Authors: Susan Nham, Alexander T M Nguyen, Andrew J A Holland...

Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a complex and resource-limited solution associated with its own morbidity and mortality. We conducted a scoping review to present a contemporary summary of the epidemiology, aetiology, pathophysiology, diagnosis, management and complications of PIPO.Conclusion: PIPO represents a rare disorder that is difficult to diagnose and challenging to treat, with significant morbitity and mortality. The only known cure is intestinal transplantation. What is Known: • Paediatric intestinal pseudo-obstruction is a rare, heterogeneous disorder that confers a high rate of morbidity and mortality • Complications of paediatric intestinal pseudo-obstruction include chronic pain, small intestine bacterial overgrowth and malrotation. Other complications can occur related to its management, such as line infections with parenteral nutrition or cardiac side effects of prokinetic medications What is New: • Progress in medical and surgical therapy in recent years has led to improved patient outcomes • Enteral autonomy has been reported in most patients at as early as 1 month post-transplantation.

Topics: Child; Chronic Disease; Humans; Intestinal Pseudo-Obstruction; Intestine, Small; Intestines; Parenteral Nutrition

PubMed: 35482095
DOI: 10.1007/s00431-021-04365-9

Review

Authors: Sohaib Khalid Hashmi, Rachel Helen Ceron, Robert O Heuckeroth...

Visceral smooth muscle is a crucial component of the walls of hollow organs like the gut, bladder, and uterus. This specialized smooth muscle has unique properties that distinguish it from other muscle types and facilitate robust dilation and contraction. Visceral myopathies are diseases where severe visceral smooth muscle dysfunction prevents efficient movement of air and nutrients through the bowel, impairs bladder emptying, and affects normal uterine contraction and relaxation, particularly during pregnancy. Disease severity exists along a spectrum. The most debilitating defects cause highly dysfunctional bowel, reduced intrauterine colon growth (microcolon), and bladder-emptying defects requiring catheterization, a condition called megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). People with MMIHS often die early in childhood. When the bowel is the main organ affected and microcolon is absent, the condition is known as myopathic chronic intestinal pseudo-obstruction (CIPO). Visceral myopathies like MMIHS and myopathic CIPO are most commonly caused by mutations in contractile apparatus cytoskeletal proteins. Here, we review visceral myopathy-causing mutations and normal functions of these disease-associated proteins. We propose molecular, cellular, and tissue-level models that may explain clinical and histopathological features of visceral myopathy and hope these observations prompt new mechanistic studies.

Topics: Cytoskeleton; Humans; Intestinal Pseudo-Obstruction; Muscle, Smooth; Mutation

PubMed: 33729000
DOI: 10.1152/ajpgi.00066.2021

Review

Authors: Jessica Piché, Patrick Piet Van Vliet, Michel Pucéat...

Preservation and development of life depend on the adequate segregation of sister chromatids during mitosis and meiosis. This process is ensured by the cohesin multi-subunit complex. Mutations in this complex have been associated with an increasing number of diseases, termed cohesinopathies. The best characterized cohesinopathy is Cornelia de Lange syndrome (CdLS), in which intellectual and growth retardations are the main phenotypic manifestations. Despite some overlap, the clinical manifestations of cohesinopathies vary considerably. Novel roles of the cohesin complex have emerged during the past decades, suggesting that important cell cycle regulators exert important biological effects through non-cohesion-related functions and broadening the potential pathomechanisms involved in cohesinopathies. This review focuses on non-cohesion-related functions of the cohesin complex, gene dosage effect, epigenetic regulation and TGF-β in cohesinopathy context, especially in comparison to hronic trial and ntestinal ysrhythmia (CAID) syndrome, a very distinct cohesinopathy caused by a homozygous Shugoshin-1 (SGO1) mutation (K23E) and characterized by pacemaker failure in both heart (sick sinus syndrome followed by atrial flutter) and gut (chronic intestinal pseudo-obstruction) with no intellectual or growth delay. We discuss the possible impact of SGO1 alterations in human pathologies and the potential impact of the SGO1 K23E mutation in the sinus node and gut development and functions. We suggest that the human phenotypes observed in CdLS, CAID syndrome and other cohesinopathies can inform future studies into the less well-known non-cohesion-related functions of cohesin complex genes. : AD: Alzheimer Disease; AFF4: AF4/FMR2 Family Member 4; ANKRD11: Ankyrin Repeat Domain 11; APC: Anaphase Promoter Complex; ASD: Atrial Septal Defect; ATRX: ATRX Chromatin Remodeler; ATRX: Alpha Thalassemia X-linked intellectual disability syndrome; BIRC5: Baculoviral IAP Repeat Containing 5; BMP: Bone Morphogenetic Protein; BRD4: Bromodomain Containing 4; BUB1: BUB1 Mitotic Checkpoint Serine/Threonine Kinase; CAID: Chronic Atrial and Intestinal Dysrhythmia; CDK1: Cyclin Dependent Kinase 1; CdLS: Cornelia de Lange Syndrome; CHD: Congenital Heart Disease; CHOPS: Cognitive impairment, coarse facies, Heart defects, Obesity, Pulmonary involvement, Short stature, and skeletal dysplasia; CIPO: Chronic Intestinal Pseudo-Obstruction; c-kit: KIT Proto-Oncogene Receptor Tyrosine Kinase; CoATs: Cohesin Acetyltransferases; CTCF: CCCTC-Binding Factor; DDX11: DEAD/H-Box Helicase 11; ERG: Transcriptional Regulator ERG; ESCO2: Establishment of Sister Chromatid Cohesion N-Acetyltransferase 2; GJC1: Gap Junction Protein Gamma 1; H2A: Histone H2A; H3K4: Histone H3 Lysine 4; H3K9: Histone H3 Lysine 9; HCN4: Hyperpolarization Activated Cyclic Nucleotide Gated Potassium and Sodium Channel 4;p HDAC8: Histone deacetylases 8; HP1: Heterochromatin Protein 1; ICC: Interstitial Cells of Cajal; ICC-MP: Myenteric Plexus Interstitial cells of Cajal; ICC-DMP: Deep Muscular Plexus Interstitial cells of Cajal; I: Pacemaker Funny Current; IP3: Inositol trisphosphate; JNK: C-Jun N-Terminal Kinase; LDS: Loeys-Dietz Syndrome; LOAD: Late-Onset Alzheimer Disease; MAPK: Mitogen-Activated Protein Kinase; MAU: MAU Sister Chromatid Cohesion Factor; MFS: Marfan Syndrome; NIPBL: NIPBL, Cohesin Loading Factor; OCT4: Octamer-Binding Protein 4; P38: P38 MAP Kinase; PDA: Patent Ductus Arteriosus; PDS5: PDS5 Cohesin Associated Factor; P-H3: Phospho Histone H3; PLK1: Polo Like Kinase 1; POPDC1: Popeye Domain Containing 1; POPDC2: Popeye Domain Containing 2; PP2A: Protein Phosphatase 2; RAD21: RAD21 Cohesin Complex Component; RBS: Roberts Syndrome; REC8: REC8 Meiotic Recombination Protein; RNAP2: RNA polymerase II; SAN: Sinoatrial node; SCN5A: Sodium Voltage-Gated Channel Alpha Subunit 5; SEC: Super Elongation Complex; SGO1: Shogoshin-1; SMAD: SMAD Family Member; SMC1A: Structural Maintenance of Chromosomes 1A; SMC3: Structural Maintenance of Chromosomes 3; SNV: Single Nucleotide Variant; SOX2: SRY-Box 2; SOX17: SRY-Box 17; SSS: Sick Sinus Syndrome; STAG2: Cohesin Subunit SA-2; TADs: Topology Associated Domains; TBX: T-box transcription factors; TGF-β: Transforming Growth Factor β; TGFBR: Transforming Growth Factor β receptor; TOF: Tetralogy of Fallot; TREK1: TREK-1 K(+) Channel Subunit; VSD: Ventricular Septal Defect; WABS: Warsaw Breakage Syndrome; WAPL: WAPL Cohesin Release Factor.

Topics: Animals; Atrial Flutter; Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; Chromosome Segregation; De Lange Syndrome; Humans; Intestinal Pseudo-Obstruction; Mice; Mice, Inbred C57BL; Proto-Oncogene Mas; Sick Sinus Syndrome; Cohesins

PubMed: 31516082
DOI: 10.1080/15384101.2019.1658476

Review

Authors: M Mutalib, J Kammermeier, R Vora...

BACKGROUND

Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity burden and have no standard management strategy. Prucalopride a highly selective serotonin receptor agonist is an effective laxative with reported extra colon action. We aim to report our experience in children with acute and chronic intestinal pseudo obstruction who responded to prucalopride and systemically review the use of prucalopride in intestinal pseudo obstruction.

METHODS

A report of clinical experience and systemic review of the relevant medical databases to identify the outcome of usage of prucalopride in patients with acute and chronic intestinal pseudo obstruction. Studies meeting the selection criteria were reviewed including abstract only and case reports.

RESULTS

All reported cases showed clinical response to prucalopride. There were three full text, two abstracts only and three case reports all reporting clinical improvement with prucalopride.

CONCLUSION

Prucalopride appears to show promising results in children and adults with acute and chronic intestinal pseudo obstruction.

Topics: Adult; Benzofurans; Child; Colon; Humans; Intestinal Pseudo-Obstruction; Laxatives

PubMed: 34599567
DOI: 10.51821/84.3.002

Review

Authors: M A Kamm

Topics: Colon; Colonic Diseases; Humans; Intestinal Pseudo-Obstruction

PubMed: 11076928
DOI: 10.1136/gut.47.suppl_4.iv84

Review

Authors: Alexandra Antonucci, Lucia Fronzoni, Laura Cogliandro...

Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.

Topics: Chronic Disease; Digestive System Surgical Procedures; Disease Progression; Enteric Nervous System; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Intestines; Muscle, Smooth; Nutritional Support; Treatment Outcome

PubMed: 18494042
DOI: 10.3748/wjg.14.2953

Review

Authors: R Durai

Colonic pseudo-obstruction is often confused with mechanical intestinal obstruction. It occurs when there is an autonomic imbalance resulting in sympathetic over-activity affecting some part of the colon. The patient is often elderly with numerous comorbidities. Once mechanical obstruction is excluded by contrast enema, the patient should be treated conservatively with nasogastric and flatus tubes for at least 48 hours, and precipitating factors should be treated. When pseudo-obstruction does not settle with waitful watching, prokinetic agents and/or colonoscopic decompression can be tried. When there is a risk of impending perforation of the caecum from massive colonic dilatation and colonic ischaemia, it should be dealt with by caecostomy or hemicolectomy. In spite of available medical and surgical interventions, the outcome remains poor.

Topics: Cecostomy; Cholinesterase Inhibitors; Colonic Pseudo-Obstruction; Digestive System Surgical Procedures; Humans; Neostigmine; Prognosis; Risk Factors

PubMed: 19352564
DOI: No ID Found

Review

Authors: V Stanghellini, R Corinaldesi, L Barbara...

Chronic intestinal pseudo-obstruction (CIP) is a clinical syndrome characterized by symptoms and signs of intestinal occlusion, in absence of any mechanical obstruction of the gut lumen. It causes impaired transit of intestinal contents and is determined by abnormalities of motor activity. The term CIP is used to indicate a heterogeneous group of disorders with many different pathogenic mechanisms. The defect in the regulation of intestinal transit can be at any level of motility control. Two main types of CIP are recognized, termed respectively myogenic (when smooth muscle cells are affected) and neurogenic (caused by abnormalities of extrinsic and/or intrinsic nervous supplies). Both types may be secondary to a variety of recognizable diseases or idiopathic. In myogenic CIP, intestinal transit is impaired because of lack of propulsive strength; in the neurogenic form, contractions are powerful but not sufficiently co-ordinated to propel intestinal contents aborally in an organized fashion. CIP belongs to the large and loosely defined group of digestive functional disorders. These disorders probably share common pathogenic mechanisms but with different expressiveness. The reasons why only some patients present recurrent symptomatological bouts resembling mechanical occlusion has not been clarified. This aspect is of great clinical relevance and deserves attention, as CIP patients, unlike other patients with severe functional disorders, may undergo repeated, useless and potentially dangerous operations. The diagnosis of CIP may be suggested by clinical features and is based on radiological, endoscopic, manometric, and histological findings. Recent technological improvements facilitate the recognition of this intriguing syndrome. In particular, manometric recording of the small bowel motility, which has long been considered an important research technique, can now also be regarded as a useful diagnostic tool.

Topics: Chronic Disease; Eating; Fasting; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Intestinal Pseudo-Obstruction; Manometry; Pressure; Syndrome

PubMed: 3289641
DOI: 10.1016/0950-3528(88)90029-2

Review

Authors: Francesca Bianco, Giulia Lattanzio, Luca Lorenzini...

Severe gut motility disorders are characterized by the ineffective propulsion of intestinal contents. As a result, the patients develop disabling/distressful symptoms, such as nausea and vomiting along with altered bowel habits up to radiologically demonstrable intestinal sub-obstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility. This syndrome occurs due to changes altering the morpho-functional integrity of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), the interstitial cells of Cajal (ICC) (mesenchymopathy), and smooth muscle cells (myopathy). In the last years, several genes have been identified in different subsets of CIPO patients. The focus of this review is to cover the most recent update on enteric dysmotility related to CIPO, highlighting (a) forms with predominant underlying neuropathy, (b) forms with predominant myopathy, and (c) mitochondrial disorders with a clear gut dysfunction as part of their clinical phenotype. We will provide a thorough description of the genes that have been proven through recent evidence to cause neuro-(ICC)-myopathies leading to abnormal gut contractility patterns in CIPO. The discovery of susceptibility genes for this severe condition may pave the way for developing target therapies for enteric neuro-(ICC)-myopathies underlying CIPO and other forms of gut dysmotility.

Topics: Humans; Intestinal Pseudo-Obstruction; Chronic Disease; Intestine, Small; Gastrointestinal Diseases; Neuromuscular Diseases

PubMed: 36551277
DOI: 10.3390/biom12121849

Authors: Yeliz Çağan Appak, Maşallah Baran, Mustafa Onur Öztan...

BACKGROUND/AIMS

Pediatric intestinal pseudo-obstruction (PIPO) is a severe disorder of gut motility. In this rare and difficult-to-manage disease, complex treatment method, such as intestinal transplantation, is sometimes needed. This study evaluated the management and follow-up results of patients with PIPO who received treatment at our center.

MATERIALS AND METHODS

The cases of 13 patients with PIPO were reviewed retrospectively. Demographic data, clinical features, etiologies, pharmacological and surgical treatments, nutritional support, anthropometric findings, small bowel transplantation (SBT), and survival rates were assessed.

RESULTS

Two of the patients were diagnosed at 1 and 5 years of age, while other patients were diagnosed during neonatal period. The etiological cause could not be identified for 5 patients. Pharmacological treatment response was observed in 38.4% of patients. Post-pyloric feeding was applied in 4 patients, but no response was observed. Gastrostomy decreased the clinical symptoms in 3 patients during the abdominal distension period. Total oral nutrition was achieved in 38.4% of the total-parenteral-nutrition (TPN)-dependent patients. It was observed that anthropometric findings improved in patients with total oral nutrition. Liver cirrhosis developed in 1 patient. Venous thrombosis developed in 4 patients. The SBT was performed on 3 patients. One of these patients has been followed up for the last 4 years.

CONCLUSION

Pediatric intestinal pseudo-obstruction is a rare disease that can present with a wide range of clinical symptoms. While some patients require intestinal transplantation, supportive care may be sufficient in others. For this reason, patients with PIPO should be managed individually.

Topics: Child; Child, Preschool; Digestive System Surgical Procedures; Female; Humans; Infant; Intestinal Pseudo-Obstruction; Intestines; Male; Nutritional Support; Outcome Assessment, Health Care; Retrospective Studies; Survival Rate; Tertiary Care Centers; Turkey

PubMed: 30666970
DOI: 10.5152/tjg.2019.18287