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Wu L, Xiang L, Chen Y, Mao H, Meng X, Wang J, Li H, Chen X, Feng J, Xiao J. Three distinct classes of myenteric ganglia in mice and humans: insights from quantitative analyses. PeerJ 2025; 13:e19329. [PMID: 40292108 PMCID: PMC12034244 DOI: 10.7717/peerj.19329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Background The myenteric plexus primarily consists of the myenteric ganglia, which include enteric neurons, synaptic neuropils, and glial cells. Abnormal myenteric plexus formation can result in gastrointestinal disorders. Comprehensive morphological classification studies of myenteric ganglia remain limited. Methods Whole-mount immunofluorescence staining was used to label myenteric ganglia in colon tissue of mice and children. The ganglionic area and the number of intraganglion neurons were quantified by the K-means clustering algorithm. The guts of embryonic day 11.5 (E11.5) mouse were cultured and immunostained to observe the characteristics of developing myenteric ganglia. Results Myenteric ganglia can be categorized into three groups in the colon tissues of mice and normal children. A similar classification was observed for Tuj1-positive neuronal cell clusters in the midgut of E11.5 mouse. Culture of the E11.5 mouse midgut revealed that the area of post-cultured clusters of developing neurons also fell into three distinct categories, with a noticeable increase compared to pre-culture. Conclusions The myenteric ganglia in mice and humans can be categorized into three groups based on both the ganglionic area and intraganglion neuron count, and distinct classes of myenteric ganglia may be present during early development.
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Affiliation(s)
- Luyao Wu
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Lei Xiang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Yingjian Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Handan Mao
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Xinyao Meng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Jing Wang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Honglin Li
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Nursing Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuyong Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Jiexiong Feng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
| | - Jun Xiao
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Center of Hirschsprung’s disease and allied disorders, Wuhan, China
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Onishi S, Ieiri S. Conditions that mimic Hirschsprung's disease, but that are not Hirschsprung's disease. WORLD JOURNAL OF PEDIATRIC SURGERY 2025; 8:e000918. [PMID: 40094120 PMCID: PMC11907078 DOI: 10.1136/wjps-2024-000918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/14/2025] [Indexed: 03/19/2025] Open
Abstract
Hirschsprung's disease (HSCR) is widely recognized in pediatric surgery. This condition has been elucidated, and therapeutic approaches have been developed. However, even when ganglion cells are present in the rectum, some patients still experience symptoms such as bowel obstruction, intestinal dilatation, and chronic constipation, which are similar to those observed in HSCR. A consensus regarding the terminology for these diseases is yet to be established. This group of diseases was defined as 'allied disorders of Hirschsprung's disease' (ADHD). They are classified into two categories based on pathology: (1) Abnormal ganglia, including immaturity of ganglia, hypoganglionosis, and intestinal neuronal dysplasia; and (2) Normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), segmental dilatation, internal anal sphincter achalasia, and chronic idiopathic intestinal pseudo-obstruction (CIIP). Hypoganglionosis, MMIHS, and CIIP are particularly severe and not curable by surgery. Guidelines were compiled to facilitate an accurate clinical diagnosis and provide appropriate treatment strategies for each disease. A full-thickness rectal biopsy with H&E and acetylcholinesterase staining is often required for a differential diagnosis. Patients are now able to survive longer with enteral nutrition combined with long-term intravenous nutrition and decompression of the gastrointestinal tract. However, all treatment strategies are symptomatic. It is necessary to improve the results of small intestine transplantation and to develop new therapies using regenerative medicine.
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Affiliation(s)
- Shun Onishi
- Department of Pediatric Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Kagoshima, Japan
| | - Satoshi Ieiri
- Department of Pediatric Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Kagoshima, Japan
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Yano K, Muto M, Sugita K, Murakami M, Onishi S, Harumatsu T, Iwamoto Y, Ogata M, Takada L, Nishida N, Kedoin C, Nagano A, Matsui M, Yamada K, Yamada W, Matsukubo M, Kawano T, Kaji T, Ieiri S. Prognostic factors for pediatric patients with severe intestinal motility disorders: a single institution's experience. Surg Today 2025; 55:380-385. [PMID: 39110212 PMCID: PMC11842528 DOI: 10.1007/s00595-024-02910-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 07/16/2024] [Indexed: 02/21/2025]
Abstract
PURPOSE To identify the prognostic factors for pediatric severe intestinal motility disorder (IMD). METHODS We reviewed the medical records of patients with severe IMD, who required total parenteral nutrition (TPN) for ≥ 60 days at our institution between April, 1984 and March, 2023, examining their characteristics to identify prognostic factors. RESULTS The types of IMD in the 14 patients enrolled in this study were as follows: isolated hypoganglionosis (IHG, n = 6), extensive aganglionosis (EAG: n = 6), and chronic idiopathic intestinal pseudo-obstruction (CIIP, n = 2). There was no significant difference in mortality among the three types of severe IMD. Weaning-off TPN and the use of the colon were not significant prognostic factors, but cholestasis was a significant prognostic factor (p = 0.005). There was a high mortality rate (50%), with the major causes of death being intestinal failure-associated liver disease (IFALD) following hepatic failure, and catheter-related blood stream infection (CRBSI). One IHG patient underwent small bowel transplantation but died of acute rejection. CONCLUSION Severe IMD is still associated with a high mortality rate and cholestasis predicts the prognosis. Thus, preventing or improving IFALD and CRBSI caused by long-term TPN is important for reducing the mortality rate.
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Affiliation(s)
- Keisuke Yano
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Mitsuru Muto
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Koshiro Sugita
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Masakazu Murakami
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Shun Onishi
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Toshio Harumatsu
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Yumiko Iwamoto
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Masato Ogata
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Lynne Takada
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Nanako Nishida
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Chihiro Kedoin
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Ayaka Nagano
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Mayu Matsui
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Koji Yamada
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Waka Yamada
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Makoto Matsukubo
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Takafumi Kawano
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan
| | - Tatsuru Kaji
- Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Satoshi Ieiri
- Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.
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Yoshimaru K, Matsuura T, Uchida Y, Sonoda S, Maeda S, Kajihara K, Kawano Y, Shirai T, Toriigahara Y, Kalim AS, Zhang XY, Takahashi Y, Kawakubo N, Nagata K, Yamaza H, Yamaza T, Taguchi T, Tajiri T. Cutting-edge regenerative therapy for Hirschsprung disease and its allied disorders. Surg Today 2024; 54:977-994. [PMID: 37668735 DOI: 10.1007/s00595-023-02741-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 08/06/2023] [Indexed: 09/06/2023]
Abstract
Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed.
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Affiliation(s)
- Koichiro Yoshimaru
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Yasuyuki Uchida
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Soichiro Sonoda
- Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shohei Maeda
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Keisuke Kajihara
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuki Kawano
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Takeshi Shirai
- Department of Pediatric Surgery, Miyazaki Prefectural Miyazaki Hospital, 5-30 Kitatakamatsu-cho, Miyazaki, Miyazaki, 880-8510, Japan
| | - Yukihiro Toriigahara
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Alvin Santoso Kalim
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Xiu-Ying Zhang
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshiaki Takahashi
- Department of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Naonori Kawakubo
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kouji Nagata
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Haruyoshi Yamaza
- Department of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Takayoshi Yamaza
- Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tomoaki Taguchi
- Fukuoka College of Health Sciences, 2-15-1 Tamura, Sawara-ku, Fukuoka, 814-0193, Japan
| | - Tatsuro Tajiri
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Kalim AS, Nagata K, Toriigahara Y, Shirai T, Kirino K, Xiu-Ying Z, Kondo T, Kawakubo N, Miyata J, Matsuura T, Tajiri T. A lmod1a mutation causes megacystis microcolon intestinal hypoperistalsis in a CRISPR/Cas9-modified zebrafish model. Pediatr Surg Int 2024; 40:225. [PMID: 39143337 DOI: 10.1007/s00383-024-05809-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/07/2024] [Indexed: 08/16/2024]
Abstract
PURPOSE Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is defined as a congenital visceral myopathy with genetic mutations. However, the etiology and pathophysiology are not fully understood. We aimed to generate a gene leiomodin-1a (lmod1a) modification technique to establish a zebrafish model of MMIHS. METHODS We targeted lmod1a in zebrafish using CRISPR/Cas9. After confirming the genotype, we measured the expression levels of the target gene and protein associated with MMIHS. A gut transit assay and spatiotemporal mapping were conducted to analyze the intestinal function. RESULTS Genetic confirmation showed a 5-base-pair deletion in exon 1 of lmod1a, which caused a premature stop codon. We observed significant mRNA downregulation of lmod1a, myh11, myod1, and acta2 and the protein expression of Lmod1 and Acta2 in the mutant group. A functional analysis of the lmod1a mutant zebrafish showed that its intestinal peristalsis was fewer, slower, and shorter in comparison to the wild type. CONCLUSION This study showed that targeted deletion of lmod1a in zebrafish resulted in depletion of MMIHS-related genes and proteins, resulting in intestinal hypoperistalsis. This model may have the potential to be utilized in future therapeutic approaches, such as drug discovery screening and gene repair therapy for MMIHS.
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Affiliation(s)
- Alvin Santoso Kalim
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kouji Nagata
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Yukihiro Toriigahara
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Shirai
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kosuke Kirino
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Zhang Xiu-Ying
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuya Kondo
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Naonori Kawakubo
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Junko Miyata
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tatsuro Tajiri
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Sakai Y, Nakayama Y, Kurasawa S, Sado T, Kato S, Hidaka N, Takamizawa S, Yoshizawa K, Yoshimaru K, Taguchi T. Multiple endocrine neoplasia type 2B diagnosed after small intestinal volvulus with progressive megacolon in an adolescent. Clin J Gastroenterol 2024; 17:640-646. [PMID: 38753051 PMCID: PMC11284186 DOI: 10.1007/s12328-024-01979-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 05/02/2024] [Indexed: 07/29/2024]
Abstract
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.
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Affiliation(s)
- Yusuke Sakai
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
| | - Shingo Kurasawa
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Tomomitsu Sado
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Sawako Kato
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Nao Hidaka
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Shigeru Takamizawa
- Department of Surgery, Nagano Children's Hospital, 3100 Toyoshina, Azumino, Nagano, Japan
| | - Katsumi Yoshizawa
- Department of Surgery, Nagano Children's Hospital, 3100 Toyoshina, Azumino, Nagano, Japan
| | - Koichiro Yoshimaru
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
- Fukuoka College of Health Sciences, Fukuoka, Japan
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Tamaki A, Kohashi K, Yoshimaru K, Hino Y, Hamada H, Kawakubo N, Taguchi T, Tajiri T, Oda Y. A Novel Objective Pathologic Criterion for Isolated Hypoganglionosis. Am J Surg Pathol 2024; 48:803-812. [PMID: 38726836 DOI: 10.1097/pas.0000000000002243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Isolated hypoganglionosis (IHG) is histologically characterized by small numbers of myenteric ganglion cells and small myenteric ganglia; however, no numerical diagnostic criteria for IHG have been established. Therefore, this study aimed to develop quantitative pathologic criteria for IHG. We evaluated 160 resected intestinal tissue specimens from 29 pediatric autopsies and 10 IHG cases. These specimens were obtained from the jejunum, ileum, ascending colon, transverse colon, and rectum. Morphologic features of the myenteric ganglion cells and myenteric ganglia were quantified and analyzed in digitized HuC/HuD-immunostained and CD56-immunostained sections, respectively. Quantitative criteria were developed with a scoring system that used parameters with the area under the receiver operating characteristic curve (AUC) values >0.7 and sensitivity and specificity exceeding 70%. The selected parameters were the number of myenteric ganglion cells per cm and the number of myenteric ganglia with an area >2500 µm 2 per cm. The score for each parameter ranged from -1 to 2, and the total score of the scoring system ranged from -2 to 4. With a cutoff value of ≥2 (AUC, 0.98; 95% CI: 0.96-1.00), the scoring system had a sensitivity of 96% (95% CI: 0.82-1.00) and a specificity of 99% (95% CI: 0.95-1.00). We devised a novel pathologic criterion based on the quantification of the number of myenteric ganglion cells and ganglia. Furthermore, this criterion showed high diagnostic accuracy and could lead to a definitive diagnosis of IHG in clinical practice.
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Affiliation(s)
- Akihiko Tamaki
- Departments of Anatomic Pathology
- Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
| | - Kenichi Kohashi
- Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka
| | | | - Yuko Hino
- Departments of Anatomic Pathology
- Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
| | - Hiroshi Hamada
- Departments of Anatomic Pathology
- Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
| | - Naonori Kawakubo
- Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
| | - Tomoaki Taguchi
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Tatsuro Tajiri
- Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
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Hu M, Fang H, Hu Y, Lu C, Chen Y, Zhong Z, Shi H, Wang Q. An Unusual Cause of Intestinal Ulcers Masquerading as Inflammatory Bowel Disease: A Case Report of Allied Disorders of Hirschsprung's Disease. J Inflamm Res 2024; 17:3093-3099. [PMID: 38779428 PMCID: PMC11110832 DOI: 10.2147/jir.s459548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/09/2024] [Indexed: 05/25/2024] Open
Abstract
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.
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Affiliation(s)
- Minli Hu
- Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Hao Fang
- Department of Traumatology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Yibing Hu
- Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Chong Lu
- Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Yuan Chen
- Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Zhifeng Zhong
- Department of Anus & Intestine Surgery, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Hongqi Shi
- Department of Pathology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
| | - Qunying Wang
- Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China
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Tayama S, Furuta Y, Morito M, Naoe H, Yoshii D, Uchida Y, Yoshimaru K, Miyamoto Y, Taguchi T, Tanaka Y. Chronic intestinal pseudo-obstruction due to adult-onset acquired isolated hypoganglionosis with muscular atrophy in the small intestine: a case report and review of literature. Clin J Gastroenterol 2024; 17:244-252. [PMID: 38193986 DOI: 10.1007/s12328-023-01902-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/28/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal disorder characterized by impaired propulsion of the digestive tract and associated with symptoms of intestinal obstruction, despite the absence of obstructive lesions. CIPO includes several diseases. However, definitive diagnosis of its etiology is difficult only with symptoms or imaging findings. CASE PRESENTATION A 56-year-old man was referred to our hospital due to a 3-year history of continuous abdominal distention. Imaging, including computed tomography of the abdomen, and endoscopy revealed marked dilatation of the entire small intestine without any obstruction point. Therefore, he was diagnosed with CIPO. Since medical therapy didn't improve his symptoms, enterostomy and percutaneous endoscopic gastro-jejunostomy were performed. These procedures improved abdominal symptoms. However, he required home central venous nutrition due to dehydration. The pathological findings of full-thickness biopsies of the small intestine taken during surgery revealed decreased number and degeneration of ganglion cells in the normal plexus. These findings led to a final diagnosis of CIPO due to acquired isolated hypoganglionosis (AIHG). CONCLUSIONS Here, we report the case of a patient with CIPO secondary to adult-onset AIHG of the small intestine. Since AIHG cannot be solely diagnosed using clinical findings, biopsy is important for its diagnosis.
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Affiliation(s)
- Sayoko Tayama
- Department of Gastroenterology and Hepatology, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan
| | - Yoki Furuta
- Department of Gastroenterology and Hepatology, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan
| | - Miyuki Morito
- Department of Gastroenterology and Hepatology, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan
| | - Hideaki Naoe
- Department of Gastroenterology and Hepatology, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan
| | - Daiki Yoshii
- Department of Diagnostic Pathology, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan
| | - Yasuyuki Uchida
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka-City, Fukuoka, 812-8582, Japan
| | - Koichiro Yoshimaru
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka-City, Fukuoka, 812-8582, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka-City, Fukuoka, 812-8582, Japan
- Fukuoka College of Health Sciences, 2-15-1 Tamura, Sawara-ku, Fukuoka, 814-0193, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan.
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10
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Yamada Y, Mori T, Takahashi N, Fujimura T, Kano M, Kato M, Takahashi M, Shimojima N, Watanabe T, Yoshioka T, Kanamori Y, Kuroda T, Fujino A. Historical Cohort Study of Congenital Isolated Hypoganglionosis of the Intestine: Determining the Best Surgical Interventions. Biomolecules 2023; 13:1560. [PMID: 37892242 PMCID: PMC10605557 DOI: 10.3390/biom13101560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 10/09/2023] [Accepted: 10/15/2023] [Indexed: 10/29/2023] Open
Abstract
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.
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Affiliation(s)
- Yohei Yamada
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (N.T.); (M.K.); (A.F.)
| | - Teizaburo Mori
- Department of Pediatric Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan; (T.M.); (M.K.); (M.T.); (Y.K.)
| | - Nobuhiro Takahashi
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (N.T.); (M.K.); (A.F.)
| | - Takumi Fujimura
- Department of Pediatric Surgery, National Hospital Organization Saitama National Hospital, Saitama 351-0102, Japan;
| | - Motohiro Kano
- Department of Pediatric Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan; (T.M.); (M.K.); (M.T.); (Y.K.)
| | - Mototoshi Kato
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (N.T.); (M.K.); (A.F.)
| | - Masataka Takahashi
- Department of Pediatric Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan; (T.M.); (M.K.); (M.T.); (Y.K.)
| | - Naoki Shimojima
- Department of Surgery, Tokyo Metropolitan Children’s Medical Center, Tokyo 183-8561, Japan;
| | - Toshihiko Watanabe
- Department of Pediatric Surgery, Tokai University School of Medicine, Kanagawa 259-1193, Japan;
| | - Takako Yoshioka
- Department of Pathology, National Center for Child Health and Development, Tokyo 157-8535, Japan;
| | - Yutaka Kanamori
- Department of Pediatric Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan; (T.M.); (M.K.); (M.T.); (Y.K.)
| | - Tatsuo Kuroda
- Kanagawa Children’s Medical Center, Yokohama 232-0066, Japan;
| | - Akihiro Fujino
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (N.T.); (M.K.); (A.F.)
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Huan PD, Lieu DQ, Dung TN, Long TB, Anh TN, Dung LQ, Phan ND, Vinh NTT, Duc NM. A case report of segmental hypoganlionosis of the ileum in an adult. Radiol Case Rep 2023; 18:2073-2077. [PMID: 37089968 PMCID: PMC10113777 DOI: 10.1016/j.radcr.2023.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 04/07/2023] Open
Abstract
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.
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Mohamed LAEF, Hegazy NA, Ghazal FAEA, Zaki AMED, Radwan AB, Hakim SA. Diagnostic utility of Bcl-2 immunohistochemical expression in pediatric functional bowel obstruction cases with ganglionated specimens. ANNALS OF PEDIATRIC SURGERY 2022; 18:73. [DOI: 10.1186/s43159-022-00212-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 10/09/2022] [Indexed: 09/01/2023] Open
Abstract
Abstract
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.
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Jiang S, Song CY, Feng MX, Lu YQ. Adult patients with allied disorders of Hirschsprung’s disease in emergency department: An 11-year retrospective study. World J Gastrointest Surg 2022; 14:656-669. [PMID: 36158276 PMCID: PMC9353751 DOI: 10.4240/wjgs.v14.i7.656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/21/2021] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the past years, only a few studies with a limited number of adult patients analyzed clinical features of allied disorders of Hirschsprung’s disease (ADHD), most of which were individual case reports or lacked detailed clinical information. Although many studies have reported patients presenting to the emergency department (ED) with recurrent abdominal symptoms for a number of disorders, there are few data involving ADHD. However, owing to a lack of awareness of the disease, misdiagnoses and mistreatments are common. Severe complications such as perforation, bleeding, malabsorption, and even death in ADHD had been reported by many studies.
AIM To assist ED clinicians in having a more comprehensive understanding of this disease and making an early suspected diagnosis of ADHD more effectively.
METHODS We enrolled 53 patients who visited the ED and were eventually diagnosed with ADHD over the past 11 years in our hospital. Their basic information, clinical manifestations, and imaging findings were analyzed. Blood indices were compared between the ADHD and irritable bowel syndrome (IBS) groups.
RESULTS Adult patients with ADHD had a mean age of 48.8 ± 14.3 years, and 77.4% had been treated before admission. The transverse colon was the most common dilated part (73.6%), and constipation (67.9%) was the most common symptom. ADHD patients can present with uncommon symptoms and false-negative imaging findings. Logistic regression analysis indicated that body mass index (BMI) [odds ratio (OR) = 0.786, P = 0.013], cholinesterase (per 1000 units; OR = 0.693, P = 0.008), and blood chlorine (OR = 0.816, P = 0.022) were determined to be independent related factors between the ADHD and IBS groups. The area under the receiver operating characteristics curve of these three indices combined was 0.812 (P < 0.001).
CONCLUSION Emergency physicians should be vigilant regarding patients with chronic constipation, abdominal pain, or abdominal distension, and consider the possibility of ADHD despite its rarity. Abdominal computed tomography examination is recommended as a useful tool in the suspected diagnosis of ADHD. BMI, cholinesterase, and blood chlorine have good discriminative abilities between ADHD and IBS. The nutritional status of adult patients with ADHD is worthy of further attention. Surgical treatment for adult patients with ADHD is important and inevitable.
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Affiliation(s)
- Shuai Jiang
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Cong-Ying Song
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Meng-Xiao Feng
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Yuan-Qiang Lu
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
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14
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Lin Y, Wu D, Shen Y, He Y, Ye J. Comparison of Outcomes between Two Surgical Techniques for Patients with Intestinal Neuronal Dysplasia. J Immunol Res 2022; 2022:9165651. [PMID: 35910855 PMCID: PMC9334036 DOI: 10.1155/2022/9165651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/22/2022] [Accepted: 06/28/2022] [Indexed: 11/18/2022] Open
Abstract
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.
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Affiliation(s)
- Yu Lin
- Pediatric Surgery Department, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000 Fujian, China
| | - Dianming Wu
- Pediatric Surgery Department, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000 Fujian, China
| | - Yong Shen
- Pediatric Surgery Department, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000 Fujian, China
| | - Yuanbin He
- Pediatric Surgery Department, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000 Fujian, China
| | - Jianxin Ye
- Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou, 350000 Fujian, China
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15
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Yin Y, Zhang Y, Tan B, Zhou W, Liu W, Zeng X. Recurrent spontaneous pneumoperitoneum secondary to intestinal dilatation caused by allied disorders of Hirschsprung’s disease: a case report. BMC Gastroenterol 2022; 22:316. [PMID: 35761190 PMCID: PMC9235130 DOI: 10.1186/s12876-022-02376-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 06/10/2022] [Indexed: 11/13/2022] Open
Abstract
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. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02376-w.
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16
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Is oral food challenge useful to avoid complete elimination in Japanese patients diagnosed with or suspected of having IgE-dependent hen's egg allergy? A systematic review. Allergol Int 2022; 71:221-229. [PMID: 34663557 DOI: 10.1016/j.alit.2021.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 09/07/2021] [Accepted: 09/09/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND IgE-mediated egg allergy is a common food allergy worldwide. Patients with egg allergy are known to easily achieve tolerance compared to other allergens such as nuts. Oral food challenge (OFC) is often performed on patients diagnosed with or suspected of having IgE-mediated food allergy, but whether hen's egg OFC is useful in IgE-dependent egg allergy patients to avoid complete elimination remains unknown. METHODS We identified articles in which OFCs were performed in Japanese patients diagnosed with or suspected of having IgE-mediated egg allergy. We evaluated whether the OFCs were useful to avoid the complete elimination of eggs by assessing the following: (1) the number of patients who could avoid complete elimination; (2) the number of patients who experienced serious adverse events (SAEs); or (3) adverse events (AEs); (4) improvement in quality of life (QOL); and (5) immunological changes. RESULTS Fifty-nine articles were selected in the study; all the references were case series or case studies in which OFC was compared to pre-challenge conditions. The overall negative ratio against egg OFC was 62.7%, but an additional 71.9% of OFC-positive patients could take eggs when expanded to partial elimination. Of the 4182 cases, 1146 showed AEs in the OFC, and two cases reached an SAE. Two reports showed an improvement in QOL and immunological changes, although the evidence was weak. CONCLUSIONS OFCs against eggs may be useful to avoid complete elimination, but medical professionals should proceed with the test safely and carefully.
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Maeda M, Kuwabara Y, Tanaka Y, Nishikido T, Hiraguchi Y, Yamamoto-Hanada K, Okafuji I, Yamada Y, Futamura M, Ebisawa M. Is oral food challenge test useful for avoiding complete elimination of cow's milk in Japanese patients with or suspected of having IgE-dependent cow's milk allergy? Allergol Int 2022; 71:214-220. [PMID: 34593320 DOI: 10.1016/j.alit.2021.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/02/2021] [Accepted: 08/17/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Cow's milk, along with hen's egg, are common causes of food allergies in children worldwide. Accidental ingestion of milk is common and often induces severe allergic reactions. Oral food challenge test (OFC) is usually performed in patients with or suspected of having a food allergy. However, the evidence of whether cow's milk OFC is useful in IgE-dependent cow's milk allergy patients to avoid total elimination is not known. METHODS After setting the clinical question and outcomes, we performed a systematic review for relevant articles published from January 1, 2000 to August 31, 2019 using PubMed® and Ichushi-Web databases. Each article was then evaluated for the level of evidence. All positive results of the OFC were defined as adverse events. RESULTS Forty articles were selected in this study. Our review revealed that cow's milk OFC was able to avoid the complete elimination of cow's milk in 66% of the patients with cow's milk allergy. We also found that adverse events occurred frequently (50.5%). CONCLUSIONS This analysis supports the recommendation of conducting cow's milk OFC to avoid complete elimination of cow's milk, however the test should be conducted with careful consideration of the patient's safety. As the methods of OFC and subjects varied among the articles selected in this study, further studies are needed to obtain higher quality evidence.
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Affiliation(s)
- Mayu Maeda
- Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
| | - Yu Kuwabara
- Department of Pediatrics, Ehime University Graduate School of Medicine Ehime, Japan
| | - Yuya Tanaka
- Department of Allergy, Kobe Children's Hospital, Hyogo, Japan
| | - Tomoki Nishikido
- Department of Pediatrics Pulmonology and Allergy, Osaka Women's and Children's Hospital, Osaka, Japan
| | - Yukiko Hiraguchi
- Department of Pediatrics, Center of Allergy and Clinical Immunology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | | | - Ikuo Okafuji
- Department of Pediatrics, Kobe City Medical Center General Hospital, Hyogo, Japan
| | - Yoshiyuki Yamada
- Division of Allergy and Immunology, Gunma Children's Medical Center, Gunma, Japan; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan
| | - Masaki Futamura
- Division of Pediatrics, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
| | - Motohiro Ebisawa
- Clinical Research Center for Allergology and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
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18
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Huang SG, Cheng Y, Li D, Sun C, Fang F, Guo WL. Systematic screen of potential circular RNA biomarkers of Hirschsprung's disease. Transl Pediatr 2022; 11:10-19. [PMID: 35242648 PMCID: PMC8825940 DOI: 10.21037/tp-21-392] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 12/22/2021] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system in which enteric ganglia are missing along a portion of the intestine. Aberrant expression of several circular RNAs (circRNAs) has been identified in the disease, but the full range of dysregulated circRNAs and their potential roles in its pathogenesis remain unclear. We used microarray profiling to systematically screen for circRNAs that were differentially expressed in HSCR, and we comprehensively analyzed the potential circRNA-miRNA-mRNA regulatory network to identify molecular mechanisms involved in the disorder. METHODS We identified circRNAs that were differentially expressed between diseased tissue and paired normal intestinal tissues from patients with HSCR. The most strongly upregulated circRNAs were then validated by quantitative reverse-transcription-PCR (RT-PCR). We also constructed a circRNA-miRNA-mRNA interaction network to determine functional interactions between miRNAs and mRNAs. RESULTS We identified 17 circRNAs that were upregulated and 10 that were downregulated in HSCR tissue compared with normal tissues. The five circRNAs that showed the greatest upregulation were verified by RT-PCR: hsa_circRNA_092493, hsa_circRNA_101965, hsa_circRNA_103118, hsa_circRNA_103279, and hsa_circRNA_104214. These five circRNAs were successfully adopted to diagnose HSCR based on receiver operating characteristic curves, and they were used to generate a circRNA-miRNA-mRNA network. The network revealed a potential function of the circRNAs as molecular sponges targeting miRNAs and mRNAs in HSCR. CONCLUSIONS This first-ever systematic dissection of the circRNA profile in HSCR may provide useful insights into improving diagnosis and therapy.
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Affiliation(s)
- Shun-Gen Huang
- Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China
| | - Yuan Cheng
- Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China
| | - Dashuang Li
- Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China
| | - Chao Sun
- Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China
| | - Fang Fang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China
| | - Wan-Liang Guo
- Department of Radiology, Children's Hospital of Soochow University, Suzhou, China
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Harada A, Shimojima N, Kobayashi M, Kamba S, Hirobe S, Sumiyama K. Visualization of the human enteric nervous system by probe confocal laser endomicroscopy: a first real-time observation of Hirschsprung's disease and allied disorders. BMC Med Imaging 2021; 21:118. [PMID: 34332524 PMCID: PMC8325866 DOI: 10.1186/s12880-021-00648-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 07/13/2021] [Indexed: 11/13/2022] Open
Abstract
Background Our group previously proved that the human enteric nervous system can be visualized with confocal laser endomicroscopy after topical application of cresyl violet using surgically resected intestine specimens. The present report documents the first in vivo visualization of the human enteric nervous system with confocal laser endomicroscopy using local cresyl violet staining. The aim of this study was to evaluate the technical feasibility and clinical efficiency of confocal laser endomicroscopy in patients with Hirschsprung’s disease and allied disorders in vivo. Methods Confocal laser endomicroscopy was performed in vivo in two patients to confirm the presence of the enteric nervous system during surgery in patients with Hirschsprung’s disease and allied disorders. Cresyl violet was gently injected from the serosal side into the muscular layer of the intestine, and scanning was performed within 30 min. Then, the scanned intestines were resected, and the visualized area of the specimens was pathologically evaluated. Results The ganglion cell nuclei and the enteric nervous system network were clearly visualized intraoperatively in both cases. The morphological findings were similar to the pathological findings of the enteric nervous system in both cases although the period of visibility was brief. Conclusion This study demonstrated the first, real-time observation of the enteric nervous system in humans using confocal laser endomicroscopy and suggest the potential to identify the enteric nervous system intra-operatively during surgery for Hirschsprung’s disease and allied disorders.
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Affiliation(s)
- Atsushi Harada
- Department of Surgery, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan
| | - Naoki Shimojima
- Department of Surgery, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan.
| | - Masakuni Kobayashi
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Shunsuke Kamba
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Seiichi Hirobe
- Department of Surgery, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan
| | - Kazuki Sumiyama
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
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Villanueva MEP, Lopez MPJ, Onglao MAS. Idiopathic megacolon and megarectum in an adult treated with laparoscopic modified Duhamel procedure. BMJ Case Rep 2021; 14:e240209. [PMID: 34187804 PMCID: PMC8245436 DOI: 10.1136/bcr-2020-240209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2021] [Indexed: 11/04/2022] Open
Abstract
Idiopathic megacolon (IMC) and idiopathic megarectum (IMR) describe an abnormality of the colon or rectum, characterised by a permanent dilatation of the bowel diameter in the absence of an identifiable cause. We present a 23-year-old woman with chronic constipation and excessive straining during defecation who presented at the emergency department in partial gut obstruction with a palpable fecaloma. Manual faecal disimpaction and a sigmoid loop colostomy was initially done. A full thickness rectal biopsy was positive for ganglion cells. Further workup led to the diagnosis of chronic IMC and IMR. The patient underwent laparoscopic modified Duhamel procedure, with an uneventful postoperative course.
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Affiliation(s)
| | - Marc Paul Jose Lopez
- Division of Colorectal Surgery, Department of Surgery, University of the Philippines-Philippine General Hospital, Manila, Philippines
| | - Mark Augustine S Onglao
- Division of Colorectal Surgery, Department of Surgery, University of the Philippines-Philippine General Hospital, Manila, Philippines
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Defective development and microcirculation of intestine in Npr2 mutant mice. Sci Rep 2020; 10:14761. [PMID: 32901096 PMCID: PMC7479618 DOI: 10.1038/s41598-020-71812-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 08/19/2020] [Indexed: 11/16/2022] Open
Abstract
Intractable gastrointestinal (GI) diseases often develop during infancy. Our group previously reported that natriuretic peptide receptor B (NPR-B)-deficient Npr2slw/slw mice exhibit severe intestinal dysfunction, such as stenosis and distention, which resembles the dysfunction observed in Hirschsprung’s disease-allied disorders. However, the root cause of intestinal dysfunction and the detailed of pathophysiological condition in the intestine are not yet clear. Here, we report that the intestine of preweaning Npr2slw/slw mice showed bloodless blood vessels, and nodes were found in the lymphatic vessel. Additionally, the lacteals, smooth muscle, blood vessel, and nerves were barely observed in the villi of preweaning Npr2slw/slw mice. Moreover, intramuscular interstitial cells of Cajal (ICC-IM) were clearly reduced. In contrast, villi and ICC-IM were developed normally in surviving adult Npr2slw/slw mice. However, adult Npr2slw/slw mice exhibited partially hypoplastic blood vessels and an atrophied enteric nervous. Furthermore, adult Npr2slw/slw mice showed markedly reduced white adipose tissue. These findings suggest that the cause of GI dysfunction in preweaning Npr2slw/slw mice is attributed to defective intestinal development with microcirculation disorder. Thus, it is suggested that NPR-B signaling is involved in intestinal development and control of microcirculation and fat metabolism. This report provides new insights into intractable GI diseases, obesity, and NPR-B signaling.
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Katayama Y, Kido S, Kai S, Nakano T, Hidaka N, Kato K. Massive atonic bleeding during cesarean delivery in a patient with chronic idiopathic intestinal pseudo-obstruction: A case report and literature review. J Obstet Gynaecol Res 2020; 46:2153-2158. [PMID: 32748506 DOI: 10.1111/jog.14363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 02/11/2020] [Accepted: 06/08/2020] [Indexed: 11/27/2022]
Abstract
A 35-year-old primigravid woman with chronic idiopathic intestinal pseudo-obstruction presented to our institution. Except for an enlarged fetal bladder, her pregnancy was almost uneventful until she developed pre-eclampsia requiring emergent cesarean section at 34 weeks gestation. After delivery, intractable uterine atony developed with blood loss reaching 3500 mL within 15 min. Following a B-Lynch suture, the bleeding attenuated but uterine atony persisted; lochia persisted for 3 months post-partum. The infant was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome after birth. The mother's clinical course and previous reports suggested that atonic bleeding was associated with the pathology of chronic idiopathic intestinal pseudo-obstruction; the infant's disease was considered to be maternal-related disease. Clinicians should be vigilant in pregnant patients with chronic idiopathic intestinal pseudo-obstruction especially with these complications.
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Affiliation(s)
- Yoshihiro Katayama
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Saki Kido
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shotaro Kai
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Nakano
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Nobuhiro Hidaka
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kiyoko Kato
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Liu YR, Ba F, Cheng LJ, Li X, Zhang SW, Zhang SC. Efficacy of Sox10 Promoter Methylation in the Diagnosis of Intestinal Neuronal Dysplasia From the Peripheral Blood. Clin Transl Gastroenterol 2019; 10:e00093. [PMID: 31789936 PMCID: PMC6970557 DOI: 10.14309/ctg.0000000000000093] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 09/19/2019] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES Intestinal neuronal dysplasia (IND) is a common malformation of the enteric nervous system. Diagnosis requires a full-thickness colonic specimen and an experienced pathologist, emphasizing the need for noninvasive analytical methods. Recently, the methylation level of the Sox10 promoter has been found to be critical for enteric nervous system development. However, whether it can be used for diagnostic purposes in IND is unclear. METHODS Blood and colon specimens were collected from 32 patients with IND, 60 patients with Hirschsprung disease (HD), and 60 controls. Sox10 promoter methylation in the blood and the Sox10 expression level in the colon were determined, and their correlation was analyzed. The diagnostic efficacy of blood Sox10 promoter methylation was analyzed by receiver operating characteristic curve. RESULTS The blood level of Sox10 promoter methylation at the 32nd locus was 100% (90%-100%; 95% confidence interval [CI], 92.29%-96.37%) in control, 90% (80%-90%; 95% CI, 82.84%-87.83%) in HD, and 60% (50%-80%; 95% CI, 57.12%-69.76%) in IND specimens. Sox10 promoter methylation in the peripheral blood was negatively correlated with Sox10 expression in the colon, which was low in control, moderate in HD, and high in IND specimens (r = -0.89). The area under the curve of Sox10 promoter methylation in the diagnosis of IND was 0.94 (95% CI, 0.874-1.000, P = 0.000), with a cutoff value of 85% (sensitivity, 90.6%; specificity, 95.0%). By applying a cutoff value of 65%, promoter methylation was more indicative of IND than HD. DISCUSSION The analysis of Sox10 promoter methylation in the peripheral blood can be used as a noninvasive method for IND diagnosis.
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Affiliation(s)
- Yu-Rong Liu
- Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang Ba
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lan-Jie Cheng
- Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xu Li
- Department of Pediatric Surgery, Capital Institute of Pediatrics of Capital Medical University, Beijing, China
| | - Shi-Wei Zhang
- Department of Pediatric Surgery, Harbin Children's Hospital, Harbin, China
| | - Shu-Cheng Zhang
- Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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25
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Affiliation(s)
- Jun Murakami
- Division of Pediatrics and Perinatology, Tottori University Faculty of Medicine, Yonago, Japan
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