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Hou J, Feng W, Zhao H, Cui M, Wang Y, Guo Z, Liu W. Robotic-assisted Swenson procedure for Hirschsprung's disease with a median age of 35 days: a single-center retrospective study. Pediatr Surg Int 2025; 41:87. [PMID: 40014151 DOI: 10.1007/s00383-025-05988-x] [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] [Accepted: 02/15/2025] [Indexed: 02/28/2025]
Abstract
PURPOSE The treatment of Hirschsprung's disease (HD) in infants with the robotic-assisted Swenson procedure has been rarely reported. In this investigation, we aimed to explore the safety and the efficacy of robotic-assisted Swenson procedure for the HD in infants. METHODS From November 2022 to July 2023, 17 cases of HD were treated with the Da Vinci robotic Xi surgical system using a three-port approach. Preoperative, intraoperative, and postoperative data were collected and compared with 43 cases of HD treated with laparoscopy by the same lead surgeon. RESULTS The robotic-assisted surgery (RAS) group included 17 infants, and the laparoscopic surgery (LS) group included 43 infants, with a median surgical age of 35 days for both groups. There were no statistically significant differences between the two groups in terms of surgical age, gender, preoperative weight, preoperative hospital stay, preoperative enema time, and incidence of preoperative enterocolitis. Estimated intraoperative blood loss and transfusion rate in the RAS group were both lower than in the LS group, with statistically significant differences. There were no statistically significant differences in early and midterm postoperative complications (anastomotic leaks, anastomotic strictures, enterocolitis, etc.) between the two groups. CONCLUSION This study demonstrates the efficacy and the safety of robotic-assisted Swenson procedure in infants.
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Affiliation(s)
- Jinfeng Hou
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China
| | - Wei Feng
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China
| | - Hanbin Zhao
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China
| | - Mengying Cui
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China
| | - Yi Wang
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China
| | - Zhenhua Guo
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China
| | - Wei Liu
- National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing Key Laboratory of Pediatrics, Department of General Surgery & Neonatal Surgery Children'S Hospital of Chongqing Medical University, Mailing Address:20 Jinyu Avenue, Liangjiang New District, Chongqing, 401122, China.
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Çoşkun N, Metin M. Scientific evolution from the definition of Hirschsprung disease to the present: a bibliometric analysis (1980-2023). Pediatr Res 2025:10.1038/s41390-025-03927-z. [PMID: 39979585 DOI: 10.1038/s41390-025-03927-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 01/17/2025] [Accepted: 01/27/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND The primary objective of this study is to define the global productivity of Hirschsprung disease (HSCR), identify influential studies, determine research directions focused on both historical and contemporary perspectives. METHODS The study obtained 2816 articles published between 1980 and 2023 related to HSCR from the Web of Science database, and comprehensive bibliometric analysis were conducted. RESULTS The top three most productive countries were the USA (n = 1283), China (n = 1167), and Japan (n = 587). The most productive institution was Université Paris Cité (n = 149), and the most productive author was Prem Puri (n = 99). The most frequently used keywords in the articles were enterocolitis (n = 191), enteric nervous system (n = 136), and transanal endorectal pull-through (n = 129). CONCLUSION Academic interest in HSCR began in 1887-1888, significantly increased in 1948 and 1964, and reached its highest peak in 1994. The findings indicate that key topics such as enterocolitis, enteric nervous system, surgical techniques, and genetic factors have been prominent in HSCR research. Previous studies, which often focused on molecular and genetic mechanisms, have shifted towards clinical and surgical applications in the last decade. Factor analysis reveals the complexity and diversity of HSCR research, with various topics examined, including clinical features, surgical treatments, pathological findings, and genetic bases. IMPACT STATEMENT This study presents a comprehensive bibliometric analysis of global research trends and future directions in Hirschsprung disease, revealing significant changes and developments in the study of the disease. The study provides an important contribution to the existing literature by detailing the historical development, main research topics, and thematic evolution of Hirschsprung disease research. The findings indicate that future research focus in Hirschsprung disease may increasingly prioritize innovative approaches, such as stem cell therapy, alongside clinical and surgical advancements. These advancements have the potential to enhance patient quality of life and guide future research strategies.
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Affiliation(s)
- Nurcan Çoşkun
- Department of Pediatric Surgery, Hitit University Erol Olçok Training and Research Hospital, Hitit University, Çorum, Turkey.
| | - Mehmet Metin
- Faculty of Medicine, Department of Pediatric Surgery, Hitit University, Çorum, Turkey
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Tjaden NEB, Liou MJ, Sax SE, Lassoued N, Lou M, Schneider S, Beigel K, Eisenberg JD, Loeffler E, Anderson SE, Yan G, Litichevskiy L, Dohnalová L, Zhu Y, Jin DMJC, Raab J, Furth EE, Thompson Z, Rubenstein RC, Pilon N, Thaiss CA, Heuckeroth RO. Dietary manipulation of intestinal microbes prolongs survival in a mouse model of Hirschsprung disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.10.637436. [PMID: 39990395 PMCID: PMC11844371 DOI: 10.1101/2025.02.10.637436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
Enterocolitis is a common and potentially deadly manifestation of Hirschsprung disease (HSCR) but disease mechanisms remain poorly defined. Unexpectedly, we discovered that diet can dramatically affect the lifespan of a HSCR mouse model ( Piebald lethal , sl/sl ) where affected animals die from HAEC complications. In the sl/sl model, diet alters gut microbes and metabolites, leading to changes in colon epithelial gene expression and epithelial oxygen levels known to influence colitis severity. Our findings demonstrate unrecognized similarity between HAEC and other types of colitis and suggest dietary manipulation could be a valuable therapeutic strategy for people with HSCR. Abstract Hirschsprung disease (HSCR) is a birth defect where enteric nervous system (ENS) is absent from distal bowel. Bowel lacking ENS fails to relax, causing partial obstruction. Affected children often have "Hirschsprung disease associated enterocolitis" (HAEC), which predisposes to sepsis. We discovered survival of Piebald lethal ( sl/sl ) mice, a well-established HSCR model with HAEC, is markedly altered by two distinct standard chow diets. A "Protective" diet increased fecal butyrate/isobutyrate and enhanced production of gut epithelial antimicrobial peptides in proximal colon. In contrast, "Detrimental" diet-fed sl/sl had abnormal appearing distal colon epithelium mitochondria, reduced epithelial mRNA involved in oxidative phosphorylation, and elevated epithelial oxygen that fostered growth of inflammation-associated Enterobacteriaceae . Accordingly, selective depletion of Enterobacteriaceae with sodium tungstate prolonged sl/sl survival. Our results provide the first strong evidence that diet modifies survival in a HSCR mouse model, without altering length of distal colon lacking ENS. Highlights Two different standard mouse diets alter survival in the Piebald lethal ( sl/sl ) mouse model of Hirschsprung disease, without impacting extent of distal colon aganglionosis (the region lacking ENS). Piebald lethal mice fed the "Detrimental" diet had many changes in colon epithelial transcriptome including decreased mRNA for antimicrobial peptides and genes involved in oxidative phosphorylation. Detrimental diet fed sl/sl also had aberrant-appearing mitochondria in distal colon epithelium, with elevated epithelial oxygen that drives lethal Enterobacteriaceae overgrowth via aerobic respiration. Elimination of Enterobacteriaceae with antibiotics or sodium tungstate improves survival of Piebald lethal fed the "Detrimental diet". Graphical abstract
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Zhong W, Lan C, Chen Y, Song K, Ma Z, Zeng J, Huang L, Zhang Y, Zhu Y, Xia H. Virus-Triggered Autoimmunity Was Associated With Hirschsprung's Disease Through Activation of Innate Immunity. J Immunol Res 2024; 2024:4838514. [PMID: 39493374 PMCID: PMC11531361 DOI: 10.1155/2024/4838514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 08/06/2024] [Accepted: 09/27/2024] [Indexed: 11/05/2024] Open
Abstract
Background: Hirschsprung's disease (HSCR) is a congenital enteric nervous system (ENS) disorder. Genetics cannot explain most sporadic cases. To explore the relationship between pathogen infection, autoantibodies, innate immune, and HSCR. Methods: Pathogen microarray was conducted in the serum of the prospective neonatal abdominal distension (NAD) cohort, consisting of 56 children followed for at least 6 months until the final diagnosis of HSCR was determined or excluded. We conducted an autoantibody microarray in an HSCR cohort, which is comprised of diagnosed HSCR patients (HSCR) and healthy control subjects (HC). RNA-seq of colon tissues from aganglionic and ganglionic segments of HSCR patients was performed. Results: Experimental results show that the serum lgM and lgG of enterovirus 71 (EV71) were significantly higher in HSCR than in the gastrointestinal dysfunction (GI) group, with a prediagnose value reaching area under the curve (AUC) over 0.76. We discovered that a group of autoantibodies were significantly higher in HSCR including neuronal pentraxin 1 (NPTX1), amyloid, neuron lysate, and myelin-associated oligodendrocytic basic protein (MOBP) than that in the HC group. These four autoantibodies could distinguish HSCR from the HC group, with a combined AUC of over 0.90 using both serum IgG and IgM. Further analysis showed that wide activation of innate immune pathways, including toll-like receptor (TLR) signaling pathway, neutrophil-to-lymphocyte ratio (NLR) signaling pathway, red cell distribution width to lymphocyte ratio (RLR) signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway in aganglionic compared to ganglionic segments of HSCR. Conclusion: This study suggested that virus-triggered autoimmunity may contribute to HSCR through activation of innate immunity, which facilitates the diagnosis and prevention of HSCR.
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Affiliation(s)
- Weiyong Zhong
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Chaoting Lan
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Yuqiong Chen
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Kai Song
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Zuyi Ma
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Jixiao Zeng
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Lihua Huang
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Yan Zhang
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Yun Zhu
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Huimin Xia
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
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Eisenberg JD, Bradley RP, Graham KD, Ceron RH, Lemke AM, Wilkins BJ, Naji A, Heuckeroth RO. Three-Dimensional Imaging of the Enteric Nervous System in Human Pediatric Colon Reveals New Features of Hirschsprung's Disease. Gastroenterology 2024; 167:547-559. [PMID: 38494035 PMCID: PMC11260536 DOI: 10.1053/j.gastro.2024.02.045] [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: 12/07/2022] [Revised: 02/08/2024] [Accepted: 02/18/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND & AIMS Hirschsprung's disease is defined by the absence of the enteric nervous system (ENS) from the distal bowel. Primary treatment is "pull-through" surgery to remove bowel that lacks ENS, with reanastomosis of "normal" bowel near the anal verge. Problems after pull-through are common, and some may be due to retained hypoganglionic bowel (ie, low ENS density). Testing this hypothesis has been difficult because counting enteric neurons in tissue sections is unreliable, even for experts. Tissue clearing and 3-dimensional imaging provide better data about ENS structure than sectioning. METHODS Regions from 11 human colons and 1 ileal specimen resected during Hirschsprung's disease pull-through surgery were cleared, stained with antibodies to visualize the ENS, and imaged by confocal microscopy. Control distal colon from people with no known bowel problems were similarly cleared, stained, and imaged. RESULTS Quantitative analyses of human colon, ranging from 3 days to 60 years old, suggest age-dependent changes in the myenteric plexus area, ENS ganglion area, percentage of myenteric plexus occupied by ganglia, neurons/mm2, and neuron Feret's diameter. Neuron counting using 3-dimensional images was highly reproducible. High ENS density in neonatal colon allowed reliable neuron counts using 500-μm2 × 500-μm2 regions (36-fold smaller than in adults). Hirschsprung's samples varied 8-fold in proximal margin enteric neuron density and had diverse ENS architecture in resected bowel. CONCLUSIONS Tissue clearing and 3-dimensional imaging provide more reliable information about ENS structure than tissue sections. ENS structure changes during childhood. Three-dimensional ENS anatomy may provide new insight into human bowel motility disorders, including Hirschsprung's disease.
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Affiliation(s)
- Joshua D Eisenberg
- Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rebecca P Bradley
- Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania
| | - Kahleb D Graham
- Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Rachel H Ceron
- Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Amanda M Lemke
- Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania
| | - Benjamin J Wilkins
- Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Ali Naji
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Robert O Heuckeroth
- Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Montalva L, Cheng LS, Kapur R, Langer JC, Berrebi D, Kyrklund K, Pakarinen M, de Blaauw I, Bonnard A, Gosain A. Hirschsprung disease. Nat Rev Dis Primers 2023; 9:54. [PMID: 37828049 DOI: 10.1038/s41572-023-00465-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/12/2023] [Indexed: 10/14/2023]
Abstract
Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes in patients.
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Affiliation(s)
- Louise Montalva
- Department of Paediatric Surgery, Robert-Debré Children's University Hospital, Paris, France.
- Faculty of Health, Paris-Cité University, Paris, France.
- NeuroDiderot, INSERM UMR1141, Paris, France.
| | - Lily S Cheng
- Division of Paediatric Surgery, Texas Children's Hospital, Houston, TX, USA
- Division of Paediatric Surgery, University of Virginia, Charlottesville, VA, USA
| | - Raj Kapur
- Department of Pathology, Seattle Children's Hospital, Seattle, WA, USA
| | - Jacob C Langer
- Division of Paediatric Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Dominique Berrebi
- Department of Pathology, Robert-Debré and Necker Children's University Hospital, Paris, France
| | - Kristiina Kyrklund
- Department of Paediatric Surgery, Helsinki University Central Hospital, Helsinki, Finland
| | - Mikko Pakarinen
- Department of Paediatric Surgery, Helsinki University Central Hospital, Helsinki, Finland
| | - Ivo de Blaauw
- Department of Surgery, Division of Paediatric Surgery, Radboudumc-Amalia Children's Hospital, Nijmegen, Netherlands
| | - Arnaud Bonnard
- Department of Paediatric Surgery, Robert-Debré Children's University Hospital, Paris, France
- Faculty of Health, Paris-Cité University, Paris, France
- NeuroDiderot, INSERM UMR1141, Paris, France
| | - Ankush Gosain
- Department of Paediatric Surgery, Children's Hospital Colorado, Aurora, CO, USA.
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Chen BN, Humenick A, Yew WP, Peterson RA, Wiklendt L, Dinning PG, Spencer NJ, Wattchow DA, Costa M, Brookes SJH. Types of Neurons in the Human Colonic Myenteric Plexus Identified by Multilayer Immunohistochemical Coding. Cell Mol Gastroenterol Hepatol 2023; 16:573-605. [PMID: 37355216 PMCID: PMC10469081 DOI: 10.1016/j.jcmgh.2023.06.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 06/14/2023] [Accepted: 06/15/2023] [Indexed: 06/26/2023]
Abstract
BACKGROUND AND AIMS Gut functions including motility, secretion, and blood flow are largely controlled by the enteric nervous system. Characterizing the different classes of enteric neurons in the human gut is an important step to understand how its circuitry is organized and how it is affected by disease. METHODS Using multiplexed immunohistochemistry, 12 discriminating antisera were applied to distinguish different classes of myenteric neurons in the human colon (2596 neurons, 12 patients) according to their chemical coding. All antisera were applied to every neuron, in multiple layers, separated by elutions. RESULTS A total of 164 combinations of immunohistochemical markers were present among the 2596 neurons, which could be divided into 20 classes, with statistical validation. Putative functions were ascribed for 4 classes of putative excitatory motor neurons (EMN1-4), 4 inhibitory motor neurons (IMN1-4), 3 ascending interneurons (AIN1-3), 6 descending interneurons (DIN1-6), 2 classes of multiaxonal sensory neurons (SN1-2), and a small, miscellaneous group (1.8% of total). Soma-dendritic morphology was analyzed, revealing 5 common shapes distributed differentially between the 20 classes. Distinctive baskets of axonal varicosities surrounded 45% of myenteric nerve cell bodies and were associated with close appositions, suggesting possible connectivity. Baskets of cholinergic terminals and several other types of baskets selectively targeted ascending interneurons and excitatory motor neurons but were significantly sparser around inhibitory motor neurons. CONCLUSIONS Using a simple immunohistochemical method, human myenteric neurons were shown to comprise multiple classes based on chemical coding and morphology and dense clusters of axonal varicosities were selectively associated with some classes.
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Affiliation(s)
- Bao Nan Chen
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Adam Humenick
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Wai Ping Yew
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Rochelle A Peterson
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Lukasz Wiklendt
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Phil G Dinning
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Nick J Spencer
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - David A Wattchow
- Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Marcello Costa
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Simon J H Brookes
- Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
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Chen K, You J, Yang S, Meng X, Chen X, Wu L, Yu X, Xiao J, Feng J. Abnormally elevated expression of ACTA2 of circular smooth muscle leads to hyperactive contraction in aganglionic segments of HSCR. Pediatr Surg Int 2023; 39:214. [PMID: 37278766 PMCID: PMC10244273 DOI: 10.1007/s00383-023-05479-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] [Accepted: 05/02/2023] [Indexed: 06/07/2023]
Abstract
BACKGROUND Actin Alpha 2 (ACTA2) is expressed in intestinal smooth muscle cells (iSMCs) and is associated with contractility. Hirschsprung disease (HSCR), one of the most common digested tract malformations, shows peristaltic dysfunction and spasm smooth muscles. The arrangement of the circular and longitudinal smooth muscle (SM) of the aganglionic segments is disorganized. Does ACTA2, as a marker of iSMCs, exhibit abnormal expression in aganglionic segments? Does the ACTA2 expression level affect the contraction function of iSMCs? What are the spatiotemporal expression trends of ACTA2 during different developmental stages of the colon? METHODS Immunohistochemical staining was used to detect the expression of ACTA2 in iSMCs of children with HSCR and Ednrb-/- mice, and the small interfering RNAs (siRNAs) knockdown technique was employed to investigate how Acta2 affected the systolic function of iSMCs. Additionally, Ednrb-/- mice were used to explore the changes in the expression level of iSMCs ACTA2 at different developmental stages. RESULTS The expression of ACTA2 is higher in circular SM in the aganglionic segments of HSCR patients and Ednrb-/- mice than in normal control children and mice. Down regulation of Acta2 weakens the contraction ability of intestinal smooth muscle cells. Abnormally elevated expression of ACTA2 of circular smooth muscle occurs since embryonic day 15.5 (E15.5d) in aganglionic segments of Ednrb-/- mice. CONCLUSIONS Abnormally elevated expression of ACTA2 in the circular SM leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.
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Affiliation(s)
- Ke Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Jingyi You
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Shimin Yang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Xinyao Meng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Xuyong Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Luyao Wu
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Xiaosi Yu
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China
| | - Jun Xiao
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China.
| | - Jiexiong Feng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430043, China.
- Hubei Clinical Center of Hirschsprung Disease and Allied Disorders, Wuhan, China.
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Heuckeroth RO. Mice Are Not Small Furry People! A New Hirschsprung Disease Model Lets Us Pretend This Is Not True. Cell Mol Gastroenterol Hepatol 2023; 15:1533-1534. [PMID: 36924799 DOI: 10.1016/j.jcmgh.2023.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 02/21/2023] [Indexed: 03/18/2023]
Affiliation(s)
- Robert O Heuckeroth
- The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Abramson Research Center, Philadelphia, Pennsylvania.
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Westfal ML, Okiemy O, Chung PHY, Feng J, Lu C, Miyano G, Tam PKH, Tang W, Wong KKY, Yamataka A, Guyer RA, Doody DP, Goldstein AM. Optimal timing for Soave primary pull-through in short-segment Hirschsprung disease: A meta-analysis. J Pediatr Surg 2022; 57:719-725. [PMID: 34330420 PMCID: PMC8776908 DOI: 10.1016/j.jpedsurg.2021.07.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 06/15/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND The optimal age for endorectal pull-through (ERPT) surgery in infants with short-segment Hirschsprung disease varies, with a trend toward earlier surgery. However, it is unclear if the timing of surgery impacts functional outcomes. We undertook the present study to determine the optimal timing of ERPT in infants with short-segment Hirschsprung disease. METHODS The NCBI PubMed database was searched for English-language manuscripts published between 2000 and 2019 analyzing functional outcomes for patient following the initial Soave ERPT for short-segment Hirschsprung disease. Raw data from these studies was obtained from the corresponding author for each manuscript. We combined data from these papers with our own institutional data and performed a meta-analysis. RESULTS A total of 780 infants were included in our meta-analysis. Constipation occurred in 1.0-31.7%, soiling 1.3-26.0%, anastomotic stricture 0.0-14.6%, and anastomotic leak 0.0-3.4%. Regarding age at ERPT, younger infants at the time of initial corrective surgery had higher rates of soiling, stricture, and leak. On sub-group analysis, patients <2.5 months at their initial corrective surgery had higher rates of soiling (25.9% vs. 11.4%, p<0.01), as well as stricture (10.0% vs 1.7%, p<0.01) and leak (5.5% vs 1.3%, p<0.01). CONCLUSION While age at Soave endorectal pull-through for short-segment Hirschsprung disease has decreased over time, functional outcomes associated with this trend have only recently been examined. Our findings suggest that patients <2.5 months old at the time of endorectal pull-through may have worse functional outcomes, emphasizing the need to consider further study of the timing of surgery in this population.
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Affiliation(s)
- Maggie L Westfal
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 1151, Boston, Massachusetts MA 02114, United States
| | - Ongoly Okiemy
- Department of Pediatric Surgery, American Memorial Hospital, Reims-Champagne-Ardennes University, Reims, France
| | | | - Jiexiong Feng
- Department of Pediatric Surgery, Tongji Hospital, Wuhan, China
| | - Changgui Lu
- Department of Pediatric Surgery, Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Go Miyano
- Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | | | - Weibing Tang
- Department of Pediatric Surgery, Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | | | - Atsuyuki Yamataka
- Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Richard A Guyer
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 1151, Boston, Massachusetts MA 02114, United States
| | - Daniel P Doody
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 1151, Boston, Massachusetts MA 02114, United States
| | - Allan M Goldstein
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 1151, Boston, Massachusetts MA 02114, United States.
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Kim SH, Cho YH, Kim HY. Assessment of defecation function beyond infantile period for transanal single-stage endorectal pull-through in Hirschsprung disease. Ann Surg Treat Res 2021; 101:231-239. [PMID: 34692595 PMCID: PMC8506020 DOI: 10.4174/astr.2021.101.4.231] [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: 05/06/2021] [Revised: 07/20/2021] [Accepted: 08/19/2021] [Indexed: 12/29/2022] Open
Abstract
Purpose Transanal single-stage endorectal pull-through (TERPT) procedure for patients with Hirschsprung disease (HD) has favorable outcomes, with a lower complication rate. Nevertheless, various degrees of bowel dysfunction and fecal incontinence can persist for a long time in some patients. The aim of this study was to assess the mid- and long-term outcomes of TERPT performed during the infantile period after the completion of toilet training. Methods We retrospectively reviewed 82 patients aged ≥4 years who underwent TERPT during the infantile period after the pathological diagnosis of HD between 2001 and 2013. Functional outcomes were investigated according to the answers of the Bowel Function Score (BFS) questionnaire, a previously validated 7-item questionnaire about bowel habits. Normal values were obtained in a previous study on BFS for children in Western countries, and a one-sample t-test was used for statistical analysis. Results Overall, BFS was similar in all investigated age groups. On comparing fecal soiling and social problems between the HD and normal populations, a lower score at an early age in patients with HD was noted; however, the scores became similar when the patients were 7 years of age. Stool frequency decreased continuously but was not significantly different between the 2 groups. Conclusion The functional outcomes of TERPT performed during the infantile period, after completing toilet training, were similar to that of the normal population. In most cases, uncomfortable symptoms were diminished and functions improved with age.
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Affiliation(s)
- Soo-Hong Kim
- Division of Pediatric Surgery, Department of Surgery, Pusan National University Yangsan Hospital and Pusan National University Children's Hospital, Yangsan, Korea
| | - Yong-Hoon Cho
- Division of Pediatric Surgery, Department of Surgery, Pusan National University Yangsan Hospital and Pusan National University Children's Hospital, Yangsan, Korea
| | - Hae-Young Kim
- Division of Pediatric Surgery, Department of Surgery, Pusan National University Hospital, Busan, Korea
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Verkuijl SJ, Friedmacher F, Harter PN, Rolle U, Broens PMA. Persistent bowel dysfunction after surgery for Hirschsprung’s disease: A neuropathological perspective. World J Gastrointest Surg 2021; 13:822-833. [PMID: 34512906 PMCID: PMC8394380 DOI: 10.4240/wjgs.v13.i8.822] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 05/12/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Hirschsprung’s disease (HD) is a congenital disorder, characterized by aganglionosis in the distal part of the gastrointestinal tract. Despite complete surgical resection of the aganglionic segment, both constipation and fecal incontinence persist in a considerable number of patients with limited treatment options. There is growing evidence for structural abnormalities in the ganglionic bowel proximal to the aganglionosis in both humans and animals with HD, which may play a role in persistent bowel dysfunction. These abnormalities include: (1) Histopathological abnormalities of enteric neural cells; (2) Imbalanced expression of neurotransmitters and neuroproteins; (3) Abnormal expression of enteric pacemaker cells; (4) Abnormalities of smooth muscle cells; and (5) Abnormalities within the extracellular matrix. Hence, a better understanding of these previously unrecognized neuropathological abnormalities may improve follow-up and treatment in patients with HD suffering from persistent bowel dysfunction following surgical correction. In the long term, further combination of clinical and neuropathological data will hopefully enable a translational step towards more individual treatment for HD.
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Affiliation(s)
- Sanne J Verkuijl
- Department of Pediatric Surgery, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt 60590, Germany
- Neurological Institute (Edinger-Institute), University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt 60528, Germany
- Department of Surgery, Division of Pediatric Surgery, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, Netherlands
| | - Florian Friedmacher
- Department of Pediatric Surgery, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt 60590, Germany
| | - Patrick N Harter
- Neurological Institute (Edinger-Institute), University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt 60528, Germany
| | - Udo Rolle
- Department of Pediatric Surgery, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt 60590, Germany
| | - Paul MA Broens
- Department of Surgery, Division of Pediatric Surgery, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, Netherlands
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Heuckeroth RO. Newly Identified Enteric Nervous System Precursors in the Mesentery Make One Skip, But Not For Joy! Cell Mol Gastroenterol Hepatol 2021; 12:378-379. [PMID: 33857486 PMCID: PMC8257452 DOI: 10.1016/j.jcmgh.2021.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 03/17/2021] [Accepted: 03/17/2021] [Indexed: 12/10/2022]
Affiliation(s)
- Robert O Heuckeroth
- Professor of Pediatrics, Irma and Norman Braman Endowed Chair for Research in GI Motility Disorders, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
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Schill EM, Wright CM, Jamil A, LaCombe JM, Roper RJ, Heuckeroth RO. Down syndrome mouse models have an abnormal enteric nervous system. JCI Insight 2019; 5:124510. [PMID: 30998504 PMCID: PMC6629165 DOI: 10.1172/jci.insight.124510] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 04/17/2019] [Indexed: 12/16/2022] Open
Abstract
Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which are hypothesized to contribute to HSCR risk. Ts65Dn and Tc1 mice have normal ENS precursor migration at E12.5 and almost normal myenteric plexus structure as adults. However, Ts65Dn and Tc1 mice have markedly reduced submucosal plexus neuron density throughout the bowel. Surprisingly, the submucosal neuron defect in Ts65Dn mice is not due to excess Dscam or Dyrk1a, since normalizing copy number for these genes does not rescue the defect. These findings suggest the possibility that the high frequency of bowel problems in children with DS and HSCR may occur because of additional unrecognized problems with ENS structure.
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Affiliation(s)
- Ellen M. Schill
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Abramson Research Center, Philadelphia, Pennsylvania, USA
| | - Christina M. Wright
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Abramson Research Center, Philadelphia, Pennsylvania, USA
| | - Alisha Jamil
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Abramson Research Center, Philadelphia, Pennsylvania, USA
| | - Jonathan M. LaCombe
- Department of Biology, Indiana University–Purdue University Indianapolis, Indianapolis, Indiana, USA
| | - Randall J. Roper
- Department of Biology, Indiana University–Purdue University Indianapolis, Indianapolis, Indiana, USA
| | - Robert O. Heuckeroth
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Abramson Research Center, Philadelphia, Pennsylvania, USA
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Law BCF, Lo OSH. A rare case of rectal prolapse after Deloyers procedure in a patient with Hirschsprung's disease: A case report. Int J Surg Case Rep 2019; 56:63-65. [PMID: 30831509 PMCID: PMC6403099 DOI: 10.1016/j.ijscr.2019.02.021] [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: 11/22/2018] [Revised: 02/14/2019] [Accepted: 02/14/2019] [Indexed: 11/25/2022] Open
Abstract
Deloyers procedure reported as a colonic salvage procedure after extensive left colon resection. Deloyers procedure has been used in long segment Hirschsprung’s disease. First case of rectal prolapse after Deloyers procedure for Hirschsprung’s disease. Potential complication after Deloyers procedure for colorectal cancer in adult patients. Further study required to ascertain long term sequelae in this group of patients. Introduction Deloyers procedure has been reported in the literature as a viable alternative to the more commonly performed Swenson, Soave and Duhamel methods. As of yet, the long term sequelae of this procedure for patients with Hirschsprung’s disease have not been studied in depth. Presentation of case We report the first case in the literatures of a 27-year-old man presenting with rectal prolapse due to colorectal anastomotic intussusception after Deloyers procedure for Hirschsprung’s disease. Discussion Few studies with low case volume have been performed investigating the long term sequelae of Deloyers procedure as a mainstay in patients undergoing operative treatment for Hirschsprung’s disease. This procedure allows for preservation of a longer segment of colon, in turn potentially improving absorption and continence compared to other methods. Studies are limited and as of yet the viability of Deloyers as a mainstay of treatment for Hirschsprung’s disease is inconclusive. Conclusion We report the first adult case of prolapsed colorectal anastomotic intussusception after Deloyers procedure for Hirschsprung’s disease. Further study is required to delineate long-term complications and viability of this method in these patients.
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Affiliation(s)
- Brandon Cheuk-Fung Law
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Oswens Siu-Hung Lo
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
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Heuckeroth RO. Even When You Know Everything, There Is Still More to Learn About Hirschsprung Disease. Gastroenterology 2018; 155:1681-1684. [PMID: 30419210 DOI: 10.1053/j.gastro.2018.11.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Robert O Heuckeroth
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia - Research Institute, Philadelphia, Pennsylvania.
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17
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Hirschsprung disease - integrating basic science and clinical medicine to improve outcomes. Nat Rev Gastroenterol Hepatol 2018; 15:152-167. [PMID: 29300049 DOI: 10.1038/nrgastro.2017.149] [Citation(s) in RCA: 179] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hirschsprung disease is defined by the absence of enteric neurons at the end of the bowel. The enteric nervous system (ENS) is the intrinsic nervous system of the bowel and regulates most aspects of bowel function. When the ENS is missing, there are no neurally mediated propulsive motility patterns, and the bowel remains contracted, causing functional obstruction. Symptoms of Hirschsprung disease include constipation, vomiting, abdominal distension and growth failure. Untreated disease usually causes death in childhood because bloodstream bacterial infections occur in the context of bowel inflammation (enterocolitis) or bowel perforation. Current treatment is surgical resection of the bowel to remove or bypass regions where the ENS is missing, but many children have problems after surgery. Although the anatomy of Hirschsprung disease is simple, many clinical features remain enigmatic, and diagnosis and management remain challenging. For example, the age of presentation and the type of symptoms that occur vary dramatically among patients, even though every affected child has missing neurons in the distal bowel at birth. In this Review, basic science discoveries are linked to clinical manifestations of Hirschsprung disease, including partial penetrance, enterocolitis and genetics. Insights into disease mechanisms that might lead to new prevention, diagnostic and treatment strategies are described.
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Abstract
Hirschsprung disease (HD) is a common cause of neonatal intestinal obstruction in which a variable segment of the distal intestinal tract lacks the normal enteric nervous system elements. Affected individuals present with varying degrees of obstructive symptoms, but today most patients are diagnosed within the first several months of life owing to the well-recognized symptoms and the ease of making the diagnosis by way of the bedside suction rectal biopsy. Thus, for the adult general or colorectal surgeon, the vast majority of patients who present for evaluation will have already undergone surgical treatment within the first year of life by a pediatric surgeon. Despite several safe operative interventions to treat patients with HD, the long-term results are far from perfect. These patients may reach adult life with ongoing defecation disorders that require a systematic evaluation by a multidisciplinary group that should be led by a surgeon with a thorough knowledge of HD operations and the potential problems. The evaluation of these patients will form the basis for the majority of this review-however, some patients manage to escape diagnosis beyond the infant and childhood period-and a section herein will briefly address the case of an older patient who is suspected of having HD.
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Affiliation(s)
- Casey M. Calkins
- Division of Pediatric General and Thoracic Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
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19
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The anal canal is the fine line between "fecal incontinence and colitis" after a pull-through for Hirschsprung disease. J Pediatr Surg 2017; 52:2011-2017. [PMID: 28941931 DOI: 10.1016/j.jpedsurg.2017.08.040] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Accepted: 08/28/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND/PURPOSE Fecal incontinence after a pull-through is associated with different factors, although damage to the anal canal seems to be the most important. The objective of this article is to identify the variables related to the presence of fecal control and colitis in a homogeneous group of children after pull-through. METHODS A retrospective cross-sectional study was performed in patients with HD for evaluation of post-operative problems from May 2014 to November 2016. The patients (39) had a transanal approach and were divided into two groups: Group 1 patients with fecal continence and Group 2 patients with fecal incontinence. RESULTS Group 1 patients (13) had the anastomosis in the rectum, no damage to the anal canal, and a positive history of colitis. Group 2 (26) had the anastomosis at the skin, anoderm, pectinate line, or a combination of these and a negative history of colitis. CONCLUSIONS We demonstrated that patients with a technical error in the anastomosis have fecal incontinence, but not colitis. Preservation of the anal canal is associated with fecal control and colitis because it is a high-pressure zone. Education for proper identification of the anal canal during a pull-through is an absolute necessity. TYPE OF STUDY Retrospective Comparative Study. LEVEL OF EVIDENCE Level III.
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Heuckeroth RO. Hirschsprung's disease, Down syndrome, and missing heritability: too much collagen slows migration. J Clin Invest 2015; 125:4323-6. [PMID: 26571392 PMCID: PMC4665790 DOI: 10.1172/jci85003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hirschsprung's disease (HSCR) causes functional intestinal obstruction due to the absence of the enteric nervous system (ENS) in the distal bowel and is usually diagnosed shortly after birth or during childhood. While several genetic and nongenetic factors have been linked to HSCR, the underlying mechanisms that prevent ENS precursors from colonizing distal bowel during fetal development are not completely understood in many affected children. In this issue of the JCI, Soret and colleagues identify a new mechanism that causes HSCR-like disease in mice and involves deposition of excess collagen VI in the intestine by migrating ENS precursors as they colonize fetal bowel. Remarkably, their findings may explain some of the so-called missing heritability of HSCR and suggest a mechanism for increased HSCR incidence in children with Down syndrome (trisomy 21).
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Redo pullthrough for Hirschsprung disease: a single surgical group's experience. J Pediatr Surg 2014; 49:1394-9. [PMID: 25148745 DOI: 10.1016/j.jpedsurg.2014.04.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Revised: 03/24/2014] [Accepted: 04/18/2014] [Indexed: 11/23/2022]
Abstract
INTRODUCTION This study presents our surgical experience for redo-pullthrough (RedoPT) for Hirschsprung disease (HD). It reviews the patient's clinical outcomes and assesses stooling patterns after RedoPT. METHODS A retrospective review of our institution's RedoPTs as well as one author's overseas cases was performed. Stooling scores were tabulated using an established survey tool and compared to primary PT matched patients. RESULTS Between 1974 and 2012, 46 individuals (52% males) underwent RedoPT, representing 3 percent of all HD pullthroughs. Median age at primary PT and RedoPT was 1year (range 1week-18years) and 3.5years (range 8weeks-41years), respectively. Indications for RedoPT were predominately for aganglionosis/transition zone pathology (71%); followed by stricture or an obstructing Duhamel pouch (19%), tight cuff (8%) and a twisted PT (4%). None were performed for an isolated clinical diagnosis of repeated bouts of enterocolitis. RedoPT surgical approach depended upon the initial pullthrough technique and any previous complications. Stooling scores were significantly (P<0.05) worse in the RedoPT patients compared to the historically-matched group of children undergoing a primary PT for HD (5.5±1.2 vs. 12.2±1.4, primary PT versus RedoPT, respectively). When breaking down this total score into individual parameters, stooling pattern scores (1.0±0.2 vs. 4.1±0.4, P=0.001) and enterocolitis scores (2.0±0.4 vs. 4.2±0.4, P=0.001) were statistically worse in the RedoPT group. Patients in both groups had similar overall continence rates. CONCLUSION Appropriately selected children undergoing a RedoPT can achieve good results, with comparable continence rates to those undergoing a primary PT.
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Abstract
Surgery has changed dramatically over the last several decades. The emergence of MIS has allowed pediatric surgeons to manage critically ill neonates, children, and adolescents with improved outcomes in pain, postoperative course, cosmesis, and return to normal activity. Procedures that were once thought to be too difficult to attempt or even contraindicated in pediatric patients in many instances are now the standard of care. New and emerging techniques, such as single-incision laparoscopy, endoscopy-assisted surgery, robotic surgery, and techniques yet to be developed, all hold and reveal the potential for even further advancement in the management of these patients. The future of MIS in pediatrics is exciting; as long as our primary focus remains centered on developing techniques that limit morbidity and maximize positive outcomes for young patients and their families, the possibilities are both promising and infinite.
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Affiliation(s)
- Hope T Jackson
- Department of Surgery, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA
| | - Timothy D Kane
- Department of Surgery, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA; Surgical Residency Training Program, Division of Pediatric Surgery, Department of Surgery, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, 111 Michigan Avenue, Northwest, Washington, DC 20010-2970, USA.
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Burkardt DD, Graham JM, Short SS, Frykman PK. Advances in Hirschsprung disease genetics and treatment strategies: an update for the primary care pediatrician. Clin Pediatr (Phila) 2014; 53:71-81. [PMID: 24002048 DOI: 10.1177/0009922813500846] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hirschsprung disease (HSCR) is a multigenic condition with variable presentation. Most commonly, it presents in the neonatal period as a functional intestinal obstruction secondary to failure of caudal migration of the enteric nervous system. Classically, this manifests as dilated proximal bowel and constricted distal bowel with absent ganglia and hypertrophic nerve trunks. When recognized early, medical and surgical therapies can be instituted to minimize associated morbidity and mortality. This article reviews current understanding of the etiology of HSCR, its multigenic associations, the historical evolution of HSCR diagnosis and treatment, and current HSCR therapies.
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Levitt MA, Hamrick MC, Eradi B, Bischoff A, Hall J, Peña A. Transanal, full-thickness, Swenson-like approach for Hirschsprung disease. J Pediatr Surg 2013; 48:2289-95. [PMID: 24210201 DOI: 10.1016/j.jpedsurg.2013.03.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Revised: 03/01/2013] [Accepted: 03/01/2013] [Indexed: 12/14/2022]
Abstract
PURPOSE Swenson's procedure for Hirschsprung disease (HD) was thought to disturb fecal, urinary, and ejaculatory functions leading to other approaches including the Soave and Duhamel techniques. Given our Center's experience with a full-thickness rectal dissection for anorectal malformations, and using the new transanal concept, we chose to apply these ideas to the primary treatment of HD, and describe technical aspects and impact on fecal, urinary, and sexual function. METHODS We reviewed our series of HD patients who underwent a transanal, Swenson-like rectosigmoid dissection, assessing for postoperative stricture, anastomotic leak, enterocolitis, and long-term results for bowel, urinary, and sexual function. RESULTS Of 67 patients, 28 had a transanal resection, 5 had transanal plus laparoscopy, and 34 had transanal plus laparotomy, of those, 28 patients had a leveling colostomy prior to referral. The average length of resection was 27 cm ± 12.7 cm. Mean follow-up was 17.2 months (range 1-96 months). 44 patients were at least three years old at follow-up and were assessed for urinary and fecal continence; all (100%) had voluntary bowel movements and urinary continence. Enterocolitis occurred in 9 patients (14%) and constipation (requiring laxatives) occurred in 21 (32%). Of 24 male patients, 21 (88%) reported the occurrence of spontaneous erections post-operatively. CONCLUSION Our data support the fact that a modification of Swenson's original transabdominal dissection concept using the recently described transanal approach is an excellent technique for Hirschsprung, and produces excellent long-term outcomes for fecal and urinary continence, and seems to preserve erectile function.
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Affiliation(s)
- Marc A Levitt
- Colorectal Center for Children, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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Kannaiyan L, Madabhushi S, Malleboyina R, Are NK, Reddy KR, Rao B. Calretinin immunohistochemistry: A new cost-effective and easy method for diagnosis of Hirschsprung's disease. J Indian Assoc Pediatr Surg 2013; 18:66-8. [PMID: 23798809 PMCID: PMC3687149 DOI: 10.4103/0971-9261.109355] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
AIM To evaluate the efficacy of calretinin immunostaining in diagnosing Hirschsprung's disease (HD). MATERIALS AND METHODS Sixty cases were studied over a period of 1 year (July 2010-June 2011). There were 36 full-thickness biopsies and 24 resected specimens. Calretinin processing was done on the paraffin-embedded blocks after routine histopathological examination. RESULTS Of the 36 biopsy specimens, in 19 cases HD was diagnosed by hematoxylin and eosin (H and E) staining earlier. In 2 patients, ganglion cells were seen and HD was ruled out. In 15 cases, there was a diagnostic dilemma and calretinin was used. Ganglion cells were found in 3 specimens and nerve fibers in 5. In all 24 resected specimens, calretinin correlated with the findings on H and E staining. CONCLUSIONS Calretinin was extremely useful in solving the suspicious and indeterminate cases of HD. It can serve as a valuable cost-effective diagnostic aid in the centers where acetylcholinesterase enzyme histochemistry is not available.
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Affiliation(s)
- Lavanya Kannaiyan
- Department of Pediatric Surgery, Niloufer Hospital for Women and Children, Osmania Medical College, Hyderabad, India
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Abstract
The surgical correction of Hirschsprung disease has undergone a complete evolution in the past decade. Refinements in the performance of both transanal and laparoscopic procedures have tremendously facilitated the advancement of these surgeries. This chapter presents the history of these procedures, and then discusses the various approaches and details of these techniques.
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Affiliation(s)
- Jacob C Langer
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
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Raveenthiran V. Knowledge of ancient Hindu surgeons on Hirschsprung disease: evidence from Sushruta Samhita of circa 1200-600 BC. J Pediatr Surg 2011; 46:2204-8. [PMID: 22075360 DOI: 10.1016/j.jpedsurg.2011.07.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Revised: 07/07/2011] [Accepted: 07/08/2011] [Indexed: 12/15/2022]
Abstract
BACKGROUND Congenital megacolon is eponymously named after Harold Hirschsprung, who accurately described the clinical features in 1886. Recent research revealed that this condition is perhaps well known for centuries before him. AIM This article is intended to examine if ancient Hindu surgeons knew about congenital megacolon. METHODS AND MATERIALS Sushruta Samhita is an ancient tome of Ayurvedic surgery compiled by Sushruta (circa 1200-600 bc). Passages of interest were identified by browsing the authentic English translation of the compendium. Accuracy of translation was verified by comparing to the original Sanskrit verses with the help of a Sanskrit scholar. RESULTS A condition called Baddha Gudodaram, described in the Samhita, closely resembles Hirschsprung disease. There are indications that ancient Indians even deciphered the etiology as defective vayu alias vata (nerves). Although the ailment was considered incurable, a palliative operation has been discussed. Descriptive details of the operation match with that of sigmoid colostomy. CONCLUSION Evidence from Sushruta Samhita indicates that Hindu surgeons of prehistoric India probably had considerable knowledge about Hirschsprung disease. Further research, corroborating other sources of evidence, is required to confirm this claim.
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Affiliation(s)
- Venkatachalam Raveenthiran
- Sri Ramasamy Memorial (SRM) Medical College, SRM University, Kattankulathur, Chennai, Tamilnadu 603203, India.
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29
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Abstract
Hirschsprung disease (HD) is characterized by aganglionosis, which mainly occurs in the rectum and distal sigmoid colon. Typical HD is seldom diagnosed in adulthood, and segmental involvement is very rare. A 37-year-old man suffered from refractory constipation for 20 years. He could only defecate once a week and frequently needed an enema for defecation. A barium enema showed an annular stenotic segment of the rectosigmoid colon of 8 cm in length, which started 10 cm above anal circulation and showed dilated colon above the stenotic segment. The distal rectum was normal. The narrowed segment of the rectum was resected. At one-year follow up, the patient had normal defecation without laxatives.
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Affiliation(s)
- Ilhami Yüksel
- From the Department of Gastroenterology, Türkiye Yüksek Ihtisas Hospital, Ankara, Turkey.
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Choe EK, Moon SB, Kim HY, Lee SC, Park KW, Jung SE. Outcomes of surgical management of total colonic aganglionosis. World J Surg 2008; 32:62-8. [PMID: 17990024 DOI: 10.1007/s00268-007-9270-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
PURPOSE The purpose of this study was to assess the long-term clinical outcomes and bowel function of patients with total colonic aganglionosis (TCA) after surgery. METHODS The hospital records of 17 TCA patients treated surgically during 1985 to 2004 were reviewed. Long-term follow-up was done by telephone interviews with the parents. RESULTS Primary enterostomy was performed in 13 (76%) patients. In three (17%) patients, TCA was not suspected initially. They underwent conservative surgery primarily, which required a second operation soon after. One had transverse colectomy with ileostomy. By pathologic review, nine (53%) patients had small bowel involvement of aganglionosis. Six (35%) patients died before corrective surgery. They all had extensive small bowel involvement. Among 11 patients who had a corrective operation, 10 were treated with Martin's procedure. Long-term (mean 74 months) follow-up was available in seven patients, and the mean weight-for-age percentiles was 27.1% (range 5-50%), the frequency of defecation was three to five times a day in four patients (57%), one or two times a day in two patients (28%), and more than five times a day in one patient (15%). CONCLUSIONS TCA is difficult to diagnose; but once it is diagnosed correctly and treated by corrective surgery, outcomes seem promising. Martin's operation brought about a good outcome and enabled patients to have acceptable bowel habits. The prognosis is highly dependent on the extent of aganglionosis.
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Affiliation(s)
- E K Choe
- Department of Surgery, College of Medicine, Seoul National University, 28 Yongon-Dong, 110-744, Seoul, Korea.
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Evaluation and management of persistent problems after surgery for Hirschsprung disease in a child. J Pediatr Gastroenterol Nutr 2008; 46:13-9. [PMID: 18162828 DOI: 10.1097/01.mpg.0000304448.69305.28] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hirschsprung disease occurs approximately once in every 5000 live-born infants. It is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Once the diagnosis of Hirschsprung disease has been made, most patients are now treated with a transanal approach to resection. We review the early and late postoperative complications. Late complications include persistent mechanical obstruction, recurrent or acquired aganglionosis, disordered motility in the proximal colon or small bowel, internal sphincter achalasia, or functional megacolon caused by stool-holding behavior. These children require complex interdisciplinary care to ensure an adequate quality of life.
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Shimotake T, Tanaka SI, Fukui R, Makino S, Maruyama R. Neuroglial disorders of central and peripheral nervous systems in a patient with Hirschsprung's disease carrying allelic SOX10 truncating mutation. J Pediatr Surg 2007; 42:725-31. [PMID: 17448776 DOI: 10.1016/j.jpedsurg.2006.12.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND/PURPOSE Recent biologic studies have revealed that enteric neuroglial deficiency causes gut functional deterioration. We studied the central and peripheral nervous systems in a SOX10 mutation-associated Hirschsprung's patient who presented persistent gut functional disorders even after definitive surgery. METHODS DNA sequences of all coding regions of the SOX10 gene (22q13) were determined using the direct DyeDeoxy Terminator Cycle method, and brain magnetic resonance images, nerve conduction velocities, and histopathology of the enteric nervous system were investigated for neurologic assessment. RESULTS DNA analysis revealed a heterozygous nucleotide deletion (778delG) in SOX10 exon 5, causing a frameshift at codon 260 and resulting in premature transcriptional termination at codon 285. Neurologic studies disclosed brain hypomyelination, peripheral dysmyelinating neuropathy, and enteric neuroglia deficiency, which exclusively implied systemic glial maldevelopment. CONCLUSION These results suggest that the enteric nervous system in patients with SOX10-associated Hirschsprung's disease is entirely subject to neuroglial impairment. This may explain persistent gut motility and absorption insufficiency after pull-through surgery, especially in children with allelic SOX10 truncating mutations.
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Affiliation(s)
- Takashi Shimotake
- Department of Pediatric Surgery, Kyoto Uji-Tokushukai General Hospital, Kyoto 611-0042, Japan.
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Skaba R. Historic milestones of Hirschsprung's disease (commemorating the 90th anniversary of Professor Harald Hirschsprung's death). J Pediatr Surg 2007; 42:249-51. [PMID: 17208575 DOI: 10.1016/j.jpedsurg.2006.09.024] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Richard Skaba
- Department of Pediatric Surgery, Second Medical School of Charles University and Motol University Hospital, Prague, V Uvalu 84, 150 06 Prague, Czech Republic.
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Masiakos PT, Ein SH. The History of Hirschsprung’s Disease: Then and Now. SEMINARS IN COLON AND RECTAL SURGERY 2006. [DOI: 10.1053/j.scrs.2006.02.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Abstract
Hirschsprung (HSCR) disease is a relatively common neonatal developmental disorder of the enteric nervous system and is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the distal intestine. This results in absent peristalsis in the affected bowel, and the development of a functional intestinal obstruction. The pathogenesis and genetic basis of the disease is yet unclear. The surgical treatment of HSCR has evolved significantly since 1949 when Swenson first proposed a trans-abdominal pull-through procedure. The transanal pull-through consists of a rectal mucosectomy, resection of the aganglionic bowel and a colo-anal anastomosis. Recent literature and clinically controversies of this minimally invasive one-stage procedure are reviewed. Although follow up is still relatively short the preliminary results appear very favorable and cost effective.
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Affiliation(s)
- Roshni Dasgupta
- Hosptial for Sick Children, University of Toronto, Ontario, Canada
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Swenson O. Hirschsprung's disease--a complicated therapeutic problem: some thoughts and solutions based on data and personal experience over 56 years. J Pediatr Surg 2004; 39:1449-53; discussion 1454-7. [PMID: 15486884 DOI: 10.1016/j.jpedsurg.2004.06.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Smith DS, Williams CS, Ferris CD. Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction. Gastroenterol Clin North Am 2003; 32:619-58. [PMID: 12858609 DOI: 10.1016/s0889-8553(03)00028-1] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Chronic gastroparesis and CIP are debilitating disorders that are difficult to treat with currently available therapies. Failure of proper migration and differentiation of enteric neurons or ICC can result from specific genetic mutations and lead to phenotypes of CIP with or without concomitant gastroparesis. Intestinal dysfunction in diabetes may reflect a depletion of NO production (and perhaps other neurotransmitters or modulators), which is manifest as a syndrome of gastroparesis, diarrhea, or constipation in individual patients. As the key molecular changes underlying these disorders are defined, clinicians will begin to understand their precise etiology and rational medical therapy may become possible. In the future, testable hypotheses regarding the etiology of other functional bowel disorders (e.g., functional dyspepsia, irritable bowel syndrome, and so forth) may be developed.
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Affiliation(s)
- D Scott Smith
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville Veterans Affairs Medical Center, Nashville, TN 37232, USA
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41
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Shimotake T, Tomiyama H, Aoi S, Iwai N. Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/SOX10 gene mutation. J Pediatr Surg 2003; 38:698-701. [PMID: 12720173 DOI: 10.1016/jpsu.2003.50186] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND/PURPOSE Recent studies have found that Hirschsrung's disease is caused by diverse genomic abnormalities. To clarify whether these pathogenic variations influence the distribution and function of enteric ganglia, the authors studied the morphology of the macroscopic and microscopic transitional zone in Hirschsprung's disease with reference to the type of genetic mutation. METHODS In 120 patients with Hirschsprung's disease, the location and morphology of the gut caliber change were recorded, and the enteric nervous system was investigated histologically using biopsy specimens. The DNA sequences of all the RET/GDNF/NTN and SOX10 coding regions were determined using the direct DyeDeoxy Terminator Cycle method. RESULTS In RET mutation carriers, the gut caliber change was almost identical to the histologic transition in cases of short segment aganglionosis, whereas these were markedly dissociated in cases exhibiting extensive aganglionosis. In contrast, SOX10 mutation carriers had a very long histologic transition and exhibited no caliber change. CONCLUSIONS The type of genetic mutation responsible for Hirschsprung's disease influences the postnatal distribution and function of enteric ganglia. The data on discrepancy between macroscopic and microscopic transitions may enable us to concentrate the sites of the leveling biopsy more accurately especially in cases of long type intestinal aganglionosis carrying RET gene mutation.
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Affiliation(s)
- Takashi Shimotake
- Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Donnellan WL. Treatment of Hirschsprung's disease. J Pediatr Surg 1998; 33:951-2. [PMID: 9660240 DOI: 10.1016/s0022-3468(98)90687-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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46
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Weinberg G, Boley SJ. Endorectal pull-through with primary anastomosis for Hirschsprung's disease. Semin Pediatr Surg 1998; 7:96-102. [PMID: 9597700 DOI: 10.1016/s1055-8586(98)70020-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- G Weinberg
- Division of Pediatric Surgery, Albert Einstein College of Medicine-Montefiore Medical Center, Bronx, NY, USA
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Madonna MB, Luck SR, Reynolds M, Schwarz DK, Arensman RM. Swenson procedure for the treatment of Hirschsprung's disease. Semin Pediatr Surg 1998; 7:85-8. [PMID: 9597698 DOI: 10.1016/s1055-8586(98)70018-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- M B Madonna
- Section of Pediatric Surgery, Children's Memorial Hospital, Northwestern University, Chicago, IL 60614, USA
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Pierro A, Fasoli L, Kiely EM, Drake D, Spitz L. Staged pull-through for rectosigmoid Hirschsprung's disease is not safer than primary pull-through. J Pediatr Surg 1997; 32:505-9. [PMID: 9094029 DOI: 10.1016/s0022-3468(97)90617-5] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Conventional treatment of Hirschsprung's disease consists of initial colostomy followed by pull-through (staged PT). During the past decade immediate definitive operation (primary PT) has been reported by several investigators with a complication rate ranging from 0% to 20%. In the authors' institution primary PT has been performed since 1992 in patients with rectosigmoid aganglionosis responsive to rectal irrigations. The authors reviewed the records of all patients (n = 124) with Hirschsprung's disease diagnosed and treated between 1989 and 1995. One hundred sixteen patients underwent a definitive operation. This study analysed the complications observed in 87 of these patients with aganglionosis limited to the rectosigmoid colon. Patients were divided into groups according to the type of surgical treatment (staged versus primary), the year of operation (1989 through 1992 versus 1992 through 1995), and the age at primary PT (15 infants age < or = 4 months versus 10 children age > 4 months). There were no deaths. There was no significant difference in complication rates between staged PT and primary PT. Similar complication rates were encountered in infants and children who underwent primary PT. The rate of postoperative complications did not change according to the year of the operation. Major complications were observed in all 3 patients who had a primary Swenson PT compared with 20% who had a primary Duhamel PT. Staged Swenson and Duhamel PT had similar complication rates. The authors conclude that (1) staged PT for rectosigmoid Hirschsprung's disease is not any safer than primary PT; (2) primary PT can be performed safely in young infants; and (3) primary Swenson PT is less satisfactory than primary Duhamel PT.
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Affiliation(s)
- A Pierro
- Institute of Child Health, London, England
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Abstract
BACKGROUND Hirschsprung's disease is a congenital disorder which is rare in adulthood. In typical cases the aganglionosis involves mainly the rectum or rectosigmoid colon and the lesion starts from the anal valve. Zonal segmental aganglionosis is a very rare type even in children. PATIENT A 54 year old women with zonal segmental aganglionosis had an aganglionic segment 18 cm in length located in the rectosigmoid colon with an 8 cm long normal appearing rectum and dilated proximal colon. Resection of the stenotic segment with end to end anastomosis was performed. CONCLUSION The functional result was excellent five years after the operation.
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Affiliation(s)
- C G Fu
- First Department of Surgery, University of Tokyo, Japan
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50
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Swenson O. Early history of the therapy of Hirschsprung's disease: facts and personal observations over 50 years. J Pediatr Surg 1996; 31:1003-8. [PMID: 8863221 DOI: 10.1016/s0022-3468(96)90074-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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