The Junction Between the Peristaltic and Non-peristaltic Bowel (Shore Break) is Found in the Transition Zone in Hirschsprung's Disease.

BACKGROUND: The junction between the peristaltic and non-peristaltic bowel, which is named the "shore break" (SB), observed on endoscopy is thought to be the boundary between normal and abnormal motility in Hirschsprung's disease (HD). The transition zone (TZ), which is the histopathological border, does not have normal motility and should be resected. This study aimed to evaluate the histopathological findings of the SB and determine the association between the SB and TZ. METHODS: A retrospective review of surgical specimens of patients with HD who underwent preoperative SB marking was conducted. The TZ was defined if nerve hypertrophy, myenteric hypoganglionosis, or partial circumferential aganglionosis was detected. RESULTS: Ten patients (9 boys and 1 girl) were studied. The median age at surgery was 30 days. The median distance from the anal verge to the marked SB site was 14 cm. No patients manifested any obstructive symptoms resulting from a residual TZ bowel. In eight patients, nerve hypertrophy was identified at the proximal margin and at the SB. Myenteric hypoganglionosis was identified in three patients at the proximal margin and SB. Partial circumferential aganglionosis was identified at the SB in two patients. As a result, in all patients, the pull-through site and SB site had histopathological features indicating TZ. CONCLUSIONS: The SB is located in the TZ. Our results suggest that the proximal part of the TZ has normal motility and that functional border points may be present in the TZ. LEVEL OF EVIDENCE: IV.

Recipient colon preoperative treatment with type I collagenase and fibronectin promotes the growth of transplanted enteric neural crest cells into Auerbach's plexus.

PURPOSE: Cell-based therapy is a potential treatment option for neurointestinal diseases by serving as a source of neural progenitor cells to replace missing or abnormal enteric neurons. Using an ex vivo transplantation model, we recently demonstrated that treatment with collagenase and fibronectin promotes infiltration of transplanted enteric neural crest cells (ENCCs) toward the colon lumen. The aim of this study was to determine whether this new method also promotes colonization of transplanted ENCCs in vivo. METHODS: Collagenase was applied locally on the anti-mesenteric area of the recipient colon using filter paper, followed by fibronectin. Neurospheres were generated from ENCCs isolated from fetal mouse intestines and transplanted into the collagenase and fibronectin-treated colon. Engraftment of neurospheres was confirmed by immunofluorescence. RESULTS: Neurospheres transplanted onto PBS- or fibronectin-treated colons were not observed to infiltrate to the muscle layer. However, when used in combination with type I collagenase and fibronectin in the recipient colon, transplanted neurospheres reached Auerbach's plexus. CONCLUSION: We demonstrated that transplanted neurospheres grow into Auerbach's plexus in the recipient colon pretreated with collagenase and fibronectin.

Transplanted neural crest cells migrate toward Auerbach's plexus layer instead of the colon surface in recipient colon pretreated with collagenase and fibronectin.

The enteric nervous system (ENS) regulates gastrointestinal motility, secretion, and absorption. Developmental ENS dysplasia causes intestinal ganglion dysfunction, including Hirschsprung's disease. Given their potential ability to replenish insufficient neurons, transplantation of enteric neural cells provides the prospect of a cure. In this study, we used an ex vivo mouse colon transplant model to demonstrate that treatment with collagenase and fibronectin altered the migration of transplanted cells from the direction of the colon surface toward the lumen. Collagenase-treated colons exhibited enhanced expression of type III and VI collagens, which inhibited fibronectin-induced enteric neural crest cell (ENCC) migration. Invasion of neurospheres into colon was dependent on preoperative treatment of recipient colon with collagenase and fibronectin, which enhanced neurosphere motility towards the direction of colon lumen. Infiltration of transplanted ENCCs into the colon increased proportionally to the degree of dedifferentiation of surrounding smooth muscle cells, which was induced in a neurosphere-dependent manner in collagenase-treated colon. Furthermore, induction of GDNF expression, a Ret ligand that promotes enteric neural cell migration, was observed in treated colons. Our results suggest that the environment provided by the extracellular matrix of the colon surface affects the direction of transplanted ENCC migration. Moreover, these findings demonstrating that ENCCs can be accepted by the recipient colon will help to refine current strategies for cell therapy.

Population-level laterality in foraging finless porpoises.

Laterality has been reported in many vertebrates, and asymmetrical cerebral hemisphere function has been hypothesized to cause a left-bias in social behavior and a right-bias in feeding behavior. In this paper, we provide the first report of behavioral laterality in free-ranging finless porpoises, which seems to support the aforementioned hypothesis. We observed the turning behavior of finless porpoises in Omura Bay, Japan, using land-based and unmanned aerial system observations. We found a strong tendency in finless porpoises to turn counterclockwise with their right side down when pursuing and catching fish at the surface of the water. Our results suggest that this population of finless porpoises shows consistent right-biased laterality. Right-biased laterality has been observed in various foraging cetaceans and is usually explained by the dominance of the right eye-left cerebral hemisphere in prey recognition; however, right-biased laterality in foraging cetaceans may have multiple causes.

Arteriovenous malformation that caused prolapse of the colon and was treated surgically in an infant: a case report.

BACKGROUND: Various terms have been used to describe vascular lesions in the intestine, including angiodysplasia, arteriovenous malformation, and telangiectasia. Such lesions are common in adults and are typified by angiodysplasia, a type of arteriovenous malformation. In contrast, these lesions are rarely seen in the pediatric population. Angiodysplasia may cause gastrointestinal bleeding, which is sometimes an indication for treatment. Considering the high rate of recurrence after surgical treatment, conservative treatments are mainly chosen. We herein report an extremely rare case of a prolapsed colon due to an arteriovenous malformation successfully treated by resection in a 1-year-old girl. We also highlight the differences between pediatric and adult cases. CASE PRESENTATION: A girl developed bloody stools at 7 months of age. She visited another hospital at 1 year of age because of continuing moderate hematochezia and recent onset of rectal prolapse. Colonoscopy showed a protruding lesion located 15 cm from the anal verge, suggesting a submucosal vascular abnormality. Contrast-enhanced computed tomography and magnetic resonance imaging at our hospital revealed the localized lesion with dilated blood vessels in part of the sigmoid colon; no other lesions were present in the gastrointestinal tract. Laparoscopic-assisted sigmoidectomy was performed. A subserosal vascular lesion was visualized and resected using end-to-end anastomosis. Pathologic examination of the 2.2 × 2.7-cm segment revealed several abnormally enlarged and ectatic blood vessels in the submucosa extending into the subserosa. The lesion was diagnosed as an arteriovenous malformation. The patient had a good clinical course without recurrence at the 2-year follow-up. CONCLUSIONS: An arteriovenous malformation in the sigmoid colon may rarely cause intussusception and prolapse of the colon. Complete resection is a radical and potentially effective treatment. Computed tomography and colonoscopy were useful for evaluation of the lesion in the present case.

Collagen VI suppresses fibronectin-induced enteric neural crest cell migration by downregulation of focal adhesion proteins.

The enteric nervous system (ENS) is a network of neurons and glia that are derived from enteric neural crest cells (ENCCs) and essential for regulating peristaltic activity of the colon. ENCCs migrate along the gastrointestinal tract to form the ENS, and disruption of ENCC motility leads to ENS disorders, such as Hirschsprung's disease. Previous ENCC-transplant experiments show that ENCCs can invade into isolated mouse intestines by age E13.5, but not after E15.5. We hypothesized that altered age-specific micro-environments in the intestine are responsible for ENCC invasion/migration. Here, we compared gene expression in the intestine between at E11.5 and E15.5 and identified 1355 differentially expressed transcripts. Among these, we found that genes encoding extracellular matrix (ECM) proteins were enriched. Notably, collagen VI (ColVI) family members were upregulated in the E15.5 mouse intestine at the mRNA and protein levels, whereas fibronectin (FN) was downregulated; however, both proteins showed colocalization at E15.5. To understand the mechanisms of ColVI and FN in ENCC migration, we examined neurosphere or individual ENCC-adherence capabilities toward the ECM. ColVI suppressed FN-induced ENCC spreading/migration, whereas ColVI induced morphologically narrow ENCC spreading and weak stress-fiber formation as compared with those with FN. Additionally, in ENCCs cultured on plates containing ColVI, the expression and phosphorylation of p130Cas, a members of focal adhesion complexes, was reduced. These data indicated an inhibitory role of ColVI in ENCC migration and suggested that ColVI suppression in the intestine might represent a novel therapeutic strategy for aganglionic colonic diseases.

Surgical approach for fecal incontinence with a patulous anus after transanal pull-through for Hirschsprung disease.

BACKGROUND: We have performed transanal pull-through (TAPT) for Hirschsprung disease since 1998. Some of our patients after TAPT showed a patulous anus and suffered from severe true fecal incontinence. We performed anal canal plasty for these patients and evaluated its efficacy in restoring anorectal function. METHODS: Thirty-one patients who were ≥5years old were previously operated on for Hirschsprung disease, and seven (22.5%) of these were indicated for this procedure. Anorectal function was evaluated using the Japanese Study Group of Anorectal Anomalies (JSGA) clinical assessment of defecation function score. For surgery, the patients were positioned in the prone jackknife posture. The posterior half of the anal canal was exposed and folded inward until the anal canal lumen was as narrow as the surgeon's index finger. External anal sphincter muscles were repaired, and the wound was closed vertically. RESULTS: The mean preoperative JSGA score was 1.42±0.4. The mean JSGA scores at 2-6months and 2years after this procedure were 5±2.1 and 5.8±2.1, respectively. Postoperatively, the JSGA score significantly improved at both times (p<0.05). CONCLUSIONS: Anal canal plasty may be effective for true fecal incontinence and a patulous anus after TAPT. This surgical approach may be useful for these conditions. LEVEL OF EVIDENCE: Type of study: Treatment study, Level IV.

Cartilage-hair hypoplasia associated with isolated hypoganglionosis: A case report.

Cartilage-hair hypoplasia is a rare metaphyseal chondrodysplasia characterized by diverse clinical manifestations and a high incidence of Hirschsprung disease. We present a male patient with cartilage-hair hypoplasia associated with severe intestinal obstruction. Genetic analysis of ribonuclease mitochondrial RNA-processing complex gene identified compound heterozygous mutations consisted with previously reported mutations: n.-14_3dupGAAGCTGAGGACGTGGT and n.183G > T. First, we considered that intestinal obstruction was due to an extensive type of Hirschsprung disease, but it was later confirmed as isolated hypoganglionosis. Isolated hypoganglionosis is rare and its therapeutic strategies are not well established. In cases of cartilage-hair hypoplasia associated with severe intestinal obstruction, the differential diagnosis of not only Hirschsprung disease, but also isolated hypoganglionosis, should be considered.