Hirschsprung's Disease Patients Research Articles

Noncoding RET variants explain the strong association with Hirschsprung disease in patients without rare coding sequence variant

The pathogenesis of Hirschsprung disease is complex. Although the RET proto-oncogene is the most frequently affected gene in Hirschsprung disease, rare coding sequence variants explain only a small part of Hirschsprung disease cases. We aimed to assess the genetic background of Hirschsprung disease using a genome-wide association analysis combined with sequencing all RET exons in samples from 105 Hirschsprung disease cases (30 familial and 75 sporadic) and 386 controls.As expected, variants in or near RET showed the strongest overall association with Hirschsprung disease and the most statistically significant association was observed when using a recessive genetic model (rs2435357, NC_000010.10:g.43582056T > C; genotype TT, OR = 17.31, P = 1.462 × 10−21). Previously published associations in variants in SEMA (rs11766001, NC_000007.13:g.84145202A > C; allele C, OR = 2.268, P = 0.009533) and NRG1 (rs4541858, NC_000008.10:g.32410309A > G; allele G, OR = 1.567, P = 0.015; rs7835688, NC_000008.10:g.32411499G > C; allele C, OR = 1.567, P = 0.015) were also replicated in the genome-wide association analysis. Sequencing revealed a total of 12 exonic RET rare variants. Of these, eight amino acid changing rare variants and two frameshift variants caused or possibly caused Hirschsprung disease.Only a minority of the Hirschsprung disease cases (9/30 familial; 7/75 sporadic) carried one of the rare variants. Excluding the rare variant carriers from the genome-wide association analysis did not appreciably change the association of rs2435357 with Hirschsprung disease. We estimate that approximately two thirds of the sporadic cases may be statistically attributed to the recessive action of the common non-coding RET variants. Thus, even though most cases do not carry rare RET variants, combinations of rare variants and the common non-coding RET variant cause the majority of the cases in our population.

Urinary Outcomes in Patients with Down's Syndrome and Hirschsprung's Disease.

Previous research in children with Hirschsprung's disease (HD) and Down's syndrome (DS) has focused on colorectal outcomes. We set out to review urinary outcomes in this patient group. The medical records of all patients aged five years and older with HD were reviewed, and patients and caregivers filled out the Vancouver Symptom Score at intake, which is designed and validated to diagnose dysfunctional elimination syndrome. A total of 104 patients with HD were included in this study. Of these, 16 (15%) patients had DS. There were no significant differences in the prevalence of enterocolitis or colorectal symptoms between patients with or without DS. Five of 88 (6%) patients without DS and 7 of 16 (44%) (p = 0.00001) with DS reported having urinary accidents. Patients with HD and DS scored higher on the Vancouver score (9 vs. 17.5; p = 0.007), indicating more severe urinary symptoms. Patients who also reported fecal accidents scored significantly higher on the Vancouver (12 vs. 9; n = 61; p = 0.016), indicating more problems. Patients with DS appear to be a unique subset of HD patients who have a higher prevalence of urinary symptoms after surgery. In the postoperative care of patients with HD and DS, a strong focus should be placed on postoperative urinary care in addition to their bowel care. This could significantly ease care and contribute to the quality of life of the parents and the patient.

Functional outcomes in Hirschsprung disease patients after transabdominal Soave and Duhamel procedures

BackgroundSeveral pull-through procedures have been described for Hirschsprung disease (HSCR) with varying functional outcomes. The voluntary bowel movement (VBM) and the absence of soiling or constipation after pull-through remain the most important markers of good outcome. We aimed to compare the functional outcomes in HSCR patients following Soave and Duhamel procedures.MethodsKrickenbeck classification was utilized to determine VBM, soiling and constipation for patients who underwent Soave and Duhamel pull-through at Dr. Sardjito Hospital, Indonesia from 2013 to 2016.ResultsFifty-three patients were ascertained (Soave: 23 males and 2 females vs. Duhamel: 22 males and 6 females, p = 0.26). Ninety-three and 88% patients had a VBM following Duhamel and Soave pull-through, respectively (p = 0.66). Constipation frequency was significantly higher in Soave than Duhamel groups (24% vs. 4%; p = 0.04) with OR of 8.5 (95% CI = 1.0–76.7), whereas soiling rate was similar between Duhamel (21%) and Soave (8%) groups (p = 0.26). Furthermore, the risk of constipation was increased ~ 21.7-fold in female patients after Soave procedure and was almost statistically significant (p = 0.05).ConclusionsThe constipation rate is higher in patients who underwent Soave than Duhamel procedure, but the VBM and soiling frequencies are similar. The constipation risk following Soave pull-through might be increased by the female gender. Furthermore, a multicenter study with a larger sample of patients is necessary to clarify and confirm our findings.

Diagnostic Accuracy of Combined Acetylcholinesterase Histochemistry and Calretinin Immunohistochemistry of Rectal Biopsy Specimens in Hirschsprung's Disease.

Acetylcholinesterase (AchE) histochemistry has been established as an accurate diagnostic tool for Hirschsprung's disease (HD). In addition, calretinin immunohistochemistry is also reported as a reliable and adjunctive method to diagnose HD. We investigated the diagnostic value of combined AchE histochemistry and calretinin immunohistochemistry in rectal suction biopsies from HD and non-HD patients. We retrospectively reviewed 99 rectal suction biopsy specimens including 4 repeat biopsies from 95 patients (34 HD and 61 non-HD). Each specimen was evaluated with hematoxylin-eosin, AchE histochemistry, and calretinin immunohistochemistry. Of 95 patients, only 21 (22.1%) showed some ganglion cells. All 61 non-HD cases revealed no abnormal AchE-positive fibers. Of 34 HD patients, 32 exhibited abnormal AchE fibers, but 2 showed no stained fibers. None of the tissues from the HD patients exhibited calretinin immunoreactivity. Test sensitivity and specificity of AchE histochemistry alone were 93.5% and 100.0%, respectively, while calretinin immunohistochemistry were 100.0% and 85.2%, respectively. AchE histochemistry is a good diagnostic method for HD, if feasible, and a combination of AchE histochemistry and calretinin immunohistochemistry will help increase the accuracy of the diagnosis of HD.

Development of Nerve Fibre Diameter in Young Infants With Hirschsprung Disease.

Finding thickened nerve fibres is one of the key elements in the diagnosis of Hirschsprung disease (HD); however, its value at different ages remains uncertain. Nerve fibre diameters <40 μm can be observed in infants younger than 8 weeks, despite the presence of HD. The aim of this study was to identify a change in maximum nerve fibre diameter in HD patients, measured before and after 8 weeks of age. Nerve fibre diameter was retrospectively evaluated in tissue of 20 infants treated for definite HD. Rectal suction biopsies (RSBs) obtained within the first 8 weeks of life (T1) and resected bowel obtained during primary surgery at an average of 24.7 weeks (T2), were assessed. The 2 thickest nerve fibre diameter recordings at T1 and T2 were compared in each subject, to examine changes in nerve trunk diameter with increasing age. In 13 cases (65%), nerve fibre diameters were ≥40 μm at T1 and T2. Six subjects (30%) had nerve trunk diameters <40 μm at T1; however, they experienced diameter increases to ≥40 μm by T2. Thus, at T2, 19 subjects (95%) had diameter recordings ≥40 μm. Nerve fibre diameter in the remaining case (5%) stayed consistent at <40 μm at T1 and T2, despite the presence of HD. After the first 8 weeks of life, nerve fibre measurements appear to be associated with HD. Measuring the 2 thickest nerve fibres can support typical HD diagnosis criteria beyond 8 weeks of age, but is not superior to histopathological confirmation of aganglionosis.

Increased expression of Semaphorin 3A in the endothelin receptor-B null mouse model of Hirschsprung disease

PurposeSemaphorins are guidance cues for developing neurons, implicated in the determination of the migratory pathway of neural crest-derived neural precursors during enteric nervous system development. Recently, it has been reported that Semaphorin 3A (SEMA3A) expression is up-regulated in the aganglionic colon in Hirschsprung disease (HD) patients, suggesting that increased SEMA3A expression may be a risk factor for HD. Thus, the aim of our study was to determine the expression of SEMA3A using Sox10-Venus mice gut. MethodsWe harvested the gut on postnatal day 2 (P2). SOX10-Venus+/EDNRB−/− mice were compared with SOX10-Venus+/EDNRB+/+ mice as controls. QRT-PCR was performed to determine gene expression of SEMA3A (n=8). Fluorescent immunohistochemistry was performed to assess protein distribution. ResultsOn P2, gene expression levels of SEMA3A were significantly increased in the HD group compared to controls in the proximal and distal colon (p<0.05). Laser scanning microscopy revealed SEMA3A expression was localized within the submucosa and muscle layer of the gut in both HD and controls. In HD, SEMA3A was highly expressed in the proximal and distal colon. ConclusionsIn the present study, we demonstrated that SEMA3A expression is increased in the EDNRB−/− HD model on P2, suggesting that SEMA3A may interfere with ENCC migration, resulting in an absence of enteric neurons.

Colonic Adventitial Fibromuscular Dysplasia: A Nonspecific Arteriopathy Associated With Hirschsprung Disease and Other Obstructive Disorders.

Background Smooth muscle differentiation ("adventitial fibromuscular dysplasia," AFD) was purported as specific to arteries in the transition zone of Hirschsprung disease (HSCR) patients. We investigated AFD in an HSCR population and controls and consider the pathogenesis and significance of the vascular pathology. Design Vascular histology in sections from colonic HSCR resections (n = 55) was compared with age- and site-matched controls with (n = 19) and without (n = 28) non-HSCR obstructive conditions. Vascular pathology was mapped, and correlations were sought between the vascular findings and bowel distension, inflammation, neuromuscular anatomy, preoperative clinical variables, and postsurgical complications. Results One of 2 forms of AFD was identified in 42% (23/55) of the HSCR resections: the previously described "mature" form with adventitial bundles of differentiated smooth muscle cells (7/23, all submucosal) and a newly described "immature" AFD characterized by densely packed myofibroblasts in the arterial adventitia (16/23, 3 submucosal, 3 serosal, and 10 both). Adventitial inflammation and/or medial necrosis was present in the immature form (6/16). Mature submucosal AFD was present in 2/28 (7.1%) nonobstructive and 5/19 (26%) obstructive non-HSCR controls ( P = .10). Immature AFD was only found in less than 1-month-olds, and mature AFD only in older patients, including the 7 affected controls. AFD did not correlate with sex, syndromic status, length of the aganglionic segment, or postoperative complications. AFD was present in grossly dilated (17/23) and narrowed (10/23) regions and in the aganglionic (2/23), ganglionic (14/23), or both (7/23) segments. In several cases, AFD existed proximal to the histological transition zone. Conclusion AFD occurs in HSCR and other obstructive conditions but is significantly less common in the colons of patients with no history of dysmotility. The pathology likely progresses from a reversible accumulation of myofibroblasts in neonates to a stable population of mature smooth muscle cells. The distribution of vascular lesions does not correlate with neuropathological findings and suggests a nonspecific form of vascular injury, possibly related to bowel distension. AFD in HSCR resections has not been shown to be clinically significant and should not influence management.

Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients

BackgroundEnteric glial cells are essential for normal gastrointestinal function. Abnormalities in glial structure, development, or function lead to disturbances in gastrointestinal physiology. Fatty acid–binding protein 7 (FABP7) is a marker of immature enteric glial cells, whereas S100 is expressed only by mature glial cells. Patients with Hirschsprung's disease (HSCR) often suffer from dysmotility and enterocolitis despite proper surgery. We designed this study to determine the distribution and expression of glial cells in patients with HSCR compared to normal controls. MethodsWe investigated FABP7, S100, and PGP 9.5 expressions in both the ganglionic and aganglionic bowel of patients with HSCR (n = 6) versus normal control colon (n = 6). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expressions were quantified using quantitative real-time polymerase chain reaction (qPCR), Western blot analysis, and densitometry. ResultsqPCR and Western blot analysis demonstrated a significantly increased FABP7 expression in ganglionic specimens compared to control specimen (P < 0.05). Confocal microscopy revealed FABP7+ glia cells lie under the colonic epithelium and in close apposition to enteric neurons in the ganglionic bowel. ConclusionsThe significantly increased number of immature enteric glial cells (EGCs) in the ganglionic bowel of HSCR patients may have adverse effect on the function of enteric neurons and intestinal barrier and thus predispose these patients to intestinal motility problems and enterocolitis.

Quality of life outcomes in children with Hirschsprung disease

BackgroundMorbidity following repair of Hirschsprung disease (HD) is common. However, quality of life (QoL) results focused on HD children are contradictory. We aimed to measure QoL outcomes in HD children using validated questionnaires. MethodsPatients with HD, managed at a large tertiary pediatric institution between 2004 and 2013, were identified. Parents completed validated questionnaires. Results were compared with published healthy population controls. QoL outcomes were measured using Pediatric Quality of Life (PedsQL) and Fecal Incontinence and Constipation Quality of Life (FIC QOL). Functional outcomes were assessed using Baylor Continence Scale, Cleveland Clinic Constipation Scoring System, and Vancouver Dysfunctional Elimination Syndrome Survey. ResultsParents of 60 HD patients [M:F 49:11; median age 6.4years (2.3–10.9)] were interviewed (59% participation). The majority (47/60, 78%) had rectosigmoid disease. There was significant reduction in psychosocial (social and emotional) QoL compared with healthy children (p=0.03). Psychosocial functioning was affected by increasing age (r=−2.72, p<0.001), fecal incontinence (r=−0.475, p=0.007), constipation (r=−1.58, p=0.006), and dysfunctional elimination (r=−2.94, p=0.004). Fecal incontinence also reduced physical functioning QoL (r=−0.306, p=0.007). Children with HD had significantly higher levels of fecal incontinence (p<0.01). ConclusionsWe have demonstrated that HD children have significant reductions in psychosocial QoL and functional outcomes. Level of evidencePrognosis Study – Level II (Prospective cohort study).

The bowel function and quality of life of Hirschsprung disease patients who have reached 18 years of age or older – the long-term outcomes after undergoing the transabdominal soave procedure

Background/purposeHirschsprung disease (HD) is considered curable, but the postoperative bowel function is not always satisfactory. In this study, we evaluated the general condition, bowel function, and social performance in adults who were older than 17years of age who had undergone definitive operations in childhood. MethodFrom 1984 to 2016, 110 patients with HD underwent definitive surgery at our institute. Sixty-three patients who had undergone the transabdominal Soave procedure reached 18years of age. Their present status and symptoms, anorectal function, genitourinary function, and social performance were evaluated during the clinical follow-up via a questionnaire survey. ResultThe mean age of the questionnaire respondents was 25.0 (19–37) years. The bowel function was mostly good. However, 56% of patients had abdominal pain more than once a week. Regarding evacuation symptoms, incontinence and soiling occurred in 18.7%. Among the respondents 33.3% were married, and 60% of those who were married had children. The respondents had achieved success in their education and professional careers. ConclusionThe bowel function of most patients was satisfactory, although some had chronic abdominal symptoms. Pediatric surgeons should continue trying to achieve complete bowel function after definitive surgery of HD. Type of studyProspective Cohort Study. Level of evidenceLevel III.

Comparison of Hirschsprung-associated enterocolitis following Soave and Duhamel procedures

BackgroundHirschsprung-associated enterocolitis (HAEC) represents the primary cause of high morbidity and mortality in Hirschsprung disease (HSCR) patients. The most common surgical methods for HSCR are the Soave and Duhamel procedures. Therefore, we aimed to compare the HAEC frequency following the Soave and Duhamel procedures. MethodsMedical records were retrospectively analyzed for patients who underwent the Soave and Duhamel pull-through at Dr. Sardjito Hospital, Indonesia from 2010 to 2015. The diagnosis of HAEC was determined using a HAEC scoring system. ResultsOne hundred patients were involved (Soave: 52 males and 19 females vs. Duhamel: 23 males and 6 females, p=0.62). There was significant difference in mean age at pull-through (Soave: 29.9±45.2 vs. Duhamel: 50.8±47.5months, p=0.04), whereas mean age of HSCR diagnosis and pre-operative enterocolitis frequency did not differ significantly between groups (Soave: 25.4±41.0 vs. Duhamel: 43.7±48.1months, p=0.06, and Soave: 7% vs. Duhamel: 14%, p=0.44, respectively). The HAEC frequency after pull-through was significantly higher in the Duhamel than the Soave group (28% vs. 10%, respectively, p=0.03). Furthermore, pre-operative enterocolitis showed a significant association with HAEC following pull-through (p=2.0×10–4) and the risk of HAEC after Soave pull-through was increased in long-segment aganglionosis compared to short-segment HSCR (p=0.015). ConclusionsThe frequency of HAEC was significantly higher after the Duhamel than the Soave procedure. Moreover, patients with pre-operative enterocolitis are prone to have HAEC following pull-through. Level of evidenceIII

Down-regulation of fibronectin and the correlated expression of neuroligin in hirschsprung disease.

The goal of this study was to investigate the expression of fibronectin (FN) and the correlated abundance of neuroligins (NLs) in the enteric nervous system (ENS) and to find a novel diagnostic marker in the serum of Hirschsprung disease (HSCR) patients. The expression levels of FN, neuroligin-1 and neuroligin-2 were detected in 114 children with or without HSCR. The expression and localization of the NLs and FN were assessed morphologically by immunohistochemical staining. Western blot analysis and real-time fluorescence quantitative PCR (qPCR) were performed to examine the correlated expression of the NLs and FN in aganglionic, transitional, and normal ganglionic colon tissues. An enzyme-linked immunosorbent assay (ELISA) was performed to evaluate and compare serum FN levels between HSCR and non-HSCRand between long-type HSCR and short-type HSCR. These studies showed that both neuroligin-1 and neuroligin-2 were expressed at low levels in aganglionic segments and at intermediate levels in transitional segments compared to their high level of expression in normal tissue. In contrast, FN expression was negatively correlated, with expression in these three samples transitioning from highest to lowest. The serum FN level was higher in HSCR than in non-HSCR, but no significant difference between short-type HSCR and long-type HSCR was observed. FN affects the expression of both neuroligin-1 and neuroligin-2 in HSCR, which may lead to the hypoplasia of ganglion cells in the ENS. This correlation may play a key role in the pathogenesis, diagnosis, or classification of HSCR.

Persistent distention of colon damages interstitial cells of Cajal through Ca2+ -ERK-AP-1-miR-34c-SCF deregulation.

Gastrointestinal motility disorders (GMDs) are attributed to loss of interstitial cells of Cajal (ICC), whose survival and function are deeply dependent on the activation of KIT/SCF signalling. Based on the facts that gastrointestinal distention is common in GMD patients and SCF produced by smooth muscle cells (SMCs) is usually decreased before ICC loss, we considered a possible contribution of persistent gastrointestinal distention/stretch to SCF deficiency. In this study, chronic colonic distention mouse model, diabetic gastrointestinal paresis mouse model, cultured mouse colonic SMCs and colon specimens from Hirschsprung's disease patients were used. The results showed that SCF was clearly decreased in distent colon of mice and patients, and microRNA array and real‐time PCR indicated a concomitant increase of miR‐34c in distent colon. A negative regulation of miR‐34c on SCF expression was confirmed by luciferase reporter assays together with knock‐down and overexpression of miR‐34c in cultured colonic SMCs. Using EMSA and ChIP assays, we further consolidated that in response to persistent stretch, the transcription factor AP‐1/c‐Jun was highly activated in colonic SMCs and significantly promoted miR‐34c transcription by binding to miR‐34c promoter. Knock‐down or overexpression of AP‐1/c‐Jun in cultured colonic SMCs leads to down‐ or up‐regulation of miR‐34c, respectively. In addition, the activation of AP‐1/c‐Jun was through ERK1/2 signalling provoked by Ca2+ overload in colonic SMCs that were subject to persistent stretch. In conclusion, our data demonstrated that persistent distention/stretch on colonic SMCs could suppress SCF production probably through Ca2+‐ERK‐AP‐1‐miR‐34c deregulation, resulting in ICC loss or impairment and GMD progress.

A Comparative Study between Swenson Abdominoperineal Pull-through and Transanal, Full Thickness, Swenson like Approach for Hirschsprung Disease

Background: Hirschsprung disease (HD) is a congenital developmental disorder of intrinsic component of enteric nervous system leading to severe complication which needs operative correction. There are different operative techniques existing and each technique has its advantages and disadvantages.Objective: The aim of the study was to evaluate the better outcome between Transanal full thickness swenson like pull through and Swenson abdomino-perineal pull through.Method: The Prospective comparative study had been carried out in the department of paediatric surgery, Dhaka Shishu (Children) Hospital during the period of January 2014 to July 2016. Total 56 patients with HD patients were included in the study irrespective of colostomy except major co-morbidities which can influence the general outcomes and who did not agree to close stoma within 12 weeks of pull-through operation. Patients were allocated in both groups by purposing sampling. Twenty eight patients with long segment HD were allocated in Group-A and operated by Swenson abdominoperineal pull through and 28 patients with short segment disease were allocated in group-B and operated by Transanal, full thickness, swenson like procedure.Result: Among the study population 32 (57.14%) were male and 24 (42.86%) were female with age range was 1 day- 96 months. Four patients developed urinary incontinence, 3 patients developed cuff abscess and 2 patients developed fecal incontinence. And in group-B no patient developed urinary incontinence but 4 developed cuff and anastomotic abscess and no patient developed fecal incontinence. The mean operation time 114.14 ± 13.02 in group-A and 68.36 ± 16.12 minutes in group-B. Mean hospital stay in group-A was 6.18 ± 1.83 days and 5.05 ± 0.43 days in group-B.Conclusion: The newer modification, Transanal, full thickness Swenson like procedure can be better technique in the management of HD.Bangladesh Crit Care J March 2017; 5(1): 23-27

Evaluation of suspicious Hirschsprung disease in children using radiologic investigation method: a prospective observational study

Background: Hirschsprung disease (HD) is a developmental disorder characterized by absence of ganglia in the distal colon, resulting in a functional obstruction. It is a common cause of pediatric intestinal obstruction. Objective of present study was to evaluate a checklist of radiologic and clinical signs to determine the probability of HD in suspicious patients.Methods: In a diagnostic accuracy study, 19 children with clinical manifestations of HD attended pediatric OPD in a tertiary care teaching hospital, Haldia from January 2014 to December 2016 were assessed. A checklist was used to evaluate the items proposed by contrast enema (CE), based on six subscales, including transitional zone, rectosigmoid index (RSI), irregular contractions in aganglionic region, cobblestone appearance, filling defect due to fecaloid materials and lack of meconium defecation during the first 48 hours after birth. The patients were classified as high score and low score. Sensitivity and specificity were calculated for identifying HD, in comparison with pathologically proved or ruled out HD.Results: Of the 19 patients, 11 (57.89%) cases had HD and 08 (42.11%) cases were without HD. The mean age was 2.793 ± 4.21 months. Abdominal distension, lack of meconium defecation, and constipation were the most common clinical symptoms with frequencies of 15 (78.9%), 11 (57.8%), and 14 (73.68%), respectively. In summary, the mean sensitivity of detecting the radiological signs of transition zone, spastic colon, reversed recto-sigmoid index and the overall impression in histological confirmed HD patients are 59.09%, 49.99%, 59.09% and 56.06% respectively.Conclusions: The mean specificity of detecting the absence of the radiological signs of transition zone, spastic colon, reversed recto-sigmoid index and the overall impression in histological confirmed non-HD patients are 68.75%, 81.25%, 87.5% and 79.17% respectively. This would in turn give an overall mean specificity rate of 79.17% in successfully excluding HD with the above mentioned radiological signs from the contrast enema.

Bowel Function and Quality of Life After Transanal Endorectal Pull-through for Hirschsprung Disease: Controlled Outcomes up to Adulthood.

The aim of this study was to define controlled outcomes up to adulthood for bowel function and quality of life (QoL) after transanal endorectal pull-through (TEPT) for Hirschsprung disease (HD). Although TEPT is the surgical standard for HD, controlled long-term follow-up studies evaluating bowel function and QoL are lacking. Patients aged ≥4 years operated for HD with TEPT between 1987 and 2011 answered detailed questionnaires on bowel function and QoL [Pediatric Quality of Life Inventory (PedsQL, age <18 yrs) or Gastrointestinal Quality of Life Index (GIQLI) and SF-36]. Patients were compared with 3 age- and gender-matched controls each randomly selected from the general population. Seventy-nine patients (64%) responded (median age 15, range 4-32 years; 86% rectosigmoid aganglionosis). Compared with controls, patients reported impairment of all aspects of fecal control (P < 0.05), except constipation. In cross-section, 75% of patients were socially continent (vs 98% of controls; P < 0.001). Soiling, fecal accidents, rectal sensation, and ability to withhold defecation improved with age to levels comparable to controls by adulthood (P = NS), but stooling frequency remained higher in 44% of patients (P < 0.05 vs controls). PedsQL domains in childhood were equal to controls (P = NS), except for proxy-reports of sadness/depression. Adults exhibited lower emotional scores, limitation of personal, and sexual relationships (P < 0.05). Compared with matched peers, significant impairment of fecal control prevails after TEPT in HD patients during childhood, but symptoms diminish with age. Although overall QoL appeared comparable to controls, impairment of emotional and sexual domains may prevail in adulthood.

A Nordic multicenter survey of long-term bowel function after transanal endorectal pull-through in 200 patients with rectosigmoid Hirschsprung disease

ObjectiveTransanal endorectal pull-through (ERPT) is the most popular technique to treat Hirschsprung disease (HD). Still, there is limited knowledge on long-term bowel function. This cross-sectional, multicenter study assessed long-term bowel function in a large HD population and examined predictors of poor outcome. MethodsPatients older than four years or their parents filled out a validated questionnaire on bowel function. Clinical details were recorded retrospectively from medical records. Results73/200 (37%) patients reported absolutely no impaired bowel function, meaning no constipation, fecal accidents, stoma, appendicostomy or need for enemas. Seven (4%) had a stoma, and 33 (17%) used antegrade or rectal colonic enemas. Most disarrangements of fecal control and constipation were significantly less common in older age group, but abnormal defecation frequency and social problems remained unchanged. Syndromic patients (n=31) experienced frequent fecal accidents (46%) more often than nonsyndromic (14%, P<0.001). Having a syndrome (adjusted OR 5.6, 95% CI 2.1–15, P=0.001) or a complete transanal ERPT (adjusted OR 2.4, 95% CI 1.1–5.7, P=0.038) was significantly associated with poor outcome defined as having a stoma, an appendicostomy, daily fecal accidents or need of regular rectal wash outs. ConclusionA significant number of HD patients experience bowel problems many years after definite surgery. Fecal control was significantly better in older than younger HD patients, but some continued to have considerable bowel problems also as adults. A total transanal ERPT was associated with poorer outcome. Long-term follow-up of HD patients is warranted.Prognosis Study: Level II.

Diagnosis, Symptoms, and Outcomes of Hirschsprung's Disease from the Perspective of Gender.

Background/Aim. Hirschsprung's disease (HD) has a skewed gender distribution, with a female to male ratio of 1 : 4. This study aims to examine differences between boys and girls with HD regarding preoperative features and postoperative treatment and outcome. Method. The first part of the study was conducted as a retrospective review of all HD patients who underwent transanal endorectal pull-through (TERPT). Pre-, peri-, immediate post-, and first-year postoperative data were collected. The second part was conducted as an observational cross-sectional study by comparing bowel function scores (BFS) determined by structured interviews of patients 4 years old and older. Results. Included were 39 boys and 12 girls. Of these, 25 boys and 9 girls were older than 4 years and participated in the BFS interview. Boys had a higher frequency of hospitalizations during the first postoperative year compared to girls (n = 20 and n = 2, p < 0.05). At long-term follow-up, more boys reported abnormal frequency of defecation, 16 compared to 2 (p < 0.05). There was no difference between genders in terms of preoperative symptoms and overall bowel function later. Conclusion. Boys with HD had more hospitalizations and a higher rate of abnormal frequency of defecation than girls with HD.

Long-term outcome of bowel function for 110 consecutive cases of Hirschsprung's disease: Comparison of the abdominal approach with transanal approach more than 30 years in a single institution – is the transanal approach truly beneficial for bowel function?

BackgroundWe compared the long-term outcomes of the bowel function (BF) in Hirschsprung's disease (HD) patients who underwent transanal endorectal pull-through (TA) with those who underwent the Soave–Denda (SD) procedure. MethodsPatient data were collected from 1984 to 2015 from 110 HD patients who underwent definitive diagnosis and operation. The follow-up data were analyzed retrospectively. BF was evaluated according to the evacuation score (ES) of the Japan Society of Anorectal Malformation Study Group at 3, 5, 7, 9, and 11years of age. ResultsThe operative procedures performed were as follows: SD: 71 (64.5%), TA: 38 (34.5%), and Duhamel: 1 (1.0%). We compared SD with TA. The ES improved chronologically after both procedures, and patients achieved satisfactory results at least 10years after operation. There was no significant difference in the total ES at all ages. The incontinence and frequency of bowel movement scores of TA patients were significantly lower than those of SD patients at several points. ConclusionTA is simple, less invasive, and adaptive for neonates and small infants. However, regarding the bowel function, TA is not always superior to SD. The surgical technique of TA must be improved according to a detailed understanding of the anatomy. Level of evidenceRetrospective study – level III.

Congenital factor VII deficiency in Hirschsprung disease patient, a novel case report

Abstract This case report presents a novel finding of Rectosigmoid Hirschsprung disease in association with Factor VII deficiency in 2 years female presented to King Abdulaziz University Hospital (KAUH). She was admitted in pediatric surgery unit. On examination; she looked ill and there were signs of infection at the colostomy site. The infection was treated and her overall health improved in 2 months. Mixing study and Factor VII level confirmed the presence of Factor VII deficiency. Congenital Factor VII deficiency is a rare autosomal recessive disease occurring at a rate of 1:500,000 individuals while Hirschsprung disease (HD) is found in 1:5000 individuals. The combination of these two disorders is extremely rare. The patient was successfully managed for both disorders and discharged in good health in stable condition with no hemorrhagic complication. This case report describes an exceptionally unusual combination of congenital factor VII deficiency and Hirschsprung Disease in same patient.