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Purpose: Skip segment Hirschsprung's disease (SS-HSCR) is defined as the occurrence of a segment of ganglionated intestine surrounded proximally and distally by aganglionosis. The presence of the skip intestinal segment often leads to clinical misdiagnosis, missed diagnosis or inadequate resection of the lesions. The purpose was to describe two new cases of SS-HSCR with the aim of proposing questions regarding the diagnosis and treatment of this rare disease.Methods: We reported two cases of infants with SS-HSCR that were admitted to our institution within the last 3 years.Results: One patient had a skip segment of ganglionated intestine in the ascending colon. In the other patient, there were no ganglionic cells in the rectum and appendix, but ganglionic cells were visible in the proximal ascending colon. The entire colons in the both cases were finally resected, and a pull-through operation was performed.Conclusion: Multipoint biopsy should be performed when the biopsy results are inconsistent with clinical manifestations. Intraoperative laparoscopic identification of the transition zone may be necessary when TCA is suspected. Multisegment biopsy is needed to as a preventative measure for SS-HSCR if TCA is indicated during surgery. Further study is required to determine the optimal length and method of retention of segments. [ABSTRACT FROM AUTHOR]

Background: Absent submucosal ganglion cells in biopsies 1-3 cm above the pectinate line establishes the pathologic diagnosis of Hirschsprung Disease (HD). Calretinin stains both ganglion cells and their mucosal neurites and has gained importance in HD diagnosis. Absent calretinin positive mucosal neurites in biopsies at the appropriate level above the pectinate line is highly specific for HD. Whether this applies to lower biopsies is uncertain. To address this, we studied anorectal canal autopsy specimens from infants. Methods: We performed an autopsy study of infant anorectal canal specimens to describe calretinin staining in this region. Calretinin staining was correlated with histologic and gross landmarks. Results: In all 15 non-HD specimens, calretinin positive mucosal neurites were present in glandular mucosa up to the anorectal line where neurites rapidly diminished. Age range was preterm 26 weeks to 3 months. Conclusions: Calretinin positive mucosal neurites are present in glandular mucosa up to the anorectal line in young infants. This is potentially important regarding neonatal HD biopsy level and diagnosis. Positive calretinin staining at the anorectal line favors normal innervation making HD unlikely. Absent calretinin positive neurites in glandular mucosa is worrisome for HD in young infants, regardless of location. [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) is the leading cause of neonatal functional intestinal obstruction. It is a rare congenital disease with an incidence of one in 3,500–5,000 live births. HSCR is characterized by the absence of enteric ganglia in the distal colon, plausibly due to genetic defects perturbing the normal migration, proliferation, differentiation, and/or survival of the enteric neural crest cells as well as impaired interaction with the enteric progenitor cell niche. Early linkage analyses in Mendelian and syndromic forms of HSCR uncovered variants with large effects in major HSCR genes including RET, EDNRB, and their interacting partners in the same biological pathways. With the advances in genome-wide genotyping and next-generation sequencing technologies, there has been a remarkable progress in understanding of the genetic basis of HSCR in the past few years, with common and rare variants with small to moderate effects being uncovered. The discovery of new HSCR genes such as neuregulin and BACE2 as well as the deeper understanding of the roles and mechanisms of known HSCR genes provided solid evidence that many HSCR cases are in the form of complex polygenic/oligogenic disorder where rare variants act in the sensitized background of HSCR-associated common variants. This review summarizes the roadmap of genetic discoveries of HSCR from the earlier family-based linkage analyses to the recent population-based genome-wide analyses coupled with functional genomics, and how these discoveries facilitated our understanding of the genetic architecture of this complex disease and provide the foundation of clinical translation for precision and stratified medicine.

Long-Segment Hirschsprung Disease (LSHD) differs clinically from short-segment disease. This review article critically appraises current literature on the definition, management, outcomes, and novel therapies for patients with LSHD. Four questions regarding the definition, management, and outcomes of patients with LSHD were generated. English-language articles published between 1990 and 2018 were compiled by searching PubMed, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar. A qualitative synthesis was performed. 66 manuscripts were included in this systematic review. Standardized nomenclature and preoperative evaluation for LSHD are recommended. Insufficient evidence exists to recommend a single method for the surgical repair of LSHD. Patients with LSHD may have increased long-term gastrointestinal symptoms, including Hirschsprung-associated enterocolitis (HAEC), but have a quality of life similar to matched controls. There are few surgical technical innovations focused on this disorder. A standardized definition of LSHD is recommended that emphasizes the precise anatomic location of aganglionosis. Prospective studies comparing operative options and long-term outcomes are needed. Translational approaches, such as stem cell therapy, may be promising in the future for the treatment of long-segment Hirschsprung disease. [ABSTRACT FROM AUTHOR]

Background: Hirschsprung's disease (HD) is a genetic disorder with a complex pattern of inheritance. Some single-nucleotide polymorphisms (SNPs) are identified to be associated with the risk of Hirschsprung's Disease (HSCR). Aims and Objectives: The aim of this study is to know the association between the rearranged during transfection (RET) proto-oncogene polymorphism and HD and to characterize the SNPs of RET proto-oncogene affecting HD. Materials and Methods: The study was conducted in the Department of Pathology in association with the Department of Pediatric Surgery. Blood samples were collected from the patients diagnosed with confirmed HD and from age- and sex-matched controls. This case–control study consisted of 53 HSCR cases and 50 controls. Genotypes of rs1800860 and rs1800861 were analysed in by polymerase chain reaction amplification and sanger sequencing. Associations with the risk of HSCR were estimated by odds ratio (OR) and their 95% confidence intervals (95% CI) using. Results: We observed that in the case of rs1800860A > G genotype AG was not associated with the increasing risk of disease (OR with 95% CI = 0.568 [0.238–1.356]) while genotype GG was associated with increasing the risk of the disease (OR with 95% CI = 2.278 [0.967–5.366]). In the case of rs1800861G > T genotype GT was associated with lowering the risk of the disease (OR with 95% CI = 0.230 [0.0981–0.539]) while genotype TT was associated with increasing the risk of the disease (OR with 95% CI = 9.647 [3.830–24.302]). The difference in the genotypic distribution of GT and TT at rs1800861G > T between Short segment disease (SSD) cases and Long Segment Disease (LSD) and total colonic aganglionosis was made by Fisher's exact test and it was statistically significant (P = 0.0476 and 0.0054). Conclusion: The results of this study support the hypothesis that variations in RET pathway might play an important role in the development of HSCR.

Abstract Background Total colonic and small bowel aganglionosis (TCSA) occurs in less than 1% of all Hirschsprung’s disease patients. Currently, the mainstay of treatment is surgery. However, in patients with TCSA, functional outcomes are often poor. A characteristic transition zone in TCSA can be difficult to identify which may complicate surgery and may often require multiple operations. Case presentation We present the case of a male infant who was diagnosed with biopsy-proven total colonic aganglionosis with extensive small bowel involvement as a neonate. The patient was diverted at one month of age based on leveling biopsies at 10 cm from the Ligament of Treitz. At 7 months of age, during stoma revision for a prolapsed stoma, intra-operative peristalsis was observed in nearly the entire length of the previously aganglionic bowel, and subsequent biopsies demonstrated the appearance of mature ganglion cells in a previously aganglionic segment. Conclusions TCSA remains a major challenge for pediatric surgeons. Our case introduces new controversy to our understanding of aganglionosis. Our observations warrant further research into the possibility of post-natal ganglion maturation and encourage surgeons to consider a more conservative surgical approach.

Introduction. Hirschsprung’s disease is a congenital anomaly characterized by the absence of ganglion cells in submucosal and intramuscular layers of intestinal wall that leads to the intestinal obstruction. 70–80 % of cases are isolated malformation but it can be combined with chromosomal abnormalities and other malformations. Coexistence of Hirschsprung’s disease with intestinal atresia is extremely rare. It can cause significant difficulties in diagnostics and treatment.Material and methods. Patient A, a boy, was transferred to the surgical department at the age of two days with a history of intestinal obstruction. He had abdominal X-ray studies: intestinal obstruction. The contrast enema showed microcolon that was coiled in the pelvis. Patient was prepared to the surgical treatment. Intraoperatively colonic atresia was identified at 10 sm from the ileocecal valve. A double colostomy was performed to the child and biopsy on the level of mucous fistula was taken. Histological study showed the aganglionosis of the distal colon. At the age of 4 months, the patient underwent Soave-Swenson endorectal pullthrough procedure with intraoperative extended express-biopsy that confirmed the absence of ganglion cells in whole distal bowel. The aganglionic part was resected, the ileocecal valve with the part of the colon of 10 cm long was mobilized and the endorectal bringing the colon down to the perineum was performed by Soave – Swenson. Postoperative recovery was uneventful.Results. A high index of suspicion is required to promptly diagnose Hirschsprung’s disease in a child with colonic atresia despite the rare combination of these two anomalies. In this case the histological study allowed to recognize association of colonic atresia with Hirschsprung’s disease and helped to avoid complications after further surgery.Conclusions. Early detection of coexisting of these two anomalies helps to prevent the development of serious postoperative complications.

To identify influence of different values of age and abnormal bowel length in HD patients selected for single stage TERPT which affects the technique of surgery. This observational study was carried out for over 2.5 years. All children younger than 14 years old with clinical suspicion for HD, typical transitional zone (TZ) on contrast enema (CE) distal to splenic flexure, preoperative diagnosis approved by full thickness biopsy, no previous surgical history and no urgency were included. The distance between the anus and TZ was considered as aganglionic length on CE. Biopsy was taken from distal to proximal of resected bowel to reach circumferentially normal innervated bowel. Paired sample Student's t -test, Pearson correlation test, receiver operating characteristic (ROC) analysis were performed. Forty-eight patients were enrolled in this study. Measured mean for aganglionic bowel length on CE and pathology were 33.5 ± 17.1 cm and 56.8 ± 33.5 cm, respectively (p < 0.01). Correlation coefficient (R) and coefficient of determination (R2) were 0.632 and 40%, respectively (p < 0.01). The difference between radiologic and pathologic measurements in females was higher than males (mean: 29.3 vs 21.9 cm) but was not statistically significant (p = 0.75). There was statistically significant difference between CE and pathologic results in the infants younger than 10 months (p =.004). Abnormal bowel length equal to 52 cm predicted requirement of laparoscopy assistance/laparotomy with 75% sensitivity and 85% specificity. Our investigation showed it is safe to attempt for single stage TERPT when aganglionic length on CE is less than 52 cm and the child with HD is older than 10 months. Chance of requiring additional laparotomy or laparoscopy assistance is low in these patients. Study of diagnostic test. Level II. [ABSTRACT FROM AUTHOR]

• Aganglionosis can follow unpredictable course. • Properly done levelling has a great impact on surgical planning, re-operation rates and patients' quality of life. • Missed Hischprung's disease cases can be attributed to the existence skipping variations. • Further investigation of the myenteric and Aurbach's cells functional and structural status could explain the skipping in those reported cases. • Special stains might tell if ganglions are present or absent but not normal or abnormal ones. Segmental aganglionosis (the absence of ganglions) is a rare presentation of Hirschsprung's disease, whereby only limited segment/segments of aganglionic bowel is interposed between segments of innervated bowel, or "skip" area of normal innervations is present within an area of aganglionosis. We reported a case of a 3 day old male newborn who presented with failure to pass meconium along with progressive abdominal distension. There were skip lesions present in between. Mikulicz double barrel enterostomy was carried out, which was followed by an uneventful postoperative period. Four months later, the patient was admitted for levelling biopsies which revealed the absence of ganglions in the terminal ileum as well as in the rectosigmoid junction. But the ganglions were present in between and proximal to the terminal ileum where the previously dilated small bowel segment was resected. This presentation was contradicted the most accepted migration theory of Hirschsprung's disease. As seen in our case, and in21 other cases published between 1954–2016, we highly recommend that leveling/mapping biopsies should definitely include the cecal pole and the small bowel segments proximal to the ileocecal valve as well as the multilevel colonic biopsies down till the rectum. Reporting of these cases brings out interesting questions with respect to the pathogenesis and serves to highlight the existence of several variants within the spectrum of Hirschsprung's disease. [ABSTRACT FROM AUTHOR]

Introduction: Hirschsprung’s Disease (HD) is a common congenital disorder characterised by absence of enteric neurons along a variable length of large bowel involving a segment of the rectum and the adjacent proximal bowel. The definitive diagnosis is based on histopathological study of rectal seromuscular biopsies. Calretinin Immunohistochemistry (IHC) staining adds to the diagnostic yield as it allows better appreciation of the mature and immature ganglion cells including the segments with paucity of ganglion cells.Aim: To assess the usefulness of calretinin IHC in the diagnosis of HD as an add-on technique to routine Haematoxylin and Eosin staining. Materials and Methods: This was a prospective study carried out in the Department of Pathology, SCB Medical College, Cuttack during the period from August 2016 to July 2018. Full thickness rectal biopsy specimens were processed and subjected to routine Hematoxylin and Eosin Stain (H&E) staining and Calretinin IHC staining. A thorough search of ganglion cells was made in both types of stained slides. The observations were tabulated and compared for diagnostic accuracy. Statistical analysis was done using Statistical Packages for Social Sciences (SPSS) Inc, Chicago IL version 15.0 windows. Through, ANOVA and Chi-square test.Results: Calretinin IHC provided superior diagnostic yield compared to routine H&E staining. A total number of 45 cases were studied. Sensitivity of 95.4% and specificity of 55.5% were obtained. It also presented higher accuracy values, than H&E (p=0.49).Conclusion: Calretinin is a superior immunohistochemical staining method that serves as a reliable additional diagnostic tool for better morphological appreciation of ganglion cells and thereby helps in establishing the diagnosis of HD.

Hirschsprung disease is the most common neurocristopathy in children, resulting in the congenital loss of enteric ganglia. Rare reports of skip lesions have previously been reported in the literature. We present a case of skip lesions known prior to surgery and managed by pull-through of the right colon that allowed the preservation of the colon.

Objective: To report a case of Hirschsprung's disease in a 23-year-old patient, diagnosed at the Santa Casa de Misericórdia Hospital in Anápolis, Goiás. Case description: A 23-year-old female patient with a history of abdominal distension and intestinal constipation since birth, with the need to use oral laxatives for evacuation. Rectal biopsy revealed the absence of ganglion cells, in addition to hyperplasia of nervous fillets and discrete hypertrophy of the muscular layer itself of the rectal mucosa, confirming an ultra-short form of aganglionose. Conclusions: The importance of recognizing the signs and symptoms of this disease is evident, which allows the early diagnosis of Hirschsprung's disease in order to bring an improvement in the patient's quality of life.

Aim:Laparoscopic-assisted transanal pull-through (LATP) is a procedure that has gained increasing popularity in the management of Hirschsprung’s disease. The purpose of this study was to compare outcomes of patients treated with LATP and transanal pull-through (TPT).Methods:Records of 45 patients with Hirschsprung’s disease who underwent surgery between 2006 and 2017 were retrospectively evaluated.Results:LATP was performed in 16 patients [13 male (81%), three female (19%)]. The median age of the patients was four months (7 days-84 months). Twenty nine patients [21 male (72.4%), eight female (27.6%)] underwent TPT. The median age of the patients was 11 months (10 days-90 months). The mean time to start feeding in LATP and TPT groups was two days (one-three days) and 2.6 days, respectively (p=0.074). The mean operative time was 2.6 hours in the LATP group (two-four hours) and 2.7 hours in the TPT group (p=0.971). The mean length of hospital stay in for LATP and TPT groups was 4.8 days (two-nine days) and six days (3-14 days), respectively (p=0.305).Conclusion:The advantages of LATP include multiple sample collection from several segments of the colonn at the same time as well as shorter time to frozen section diagnosis. In addition, the possibility of intraabdominal dissection allows transanal surgery to be faster and more effective.

Introduction: Hirschsprung’s Disease (HD) is a common congenital disorder characterised by absence of enteric neurons along a variable length of large bowel involving a segment of the rectum and the adjacent proximal bowel. The definitive diagnosis is based on histopathological study of rectal seromuscular biopsies. Calretinin Immunohistochemistry (IHC) staining adds to the diagnostic yield as it allows better appreciation of the mature and immature ganglion cells including the segments with paucity of ganglion cells. Aim: To assess the usefulness of calretinin IHC in the diagnosis of HD as an add-on technique to routine Haematoxylin and Eosin staining. Materials and Methods: This was a prospective study carried out in the Department of Pathology, SCB Medical College, Cuttack during the period from August 2016 to July 2018. Full thickness rectal biopsy specimens were processed and subjected to routine Hematoxylin and Eosin Stain (H&E) staining and Calretinin IHC staining. A thorough search of ganglion cells was made in both types of stained slides. The observations were tabulated and compared for diagnostic accuracy. Statistical analysis was done using Statistical Packages for Social Sciences (SPSS) Inc, Chicago IL version 15.0 windows. Through, ANOVA and Chi-square test. Results: Calretinin IHC provided superior diagnostic yield compared to routine H&E staining. A total number of 45 cases were studied. Sensitivity of 95.4% and specificity of 55.5% were obtained. It also presented higher accuracy values, than H&E (p=0.49). Conclusion: Calretinin is a superior immunohistochemical staining method that serves as a reliable additional diagnostic tool for better morphological appreciation of ganglion cells and thereby helps in establishing the diagnosis of HD. [ABSTRACT FROM AUTHOR]

Background: In cases of Hirschsprung disease, complete and reproducible resection of the aganglionic bowel is ideal to achieve good postoperative bowel function. Reliable identification of the upper margin of the surgical anal canal, which is the squamous-columnar junction, is necessary during transanal pull-through. Here, we describe a novel staining technique using Lugol's iodine stain to visualize the upper margin of the surgical anal canal.Methods: Lugol's iodine staining was performed in five patients with Hirschsprung disease treated using a single-stage laparoscopic transanal pull-through modified Swenson procedure. In two of these patients, endocytoscopic observation with ultra-high magnification was performed using methylene blue and crystal violet to mark the border of the squamous epithelium at 1 week before surgery. The alignment between the incisional line, which was revealed using Lugol's iodine staining and endocytoscopic marking, was evaluated. Complications, including postoperative bowel dysfunction, were evaluated.Results: In all cases, Lugol's iodine staining produced a well-demarcated line. The endocytoscopic marking of the upper margin of the surgical anal canal was aligned with the line revealed by Lugol's iodine staining. There were no complications associated with the transanal pull-through procedure, including postoperative bowel dysfunction.Conclusions: Lugol's iodine staining could be a safe and practical method to visualize the upper margin of the surgical anal canal intraoperatively. This finding may be useful for surgeons to make a consistent removal of the aganglionic bowel during surgery for Hirschsprung disease. [ABSTRACT FROM AUTHOR]

Appropriately balanced RET signaling is of crucial importance during embryonic neural crest cell migration, proliferation and differentiation. RET deficiency, for example, leads to intestinal aganglionosis (Hirschsprung disease), whereas overactive RET can lead to multiple endocrine neoplasia (MEN) syndromes. Some RET mutations are associated with both intestinal aganglionosis and MEN-associated tumors. This seemingly paradoxical occurrence has led to speculation of a 'Janus mutation' in RET that causes overactivation or impairment of RET activity depending on the cellular context. Using an intestinal catenary culture system to test the effects of GDNF-mediated RET activation, we demonstrate the concurrent development of distal colonic aganglionosis and intestinal ganglioneuromas. Interestingly, the tumors induced by GDNF stimulation contain enteric neuronal progenitors capable of reconstituting an enteric nervous system when transplanted into a normal developmental environment. These results suggest that a Janus mutation may not be required to explain co-existing Hirschsprung disease and MEN-associated tumors, but rather that RET overstimulation alone is enough to cause both phenotypes. The results also suggest that reprogramming tumor cells toward non-pathological fates may represent a possible therapeutic avenue for MEN-associated neoplasms. [ABSTRACT FROM AUTHOR]

Occurrence of Hirschsprung's disease in anorectal malformation (ARM) patients is rare, but many surgeons still ask to pathologists to search for ganglia in the terminal rectum/fistula; the histological procedure is time and money consuming and the results confounding. A consecutive series of ARM patients, in which the presence of ganglia in terminal rectum was revised, is herein presented. Rectal specimens of ARM patients who underwent corrective surgery in the last 6 years were retrieved. The histological protocol included H&E staining and calretinin immunohistochemistry. Each specimen is processed until all material is examined if no ganglia are retrieved after the first twelve sections. Forty cases were examined. Eight patients were younger than 1 month of age at operation. The mean length of the specimen was 1.5cm (range: 1–3 cm). Upon clinical request, ganglia were searched in 15/40 cases (37.5%) and resulted absent in 10/15 (66.5%). All patients have been followed and none developed signs or symptoms suggestive for Hirschsprung. The practice to search for ganglia in the terminal rectum/fistula in ARM patients should be abandoned, as incidence of associated colorectal diseases is rare. Moreover, the procedure is expensive both in terms of laboratory's reagents and working time of expert pathologists and technicians. Level IV (Case Series with no Comparison Group) [ABSTRACT FROM AUTHOR]

The outcome in HD has not been always satisfactory even after a technically sound operation. To define the characteristic histopathological features of the pulled-through colon in patients with HD, and it is impact on clinical outcome. The study included patients with HD who underwent surgical repair between 2010 through 2016. The proximal margin of resected bowel segments (which corresponds to the pulled through colon) was subjected to detailed histopathological examination by two experienced pathologists. Based on the frequency of postoperative attacks of HAEC (fever, vomiting, abdominal distention, fluid offensive stools), cases included in the study were divided into two groups: Group A, those with less frequent attacks of HAEC; and Group B, those with recurrent attacks of HAEC (more than 3). The study included 35 patients (25 in group A; and 10 in group B). Their age ranged from 0.2 to 144 months (median 6 months). Comparing the histopathological findings in the two clinical groups, we have found that Group B (recurrent attacks of HAEC) had significantly more frequent focal disarray of nerve bundles and thicker nerve bundle diameter. Also, histopathological features of acute inflammation were more prevalent in examined specimens from group B. Several histopathological features of the examined bowel specimens in HD, other than presence or absence of ganglion cells, are indicative of postoperative functional outcome. These include the thickness and maturity of nerve bundles, in addition to the presence of histopathological features of acute inflammation. This is a case control study (level III evidence). [ABSTRACT FROM AUTHOR]

Introduction: Recent studies suggest that some of the post-surgical morbidity in Hirschsprung disease (HSCR) is due to enteric nervous system structural defects in the proximal, ganglionated bowel that remains after surgery. We hypothesized that resection margin histology would predict intermediate-term outcomes in HSCR patients. Methods: Following IRB approval, HSCR patients with rectosigmoid disease born between 2009 and 2016 were reviewed and tissue blocks were obtained for new analyses. Proximal resection margins were analyzed for ganglion size, Hu + neurons/ganglion, and % nitric oxide synthase (NOS) neurons/ganglion as compared to control (non-HSCR) patient samples. Chart reviews were performed for 1- and 2-year outcomes. Patients were contacted for survey to determine Rintala bowel function score. Results: 45 patients had recto-sigmoid disease and were further analyzed. HSCR patients had significantly smaller individual ganglion size (4533 μm2, range 1744–16,287 vs. 6492 μm2, range 1932–30,838, p = 0.0192) and fewer HuC/D + neurons per ganglion (15, range 5.2–34 vs. 21, range 5.2–6.7, p = 0.0214). HSCR patients demonstrated a markedly increased percentage of NOS (relaxation neurotransmitter) neurons (50, range 22–85 vs. 37, range 16–80, p = 0.0266). None of the histology measures correlated with presence/absence of constipation at 1–2 year follow-up (p = NS). However, smaller ganglion size and higher percentage of NOS neurons correlated with decreased patient-reported quality of life (r = 0.3838, r = − 0.1809). Conclusion: 1–2 year follow-up may be insufficient to determine if resection margin histology correlates with outcomes. Patient-reported quality of life surveys, although limited in number, suggest that neurotransmitter imbalance at the resection margin may predict poor outcomes in HSCR patients. This study supports the concept that the ganglionated portion of the remaining colon post-surgery may not sustain normal bowel function. [ABSTRACT FROM AUTHOR]

Background: Hirschsprung's disease (HD) is a genetic disorder with a complex pattern of inheritance. Some single-nucleotide polymorphisms (SNPs) are identified to be associated with the risk of Hirschsprung's Disease (HSCR).Aims and Objectives: The aim of this study is to know the association between the rearranged during transfection (RET) proto-oncogene polymorphism and HD and to characterize the SNPs of RET proto-oncogene affecting HD.Materials and Methods: The study was conducted in the Department of Pathology in association with the Department of Pediatric Surgery. Blood samples were collected from the patients diagnosed with confirmed HD and from age- and sex-matched controls. This case-control study consisted of 53 HSCR cases and 50 controls. Genotypes of rs1800860 and rs1800861 were analysed in by polymerase chain reaction amplification and sanger sequencing. Associations with the risk of HSCR were estimated by odds ratio (OR) and their 95% confidence intervals (95% CI) using.Results: We observed that in the case of rs1800860A > G genotype AG was not associated with the increasing risk of disease (OR with 95% CI = 0.568 [0.238-1.356]) while genotype GG was associated with increasing the risk of the disease (OR with 95% CI = 2.278 [0.967-5.366]). In the case of rs1800861G > T genotype GT was associated with lowering the risk of the disease (OR with 95% CI = 0.230 [0.0981-0.539]) while genotype TT was associated with increasing the risk of the disease (OR with 95% CI = 9.647 [3.830-24.302]). The difference in the genotypic distribution of GT and TT at rs1800861G > T between Short segment disease (SSD) cases and Long Segment Disease (LSD) and total colonic aganglionosis was made by Fisher's exact test and it was statistically significant (P = 0.0476 and 0.0054).Conclusion: The results of this study support the hypothesis that variations in RET pathway might play an important role in the development of HSCR. [ABSTRACT FROM AUTHOR]

Introduction:  "Tuft" cells, also known as brush or caveolated cells, are characteristically fusiform shaped, with a distinct apical "tuft" of microvilli extending into the lumen. Double cortin-like kinase 1 (DCLK1) is a microtubule kinase and is a specific marker of intestinal tuft cells. DCLK1-positive tuft cells have been shown to play a key role in gastrointestinal chemosensation, inflammation, and neurotransmission. DCLK1 and Choline acetyltransferase (ChAT), the enzymes responsible for acetylcholine production, are reported to be coexpressed within the gastrointestinal tract. We designed this study to investigate the hypothesis that DCLK1 gene expression is altered in Hirschsprung's disease (HSCR).Materials and Methods:  HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was undertaken to quantify DCLK1 gene expression, and immunolabeling of DCLK1-positive tuft cells was visualized using confocal microscopy.Results:  qRT-PCR analysis revealed significant downregulation of the DCLK1 gene in both aganglionic and ganglionic HSCR specimens compared with controls (p < 0.05). Confocal microscopy revealed DCLK1-positive tuft cell expression within the colonic mucosa, with a reduction in expression in both aganglionic and ganglionic HSCR colon compared with controls.Conclusion:  DCLK1 is significantly downregulated in HSCR colon, suggesting a role for tuft cells in cholinergic neurotransmission of the distal colon. The marked decrease in DCLK1 expression within ganglionic specimens highlights the physiologically abnormal nature of this segment in HSCR patients. [ABSTRACT FROM AUTHOR]

Hirschsprung-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). It has been proposed that gut microbiota, which have an essential role in gut-homeostasis, are associated with HAEC. Recent studies demonstrated an increase in alpha diversity of fecal microbiota over time in HSCR mice and a decrease in diversity after surgery. In addition, clinical studies have reported a reduction in bacterial richness in HSCR children after surgery. Some studies revealed a difference in microbiota between the proximal ganglionic and distal aganglionic intestine and found a difference in bacterial character between fecal and colonic specimens. HAEC studies found an increase in Proteobacteria, especially Escherichia and Enterobacteriaceae, with a decrease in Firmicutes and Bifidobacterium in HAEC patients. However, the direction of alpha diversity in HAEC patients is still controversial. The self-comparison of microbiota in treatment periods suggested that probiotics might improve gut dysbiosis and decrease the frequency of enterocolitis, but some reported contradictory findings. This review comprehensively summarizes and discusses key findings from animal and clinical data of the distinct microbiome associated with HCSR and the association of gut dysbiosis with the development of HAEC. This information should be useful in the establishment of novel interventions to improve gut dysbiosis and prevent enterocolitis in HSCR patients.

Objectives: Since 2010, several researches demonstrated that microbiota dynamics correlate and can even predispose to Hirschsprung (HSCR) associated enterocolitis (HAEC). This study aims at assessing the structure of the microbiota of HSCR patients in relation to extent of aganglionosis and HAEC status.Methods: All consecutive HSCR patients admitted to Gaslini Institute (Genova, Italy) between May 2012 and November 2014 were enrolled. Institutional review board (IRB) approval was obtained. Stools were sampled and 16S rDNA V3-V4 regions were sequenced using the Illumina-MiSeq. Taxonomy assignments were performed using QIIME RDP. Alpha diversity indexes were analyzed by Shannon and Simpson Indexes, and Phylogenetic Diversity.Results: We enrolled 20 patients. Male to female ratio was 4:1. Six patients suffered from Total Colonic Aganglionosis (TCSA). Considering sample site (i.e., extent of aganglionosis), we confirmed the known relationship between sample site and both biodiversity and composition of intestinal microbiota. Patients with TCSA showed lower biodiversity and increased Proteobacteria/Bacteroidetes relative abundance ratio. When addressing biodiversity, composition and dynamics of TCSA patients we could not find any significant relationship with regard to HAEC occurrences.Conclusions: The composition of HAEC predisposing microbiota is specific to each patient. We could confirm that total colon resections can change the composition of intestinal microbiota and to dramatically reduce microbial diversity. The subsequent reduction of system robustness could expose TCSA patients to environmental microbes that might not be part of the normal microbiota. Future long-term studies should investigate both patients and their family environment, as well as their disease history.

Abstract Background and Aim Congenital segmental intestinal dilatation (CSID) is a neonatal condition with unclear etiology and pathogenesis. Typically, the newborn with CSID presents with a limited (circumscribed) bowel dilatation, an abrupt transition between normal and dilated segments, neither intrinsic nor extrinsic perilesional obstruction, and no aganglionosis or neuronal intestinal dysplasia. We aimed to review this disease and the long-term follow-up at the Children's Hospital of the Medical University of Innsbruck, Tyrol, Austria. Study Design Retrospective 25-year review of medical charts, electronic files, and histopathology of neonates with CSID. Results We identified four infants (three girls and one boy) with CSID. The affected areas included duodenum, ileum, ascending colon, and sigmoid colon. Noteworthy, all patients presented with a cardiovascular defect, of which two required multiple cardiac surgical interventions. Three out of the four patients recovered completely. To date, the three infants are alive. Conclusion This is the first report of patients with CSID and cardiovascular defects. The clinical and surgical intervention for CSID also requires a thorough cardiologic evaluation in these patients. CSID remains an enigmatic entity pointing to the need for joint forces in identifying common loci for genetic investigations.

Aim Of the Study: Potassium (K+) channels with a two-pore domain (K2P) are a large family of hyperpolarising ion channels which play a key role in cell excitability. This family comprises three members: TREK-1, TREK-2 and TRAAK. TRAAK channels have previously been reported to be expressed in murine enteric ganglia. To date, no data exist regarding TRAAK channel expression in the human colon. Thus, we designed this study to investigate TRAAK gene expression in the normal human colon and in Hirschsprung's disease (HSCR).Methods: HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify TRAAK gene expression, and immunolabelling of TRAAK proteins was visualized using confocal microscopy.Main Results: Confocal microscopy revealed TRAAK protein expression within both neurons and interstitial cells of Cajal in the myenteric plexus, with a reduction in both ganglionic HSCR colon and aganglionic HSCR colon, compared to controls. qRT-PCR analysis revealed a significant downregulation of the TRAAK gene in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05).Conclusions: TRAAK gene expression is significantly downregulated in HSCR colon, suggesting a role for these ion channels in colonic neurotransmission. TRAAK downregulation within ganglionic specimens highlights the dysfunctional nature of ganglia in this region. [ABSTRACT FROM AUTHOR]

Retained transition zone is a leading cause of obstructive symptoms after pull-through operation in Hirschsprung's disease. We aimed to evaluate the extent of the histological transition zone in patients with Hirschsprung's disease. We performed an observational study. DAB + immunohistochemistry for Protein Gene Product 9.5 was used to evaluate the neuronal networks in serial sections of pull-through specimens obtained from children with Hirschsprung's disease (n = 12). Reference ranges for ganglion size/density and nerve trunk diameter were statistically determined using healthy controls obtained from colostomy specimens from children with anorectal malformations (n = 8). The transition zone was defined as ganglionic bowel exhibiting ganglion hypoplasia, hypertrophic nerve trunks, or partial circumference aganglionosis. The mean submucosal nerve trunk diameter in controls was 19.56 μm +/− 3.87 μm. The median age at pull-through for Hirschsprung's disease was 5 months (3–14 months). The median length of the transition zone across the population was 8 cm (4–22 cm). Median transition zone extent was significantly longer in patients with long-segment aganglionosis (n = 6) compared to rectosigmoid aganglionosis (n = 6, 13 cm vs 6 cm, p = 0.041). Due to the age of the patients enrolled, long-term follow-up of bowel function is not yet available. Our data suggest that, in children with rectosigmoid Hirschsprung's disease, the transition zone can extend for up to 13 cm. In children with long-segment disease, a longer transition zone is possible. Extended resection at a minimum 5 cm beyond the most distal ganglionic intra-operative biopsy and intra-operative histological examination of the proximal resection margin are required to minimize transition zone pull-through. 2. [ABSTRACT FROM AUTHOR]

Hirschsprung's disease (HSCR) is characterized by a lack of enteric nervous system ganglion cells (aganglionosis) in a variable extent of distal bowel. It is the most common congenital bowel motility disorder and affected neonates usually present with distal intestinal obstruction in the first few days of life. Current treatment involves resection of the aganglionic bowel and a 'pull through' procedure to bring the normally innervated bowel down to the anal margin. Despite advances in surgery, outcomes can be poor, especially in long-segment HSCR in which a longer segment of bowel or the entire colon is aganglionic. Children are more prone to enterocolitis and up to 75% have problems with incontinence or constipation. Some children require a long-term colostomy. This article aims to provide an overview of Hirschsprung's disease, outlining the aetiology of HSCR and management of children with HSCR. [ABSTRACT FROM AUTHOR]

Background: Lack of ganglion cells on adequate suction rectal biopsy is the gold standard for diagnosis of neonatal Hirschsprung disease (HD), and the presence of ganglion cells precludes such a diagnosis. Case report: A 10-day old male neonate presented with clinical symptoms concerning for HD. However, suction rectal biopsies demonstrated submucosal ganglion cells on the distal suction rectal biopsies (2 cm from anal verge) and not on the proximal (3 cm from anal verge), with similar findings on repeat biopsies. Clinical suspicion remained high, and diagnostic laparoscopy with intraoperative biopsies confirmed aganglionosis with a sigmoid transition. A pull through resection confirmed the diagnosis of distal rectal skip segment HD (SSHD) with a ∼6 cm length of circumferential aganglionosis extending into the proximal sigmoid. Conclusions: Discordant results on suction rectal biopsies should raise the possibility of SSHD. Awareness of the entity can facilitate timely definitive management in neonatal period. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have suggested that there may be ethnic variations in the prevalence of Hirschsprung disease (HD) but no study has systematically investigated this issue or potential ethnic variations in the extent of aganglionosis in HD. This study aimed to investigate this in a childhood population in New Zealand. Methods: A multicentre national retrospective review was undertaken of all newly diagnosed cases of HD at each of the four paediatric surgical centres in New Zealand over a 16‐year period (January 2000 to December 2015). Original histological, radiological and operative reports were obtained and analysed. Self‐identified ethnicity was recorded from admission documents. Birth statistics were obtained from Statistics New Zealand. Results: A total of 246 cases of HD were identified. The prevalence of HD was 1:3790 live births for European, 1:6610 among Māori, 1:1834 among Pacific Peoples, 1:3847 among Asian and 1:5694 among Middle Eastern. The prevalence of HD was statistically significantly greater in Pacific Peoples (P < 0.0005). The proportion of children with long‐segment HD was also significantly greater in Pacific and Asian populations than others (P = 0.04). These findings were not due to differences in the proportion of familial cases of HD among the different populations. Conclusions: The prevalence and phenotype of HD varies significantly between different ethnic groups within New Zealand. This may well be related to variations in the frequencies of HD‐associated gene mutations within these populations. [ABSTRACT FROM AUTHOR]

Synoptic, or standardized, reporting of surgery and pathology reports has been widely adopted in surgical oncology. Patients with Hirschsprung disease may experience morbidity related to surgical factors or underlying pathology and often undergo multiple operations. Our aim is to improve the postoperative outcome and care of patients with Hirschsprung disease by proposing a standardized set of data that should be included in every surgery and pathology report. Members of the American Pediatric Surgical Association Hirschsprung Disease Interest Group and experts in pediatric pathology of Hirschsprung disease participated in group discussions, performed literature review and arrived at expert consensus guidelines for surgery and pathology reporting. The importance of accurate operative and pathologic reports and the implications of inadequate documentation in patients with Hirschsprung disease are discussed and guidelines for standardizing these reports are provided. Adherence to the principles of reporting for operations and surgical pathology may improve outcomes for Hirschsprung disease patients and will facilitate identification of correlations among morphology, function, genetics and outcomes, which are required to improve the overall management of these patients. V. [ABSTRACT FROM AUTHOR]

Aim Of the Study: Ryanodine receptors are the largest of all ion channels, named after their exogenous ligand, ryanodine. The ryanodine receptor calcium release channel is central to cytoplasmic Ca2+ signalling in skeletal muscle, the heart, and many other tissues, playing a vital role in muscular contraction. Three ryanodine receptors exist, Ryr1, Ryr2 and Ryr3. The ryanodine receptor, Ryr3, is encoded by the Ryr3 gene, which has been reported to be highly specific to colonic smooth muscle cells in mice. We designed this study to investigate Ryr1, Ryr2 and Ryr3 gene expression in the normal human colon and in Hirschsprung's disease (HSCR).Methods: HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify Ryr1, Ryr2 and Ryr3 gene expression, and immunolabelling of Ryr1, Ryr2 and Ryr3 proteins was visualised using confocal microscopy.Main Results: qRT-PCR analysis revealed a significant downregulation of the Ryr1 and Ryr3 genes in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed Ryr1, Ryr2 and Ryr3 protein expressions within the smooth muscle, with a reduction in aganglionic and ganglionic HSCR colon compared to controls.Conclusions: Ryr1 and Ryr3 gene expression is significantly downregulated in HSCR colon, suggesting a role for these genes in colonic smooth-muscle motility. Ryr1 and Ryr3 downregulations within ganglionic specimens highlight the physiologically abnormal nature of this segment which may explain the occurrence of persistent bowel symptoms in some HSCR patients following a properly performed pull-through operation. [ABSTRACT FROM AUTHOR]

Hirschsprung's disease (HSCR) is caused by incomplete colonization of enteric neural crest-derived cell (ENCC) in the bowel, the failure of ENCCs to proliferate, differentiate, and migrate leads to an absence of enteric neurons in the distal colon, resulting in colonic motility dysfunction. Various animal models of HSCR have been important in the understanding of the anatomy and pathophysiology of the disease and in the discovery of genes involved in HSCR. Four types of HSCR animal models have been developed: teratogen-induced, surgically created, naturally occurring models, and knockout models. Mutations in several genes affect enteric nervous system (ENS) development and can have pleiotropic effects on this system. Furthermore, certain animal models are informative regarding how such molecules control the development and functional differentiation of the ENS. In this article, we summarize recent advances in this field and highlight opportunities for new discoveries. [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) is a common cause of intestinal obstruction in the newborn. Hirschsprung-associated enterocolitis (HAEC) is a significant and life-threatening complication of HSCR, affecting up to 60% of patients. Animal models of endothelin receptor B (EdnrB) mutation reliably model human HSCR and HAEC. We previously demonstrated intestinal dysbiosis and a gut-specific deficiency of B-lymphocyte-produced secretory IgA (sIgA), the primary effector molecule of mucosal immunity, in mice with homozygous neural crest cell-conditional deletion of EdnrB (EdnrBNCC-/-). To determine mechanisms for sIgA deficiency, we examined intrinsic and extrinsic aspects of B-lymphocyte development and function. Expression of the endothelin axis components [endothelin-1 (ET-1), endothelin-3 (ET-3), endothelin receptor A (EdnrA), EdnrB] were determined over a developmental time course. B-lymphocyte survival and Ig production were assayed in vitro. Polymeric Ig receptor (pIgR)-mediated IgA transport into the intestinal lumen was interrogated. We found endothelin axis component (EdnrA, EdnrB, ET-1, ET-3) expression in developing extramedullary hematopoietic organs and that some splenic B lymphocytes express EdnrB. Splenic B lymphocytes from EdnrBNCC-/- mice showed no intrinsic defect in survival vs. wild-type (WT) B lymphocytes. In vitro stimulation of splenic B lymphocytes demonstrated decreased IgA, IgG, and IgM production in EdnrBNCC-/-vs. WT mice. Additionally, small intestinal pIgR was decreased ~50% in EdnrBNCC-/- mice. These results suggest an intrinsic B-lymphocyte defect in antibody production as well as an extrinsic defect in IgA transport in the EdnrBNCC-/- model of HAEC. Our results are consistent with human HAEC observations of decreased luminal sIgA and mouse models of other inflammatory bowel diseases, in which decreased pIgR is seen in concert with a dysregulated microbiota. Finally, our results suggest targeting the dysbiotic microbiome and pIgR-mediated sIgA transport as potential therapeutic approaches in prevention and treatment of HAEC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the function and quality of life of Hirschsprung's Disease (HD) beyond adolescence and relate it to matched controls.Methods: All 203 patients diagnosed with HD at our department from 1961 to 1995 were identified. 21 had died, 43 had unclear diagnosis and 16 could not be traced. The remaining 123 patients were sent bowel function and SF-36 quality of life questionnaires. 69 patients (mean age 37.8, range 22-58, 13 female) responded and were matched with 138 age and sex-matched controls.Results: Function: HD-patients had significantly higher number of bowel movements per week, higher incidence of soiling, urgency, permanent stomas, use of laxatives, enemas and loperamide. HD-patients also scored significantly lower in their satisfaction with their bowel function. There was, however, no significant difference in Miller Incontinence score. QOL: HD-patients reported a significantly higher incidence of negative impact by their bowel function on daily life, social interaction and ability to go on vacation. There were no significant differences in SF-36-scores.Conclusions: Bowel function has a lifelong negative impact on the lives of patients with HD. This strongly indicates a need for structured follow-up beyond adolescence. [ABSTRACT FROM AUTHOR]

Introduction:  The U.K. National Institute for Health and Clinical Excellence (NICE) specify the following indications for performing rectal biopsy to rule out Hirschsprung's disease (HSD): (1) passage of meconium > 48 hours; (2) constipation since first few weeks of life; (3) chronic abdominal distension with vomiting; (4) family history of HSD; and (5) faltering growth in addition to any other indication. The aim of this study was to assess the compliance of a tertiary referral center with the current U.K. NICE guidelines for performing rectal biopsies to rule out HSD. Secondary aims included assessing alternative indications and complication rates.Materials and Methods:  Retrospective analysis of patients undergoing open or suction rectal biopsies to investigate HSD, from 2009 to 2014.Results:  A total of 188 patients underwent 214 biopsies (suction: n = 154, open: n = 60). Note that 128 patients (68.1%) had biopsies indicated by NICE. A total of 84.4% of indicated biopsies were ganglionic versus 91.7% of unindicated biopsies (p = 0.17). Twenty-five patients were diagnosed with HSD (mean age: 13.2 weeks, range: 3 days-3.2 years). Only 80% of HSD patients had NICE-indicated biopsies. Presentations for patients with biopsies not indicated by NICE included constipation, distension, and vomiting that did not strictly meet the guidelines. The majority of biopsies were uncomplicated (suction 82.5% vs. open 95.0%)-inadequate/indeterminate histology was the most common complication (16.2% suction vs. 5% open).Conclusion:  A significant number of unindicated biopsies were performed, the majority of which were ganglionic. Rectal biopsies are generally safe and strict adherence to the NICE guidelines could have led to missed HSD diagnoses with potential significant morbidity and mortality. [ABSTRACT FROM AUTHOR]

The simultaneous occurrence of Hirschsprung disease (HD) and anorectal malformation (ARM) is extremely rare, with only a very limited amount of cases published in the literature. Constipation is a major problem in patients operated for ARM, and biopsies from the distal rectum in patients with ARM may not show ganglion cells owing to different reasons, leading to a false positive diagnosis of HD. A pull-through procedure for HD after previous anorectoplasty for ARM always leads to fecal incontinence. The aim of the present study was to assess the incidence of simultaneous diagnoses of ARM and HD in a single large cohort of ARM patients and to demonstrate that biopsies from the anal canal, which are negative for ganglion cells, may mislead to a diagnosis of HD. A retrospective review of our database from 1980 to 2018 identified 164 patients with HD and 2397 patients with ARM. Four patients suffered from both HD and ARM. The incidence of HD in ARM patients was 4/2397 = 0.17%, and the incidence of ARM in HD patients was 4/164 = 2.4%. Our results strongly suggest that the association of ARM and HD is less common than previously reported. Therapeutic IV [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) is characterized by the absence of neuronal ganglion cells in a distal portion of the intestinal tract [ 1 ]. In 1691, Frederick Ruysch described the disease as congenital megacolon. HSCR-associated congenital anomalies have been reported in 5–32% of affected patients [ 2 ]. The clinical symptoms of HSCR are usually evident in the neonatal period. However, in some cases where the extent of the aganglionic segment is short, symptoms may become clinically relevant later in childhood [ 3 ]. HSCR is one of the most difficult diseases to identify in pediatric surgery due to its multiple clinical, histological and radiological variations [ 2 , 3 ]. The goal of surgical management is to remove the aganglionic segment and reconstruct the intestinal tract through techniques such as Swenson, Duhamel and Soave [ 4 ]. The following case consists of a 4-year-old patient with a chronic presentation of constipation secondary to ultrashort-segment Hirschsprung disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the long-term outcome after surgical correction of Hirschsprung's disease using a standardised questionnaire designed specifically to address the long-term results, in correlation to the physical examination of each patient. The data was collected from the medical records of patients treated over a 15 year period (2000-2014). Sixty-two patients were treated, 33 using one-stage and 29 using multistage surgical procedures. Twenty-seven children took part in the whole study, which consisted of personal interview, completing the questionnaire and physical examination. The Duhamel-Martin and transanal endorectal pull through techniques were used. Statistical analysis was performed using STATISTICA 10. The statistical significance was set at p < 0.05. The Mann-Whitney's test and the Spearman's rank correlation coefficient were used. The most common side effect after surgical treatment was faecal incontinence (23 patients). There was no correlation between the method of the surgery and number of side effects. Postoperatively, there were significant correlations (p < 0.05) between the number of loose stools and the growth of these patients, 48% of the children were outside the normal centile (10-90) and 74% for weight, with consideration to their sex and age. This group of patients was below the 10th centile for weight and growth. There are significant deviations in the patients' development after surgical treatment of Hirschsprung's disease. The long-term results after surgical procedure were satisfactory for children and their parents. [ABSTRACT FROM AUTHOR]

Purpose: The Soave procedure (SO) is performed most commonly for Hirschsprung disease. SO reduces the risk of injury to the pelvic structures; however, a residual aganglionic muscle cuff could interfere with bowel movement and lead to obstructive enterocolitis. The Swenson procedure is considered ideal in terms of peristalsis. Currently, laparoscopic surgery provides better visualization and facilitates precise dissection, possibly leading to feasible performance of the laparoscopic modified Swenson procedure (SW). We present our operative technique and the efficacy of the SW compared with that of SO.Methods: We retrospectively reviewed the records of 16 and 27 patients who underwent SW and SO, respectively, between 2012 and 2017.Results: Operative time, blood loss, length of stay, and frequency of bowel movements showed no significant difference between the two groups. In the SW group, temporary dysuria occurred in one patient, postoperative enterocolitis in two, wound infection in one, and severe perianal excoriation in four, whereas in the SO group, obstructive symptoms occurred in three patients, small-bowel obstruction in one, and severe perianal excoriation in three. The complications and outcomes were comparable between both groups.Conclusion: Laparoscopic SW was safe and feasible for the short-term follow-up outcomes. [ABSTRACT FROM AUTHOR]

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Transplacental bone morphogenetic protein (BMP)4 RNA interference (RNAi) is a technique used to knockdown genes in embryos. BMP4 are essential for the development of nervous system in the differentiation of neural crest stem cells (NCSCs). The failure of differentiation and migration of NCSCs may lead to aganglionosis. In the present study, pregnant mice were divided into three groups: Ringer's group, pSES group and RNAi‑BMP4 group. In order to silence the BMP4 gene in the first generation (F1), 11.5 day pregnant mice were injected with the small interfering RNA BMP4 plasmid, pSES or Ringer's solution via the tail vein. Semi‑quantitative reverse transcriptase‑polymerase chain reaction (RT‑PCR)and western blotting were employed to ensure the downregulation of BMP4. Finally, X‑rays were performed following a barium enema. Aganglionosis was diagnosed by general anatomy and immunohistochemistry. Compared with the control group, transplacental RNAi was able to downregulate the BMP4‑Smad4 of 11.5 day embryos, as determined by semi‑quantitative RT‑PCR and western blotting. The megacolons of the mice were demonstrated by X‑ray and confirmed by general anatomy. Aganglionosis of colonic mucosa and submucosa were diagnosed by pathology, and immunohistochemistry. Knockdown of BMP4 in pregnant mice at the middle embryonic stage led to aganglionosis. It was therefore demonstrated that BMP‑Smad was essential to the NCSCs of middle stage embryos. BMP‑Smad served important roles in the generation of aganglionosis. This technique of knockdown BMP4 gene may be used to establish an aganglionosis mouse model. [ABSTRACT FROM AUTHOR]