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Nature Reviews. Disease Primers Oct 2023Hirschsprung 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... (Review)
Review
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.
Topics: Infant, Newborn; Humans; Hirschsprung Disease; Down Syndrome; Waardenburg Syndrome; Anal Canal; Intellectual Disability
PubMed: 37828049
DOI: 10.1038/s41572-023-00465-y -
Medicina (Kaunas, Lithuania) Nov 2020Hirschsprung's disease is a neurocristopathy, caused by defective migration, proliferation, differentiation and survival of neural crest cells, leading to gut... (Review)
Review
Hirschsprung's disease is a neurocristopathy, caused by defective migration, proliferation, differentiation and survival of neural crest cells, leading to gut aganglionosis. It usually manifests rapidly after birth, affecting 1 in 5000 live births around the globe. In recent decades, there has been a significant improvement in the understanding of its genetics and the association with other congenital anomalies, which share the pathomechanism of improper development of the neural crest. Apart from that, several cell populations which do not originate from the neural crest, but contribute to the development of Hirschsprung's disease, have also been described, namely mast cells and interstitial cells of Cajal. From the diagnostic perspective, researchers also focused on "Variants of Hirschsprung's disease", which can mimic the clinical signs of the disease, but are in fact different entities, with distinct prognosis and treatment approaches. The treatment of Hirschsprung's disease is usually surgical resection of the aganglionic part of the intestine, however, as many as 30-50% of patients experience persisting symptoms. Considering this fact, this review article also outlines future hopes and perspectives in Hirschsprung's disease management, which has the potential to benefit from the advancements in the fields of cell-based therapy and tissue engineering.
Topics: Hirschsprung Disease; Humans
PubMed: 33202966
DOI: 10.3390/medicina56110611 -
Current Opinion in Gastroenterology Jan 2021To provide the definition, causes, and current recommendations for workup and treatment of acute infectious colitis in adults, a common medical problem of diverse cause. (Review)
Review
PURPOSE OF REVIEW
To provide the definition, causes, and current recommendations for workup and treatment of acute infectious colitis in adults, a common medical problem of diverse cause.
RECENT FINDINGS
The management of acute colitis in adults depend upon establishment of cause. Most forms of infectious colitis are treatable with antimicrobials. Multiplex polymerase chain reaction (PCR) followed by guided culture on PCR-positive pathogens can often confirm active infection while standard culture methods provide isolates for antibiotic susceptibility testing, subtyping, and Whole Genome Sequencing.
SUMMARY
Patients with colitis may be suffering from a range of etiologies including infectious colitis, neutropenic colitis, drug-induced colitis, and inflammatory bowel disease. The present review was prepared to provide an approach to prompt diagnosis and management of acute colitis to prevent severe complications (e.g. dehydration and malnutrition, or toxic megacolon) and provide recommendations for antimicrobial therapy.
Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Colitis; Humans; Inflammatory Bowel Diseases; Megacolon, Toxic
PubMed: 33105253
DOI: 10.1097/MOG.0000000000000693 -
Orphanet Journal of Rare Diseases Jun 2020Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to... (Review)
Review
BACKGROUND
Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management.
AIMS
This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders.
METHODS
Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted.
RESULTS
Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion.
CONCLUSION
In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.
Topics: Adult; Consensus; Europe; Hirschsprung Disease; Humans; Prevalence
PubMed: 32586397
DOI: 10.1186/s13023-020-01362-3 -
Seminars in Pediatric Surgery Apr 2022The enteric nervous system (ENS) is a rich network of neurons and glial cells that comprise the gastrointestinal tract's intrinsic nervous system and are responsible for... (Review)
Review
The enteric nervous system (ENS) is a rich network of neurons and glial cells that comprise the gastrointestinal tract's intrinsic nervous system and are responsible for controlling numerous complex functions, including digestion, transit, secretion, barrier function, and maintenance of a healthy microbiome. Development of a functional ENS relies on the coordinated interaction between enteric neural crest-derived cells and their environment as the neural crest-derived cells migrate rostrocaudally along the embryonic gut mesenchyme. Congenital or acquired disruption of ENS development leads to various neurointestinal diseases. Hirschsprung disease is a congenital neurocristopathy, a disease of the neural crest. It is characterized by a variable length of distal colonic aganglionosis due to a failure in enteric neural crest-derived cell proliferation, migration, differentiation, and/or survival. In this review, we will review the science of Hirschsprung disease, targeting an audience of pediatric surgeons. We will discuss the basic biology of normal ENS development, as well as what goes awry in ENS development in Hirschsprung disease. We will review animal models that have been integral to studying this disease, as well as current hot topics and future research, including genetic risk profiling, stem cell therapy, non-invasive diagnostic techniques, single-cell sequencing techniques, and genotype-phenotype correlation.
Topics: Animals; Enteric Nervous System; Hirschsprung Disease; Humans; Neural Crest; Stem Cell Transplantation
PubMed: 35690468
DOI: 10.1016/j.sempedsurg.2022.151157 -
Archives of Pathology & Laboratory... May 2022Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has...
CONTEXT.—
Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has been established by histopathologic analysis of rectal biopsies. However, the criteria for the diagnosis have been questioned and modified, hindering diagnostic practice.
OBJECTIVE.—
To analyze the applicability of PTEN immunohistochemistry in the diagnosis of IND B and to compare with control cases and cases of Hirschsprung disease (HD).
DESIGN.—
PTEN immunohistochemical expression was analyzed in colorectal samples from 29 cases of IND B and compared with 4 control cases and 6 cases of HD. The pattern of PTEN immunoexpression was analyzed in glial cells of the submucosal and myenteric nerve plexuses and in neural fibrils of the muscularis propria using a scoring system.
RESULTS.—
Marked reduction or absence of PTEN expression was observed in glial cells of the submucosal nerve plexuses in all cases of the IND B group and in the myenteric nerve plexuses in 28 of 29 cases (96.5%). Lack of PTEN expression was detected in neural fibrils within the muscularis propria in 21 of 29 cases (72%) of the IND B group. PTEN expression was positive in the same neural structures of the control and HD groups.
CONCLUSIONS.—
PTEN immunohistochemistry may be a valuable tool in the diagnostic evaluation of IND B. Lack of or reduction of PTEN expression in neural fibrils within the muscularis propria suggests that involvement of the neuromuscular junction may be a key event in the pathogenesis of the motility disturbance occurring in IND B.
Topics: Humans; Immunohistochemistry; Enteric Nervous System; Myenteric Plexus; Hirschsprung Disease; Constipation; PTEN Phosphohydrolase
PubMed: 35943858
DOI: 10.5858/arpa.2021-0424-OA -
The EMBO Journal Jan 2023Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which...
Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest-derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype in vitro and in vivo. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short-chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of Bacteroides and Clostridium, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome-wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA-mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short-chain fatty acid metabolism-induced MEK1/2 signaling.
Topics: Rats; Animals; Fecal Microbiota Transplantation; Hirschsprung Disease; Signal Transduction; Fatty Acids, Volatile; Cell- and Tissue-Based Therapy
PubMed: 36382711
DOI: 10.15252/embj.2022111139 -
ANZ Journal of Surgery Oct 2017
Topics: Hirschsprung Disease; Humans; Mutation
PubMed: 28975740
DOI: 10.1111/ans.14149 -
Histochemistry and Cell Biology Apr 2021
Topics: Animals; Collagen Type I; Fatty Acid-Binding Proteins; Humans; Megacolon; Neurons; Spinal Cord; Trypanosoma cruzi
PubMed: 33846859
DOI: 10.1007/s00418-021-01986-x -
Seminars in Pediatric Surgery Apr 2022Hirschsprung disease (HD) is a complex surgical and medical problem that appears to have varied health and social outcomes with the age and neurodevelopmental state of...
Hirschsprung disease (HD) is a complex surgical and medical problem that appears to have varied health and social outcomes with the age and neurodevelopmental state of patients. In general, long-term outcomes are thought to be good for the majority of patients despite recognized problems with constipation and/or fecal incontinence. However, there are no universally accepted pathways regarding post-operative bowel management programs nor clearly defined follow-up pathways making the current outcome measures difficult to interpret. Further, other factors that may influence outcome including age at the time of procedure and procedure type continue to lack consensus. Improved support of children in resource limited environments and during periods of transition into the adult medical care environment are needed to improve outcome. Recent proliferation of multidisciplinary care teams and consortia may help to better understand outcomes and address current knowledge gaps. Continuing these collaborations will be imperative to continuing improvements in care which may ultimately impact outcome.
Topics: Adult; Child; Constipation; Fecal Incontinence; Hirschsprung Disease; Humans; Postoperative Complications; Treatment Outcome
PubMed: 35690462
DOI: 10.1016/j.sempedsurg.2022.151160