) and q RT-PCR(neuroligin-1: 9.58 × 10-5 ± 9.94 × 10-6 vs 2.49 × 10-5 ± 1.38 × 10-6, 9.58 × 10-5 ± 9.94 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, and 2.49 × 10-5 ± 1.38 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, P < 0.005). Serum Glu level was the highest to lowest in the non-HSCR, short-type HSCR and long-type HSCR samples based on ELISA(in nmol/μL, 0.93 ± 0.31 vs 0.57 ± 0.25, 0.93 ± 0.31 vs 0.23 ± 0.16, and 0.57 ± 0.25 vs 0.23 ± 0.16, P < 0.005).CONCLUSION: Neuroligin-1 and Glu may represent new markers of ganglion cells, whose expression may correlate with the pathogenesis, diagnosis, differential diagnosis or classification of HSCR.

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.

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.

Literature Review of the Frequency of Reoperations 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) has gained worldwide acceptance. However surgical success is often reported separately, while the necessity for true reoperation is difficult to establish. Aim: To evaluate the incidence of reoperations following TERPT procedure. The findings will be important in counseling and planning childcare for HD patients as well as providing a benchmark for single centers clinical results. Methods: A literature review of reported TERPT operations on children with HD between 1998 through 2011 was performed. Only planned TERPT operation reports were included. Information was collected with particular emphasis on reoperations and their reasons. Results: Out of 26 published articles 23 were included, reporting on 836 children, female/male ratio: 1/3.3, undergoing the TERPT procedure as the only operative intervention with described postoperative courses. The children comprised neonates, 3 years of age (12%). The average follow up was 18.5 (6 - 38) months. The resected bowel length mean was 20.5 cm. Forty-one reoperations were reported (4.9%), including 24 laparotomies, 8 laparoscopies, 6 colostomies and ileostomies in 3 children. Only 2 re-do TERPT were reported (0.2%). Seven patients were considered TERPT failures (0.8%) with 5 requiring diverting colostomies and additional transabdominal pull-through operations. Two myectomies were performed (0.2%). One child with aganglionosis underwent a Duhamel pull through. Two (0.2%) had serious damage to the urinary tract also one child with a vas deferens lesion was reoperated. Two bowel obstructions required adhesiolysis. Eight anastomotic dehiscences (0.9%) required surgery after reparation. One prolapse of the pulled through colon was reported. Six patients (0.7%) suffered anastomotic leaks. Anastomotic strictures rate was 2.8%, all repaired with anal dilatation. Conclusion: The review supports the low incidence of reported reoperations for the TERPT procedure.

Reoperation in an adult female with "right-sided" Hirschsprung's disease complicated by refractory hypertension and cough

Hirschsprung's disease(HD) is an intestinal malformation caused by the innate absence of ganglion cells in the neural plexus of the colorectal wall, and is most common in male infants. It is rare in adult, and is usually left-sided. Herein we reported based on the CARE guidelines a case of a 47-year-old adult female suffering from "right-sided" HD complicated by refractory hypertension and cough. The patient with a history of cesarean section and with digestive unfitness(abdominal pain, distention, and constipation) only since 20 years old had recurrence of HD after initial surgery due to the incomplete removal of the HD-affected bowel based on a diagnosis of "chronic ileus", leading to the relapse of the digestive symptoms and the emergence of some intractable circulatory and respiratory complications which could be hardly controlled by conservative treatment. During the long interval before coming to our department for help, she had been re-hospitalized for several times with various misdiagnoses and supplied merely with symptomatic treatment which could only achieve temporary symptomatic relief. At her admission to our department, the imaging examinations strongly indicated recurrent HD which was further supportedb y p a t h o l o g i c a l e x a m i n a t i o n s, a n d r i g h t h e m i-colectomy was performed to remove the remnant aganglionic intestinal segment. Intraoperative and postoperative pathology supported the completeness of the definitive resection. Post-operation, the patient's bowel motility significantly improved, and interestingly, the complications disappeared. For adult patients with long-term constipation combined with cough and hypertension, rare diseases like HD which requires definite surgery and which could be "right-sided" should not be overlooked. It is vital to diagnose and cure HD patients in childhood. Through the comparison of the two surgeries, it is noteworthy that for diagnosed HD, sufficient removal of the non-functional intestine confirmed by intraoperative pathology is essential.

Mutation of RET proto-oncogene in Hirschsprung's disease and intestinal neuronal dysplasia

AIM： To investigate the genetic relationship between Hirschsprung＇s disease （HD） and intestinal neuronal dysplasia （IND） in Chinese population.METHODS： Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control. Genomic DNA was extracted according to standard procedure. Exons 11,13,15,i7 of RET proto-oncogene were amplified by polymerase chain reaction （PCR）. The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism （SSCP） and sequencing of the positive amplified products was performed.RESULTS： Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11 at nucleotide 15165 G→A （G667S）, 2 frameshifc mutations in exon 13 at nucleotide 18974 （18974insG）, 1 missense mutation in exon 13 at nucleotide 18919 A→G （K756E） and 1 silent mutation in exon 15 at nucleotide 20692 G→A（Q916Q） were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G→A and 1 silent mutation in exon 13 at nucleotide 18888 T→G （L745L） were detected. No mutation was found in IND patients and controls.CONCLUSION： Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of REr proto-oncogene mutation is quite different between IND and HD in Chinese population, IND is a distinct clinical entity genetically different from HD.

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.