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Rentea RM, Bokova E, Frischer JS, Gosain A, Langer JC, Levitt MA, Nandivada P, Rialon KL, Rollins MD, Segura B, Wood RJ, Lim IIP. Evaluation and Management of Total Colonic Hirschsprung Disease: A Comprehensive Review From the American Pediatric Surgical Association (APSA) Hirschsprung Disease Interest Group. J Pediatr Surg 2024; 59:161677. [PMID: 39217005 DOI: 10.1016/j.jpedsurg.2024.08.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 07/24/2024] [Accepted: 08/04/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Children with total colonic Hirschsprung disease (TCHD) are a unique group of patients with pre- and postoperative management challenges. This review provides a rational, expert-based approach to diagnosing and managing TCHD. METHODS The guidelines were developed by the Hirschsprung Disease Interest Group members established by the American Pediatric Surgical Association (APSA) Board of Governors. Group discussions, literature review, and expert consensus were used to summarize the current knowledge regarding diagnosis, staged approach, the timing of pull-through, and pre-and postoperative management in children with TCHD. RESULTS This paper presents recommendations for managing TCHD before and after reconstruction, including diagnostic criteria, surgical approaches, bowel management, diet, antibiotic prophylaxis, colonic irrigations, and post-surgical considerations. CONCLUSIONS A clear understanding of the unique challenges posed by TCHD and consensus on its treatment are lacking in the literature. This review standardizes this patient group's pre- and postoperative management. LEVEL OF EVIDENCE V.
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Affiliation(s)
- Rebecca M Rentea
- Comprehensive Colorectal Center, Section of Colorectal and Pelvic Reconstructive Surgery, Department of Pediatric Surgery, Children's Mercy Kansas City, Kansas City, MO, 64108, USA; Department of Surgery, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
| | - Elizaveta Bokova
- Comprehensive Colorectal Center, Section of Colorectal and Pelvic Reconstructive Surgery, Department of Pediatric Surgery, Children's Mercy Kansas City, Kansas City, MO, 64108, USA
| | - Jason S Frischer
- Colorectal Center for Children, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ankush Gosain
- Department of Pediatric Surgery, Children's Hospital of Colorado, University of Colorado, Aurora, CO, USA
| | - Jacob C Langer
- Department of Surgery, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Marc A Levitt
- Division of Colorectal and Pelvic Reconstruction, Children's National Medical Center, Washington, DC, 20001, USA
| | - Prathima Nandivada
- Colorectal and Pelvic Malformation Center, Department of Surgery, Boston Children's Hospital, Boston, MA, 02115, USA
| | - Kristy L Rialon
- Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Texas, USA
| | - Michael D Rollins
- Department of Surgery, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA
| | - Bradley Segura
- University of Minnesota, Department of Pediatric Surgery, MHealth Fairview Masonic Children's Hospital, Minneapolis, MN, USA
| | - Richard J Wood
- Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital, Columbus, OH, USA
| | - Irene Isabel P Lim
- Comprehensive Colorectal Center, Section of Colorectal and Pelvic Reconstructive Surgery, Department of Pediatric Surgery, Children's Mercy Kansas City, Kansas City, MO, 64108, USA; Department of Surgery, University of Missouri-Kansas City, Kansas City, MO, 64108, USA
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Cheng LS, Wood RJ. Hirschsprung disease: common and uncommon variants. WORLD JOURNAL OF PEDIATRIC SURGERY 2024; 7:e000864. [PMID: 39224573 PMCID: PMC11367348 DOI: 10.1136/wjps-2024-000864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024] Open
Affiliation(s)
- Lily S Cheng
- Department of Surgery, Division of Pediatric Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Richard J Wood
- Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital, Columbus, Ohio, USA
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3
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Yu Q, Liu L, Du M, Müller D, Gu Y, Gao Z, Xin X, Gu Y, He M, Marquardt T, Wang L. Sacral Neural Crest-Independent Origin of the Enteric Nervous System in Mouse. Gastroenterology 2024; 166:1085-1099. [PMID: 38452824 DOI: 10.1053/j.gastro.2024.02.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 02/18/2024] [Accepted: 02/22/2024] [Indexed: 03/09/2024]
Abstract
BACKGROUND & AIMS The enteric nervous system (ENS), the gut's intrinsic nervous system critical for gastrointestinal function and gut-brain communication, is believed to mainly originate from vagal neural crest cells (vNCCs) and partially from sacral NCCs (sNCCs). Resolving the exact origins of the ENS is critical for understanding congenital ENS diseases but has been confounded by the inability to distinguish between both NCC populations in situ. Here, we aimed to resolve the exact origins of the mammalian ENS. METHODS We genetically engineered mouse embryos facilitating comparative lineage-tracing of either all (pan-) NCCs including vNCCs or caudal trunk and sNCCs (s/tNCCs) excluding vNCCs. This was combined with dual-lineage tracing and 3-dimensional reconstruction of pelvic plexus and hindgut to precisely pinpoint sNCC and vNCC contributions. We further used coculture assays to determine the specificity of cell migration from different neural tissues into the hindgut. RESULTS Both pan-NCCs and s/tNCCs contributed to established NCC derivatives but only pan-NCCs contributed to the ENS. Dual-lineage tracing combined with 3-dimensional reconstruction revealed that s/tNCCs settle in complex patterns in pelvic plexus and hindgut-surrounding tissues, explaining previous confusion regarding their contributions. Coculture experiments revealed unspecific cell migration from autonomic, sensory, and neural tube explants into the hindgut. Lineage tracing of ENS precursors lastly provided complimentary evidence for an exclusive vNCC origin of the murine ENS. CONCLUSIONS sNCCs do not contribute to the murine ENS, suggesting that the mammalian ENS exclusively originates from vNCCs. These results have immediate implications for comprehending (and devising treatments for) congenital ENS disorders, including Hirschsprung's disease.
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Affiliation(s)
- Qi Yu
- Department of Neurology of the Second Affiliated Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, China; Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China
| | - Li Liu
- Department of Pediatric General Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Mengjie Du
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Daniel Müller
- Interfaculty Chair of Neurobiology, Clinic for Neurology, RWTH Aachen University Medicine (UKA) and Institute for Biology 2, Faculty for Mathematics, Computer and Natural Sciences, Aachen, Germany
| | - Yan Gu
- Center of Stem Cell and Regenerative Medicine, and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhigang Gao
- Department of Pediatric General Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Xiaolong Xin
- Department of Neurology of the Second Affiliated Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanlan Gu
- Department of Neurology of the Second Affiliated Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou, China
| | - Miao He
- Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Neurobiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Till Marquardt
- Interfaculty Chair of Neurobiology, Clinic for Neurology, RWTH Aachen University Medicine (UKA) and Institute for Biology 2, Faculty for Mathematics, Computer and Natural Sciences, Aachen, Germany.
| | - Liang Wang
- Department of Neurology of the Second Affiliated Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, China; Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China.
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Dershowitz LB, Kaltschmidt JA. Enteric Nervous System Striped Patterning and Disease: Unexplored Pathophysiology. Cell Mol Gastroenterol Hepatol 2024; 18:101332. [PMID: 38479486 PMCID: PMC11176954 DOI: 10.1016/j.jcmgh.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 03/08/2024] [Accepted: 03/08/2024] [Indexed: 04/04/2024]
Abstract
The enteric nervous system (ENS) controls gastrointestinal (GI) motility, and defects in ENS development underlie pediatric GI motility disorders. In disorders such as Hirschsprung's disease (HSCR), pediatric intestinal pseudo-obstruction (PIPO), and intestinal neuronal dysplasia type B (INDB), ENS structure is altered with noted decreased neuronal density in HSCR and reports of increased neuronal density in PIPO and INDB. The developmental origin of these structural deficits is not fully understood. Here, we review the current understanding of ENS development and pediatric GI motility disorders incorporating new data on ENS structure. In particular, emerging evidence demonstrates that enteric neurons are patterned into circumferential stripes along the longitudinal axis of the intestine during mouse and human development. This novel understanding of ENS structure proposes new questions about the pathophysiology of pediatric GI motility disorders. If the ENS is organized into stripes, could the observed changes in enteric neuron density in HSCR, PIPO, and INDB represent differences in the distribution of enteric neuronal stripes? We review mechanisms of striped patterning from other biological systems and propose how defects in striped ENS patterning could explain structural deficits observed in pediatric GI motility disorders.
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Affiliation(s)
- Lori B Dershowitz
- Department of Neurosurgery, Stanford University School of Medicine, Stanford, California; Wu Tsai Neurosciences Institute, Stanford University, Stanford, California
| | - Julia A Kaltschmidt
- Department of Neurosurgery, Stanford University School of Medicine, Stanford, California; Wu Tsai Neurosciences Institute, Stanford University, Stanford, California.
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Boesmans W, Nash A, Tasnády KR, Yang W, Stamp LA, Hao MM. Development, Diversity, and Neurogenic Capacity of Enteric Glia. Front Cell Dev Biol 2022; 9:775102. [PMID: 35111752 PMCID: PMC8801887 DOI: 10.3389/fcell.2021.775102] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 12/09/2021] [Indexed: 12/15/2022] Open
Abstract
Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the "support" cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.
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Affiliation(s)
- Werend Boesmans
- Biomedical Research Institute (BIOMED), Hasselt University, Hasselt, Belgium
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Amelia Nash
- Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australia
| | - Kinga R. Tasnády
- Biomedical Research Institute (BIOMED), Hasselt University, Hasselt, Belgium
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Wendy Yang
- Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australia
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan, Taiwan
| | - Lincon A. Stamp
- Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australia
| | - Marlene M. Hao
- Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australia
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Arbizu R, Freiberg B, Rodriguez L. Lower Gastrointestinal Functional and Motility Disorders in Children. Pediatr Clin North Am 2021; 68:1255-1271. [PMID: 34736588 DOI: 10.1016/j.pcl.2021.07.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Functional and motility gastrointestinal disorders are the most common complaints to the pediatric gastroenterologist. Disorders affecting the small intestine carry a significant morbidity and mortality due to the severe limitation of therapeutic interventions available and the complications associated with such interventions. Congenital colorectal disorders are rare but also carry significant morbidity and poor quality of life plus the social stigma associated with its complications. In this review, we summarize the clinical presentation, diagnostic evaluations, and the therapeutic interventions available for the most common and severe gastrointestinal functional and motility disorders of the small bowel, colon, and anorectum.
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Affiliation(s)
- Ricardo Arbizu
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Pediatric Gastroenterology and Hepatology, Neurogastroenterology and Motility Center, Yale School of Medicine, Yale University School of Medicine, Yale New Haven Children's Hospital, 333 Cedar Street, LMP 4093, PO Box 208064, New Haven, CT 06520, USA
| | - Ben Freiberg
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Pediatric Gastroenterology and Hepatology, Neurogastroenterology and Motility Center, Yale School of Medicine, Yale University School of Medicine, Yale New Haven Children's Hospital, 333 Cedar Street, LMP 4093, PO Box 208064, New Haven, CT 06520, USA
| | - Leonel Rodriguez
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Pediatric Gastroenterology and Hepatology, Neurogastroenterology and Motility Center, Yale School of Medicine, Yale University School of Medicine, Yale New Haven Children's Hospital, 333 Cedar Street, LMP 4093, PO Box 208064, New Haven, CT 06520, USA.
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Skip segment Hirschsprung's disease: report of two rare cases and management. Pediatr Surg Int 2021; 37:1563-1568. [PMID: 34398296 DOI: 10.1007/s00383-021-04981-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/06/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Skip segment Hirschsprung's disease (SS-HSCR) is defined as the occurrence of a segment of ganglionated intestine surrounded proximally and distally by aganglionosis. The presence of the skip intestinal segment often leads to clinical misdiagnosis, missed diagnosis or inadequate resection of the lesions. The purpose was to describe two new cases of SS-HSCR with the aim of proposing questions regarding the diagnosis and treatment of this rare disease. METHODS We reported two cases of infants with SS-HSCR that were admitted to our institution within the last 3 years. RESULTS One patient had a skip segment of ganglionated intestine in the ascending colon. In the other patient, there were no ganglionic cells in the rectum and appendix, but ganglionic cells were visible in the proximal ascending colon. The entire colons in the both cases were finally resected, and a pull-through operation was performed. CONCLUSION Multipoint biopsy should be performed when the biopsy results are inconsistent with clinical manifestations. Intraoperative laparoscopic identification of the transition zone may be necessary when TCA is suspected. Multisegment biopsy is needed to as a preventative measure for SS-HSCR if TCA is indicated during surgery. Further study is required to determine the optimal length and method of retention of segments.
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Chang X, Li S, Li K, Cao G, Zhang X, Li S, Yang D, Tang S. Skip segment Hirschsprung's disease: diagnostic clues and surgical management. Pediatr Surg Int 2021; 37:799-805. [PMID: 33884477 DOI: 10.1007/s00383-021-04902-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/26/2021] [Indexed: 11/27/2022]
Abstract
It is challenging to establish a definitive diagnosis and initiate timely management for skip segment Hirschsprung's disease (SSHD). Herein, we report three cases of SSHD at our institution between December 2008 and March 2018. Patient #1 was misdiagnosed and underwent three successive operations within 2 years. Patient #2 and #3 were diagnosed timely based on previous experience. A segmental narrowing detected by barium enema may raise the possibility of SSHD. Laparoscopic-guided multipoint biopsy is regarded as a mini-invasive and purposeful way to take representative samples after locating the segmental narrowing intraoperatively and accurate the final diagnosis. The laparoscopic-assisted pull-through procedure with radical resection from the distal rectum to the most proximal margin of the diseased skip segment is safe and effective in treating patients with SSHD.Level of evidence: Level III.
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Affiliation(s)
- Xiaopan Chang
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shuai Li
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kang Li
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Guoqing Cao
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xi Zhang
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shuai Li
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dehua Yang
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shaotao Tang
- Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Ahmad H, Vilanova-Sánchez A, Amengual I, Guerra-Pastrian L, Garrido-Pontnou M, Montalvo C, Bueno A, Langer J, Wood RJ, Levitt MA. Skip Segment Hirschsprung Disease Managed by Pull-Through of the Right Colon. European J Pediatr Surg Rep 2021; 9:e28-e32. [PMID: 33777642 PMCID: PMC7994106 DOI: 10.1055/s-0041-1726347] [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: 08/14/2020] [Accepted: 01/18/2021] [Indexed: 11/12/2022] Open
Abstract
Hirschsprung disease is the most common neurocristopathy in children, resulting in the congenital loss of enteric ganglia. Rare reports of skip lesions have previously been reported in the literature. We present a case of skip lesions known prior to surgery and managed by pull-through of the right colon that allowed the preservation of the colon.
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Affiliation(s)
- Hira Ahmad
- Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital Columbus, Ohio, United States
| | | | - Isabel Amengual
- Department of Pathology, Son Espases University Hospital, Palma de Mallorca, Illes Balears, Spain
| | | | - Marta Garrido-Pontnou
- Department of Pathology, Vall d'Hebron Hospital Universitari, Barcelona, Catalunya, Spain
| | - Cristina Montalvo
- Department of Pediatric Surgery, Son Espases University Hospital, Palma de Mallorca, Illes Balears, Spain
| | - Alba Bueno
- Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, Madrid, Madrid, Spain
| | - Jacob Langer
- Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital Columbus, Ohio, United States.,Division of General and Thoracic Surgery, SickKids, Toronto, Ontario, Canada
| | - Richard J Wood
- Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital Columbus, Ohio, United States
| | - Marc A Levitt
- Division of Colorectal and Pelvic Reconstructive Surgery, Children's National Medical Center, Washington, District of Columbia, United States
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Case report of a skip segment Hirschsprung's disease: A real phenomenon. Int J Surg Case Rep 2021; 80:105630. [PMID: 33592418 PMCID: PMC7893424 DOI: 10.1016/j.ijscr.2021.02.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/04/2021] [Accepted: 02/04/2021] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION AND IMPORTANCE Hirschsprung's disease is a congenital anomaly that results from an incomplete craniocaudal migration and maturation of intestinal ganglion progenitor cells leading to distal intestinal aganglionosis. Skip segment Hirschsprung's disease is an extremely rare phenomenon. We report a case involving only the small bowel with confirmed colonic ganglionosis. CASE PRESENTATION A case report of a 14-month-old with a skipped segment involving the distal 50 cm of the small bowel associated with colonic ganglionosis is presented. A current review of the literature is discussed. CLINICAL DISCUSSION Our patient had persistent obstructive symptoms despite undergoing a technically good, ganglionic pull-through operation at an outside institution. A laparoscopic-assisted pull-through might have documented a small bowel wall diameter discrepancy. CONCLUSION Although rare, skip segment Hirschsprung's disease is a real phenomenon that paediatric surgeons should be aware of and could involve small and large bowels.
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Mesenteric Neural Crest Cells Are the Embryological Basis of Skip Segment Hirschsprung's Disease. Cell Mol Gastroenterol Hepatol 2020; 12:1-24. [PMID: 33340715 PMCID: PMC8082118 DOI: 10.1016/j.jcmgh.2020.12.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 12/14/2020] [Accepted: 12/14/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Defective rostrocaudal colonization of the gut by vagal neural crest cells (vNCCs) results in Hirschsprung's disease (HSCR), which is characterized by aganglionosis in variable lengths of the distal bowel. Skip segment Hirschsprung's disease (SSHD), referring to a ganglionated segment within an otherwise aganglionic intestine, contradicts HSCR pathogenesis and underscores a significant gap in our understanding of the development of the enteric nervous system. Here, we aimed to identify the embryonic origin of the ganglionic segments in SSHD. METHODS Intestinal biopsy specimens from HSCR patients were prepared via the Swiss-roll technique to search for SSHD cases. NCC migration from the neural tube to the gut was spatiotemporally traced using targeted cell lineages and gene manipulation in mice. RESULTS After invading the mesentery surrounding the foregut, vNCCs separated into 2 populations: mesenteric NCCs (mNCCs) proceeded to migrate along the mesentery, whereas enteric NCCs invaded the foregut to migrate along the gut. mNCCs not only produced neurons and glia within the gut mesentery, but also continuously complemented the enteric NCC pool. Two new cases of SSHD were identified from 183 HSCR patients, and Ednrb-mutant mice, but not Ret-/- mice, showed a high incidence rate of SSHD-like phenotypes. CONCLUSIONS mNCCs, a subset of vNCCs that migrate into the gut via the gut mesentery to give rise to enteric neurons, could provide an embryologic explanation for SSHD. These findings lead to novel insights into the development of the enteric nervous system and the etiology of HSCR.
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12
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Zhu CZ, Zhao HW, Lin HW, Wang F, Li YX. Latest developments in chronic intestinal pseudo-obstruction. World J Clin Cases 2020. [DOI: 10.12998/wjcc.v8.i23.5850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Zhu CZ, Zhao HW, Lin HW, Wang F, Li YX. Latest developments in chronic intestinal pseudo-obstruction. World J Clin Cases 2020; 8:5852-5865. [PMID: 33344584 PMCID: PMC7723695 DOI: 10.12998/wjcc.v8.i23.5852] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 10/02/2020] [Accepted: 10/19/2020] [Indexed: 02/05/2023] Open
Abstract
Chronic intestinal pseudo-obstruction (CIPO) is a type of intestinal dysfunction presenting as symptoms of intestinal obstruction but without actual mechanical obstruction. An extremely low incidence, non-specific clinical symptoms, strong heterogeneity, and no definitive cause in some patients make CIPO very difficult to diagnose correctly. Imaging and gastrointestinal manometry are commonly used. Most patients have progressive worsening of their symptoms and require intervention, and nutritional assessment and treatment are very important to determine the prognosis. With improvements in surgical techniques, small bowel transplantation is a feasible treatment option for patients with advanced CIPO; however, the long-term prognosis for CIPO patients remains unsatisfactory. Generally, the disease is rare and difficult to diagnose, which leads to clinicians' lack of understanding of the disease and results in a high rate of misdiagnosis. This review describes the characteristics of CIPO and the latest developments in diagnosis and treatment, in detail. The goal of our review is to improve clinicians' understanding of CIPO so that the disease is identified quickly and accurately, and treated as early as possible to improve patients' quality of life.
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Affiliation(s)
- Chang-Zhen Zhu
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Hong-Wei Zhao
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Hong-Wei Lin
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Feng Wang
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yuan-Xin Li
- Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
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Sharma N, Sharma M, Singh BP, Chandrakar K, Chandrakar RK, Verma SR. Predictability of 48-h delayed retention of contrast in barium enema in cases of chronic constipation. Afr J Paediatr Surg 2020; 17:15-17. [PMID: 33106447 PMCID: PMC7818665 DOI: 10.4103/ajps.ajps_35_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
INTRODUCTION Diagnosis of Hirschsprung's disease depends on rectal biopsy. This study was designed to find an alternate diagnostic modality to exclude Hirschsprung's disease. AIM The aim of this study was to find the predictive value of delayed retention of contrast in excluding Hirschsprung's disease. MATERIALS AND METHODS All cases of chronic constipation presenting during the study duration from June 2014 to June 2016 were included. Those without any obvious history of conservative management were excluded. Parameters considered in barium enema were initial film, routine films, and delayed retention of contrast at 24, 48, and 72 h. They were then subjected to rectal biopsy. The results of rectal biopsy and barium enema were analyzed. RESULTS One hundred and thirty-eight patients presented during the study duration. One hundred and twenty-eight formed the study group. The average age of presentation was 48 months (range, 1-144). The average duration of prior medical management was 8 months (range, 6-48 months). Forty-two cases were diagnosed as Hirschsprung's disease on rectal biopsy. The symptoms resolved in 31 cases after rectal biopsy and 42 cases after definitive surgery. In the remaining 55 cases, dietary modification along with laxatives was instituted, and they were kept under follow-up. The average follow-up was 12 months (range, 6-48 months). Of the various parameters in barium enema, delayed retention of contrast at 48 h had the highest negative predictive value of 99.67%. CONCLUSION Delayed retention of contrast at 48 h has the highest negative predictive value in excluding Hirschsprung's disease. This can safely be used to exclude Hirschsprung's disease in cases of chronic constipation.
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Affiliation(s)
- Nitin Sharma
- Department of Paediatric Surgery, Pt JNM Medical college and DKS Hospital, Raipur, Chhattishgarh, India
| | - Mini Sharma
- Department of Community Medicine, Pt JNM Medical College, Raipur, Chhattisgarh, India
| | - Bhalendu Pratap Singh
- Department of Paediatrics, CM Hospital and Associated Medical College, Bhilai, Chhattishgarh, India
| | - Kunal Chandrakar
- Department of Radiodiagnosis, CM Hospital and Associated Medical College, Bhilai, Chhattishgarh, India
| | - R K Chandrakar
- Department of Pathology, CM Hospital and Associated Medical College, Bhilai, Chhattishgarh, India
| | - Sewak Ram Verma
- Department of Anaesthesiology, CM Hospital and Associated Medical College, Bhilai, Chhattishgarh, India
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15
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Smith C, Ambartsumyan L, Kapur RP. Surgery, Surgical Pathology, and Postoperative Management of Patients With Hirschsprung Disease. Pediatr Dev Pathol 2020; 23:23-39. [PMID: 31747833 DOI: 10.1177/1093526619889436] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Endorectal pullthrough surgery is integral in the treatment of patients with Hirschsprung disease. Several different surgical procedures exist, which share as common goals to excise the aganglionic segment and upstream transition zone and attach ganglionic bowel just proximal to the anal canal. The operation requires collaboration between surgeon and pathologist to localize ganglionic bowel and prevent retention of transition zone. Intraoperative frozen sections are extremely important, first to establish that ganglion cells are present and subsequently to exclude features of transition zone (partial circumferential aganglionosis, myenteric hypoganglionosis, and submucosal nerve hypertrophy) at the proximal surgical (anastomotic) margin. Postoperative histopathological analysis of resection specimens should be tailored to document distal aganglionosis, document the length of the aganglionic segment and its proximity to the anastomotic margin, and confirm that transition zone has been resected completely. Adherence to the recommendations described in this review will reduce the likelihood of transition zone pullthrough and should decrease the incidence of persistent postoperative obstructive symptoms.
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Affiliation(s)
- Caitlin Smith
- Department of Pediatric Surgery, Seattle Children's Hospital and University of Washington, Seattle, Washington
| | - Lusine Ambartsumyan
- Department of Gastroenterology, Seattle Children's Hospital and University of Washington, Seattle, Washington
| | - Raj P Kapur
- Department of Pathology, Seattle Children's Hospital and University of Washington, Seattle, Washington
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16
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Shenoy A, De Los Santos Y, Johnson KN, Petroze R. Distal rectal skip segment Hirschsprung disease: Case report and review of literature. Fetal Pediatr Pathol 2019; 38:437-443. [PMID: 31032690 DOI: 10.1080/15513815.2019.1608606] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Background: Lack of ganglion cells on adequate suction rectal biopsy is the gold standard for diagnosis of neonatal Hirschsprung disease (HD), and the presence of ganglion cells precludes such a diagnosis. Case report: A 10-day old male neonate presented with clinical symptoms concerning for HD. However, suction rectal biopsies demonstrated submucosal ganglion cells on the distal suction rectal biopsies (2 cm from anal verge) and not on the proximal (3 cm from anal verge), with similar findings on repeat biopsies. Clinical suspicion remained high, and diagnostic laparoscopy with intraoperative biopsies confirmed aganglionosis with a sigmoid transition. A pull through resection confirmed the diagnosis of distal rectal skip segment HD (SSHD) with a ∼6 cm length of circumferential aganglionosis extending into the proximal sigmoid. Conclusions: Discordant results on suction rectal biopsies should raise the possibility of SSHD. Awareness of the entity can facilitate timely definitive management in neonatal period.
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Affiliation(s)
- Archana Shenoy
- University of Florida College of Medicine , Gainesville , USA
| | | | - Kevin Neil Johnson
- Division of Pediatric Surgery, Department of Surgery, University of Florida College of Medicine , Gainesville , USA
| | - Robin Petroze
- Division of Pediatric Surgery, Department of Surgery, University of Florida College of Medicine , Gainesville , USA
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17
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Jehangir S, Soundappan SVS, Krivanek M, Arbuckle S, Graf N. Pullthrough Operation for Hirschsprung's Disease: Importance of a Circumferential (Donut) Biopsy at the Level of the Anastomosis. European J Pediatr Surg Rep 2019; 7:e55-e57. [PMID: 31312590 PMCID: PMC6629996 DOI: 10.1055/s-0039-1693494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 06/07/2019] [Indexed: 12/02/2022] Open
Abstract
Hirschsprung's disease is characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. It is managed by excision of the aganglionic segment and anastomosis of the ganglionated bowel just above the dentate line. The level of aganglionosis is determined by performing multiple seromuscular biopsies and/or full thickness biopsy on the antimesenteric border of the bowel to determine the level of pullthrough. The transition zone is described as being irregular, and hence a doughnut biopsy is recommended so that the complete circumference can be assessed. Herein, we described a child in whom there was a selective absence of ganglion cells in 30% of the circumference of the bowel along the mesenteric border for most of the transverse colon. This case defies the known concept of neural migration in an intramural and transmesenteric fashion and emphasizes the importance of a doughnut biopsy of the pulled-down segment.
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Affiliation(s)
- Susan Jehangir
- Department of Paediatric Surgery, Christian Medical College, Vellore, India.,Department of Paediatric Surgery, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | | | - Micheal Krivanek
- Department of Anatomical Pathology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | - Susan Arbuckle
- Department of Anatomical Pathology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | - Nicole Graf
- Department of Anatomical Pathology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
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18
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Abstract
Chronic intestinal pseudo-obstruction (CIP) is defined by either continuous or intermittent symptoms of bowel obstruction in the absence of fixed lumen excluding lesion. CIP includes a heterogeneous group of disorders which result either from diseases affecting the enteric neurons and smooth muscle lining or those involving the autonomic innervation of the bowel. Symptoms associated with CIP are nonspecific, which can sometimes contribute to the delay in recognizing the condition and making the correct diagnosis. The diagnostic workup should include imaging and manometry studies and, occasionally, full-thickness bowel biopsies for histopathological examination may be required. Multidisciplinary team approach for the management of these patients is recommended, and the team members should include a gastroenterologist, surgeon, chronic pain specialist, clinical nutritionist, and a psychologist. The treatment goals should include optimizing the nutritional status and preventing or delaying the development of intestinal failure. The majority of the patients require enteral or parenteral nutrition support, and chronic pain is a common and distressing symptom. Small bowel transplantation may be required if patients develop liver complications due to parenteral nutrition, have difficult central line access, or have poor quality of life and worsening pain despite aggressive medical management.
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Affiliation(s)
- Khalil El-Chammas
- Division of Pediatric Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Manu R Sood
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin.,Division of Pediatric Gastroenterology, Children's hospital of Wisconsin, Milwaukee, Wisconsin
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19
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Mohanty S, Kini U, Das K, Puttegowda D, Yadav L, Babu MK, Mahadevappa K, Kumar P, Mahadevaiah SA, Deb M. Appendicular Biopsy in Total Colonic Aganglionosis: A Histologically Challenging and Inadvisable Practice. Pediatr Dev Pathol 2017; 20:277-287. [PMID: 28727975 DOI: 10.1177/1093526617692913] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background The reliability of intraoperative evaluation of ganglion cells in the appendix as a guide to a diagnosis of total colonic aganglionosis is unclear. Objective To evaluate the diagnostic utility of appendicular innervation in colonic Hirschsprung disease (HD) and TCA. Methods Prospective, systematic study of ganglion cells and the neural plexii in appendices from cases (HD and TCA) and age matched controls with frozen and paraffin sections, rapid acetylcholinesterase (AChE) and immunohistochemistry. Results A total of 48 appendices (28 controls, 20 cases; 19 frozen) were evaluated. Of these 48, 30 were neonates. Ganglion cell clusters were smaller in controls (28) and HD (6) than those in the rectum, distorted at places and mimicked lymphocytes and endothelial cells, especially in neonates. Complete study of 13 appendices in TCA showed absence of ganglion cells, hypertrophic nerves, AChE activity, and calretinin staining. In 2/13 TCA, an erroneous frozen section identification of ganglia was later corrected based on AChE histochemistry and a panel of IHC stains. Ileal biopsies guided the placement of a ganglionic ileostomy in all. One case each of skip segment aganglionosis in a TCA and variable hypoganglionosis in long segment colonic HD is reported. Conclusion Intraoperative characterization of appendicular innervation as a guide to the diagnosis of TCA is unreliable, in part because of the possibility of skip segment disease/variable hypoganglionosis. We propose terminal ileal biopsies for diagnosis and leveling of aganglionosis. AChE on frozen/calretinin on paraffin tissue is the best approach to avoid diagnostic errors.
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Affiliation(s)
- Suravi Mohanty
- 1 Department of Pathology, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Usha Kini
- 1 Department of Pathology, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Kanishka Das
- 2 Department of Paediatric Surgery, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Divya Puttegowda
- 1 Department of Pathology, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Lokendra Yadav
- 1 Department of Pathology, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Manjally Kunjipapu Babu
- 1 Department of Pathology, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Kiran Mahadevappa
- 2 Department of Paediatric Surgery, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Prasanna Kumar
- 2 Department of Paediatric Surgery, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Shubha Attibele Mahadevaiah
- 2 Department of Paediatric Surgery, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Mainak Deb
- 2 Department of Paediatric Surgery, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India
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20
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Takahashi H, Matsubara D, Ono S, Hirose N, Matsubara S. Novel ultrasound finding of a fetus with Hirschsprung's disease: A caliber change sign. Eur J Obstet Gynecol Reprod Biol 2017. [PMID: 28624310 DOI: 10.1016/j.ejogrb.2017.06.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Hironori Takahashi
- Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
| | | | - Shigeru Ono
- Department of Pediatric Surgery, Jichi Medical University, Tochigi, Japan
| | - Noriko Hirose
- Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan
| | - Shigeki Matsubara
- Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan
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21
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Sergi CM, Caluseriu O, McColl H, Eisenstat DD. Hirschsprung's disease: clinical dysmorphology, genes, micro-RNAs, and future perspectives. Pediatr Res 2017; 81:177-191. [PMID: 27682968 DOI: 10.1038/pr.2016.202] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 09/05/2016] [Indexed: 01/17/2023]
Abstract
On the occasion of the 100th anniversary of Dr. Harald Hirschsprung's death, there is a worldwide significant research effort toward identifying and understanding the role of genes and biochemical pathways involved in the pathogenesis as well as the use of new therapies for the disease harboring his name (Hirschsprung disease, HSCR). HSCR (aganglionic megacolon) is a frequent diagnostic and clinical challenge in perinatology and pediatric surgery, and a major cause of neonatal intestinal obstruction. HSCR is characterized by the absence of ganglia of the enteric nervous system, mostly in the distal gastrointestinal tract. This review focuses on current understanding of genes and pathways associated with HSCR and summarizes recent knowledge related to micro RNAs (miRNAs) and HSCR pathogenesis. While commonly sporadic, Mendelian patterns of inheritance have been described in syndromic cases with HSCR. Although only half of the patients with HSCR have mutations in specific genes related to early embryonic development, recent pathway-based analysis suggests that gene modules with common functions may be associated with HSCR in different populations. This comprehensive profile of functional gene modules may serve as a useful resource for future developmental, biochemical, and genetic studies providing insights into the complex nature of HSCR.
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Affiliation(s)
- Consolato Maria Sergi
- Department of Orthopedics, Wuhan University of Science and Technology, Hubei, P.R. China.,Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.,Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Oana Caluseriu
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.,Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
| | - Hunter McColl
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - David D Eisenstat
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.,Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
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22
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Skip segment Hirschsprung's disease in a patient with Shah-Waardenburg Syndrome. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2016. [DOI: 10.1016/j.epsc.2016.08.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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23
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O'Hare T, McDermott M, O'Sullivan M, Dicker P, Antao B. A Retrospective Cohort Study of Total Colonic Aganglionosis: Is the Appendix a Reliable Diagnostic Tool? J Neonatal Surg 2016; 5:44. [PMID: 27896152 PMCID: PMC5117267 DOI: 10.21699/jns.v5i4.460] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Accepted: 09/08/2016] [Indexed: 11/30/2022] Open
Abstract
Background: Hirschsprung's disease (HD) is characterized by a lack of ganglion cells in the myenteric and submucosal plexus, associated with increased numbers of acetyl cholinesterase (AChE) positive nerve fibres. In approximately 10% of patients with HD the entire colon will be affected; a condition known as Total Colonic Aganglionosis (TCA). Aganglionosis of the appendix has long been considered to be an important finding in a patient in whom TCA is suspected, but its reliability for diagnosis has seldom been discussed. The aim of our study was to assess the reliability of the appendix as a histological specimen for the diagnosis of TCA, and to evaluate the long-term outcome of TCA.
Methods: A retrospective cohort study was performed of all pathological specimens of patients with confirmed HD in our institution between March 2006 and April 2016.
Results: Out of a total of 91 patients identified, 15 patients also had histopathological analysis of the appendix. Nine of these cases were confirmed as having TCA. The remaining 6 patients had HD involving the rest of the bowel up to the ascending colon, with normal ganglion present in the caecum. The appendix was removed in all the 15 cases. All 9 patients with confirmed TCA had aganglionosis of the appendix as well. The remaining 6 cases of short and long segment HD not involving the caecum, demonstrated normal ganglion cells within the appendix.
Conclusion: Aganglionosis of the appendix is a reliable tool in the diagnosis of TCA. The authors recommend that at the time of levelling biopsies, if aganglionosis extends to the mid-transverse colon, an ileostomy be performed and appendix sent for definitive confirmation of TCA. However, at the time of definitive surgery, a frozen section of pull-through segment of bowel is recommended to confirm the presence of ganglion cells.
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Affiliation(s)
- T O'Hare
- Department of Paediatric Surgery, Our Lady's Children's Hospital, Dublin, Ireland
| | - M McDermott
- Department of Histopathology, Our Lady's Children's Hospital, Dublin, Ireland
| | - M O'Sullivan
- Department of Histopathology, Our Lady's Children's Hospital, Dublin, Ireland
| | - P Dicker
- School of Postgraduate Studies, Faculty of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - B Antao
- Department of Paediatric Surgery, Our Lady's Children's Hospital, Dublin, Ireland
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24
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Coe A, Avansino JR, Kapur RP. Distal Rectal Skip-Segment Hirschsprung Disease and the Potential for False-Negative Diagnosis. Pediatr Dev Pathol 2016; 19:123-31. [PMID: 26372258 DOI: 10.2350/15-08-1686-oa.1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
In skip-segment Hirschsprung disease (SS-HSCR), an aganglionic segment of bowel, which extends proximally from the distal rectum, is interrupted by a ganglionated "skip segment." Skip segments are usually located far proximal to the rectum where they do not interfere with initial diagnosis, although the possibility of distal SS-HSCR should be considered during interpretation of intraoperative biopsies or patients with atypical postoperative courses. We report 2 cases of SS-HSCR with skip areas in the distal rectum, 1 of which led to a false-negative diagnosis by suction rectal biopsy. These 2 cases of SS-HSCR, along with others in the literature, highlight the point that ganglionic skip segments can confuse clinicians and lead to inadequate bowel resection, diagnostic delay, or a false-negative diagnosis. The pathogenesis of SS-HSCR is discussed in light of recent discoveries regarding transmesenteric migration of vagal neural crest cells and the role of sacral neural crest cells in hindgut neurodevelopment.
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Affiliation(s)
- Alexander Coe
- 1 University of Nevada School of Medicine, Reno, NV, USA
| | - Jeffrey R Avansino
- 2 Department of Surgery, University of Washington and Seattle Children's Hospital, Seattle, WA, USA
| | - Raj P Kapur
- 3 Department of Pathology, University of Washington and Seattle Children's Hospital, Seattle, WA, USA
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25
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Gross ER, Geddes GC, McCarrier JA, Jarzembowski JA, Arca MJ. Skip segment Hirschsprung disease and Waardenburg syndrome. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2015. [DOI: 10.1016/j.epsc.2015.02.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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26
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Wong CWY, Lau CT, Chung PHY, Lam WMW, Wong KKY, Tam PKH. The value of the 24-h delayed abdominal radiograph of barium enema in the diagnosis of Hirschsprung's disease. Pediatr Surg Int 2015; 31:11-5. [PMID: 25348880 DOI: 10.1007/s00383-014-3632-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/21/2014] [Indexed: 10/24/2022]
Abstract
AIM OF STUDY The objective of this study is to determine the diagnostic value of the 24-h delayed film for Hirschsprung's disease (HD). Other features of the barium enema were also examined, in particular the correlation between the radiological transition zone (TZ) and the final pathology. METHODS All patients with suspected HD from 2003 to 2013 who had undergone barium enema and rectal biopsy were reviewed retrospectively to study the correlation between radiological features of barium enema with the final diagnosis as well as severity. RESULTS A total of 182 patients were admitted for suspected HD during the study period, of which 82 had both investigations done. 68 patients had radiological features suggestive of the disease and ultimately, 12 patients had the disease confirmed with rectal biopsy. Among those without radiological features of HD, 2 patients were found to have the disease. Thus, the sensitivity of the 24-h delayed film was 85.7 % and the specificity was 17.6 %. The positive predictive value (PPV) of this test was 20.6 % and the negative predictive value (NPV) was 85.7 %. Regarding the level of TZ, it was not detected in the barium enema in 7 (50 %) out of the 14 patients. For those with the presence of TZ, 6 (85.7 %) of them correlated well with the intra-operative findings and 4 (57.1 %) of them correlated well with the final histology. CONCLUSION The 24-h delayed film of barium enema has a high NPV and is useful to rule out HD. However, rectal biopsy is still suggested for disease confirmation given its low PPV. Lastly, once present, the level of radiological TZ is also a useful predictor for the actual disease involvement.
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Affiliation(s)
- C W Y Wong
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong
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27
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A rare case of multiple skip segment Hirschsprung's disease in the ileum and colon. Pediatr Surg Int 2014; 30:349-51. [PMID: 24178302 DOI: 10.1007/s00383-013-3428-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/22/2013] [Indexed: 10/26/2022]
Abstract
As a rare form of Hirschsprung's disease, skip segment Hirschsprung's disease (SSHD) involves a "skip area" in normally ganglionated intestine, surrounded by aganglionosis. We report a case of multiple SSHD in the ileum and colon with total colonic aganglionosis. To our knowledge, this is the 27th case of SSHD, the third paper on multiple-segment SSHD, and the second patient with SSHD in the ileum to be reported in the English literature.
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28
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Skip segment Hirschsprung's disease: a case report and novel management technique. Pediatr Surg Int 2014; 30:119-22. [PMID: 23948815 DOI: 10.1007/s00383-013-3367-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/07/2013] [Indexed: 10/26/2022]
Abstract
Skip segment Hirschsprung's disease is a condition where an area of normally ganglionated intestine is interspersed proximally and distally by aganglionic segments. The occurrence of skip segment has no clear embryological explanation, contrary to the present concept of failure of cranio-caudal migration of neural crest-derived cells in Hirschsprung's disease. Only 25 case reports have been published in literature so far and this is possibly the first to be reported from Asia. We report one such case with novel surgical management.
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29
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Newgreen DF, Dufour S, Howard MJ, Landman KA. Simple rules for a "simple" nervous system? Molecular and biomathematical approaches to enteric nervous system formation and malformation. Dev Biol 2013; 382:305-19. [PMID: 23838398 PMCID: PMC4694584 DOI: 10.1016/j.ydbio.2013.06.029] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 06/28/2013] [Accepted: 06/28/2013] [Indexed: 11/17/2022]
Abstract
We review morphogenesis of the enteric nervous system from migratory neural crest cells, and defects of this process such as Hirschsprung disease, centering on cell motility and assembly, and cell adhesion and extracellular matrix molecules, along with cell proliferation and growth factors. We then review continuum and agent-based (cellular automata) models with rules of cell movement and logistical proliferation. Both movement and proliferation at the individual cell level are modeled with stochastic components from which stereotyped outcomes emerge at the population level. These models reproduced the wave-like colonization of the intestine by enteric neural crest cells, and several new properties emerged, such as colonization by frontal expansion, which were later confirmed biologically. These models predict a surprising level of clonal heterogeneity both in terms of number and distribution of daughter cells. Biologically, migrating cells form stable chains made up of unstable cells, but this is not seen in the initial model. We outline additional rules for cell differentiation into neurons, axon extension, cell-axon and cell-cell adhesions, chemotaxis and repulsion which can reproduce chain migration. After the migration stage, the cells re-arrange as a network of ganglia. Changes in cell adhesion molecules parallel this, and we describe additional rules based on Steinberg's Differential Adhesion Hypothesis, reflecting changing levels of adhesion in neural crest cells and neurons. This was able to reproduce enteric ganglionation in a model. Mouse mutants with disturbances of enteric nervous system morphogenesis are discussed, and these suggest future refinement of the models. The modeling suggests a relatively simple set of cell behavioral rules could account for complex patterns of morphogenesis. The model has allowed the proposal that Hirschsprung disease is mostly an enteric neural crest cell proliferation defect, not a defect of cell migration. In addition, the model suggests an explanations for zonal and skip segment variants of Hirschsprung disease, and also gives a novel stochastic explanation for the observed discordancy of Hirschsprung disease in identical twins.
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Affiliation(s)
- Donald F Newgreen
- The Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia.
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30
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Takahashi Y, Sipp D, Enomoto H. Tissue interactions in neural crest cell development and disease. Science 2013; 341:860-3. [PMID: 23970693 DOI: 10.1126/science.1230717] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The neural crest is a transient population of migratory cells in the embryo that gives rise to a wide variety of different cell types, including those of the peripheral nervous system. Dysfunction of neural crest cells (NCCs) is associated with multiple diseases, such as neuroblastoma and Hirschsprung disease. Recent studies have identified NCC behaviors during their migration and differentiation, with implications for their contributions to development and disease. Here, we describe how interactions between cells of the neural crest and lineages such as the vascular system, as well as those involving environmental signals and microbial pathogens, are critically important in determining the roles played by these cells.
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Affiliation(s)
- Yoshiko Takahashi
- Department of Zoology, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
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Moore SW, Sidler D, Schubert PAW. Segmental aganglionosis (zonal aganglionosis or "skip" lesions) in Hirschsprungs disease: a report of 2 unusual cases. Pediatr Surg Int 2013; 29:495-500. [PMID: 23456285 DOI: 10.1007/s00383-013-3286-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/14/2013] [Indexed: 10/27/2022]
Abstract
INTRODUCTION There is accumulating evidence that "skip" lesions or zonal aganglionosis do occur in HSCR disease, albeit rarely. They are of interest because it may cause confusion in interpreting surgical margins as well as understanding the pathophysiology of HSCR disease. Normally described as "a skip area" of normally ganglionated bowel, surrounded proximally and distally by aganglionosis with variations may occur. CASE REPORTS We report two cases of infants with unusual types of "skip lesions", identified within the last 5 years. RESULTS One patient had an area of zonal aganglionosis in the transverse colon and recto-sigmoid, bordered by areas of normally enervated bowel in the right and descending colon. In the second patient, the terminal ileum, transverse, descending and sigmoid colons and rectum were histologically aganglionic, but focal patches of ganglion cells were identified in 21 cm of the right ascending colon and the appendix, suggesting some ENS plasticity and possible incomplete apoptosis. CONCLUSION These cases illustrate the point that the presence of ganglion cells at the resection line is not sufficient to guarantee postoperative function and "skip" lesions may uncommonly confuse the picture. In addition, they raise questions as to its pathophysiology and favor an alternate hypothesis of local changes promoting neuroblast apoptosis as the possible cause.
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Affiliation(s)
- S W Moore
- Division of Pediatric Surgery, Department of Surgical Sciences, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, South Africa.
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Musser MA, Michelle Southard-Smith E. Balancing on the crest - Evidence for disruption of the enteric ganglia via inappropriate lineage segregation and consequences for gastrointestinal function. Dev Biol 2013; 382:356-64. [PMID: 23376538 DOI: 10.1016/j.ydbio.2013.01.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2012] [Revised: 01/21/2013] [Accepted: 01/22/2013] [Indexed: 01/28/2023]
Abstract
Normal enteric nervous system (ENS) development relies on numerous factors, including appropriate migration, proliferation, differentiation, and maturation of neural crest (NC) derivatives. Incomplete rostral to caudal migration of enteric neural crest-derived progenitors (ENPs) down the gut is at least partially responsible for the absence of enteric ganglia that is a hallmark feature of Hirschsprung disease (HSCR). The thought that ganglia proximal to aganglionosis are normal has guided surgical procedures for HSCR patients. However, chronic gastrointestinal dysfunction suffered by a subset of patients after surgery as well as studies in HSCR mouse models suggest that aberrant NC segregation and differentiation may be occurring in ganglionated regions of the intestine. Studies in mouse models that possess enteric ganglia throughout the length of the intestine (non-HSCR) have also found that certain genetic alterations affect neural crest lineage balance and interestingly many of these mutants also have functional gastrointestinal (GI) defects. It is possible that many GI disorders can be explained in part by imbalances in NC-derived lineages. Here we review studies evaluating ENS defects in HSCR and non-HSCR mouse models, concluding with clinical implications while highlighting areas requiring further study.
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Affiliation(s)
- Melissa A Musser
- Division of Genetic Medicine, Department of Medicine and the PhD Program in Human Genetics, Center for Human Genetic Research, Vanderbilt University School of Medicine, Nashville, TN, USA
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Small bowel skip segment Hirschprung's disease presenting with perforated Meckel's diverticulum. Pediatr Surg Int 2012; 28:645-8. [PMID: 22207458 DOI: 10.1007/s00383-011-3050-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/19/2011] [Indexed: 10/14/2022]
Abstract
Skip segment Hirschprung's disease (SSHD) is an uncommon variant of Hirschprung's disease where normal intestine is interspersed proximally and distally by abnormal, aganglionated intestine. These segmental changes have no well-defined embryological explanation. We present a case of SSHD in the small bowel and concomitant perforated Meckel's diverticulum, with review of the literature relevant to SSHD.
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Castle S, Suliman A, Shayan K, Kling K, Bickler S, Losasso B. Total colonic aganglionosis with skip lesions: report of a rare case and management. J Pediatr Surg 2012; 47:581-4. [PMID: 22424357 DOI: 10.1016/j.jpedsurg.2011.11.067] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Revised: 11/19/2011] [Accepted: 11/21/2011] [Indexed: 11/25/2022]
Abstract
We present an unusual case of total colonic aganglionosis with well-documented skip lesions and discuss our staged approach for diagnosis and surgical management. To date, there have been few reported cases of total colonic aganglionosis with skip areas. This type of presentation challenges the accepted theory regarding the etiology of colonic aganglionosis. Although skip lesions in Hirschsprung disease are extremely rare, their existence must be appreciated especially when a patient's clinical and pathologic findings do not support classic Hirschsprung disease. If not considered, additional areas of aganglionosis can be missed at initial presentation, leading to a delay in definitive treatment. This case illustrates how careful mapping of bowel via multiple biopsies can identify and thereby preserve intervening segments of bowel with normal ganglions cells to yield the maximal amount of bowel possible.
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Burjonrappa S, Rankin L. 'Hop the skip' with extended segment intestinal biopsy in Hirschsprung's disease. Int J Surg Case Rep 2012; 3:186-9. [PMID: 22449568 DOI: 10.1016/j.ijscr.2012.02.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Revised: 02/08/2012] [Accepted: 02/13/2012] [Indexed: 10/28/2022] Open
Abstract
INTRODUCTION Skip segment Hirschsprung's is an extremely rare condition, with only 25 reported cases in the English language literature. Diagnosis of skip segment Hirschsprung's may be missed as it is rarely suspected at initial surgery. PRESENTATION OF CASE A case report of an infant with total colonic aganglionosis and a skip segment Hirschsprung's in the cecum is presented. A review of literature on current surgical practice is presented along with our suggested modification to the diagnostic and therapeutic algorithm of this rare condition. DISCUSSION In our patient the initial leveling colostomy was incorrectly sited at the level of the first detected ganglionated segment. Subsequent recurrent episodes of enterocolitis led to a diagnosis of a long skip segment involving the ascending colon, cecum and terminal ileum. Correct leveling colostomy and a subsequent Duhamel procedure led to a good outcome. CONCLUSION Determination of the transition zone in Hirschsprung's may be incorrect if intestinal biopsies are terminated at the first evidence of ganglion cells. Extended segment intestinal biopsies should be included in the algorithm for management of long segment Hirschsprung's disease and will enable the surgeon to correctly detect rare manifestations such as skip segment disease at the initial procedure.
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Affiliation(s)
- Sathyaprasad Burjonrappa
- Maimonides Medical Center, Division of Pediatric Surgery, Department of Surgery, 921 49th St, USA
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Wallace AS, Tan MX, Schachner M, Anderson RB. L1cam acts as a modifier gene for members of the endothelin signalling pathway during enteric nervous system development. Neurogastroenterol Motil 2011; 23:e510-22. [PMID: 21395909 DOI: 10.1111/j.1365-2982.2011.01692.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The enteric nervous system originates from neural crest cells that migrate into the embryonic foregut and then sequentially colonize the midgut and hindgut. Defects in neural crest migration result in regions of the gut that lack enteric ganglia, a condition in humans called Hirschsprung's disease. The high degree of phenotypic variability reported in Hirschsprung's disease suggests the involvement of modifier genes. METHODS We used a two-locus complementation approach to screen for genetic interactions between L1cam and members of the endothelin signalling pathway. Immunohistochemistry was used to label PGP9.5(+) enteric neurons and Sox10(+) neural crest-derived cells in wholemount preparations of embryonic gut. Key Results Loss or haploinsufficiency of L1cam significantly increased the severity of aganglionosis in Et-3 and Ednrb null mutant embryos. Furthermore, the colonization of the developing gut by neural crest-derived cells was significantly delayed in L1cam(-/y) ; Et-3(-/-) and L1cam(-/y) ;Ednrb(sl/sl) embryos. CONCLUSIONS & INFERENCES We have identified the X-linked gene, L1cam, as the first modifier gene for members of the endothelin signalling pathway during development of the enteric nervous system. Mutations in L1CAM may act to modulate the severity of aganglionosis in some cases of Hirschsprung's disease.
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Affiliation(s)
- A S Wallace
- Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Melbourne, Victoria, Australia
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Doi T, O'Donnell AM, McDermott M, Puri P. Skip segment Hirschsprung's disease: a rare phenomenon. Pediatr Surg Int 2011; 27:787-9. [PMID: 21516498 DOI: 10.1007/s00383-011-2903-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/04/2011] [Indexed: 11/26/2022]
Abstract
Skip segment Hirschsprung's disease (SSHD) involves a skip area of normally ganglionated intestine, surrounded proximally and distally by aganglionosis. We report a case of SSHD in infant with total colonic aganglionosis (TCA). Although SSHD is a rare and controversial condition, it should be considered a definite entity in the evaluation of Hirschsprung's disease.
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Affiliation(s)
- Takashi Doi
- The Children's Research Centre, Dublin, Ireland.
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