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Background
Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as “allied disorders of Hirschsprung's disease” and compiled these guidelines to facilitate acc...
Context in source publication
Context 1
... in this disease group, including pediatric sur- geons, pediatricians, pathologists, and physicians from the adult domain, have repeatedly discussed the disease concept and the classification. The following seven diseases are defined as allied disorders of Hirschsprung's disease: (i) immaturity of ganglia; (ii) isolated hypoganglionosis; (iii) intestinal neuronal dysplasia (IND); (iv) megacystis micro- colon intestinal hypoperistalsis syndrome (MMIHS); (v) seg- mental dilatation of intestine; (vi) internal anal sphincter achalasia (IASA); and (vii) chronic idiopathic intestinal pseudo-obstruction (CIIP; Table 1). ...
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Background
Sera anti‐enteric neuronal antibodies (AENA), neuronal inflammation, and degeneration in myenteric plexus in patients with irritable bowel syndrome (IBS) were reported. Effects of sera AENA in patients with IBS are unclear.
Methods
Patients with IBS met Rome III criteria were enrolled. Controls included healthy subjects (HS) and patient...
Citations
... Typical clinical origins of colonic ulcers encompass intestinal infections (bacterial, parasitic, tuberculosis, viral, etc.), ischemic bowel disease, inflammatory bowel disease, lymphoma, autoimmune disorders, or tumor involvement 3,4 A previously documented case presented a combination of colonic ulcer and pseudomembranous colitis, with the colonic ulcer being attributed to Clostridium difficile infection. 5 Nevertheless, a comprehensive examination revealed no indications of intestinal or other organ infections, tumors, or any other aforementioned factors contributing to colonic ulcers in this particular case. Consequently, we posit that the development of colonic ulcers is primarily associated with the individual's underlying condition. ...
... Additionally, this reduction or absence hinders the normal movement of the bowel, leading to a lack of normal dilation in affected segments on barium enema contrast and instead presenting with persistent contractile spasm. 5 Secondly, the activation and infiltration of inflammatory cells, including pro-inflammatory macrophages, at varying degrees contributes to the formation of crypt abscesses and mucosal damage, ultimately resulting in the manifestation of colonic ulcers. 4,5 ADHD is classified into two categories according to pathology: (1) abnormal ganglia, including immaturity of ganglia, hypoganglionosis, and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome, segmental dilatation, internal anal sphincter achalasia, and chronic idiopathic intestinal pseudo-obstruction. ...
... 5 Secondly, the activation and infiltration of inflammatory cells, including pro-inflammatory macrophages, at varying degrees contributes to the formation of crypt abscesses and mucosal damage, ultimately resulting in the manifestation of colonic ulcers. 4,5 ADHD is classified into two categories according to pathology: (1) abnormal ganglia, including immaturity of ganglia, hypoganglionosis, and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome, segmental dilatation, internal anal sphincter achalasia, and chronic idiopathic intestinal pseudo-obstruction. 5 Full-thickness pathological examination is the gold standard for the diagnosis of ADHD. ...
Background
Allied disorders of Hirschsprung’s disease (ADHD) exhibit symptoms akin to those of Hirschsprung’s disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa.
Case Report
A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient’s symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient’s symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition.
Conclusion
Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.
... In patients with megacolon, it is crucial to differentiate it from Hirschsprung's disease [15,16]. Hirschsprung's disease is characterized by a transit disorder of intestinal content, delayed meconium excretion, abdominal distention, bilious vomiting, constipation, and intestinal dilatation (megacolon) at the proximal side, resulting from dysperistalsis and a lack of a recto-anal reflex caused by aganglionosis of the intestinal tract at the distal side [17]. Transanal rectal biopsy has been proposed as a valid procedure to differentiate Hirschsprung disease from MEN 2B by detecting the presence of ganglion cells in the rectum [13,18,19]. ...
... A review of previous reports evaluating the intestinal histopathology of MEN [13,23]. In Japan, IND is currently classified as a subgroup of ADHD [17]. Additionally, ADHD is a disease group characterized by symptoms and signs similar to those of Hirschsprung's disease, despite the presence of ganglionic cells in the rectum. ...
... Intestinal neuronal dysplasia type B accounts for up to 95% of IND cases. In terms of pathology, malformation of the intestinal parasympathetic nervous system is present, and AChE staining shows evidence of submucosal giant ganglia, hyperganglionosis, ectopic ganglia, and the growth of AChE-positive nerve fibers [17]. Histopathological differences between ganglioneuromatosis-like hyperplasia and IND type B remains controversial [24]. ...
Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung’s disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed . Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.
... To achieve this goal, obtaining adequate surgical samples is of paramount importance. If CIHG is suspected preoperatively or intraoperatively and Hirschsprung disease is ruled out based on the presence of ganglion cells, the guidelines established in Japan suggest multiple full-thickness biopsy specimens, including those of the sigmoid colon, ileum, and jejunum, be collected when the initial stoma is created [18]. Additionally, immunohistochemical staining with Hu C/D helps to quantify ganglion cells; the number of ganglion cells in the normal intestine obtained from age-matched control samples ranged from 41.0 to 71.0 cm, while that in CIHG was below 20-30 cm [14,16]. ...
No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop–Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.
... Since then, various terms have been used to describe this group of diseases, including Hirschsprung's disease-related disorders, variant Hirschsprung's disease, allied disorders of Hirschsprung's disease, and Hirschsprung's disease-related neuromuscular disorders of the intestine. The following seven diseases are defined as allied disorders of Hirschsprung's disease: (i) immaturity of ganglia; (ii) isolated hypoganglionosis; (iii) intestinal neuronal dysplasia; (iv) megacystis microcolon intestinal hypoperistalsis syndrome; (v) segmental dilatation of the intestine; (vi) internal anal sphincter achalasia; and (vii) chronic idiopathic intestinal pseudo-obstruction [4] . Up to 15% of other disorders associated with Hirschsprung's disease, even in milder forms, can be attributed to congenital hypoganglionosis. ...
Intestinal hypoganglionosis in adults is quite uncommon, and hypoganglionosis of the ileum has not been documented to date. The majority of studies on this disorder are single case reports and brief case series. We describe a 30-year-old male patient with bowel obstruction and intestinal hypoganglionosis of the ileum and we review the literature on the disorder.
... Since then, various terms have been used to describe this group of diseases, including Hirschsprung's disease-related disorders, variant Hirschsprung's disease, allied disorders of Hirschsprung's disease, and Hirschsprung's disease-related neuromuscular disorders of the intestine. The following seven diseases are defined as allied disorders of Hirschsprung's disease: (i) immaturity of ganglia; (ii) isolated hypoganglionosis; (iii) intestinal neuronal dysplasia; (iv) megacystis microcolon intestinal hypoperistalsis syndrome; (v) segmental dilatation of the intestine; (vi) internal anal sphincter achalasia; and (vii) chronic idiopathic intestinal pseudo-obstruction [4] . Up to 15% of other disorders associated with Hirschsprung's disease, even in milder forms, can be attributed to congenital hypoganglionosis. ...
Intestinal hypoganglionosis in adults is quite uncommon, and hypoganglionosis of the ileum has not been documented to date. The majority of studies on this disorder are single case reports and brief case series. We describe a 30-year-old male patient with bowel obstruction and intestinal hypoganglionosis of the ileum and we review the literature on the disorder.
... They clinically resemble Hirschsprung's disease (HD), despite the presence of ganglion cells in rectal suction biopsies and require specific histological, immunohistochemical and electron microscopic investigations to diagnose them. They include intestinal neuronal dysplasia, intestinal ganglioneuromatosis, isolated hypoganglionosis, immature ganglia, absence of the argyrophil plexus, internal anal sphincter achalasia and congenital smooth muscle cell disorders, malformations of the muscularis propria, degenerative leiomyopathy, leiomyositis, and mitochondriopathies [8,9]. ...
Dysfunctional elimination syndrome is a constellation of symptoms related to the urinary, genital and colorectal dysfunction of the psycho-neuro-endocrine-target organs axis origin secondary to congenital and acquired disorders
... They include intestinal neuronal dysplasia, intestinal ganglioneuromatosis, isolated hypoganglionosis, immature ganglia, absence of the argyrophil plexus, internal anal sphincter achalasia and congenital smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome, intestinal pseudo-obstruction, ganglionitis, degenerative neuropathy, diffuse ganglioneuromatosis, malformations of the muscularis propria, degenerative leiomyopathy, leiomyositis, and mitochondriopathies [15,16]. These colorectal motility disorders of their own may remain silent but during psychological stress to the fetus, infant or child; the flight or fight mode is on and the imbalance between the sympathetic and parasympathetic nervous system leads to incoordination between involuntary internal sphincter and voluntary pelvic sphincter muscles in the bowel, bladder and cervical regions leading to increased resistance to evacuate the contents with retention reservoir associated with increased risk of growth and development of resistant microbes and lead to back pressure with reflux into the ileocecal valve, vesicoureteral reflux or retrograde flow into the fallopian tubes into the peritoneal cavity with dysmenorrhea, menorrhagia, retrograde menstruation, recurrent vulvovaginitis or ascending pelvic infection and infertility. ...
... A number of congenital neurodysplastic conditions exist that cause varying degrees of functional disturbances of the gastrointestinal tract. Some patients have symptoms similar to those of Hirschsprung's disease (HSCR) (HSCR-like conditions) despite the presence of ganglion cells in the rectum [4]. Detailed data on patients with allied disorders of Hirschsprung's disease (ADHD) is limited. ...
Background
Functional disturbances of the gastrointestinal tract are caused by a number of neurodysplastic conditions, including diseases that are rarer than Hirschsprung’s disease (HSCR), such as ganglion cell immaturity and intestinal neuronal dysplasia (IND). Bcl-2 shows positive immunoreactivity in degenerative and immature ganglion cells (IGCs). This work evaluates the implication of the immunohistochemical expression of Bcl-2 in cases of pediatric intestinal pseudo-obstruction (IPO) with ganglionated specimens.
This 2-year prospective observational study was conducted from January 2017 to December 2019 on all intestinal specimens for cases referred from a pediatric surgery department with clinical data suggesting IPO (abdominal distension > 3 months, intermittent bilious vomiting, no radiological evidence of the transitional zone of HSCR or evidence of mechanical obstruction). The exclusion criteria were patients with IPO related to myopathic disorders, aganglionic biopsies, and specimens with inadequate tissue blocks. The same number of intestinal specimens of cases without IPO was used as a control group. All specimens underwent a histologic examination of ganglion cells and nerve bundles and were also evaluated for Bcl-2 immunohistochemical expression.
Results
Twenty-one specimens were analyzed, including six colonic resection specimens and 15 intestinal biopsies taken by full-thickness transanal biopsy ( n = 12) or incisional biopsy from inadequately functioning stomas ( n = 3). The mean ± standard deviation age of the patient cohort was 22 ± 7.4 months (range, 19–153 months), and there were 13 (61.9%) male patients. Bcl-2 protein was strongly positive in 57.1% of the cases, weakly positive in 19%, and negative in 23.8% as well as in all 21 control specimens. A highly significant correlation was observed between Bcl-2 expression and ganglion cell number ( P < 0.001), where all hyperganglionic specimens showed strong positivity compared with the hypoganglionic and adequately ganglionic specimens. A positive association was also found between Bcl-2 expression and IND compared with other disorders of dysganglionosis ( P = 0.04) and post-HSCR cases ( P = 0.002).
Conclusion
Bcl-2 immunohistochemistry is a valuable tool to diagnose allied disorders of HSCR through its expression in IGCs, which are difficult to identify by conventional hematoxylin and eosin staining.
... Multisite full-thickness colorectal biopsy is a reliable means to confirm HAD [4][5][6]. Some of these children can present with progressive abdominal distention, vomiting, and constipation within three months of birth, which can lead to failure to feed in serious cases and even intestinal obstruction, intestinal necrosis, and perforation, requiring emergency surgery [7]. The clinical treatment of such children is difficult. ...
Objective:
Hirschsprung disease (HSCR) is a serious congenital intestinal disease with a prevalence of 1/5000. HSCR remains one of the most severe congenital malformations of the abdominal organs in children that require complex reconstructive surgery. This study is aimed at investigating the clinical analysis of ileal Santulli stoma and ileal double-lumen stoma in children diagnosed with intestinal neuronal dysplasia (IND).
Methods:
Retrospective analysis was performed on the children who were admitted to our hospital for intestinal obstruction from January 2014 to January 2019, underwent fistula operation and fistula closure operation, and were diagnosed with IND. According to the different modes of fistula, the children were divided into ileal Santulli stoma group and ileal double-lumen stoma group. The body weight of the children in the two groups during the second stage of fistula closure operation was compared. The number of hospitalizations due to enteritis and dehydration during the two operations was compared.
Results:
A total of 23 cases (12 males and 11 females) were included in this study, including 10 cases in the Santulli group and 13 cases in the ileal double-lumen stoma group. There were no significant differences in baseline data and fistula location between the two groups. Compared with the ileal double-lumen stoma group, the Santulli stoma group had significantly higher weight of fistula precursor (P < 0.05), the interval between two operations was shorter (P < 0.05), there is less hospitalization for enteritis and dehydration during the two operations (P < 0.05), and there is less economic cost after fistula (P < 0.05).
Conclusion:
The clinical effect of ileum Santulli fistula is significantly better than double-lumen ileum fistula, which is not only beneficial to the growth and development of children after the first fistula but also can shorten the time of fistula closure, reduce the incidence of dehydration, and reduce the economic burden of family members. Therefore, it is worthy of clinical promotion and application.
... ADHD were first reported by Ravitch as "pseudo Hirschsprung's disease" in the Annals of Surgery in 1958 [3], and have been referred to a disease group that clinically resemble Hirschsprung's disease, despite the presence of ganglion cells in the terminal rectum [1]. According to the literature, ADHD was classified into two categories depending on the pathological findings, which is consisted of seven diseases: (1) abnormal ganglia, including immaturity of ganglia, isolated hypoganglionosis, and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome, segmental dilatation of intestine, internal anal sphincter achalasia, and chronic idiopathic intestinal pseudo-obstruction [4]. ...
... As for treatment, intestinal decompression and enteral or parenteral nutrition are currently recommended. Radical surgery is controversial and no drug can be recommended to effectively improve functional gastrointestinal disorders or symptoms [4]. In this case, subtotal colectomy was performed because of severe luminal dilatation of colons, and the chronic constipation was relieved, while abdominal distention and intestinal dilatation were still existed and even progressed to recurrent spontaneous pneumoperitoneum. ...
... Physicians are advised to consider ADHD in these patients after differential diagnosis. A full-thickness biopsy of the gastrointestinal tract (especially the small intestine and sigmoid colon) is recommended for the definitive diagnosis [4]. While the disease has a poor prognosis, timely and long-term treatment with intestinal decompression and nutritional therapy could help relieve symptoms and provide a better quality of life for such patients. ...
Background
Allied disorders of Hirschsprung’s disease (ADHD) mainly present with bowel obstruction, intestinal dilatation, and chronic constipation, while recurrent spontaneous pneumoperitoneum was rarely reported. We aimed to report a case of recurrent spontaneous pneumoperitoneum caused by ADHD.
Case presentation
A 59-year-old female patient presented with progressive and severe constipation in the past 30 years. She suffered from abdominal discomfort, which was described as ‘gurgling’ during the last three years. Radiography showed free-air and intestinal dilatation, without any other diseases, and she was identified with recurrent spontaneous pneumoperitoneum. Gastrointestinal transit test indicated gastrointestinal motility disorder, and anorectal manometry confirmed the presence of rectal anus-suppressing reflex. Subtotal colectomy was performed to relieve apparent constipation, and the postoperative pathological examination of the colon demonstrated proliferation of nerve fibers and hyperplasia of myenteric plexuses, as well as a relatively scarcity of ganglion cells in the myenteric plexus. Based on the presentations and the postoperative pathology, she was diagnosed with ADHD. The recurrent spontaneous pneumoperitoneum was regarded as the gas escape from dilated intestines, which was in high pressure. All the symptoms and her mental state were improved after the treatment with gastrointestinal decompression and enteral nutrition. However, during follow-up visits, she had intestinal infection, and suffered from severe diarrhea and water-electrolyte imbalance, and the patient eventually died at 17 months after the diagnosis.
Conclusion
ADHD could be a rare cause of recurrent spontaneous pneumoperitoneum, and are mainly undiagnosed or misdiagnosed. A full-thickness biopsy of the gastrointestinal tract (especially the small intestine and sigmoid colon) and differential diagnosis are recommended for the definitive diagnosis. While the ADHD have shown a poor prognosis, timely and long-term treatment with intestinal decompression and nutritional therapy could help relieve symptoms and provide a better quality of life for such patients.
