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Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers. Increased use of ICI has led to the onset of new adverse events. Neurological immune-related adverse events are rare, heterogenous, and potentially life-threatening. Chronic intestinal pseudo-obstruction (CIPO) is an immune-related autonomic plexus neuropathy that may be caused by infiltration of the myenteric plexus by CD8 + T cells. It is a rare and potentially fatal side effect that can be difficult to diagnose early because of initial nonspecific clinical presentation including vomiting, nausea, diarrhea, and constipation. Some rare cases have been described in the literature reporting a frequent resistance to corticosteroids making it necessary to use other immunosuppressive therapy. Vedolizumab is an antibody (Ab) blocking integrin α4-β7 used to treat inflammatory bowel disease. We report the first three cases of ICI-induced CIPO-treated with vedolizumab after corticosteroid failure, with very limited benefits (only one patient with transitory improvement). Based on our results in three cases, vedolizumab does not currently appear to be a therapeutic option. Earlier administration with a standardized dose and frequency schedule may provide better outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is reported to be a secondary cause of chronic intestinal pseudo-obstruction (CIPO). Although few case reports have described CIPO in MELAS, effective treatment for CIPO has not been established. Here, we present a case report of amelioration of CIPO symptoms using acotiamide in a patient with MELAS. Case Presentation: A 51-year-old Japanese female with a mitochondrial disorder with m.3243A>G mutation and a history of anorexia for 2 years presented to our hospital with a left temporal headache and acute paraphasia. A stroke-like episode of MELAS was suspected and combined therapy with arginine, edaravone, and levetiracetam was initiated. Although her symptoms improved, she presented with nausea and vomiting and abdominal distension 6 days following admission. Abdominal contrast-enhanced computed tomography revealed dilatation from the stomach to the intestine, particularly marked the stomach, with neither obstruction nor impaired blood flow in the intestine. CIPO exacerbation with MELAS was suspected, and the patient’s symptoms gradually improved with acotiamide. Conclusion: Patients with MELAS could possibly experience stroke-like episodes during CIPO. Since acetylcholine possibly plays an important role in the pathophysiology of CIPO and acotiamide possesses prokinetic activity by inhibiting acetylcholinesterase, acotiamide could possibly improve CIPO symptoms. [ABSTRACT FROM AUTHOR]

The aim of this work is to discuss the known causes of chronic intestinal pseudo-obstruction. Determining the etiology of the symptoms reported by the patient, such as: abdominal pain, bloating, nausea, constipation, heartburn or regurgitation, the cause of which cannot be clearly identified in imaging tests as mechanical intestinal obstruction, is necessary to implement proper therapy. We distinguished, among others: infections, gene mutations, cancer and paraneoplastic syndromes and autoimmune diseases. This broad range of causes shows the complexity of this disease. Among pathogens, the most common cause are viruses, especially herpesviruses, what is more bacterial infections and gut dysbiosis must be taken under consideration. We found that specific pathway gene mutations can cause obturation symptoms which need extended diagnostic tests. Paraneoplastic syndromes should be examined as a possible etiological factor while looking for the cause of this disease and anticancer treatment can be either a solution for the chronic intestinal pseudo-obstruction symptoms or a cause of them. Lastly we discussed autoimmune diseases as a part of the inflammation problem of the bowel. The goal is to emphasize how important it is to draw attention to the need of looking at the patient and his ailments integrally, which will enable an accurate diagnosis to be made and the appropriate treatment to be effectively selected. We found it very important to think unconventionally with every patient we deal with and what can be done thanks to a great amount of knowledge provided by other doctors.

Objective To discuss the clinical features, differential diagnosis and complication treatment of a patient with genetic visceral myopathy. Methods Medical history, physical examination and laboratory results of the patient were collected in detail. The pathology of previous surgery was reviewed. The patient's peripheral blood DNA was extracted and submitted for whole-exome sequencing. Subsequent Sanger sequencing was used to complete the pedigree verification of the mutation site. Results The patient was a young female presented with repeated incomplete intestinal obstruction since early childhood. She used to be misdiagnosed as Hirschsprung's disease for a long period and underwent multiple gastrointestinal segment resections. Her intestinal obstruction symptoms were temporarily relieved by surgeries, but severe diarrhea, mucus and bloody stools and malnutrition gradually occurred after the last operation. The patient had bacterial overgrowth in small intestinal tract and followed by intestinal opportunistic infections secondary to chronic intestinal pseudo-obstruction. The symptoms improved after anti-infection and enteral element diet treatment. Further pathological consultation and whole-exome gene sequencing confirmed the diagnosis of visceral myopathy related to ATCG2 R148L mutation. Conclusions Patients with early onset of chronic intestinal pseudo-obstruction and have poor response to conventional treatment are recommended to perform genetic test. The patients with hereditary visceral myopathy are susceptible to opportunistic intestinal infection. Attentions should also be paid to the prevention and treatment of complications to avoid unnecessary surgery.

Key clinical message: Small cell lung cancer (SCLC), a neuroendocrine aggressive subtype of lung cancer, is associated with paraneoplastic disorders in about 9% of patients. In this report, we describe a middle‐aged man who presented with chronic bowel obstruction caused by chronic intestinal pseudo‐obstruction (CIPO) due to SCLC. [ABSTRACT FROM AUTHOR]

T-lymphocytic intestinal leiomyositis is a rare cause of "pediatric intestinal pseudoobstructions." Diagnosis may be difficult and requires full-thickness bowel biopsies during laparotomy or laparoscopy with possible enterostomy. Currently, immunosuppressive therapy is the only available treatment. A delay in diagnosis and therapy may negatively affect the prognosis because of ongoing fibrotic alterations; therefore, early diagnosis and consequent treatment are crucial. This review summarizes the available information on the nosology, diagnostic steps, and treatment modalities. Here, we report the youngest case of enteric leiomyositis reported in the last two decades and analyze its management by reviewing previous cases. [ABSTRACT FROM AUTHOR]

Summary: This report describes a rare case of chronic intestinal pseudo‐obstruction (CIPO) in a 12‐year‐old Quarter Horse gelding, caused by lymphocytic myenteric ganglionitis (MG) associated with equine herpesvirus 1 (EHV‐1) and equine herpesvirus 5 (EHV‐5) infection. The horse presented with recurrent colic and weight loss over 1.5 years. Repetitive transrectal examinations consistently revealed small colon impaction and enlargement. During postmortem examination alternating segments of enlarged and reduced luminal diameter were observed throughout the entire intestinal tract. MG with lymphocytic infiltrates and neuronal degeneration of the large intestine were found on histopathological analysis. Additionally, polymerase chain reaction (PCR) analysis confirmed the presence of EHV‐1 and EHV‐5 DNA in affected intestinal tissues. Further research is needed to understand the pathophysiology of MG and its association with herpesviruses. Early recognition and diagnosis of MG‐associated CIPO may improve treatment approaches and outcomes for future cases. [ABSTRACT FROM AUTHOR]

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Background: Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal disorder characterized by impaired propulsion of the digestive tract and associated with symptoms of intestinal obstruction, despite the absence of obstructive lesions. CIPO includes several diseases. However, definitive diagnosis of its etiology is difficult only with symptoms or imaging findings. Case presentation: A 56-year-old man was referred to our hospital due to a 3-year history of continuous abdominal distention. Imaging, including computed tomography of the abdomen, and endoscopy revealed marked dilatation of the entire small intestine without any obstruction point. Therefore, he was diagnosed with CIPO. Since medical therapy didn't improve his symptoms, enterostomy and percutaneous endoscopic gastro-jejunostomy were performed. These procedures improved abdominal symptoms. However, he required home central venous nutrition due to dehydration. The pathological findings of full-thickness biopsies of the small intestine taken during surgery revealed decreased number and degeneration of ganglion cells in the normal plexus. These findings led to a final diagnosis of CIPO due to acquired isolated hypoganglionosis (AIHG). Conclusions: Here, we report the case of a patient with CIPO secondary to adult-onset AIHG of the small intestine. Since AIHG cannot be solely diagnosed using clinical findings, biopsy is important for its diagnosis. [ABSTRACT FROM AUTHOR]

L'atteinte digestive au cours de la sclérodermie systémique peut être sévère et occasionner une véritable pseudo-obstruction intestinale chronique, secondaire à des troubles profonds de la motilité de l'intestin grêle. Elle est associée à certaines caractéristiques cliniques et biologiques, notamment la positivité des anticorps anti fibrillarine/U3RNP. La pseudo-obstruction intestinale chronique se complique d'une pullulation microbienne qui nécessite une antibiothérapie cyclique. Elle entraîne nécessairement une réduction du bol alimentaire compte-tenu des symptômes douloureux, nausées et vomissements engendrés par les repas et, in fine , une dénutrition sévère. La stratégie de fractionnement des repas n'est souvent que transitoirement efficace et les patients nécessitent un authentique support nutritionnel, principalement par voie parentérale. La sclérodermie systémique ne constitue pas un frein à l'initiation et la poursuite de ce traitement dans le temps. Les dispositifs veineux implantables ne s'accompagnent pas d'un surrisque de complications locales ou infectieuses. La poursuite d'une nutrition parentérale au long cours nécessite toutefois un suivi conjoint dans un centre expert en nutrition, afin d'adapter les volumes et apports nutritifs et d'en limiter les complications cardiaques et hépatobiliaires potentiellement mortelles. À la nutrition s'associent des traitements prokinétiques dont les effets secondaires – notamment antagonistes sur la motilité digestive – doivent être connus, ainsi que des procédures invasives dont la balance bénéfice-risque doit être évaluée avec précaution. Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively. [ABSTRACT FROM AUTHOR]

Background: Chronic intestinal pseudo‐obstruction (CIPO) may be a primary or secondary phenomenon and is often multifactorial. Treatment is largely directed at improving colonic motility. The use of cholinesterase inhibitors such as pyridostigmine has been hypothesized to increase acetylcholine in the bowel, improving symptoms and transit times. Methods: A systematic review of the use of pyridostigmine in CIPO was conducted using scientific and commercial search engines identifying scientific studies enrolling adult human subjects, published from 2000 to 2022 in the English language. Results: Four studies were identified including two randomized controlled trials (RCT) and two observational studies. The studies had heterogenous inclusion criteria, dosing regimens and reported outcomes. Two studies were identified as being at high risk of bias. All studies reported improved patient outcomes with use of pyridostigmine, and low rates (4.3%) of mild cholinergic side effects. No major side effects were reported. Conclusion: The use of pyridostigmine in management of CIPO is biologically plausible due to its ability to increase colonic motility, and early studies on its role are uniformly suggestive of benefit with low side‐effect profile. Four clinical studies have been conducted to date, with small sample sizes, heterogeneity and high risk of bias. Further high‐quality studies are required to enable assessment of pyridostigmine's utility as an effective management strategy in CIPO. [ABSTRACT FROM AUTHOR]

L'atteinte digestive de la sclérodermie systémique concerne plus de 90 % des patients mais est d'expression clinique hétérogène. Elle peut potentiellement intéresser tout le tractus intestinal et être responsable à terme d'une malnutrition multifactorielle, fréquente dans cette pathologie. Elle est une source majeure d'altération de la qualité de vie et peut même mettre en jeu le pronostic vital. La prise en charge est complexe et multidisciplinaire, allant de simples mesures hygiénodiététiques, à des procédures interventionnelles endoscopiques ou chirurgicales spécialisées, en passant par des médicaments, notamment inhibiteurs de la pompe à proton et prokinétiques, non dénués d'effets secondaires. Des perspectives de nouveaux outils diagnostiques et thérapeutiques font espérer une amélioration de la prise en charge et du pronostic de ces patients. Gastrointestinal tract involvement in systemic sclerosis concerns more than 90% of patients but is of heterogeneous clinical expression. It can involve the entire intestinal tract and be responsible for multifactorial malnutrition, which is frequent in this disease. It is a major source of deterioration in the quality of life and can even be life-threatening. Management is complex and multidisciplinary, ranging from simple hygienic and dietary measures, to specialized endoscopic or surgical interventional procedures, also including medical treatments, particularly proton pump inhibitors and prokinetics, with potential side effects. Ongoing research for new diagnostic and therapeutic tools promises to improve the management and prognosis of these patients. [ABSTRACT FROM AUTHOR]

Dilatation of the gut occurs in response to either mechanical obstruction or aperistalsis. The hallmark features are symptoms of bowel obstruction with vomiting, constipation, abdominal pain and distension. This review will primarily deal with the non-mechanical causes of gut dilatation, both intestinal and colonic, and differentiate between acute and chronic presentations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Paraneoplastic chronic intestinal pseudo-obstruction (CIPO) is a rare manifestation associated with small cell lung carcinoma and other malignancies. In this report, we present a challenging case involving a 60-year-old man with small cell lung carcinoma who developed symptoms of intestinal pseudo-obstruction, including abdominal distention, pain, and obstipation. Despite receiving extensive treatment with intravenous gamma globulin and glucocorticoids, the patient's symptoms did not improve, ultimately resulting in irreversible nervous system damage. Through a comprehensive literature review, we explore the underlying mechanisms of paraneoplastic CIPO and discuss its diagnostic and therapeutic approaches. We emphasize the significance of timely detection of related antibodies for early diagnosis and treatment of CIPO to improve patient outcomes.

Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by signs of intestinal obstruction lasting for 6 months or more, in the absence of a definitive cause of obstruction. We report a case of CIPO in a 49-year-old female patient with a 6-month history of ongoing irregular bowel movements, manifested as constipation and diarrhea accompanied by abdominal pain and bloated feeling. Contrast-enhanced abdominal computed tomography and magnetic resonance enterography revealed focal thickening of a segment of the lienal flexure and intermittent areas of wider and narrower caliber along the sigmoid colon. No signs of a definitive cause of obstruction were found, but evidence for dolichosigma was revealed, which was later confirmed with colonoscopy. Due to persisting symptoms, the patient agreed to elective resection of the sigmoid colon. Following the procedure, symptoms regressed with a significant improvement in the quality of life. The patient has been regularly monitored in an outpatient setting and reports absence of the symptoms since the procedure. Pathophysiology of the resected section revealed more prominent lymphatic tissue, follicular arrangement, and reactively altered germinal centers, which can suggest CIPO.

Chronic intestinal pseudo-obstruction (CIPO) is caused by metabolic and endocrine factors, but it can also be caused by the cancer's paraneoplastic effect. The cancers most associated with paraneoplastic syndromes are lung cancers and are generally associated with small cell lung cancers. Lung adenocarcinomas may rarely cause paraneoplastic syndromes, however, they mostly cause general effects such as cachexia and leukocytosis. The goal of this case report was to provide a case of non-mechanical obstruction due to lung adenocarcinoma as a very unusual cause of intestinal pseudo-obstruction, together with clinical, laboratory, and imaging results. [Med-Science 2022; 11(1.000): 410-2]

ABSTRACT: Chronic intestinal pseudo-obstruction (CIPO) is a severe form of gastrointestinal dysmotility (often due to derangement of the innervation and/or smooth muscle and/or interstitial cells of Cajal) with recurrent episodes of intestinal sub-occlusion. We describe a clinical setting and radiological features of CIPO in an 11-year-old girl with periodic relapses. Our attention was focused firstly on surgical causes, leading to a delay in the diagnosis; thus, is important detecting equivocal symptoms and considering the possible correlation to the CIPO for an early diagnosis and related prevention of acute episodes improving prognosis and quality of life of pediatric patients.

Background: Pediatric Intestinal Pseudo-obstruction (PIPO) is a congenital enteric disorder characterized by severe gastrointestinal (GI) dysmotility, without mechanical obstruction. Although several genes have been described to cause this disease, most patients do not receive a genetic diagnosis. Here, we aim to identify the genetic cause of PIPO in a patient diagnosed with severe intestinal dysmotility shortly after birth.Methods: Whole exome sequencing (WES) was performed in the patient and unaffected parents, in a diagnostic setting. After identification of the potential disease-causing variant, its functional consequences were determined in vitro and in vivo. For this, expression constructs with and without the causing variant, were overexpressed in HEK293 cells. To investigate the role of the candidate gene in GI development and function, a zebrafish model was generated where its expression was disrupted using CRISPR/Cas9 editing.Results: WES analysis identified a de novo heterozygous deletion in TFAP2B (NM_003221.4:c.602-5_606delTCTAGTTCCA), classified as a variant of unknown significance. In vitro studies showed that this deletion affects RNA splicing and results in loss of exon 4, leading to the appearance of a premature stop codon and absence of TFAP2B protein. Disruption of tfap2b in zebrafish led to decreased enteric neuronal numbers and delayed transit time. However, no defects in neuronal differentiation were detected. tfap2b crispants also showed decreased levels of ednrbb mRNA, a downstream target of tfap2b.Conclusion: We showed that TFAP2B haploinsufficiency leads to reduced neuronal numbers and GI dysmotility, suggesting for the first time, that this gene is involved in PIPO pathogenesis.

• CIPO is a rare syndromic entity that results in repeated episodes of digestive "obstruction" without true mechanical obstacle. It is characterized by disorders of intestinal motility. • CIPO can be primary, acquired or congenital, or secondary to a systemic pathology (neurological, metabolic, etc.) resulting in neurogenic or muscular damage involving the intestinal tract. • Abdomino-pelvic CT must be performed to rule out a mechanical obstruction. Another reference examination is manometry of the small intestine, although it is rarely performed in practice. • Apart from CIPO secondary to a treatable pathology, management is mainly symptomatic and aims essentially at maintaining stable nutritional status and providing effective pain relief. Surgery, which is rarely efficacious, often deleterious, and must be avoided as much as possible. Chronic intestinal pseudo-obstruction (CIPO) is a syndrome associating chronic or recurrent obstructive symptoms with intestinal dilation on imaging but without organic obstruction in the digestive tract. It is a rare disease with varying severity whose diagnosis is very complex. The diagnosis is based on clinical and paraclinical arguments in the context of repetitive occlusive syndromes when no mechanical obstruction of the digestive lumen is observed. Abdomino-pelvic computerized tomography (CT) must be performed to rule out a mechanical obstruction. An additional reference examination is trans-duodenal manometry of the small intestine, which is almost never normal in CIPO, but the test is rarely systematically performed. CIPO can be primary (acquired or congenital) or secondary to a systemic pathology (neurological, metabolic, etc.) resulting in neuromuscular damage to the intestinal tract. There are familial forms associated with genetic mutations. The majority of CIPO cases are idiopathic. Symptoms of the CIPO syndrome should be investigated with a complete assessment, guided by questioning and clinical examination that should also focus on urinary, neurological and cardiac involvement. Pathological tissue analysis is interesting for the etiological classification but is difficult to obtain. CIPO must be distinguished from non-CIPO intestinal dysmotility. Management must be carried out in an expert center with multidisciplinary care involving gastroenterologists, nutritionists, psychologists, radiologists, pathologists and digestive surgeons. It is essentially based on symptomatic management (especially with pro-kinetic agents and analgesics), nutritional support, as well as psychological support in view of its impact on quality of life. Surgical management is sometimes necessary. [ABSTRACT FROM AUTHOR]

Chronic intestinal pseudo-obstruction a rare violation of the motor skills of the gastrointestinal complex, similar to mechanical obstruction, but without a mechanical obstacle. The development of chronic intestinal pseudo-obstruction is caused by a disturbance on the part of the smooth muscles and the nervous system of the gastrointestinal system. Common symptoms include constipation, abdominal pain, nausea, vomiting, bloating. Violation of peristalsis leads to food stagnation in the hinges of the small intestine, their dilation, the development of bacterial insemination syndrome. Eating disorders, bacterial contamination syndrome (CDDs) lead to impaired suction syndrome, cahexia. Treatment is aimed at providing adequate nutrition, the use of drugs that activate motor skills, suppress the growth of microbes in the small intestine, the implementation of intestinal decompression. Surgical treatment: resection of the affected segment of the gut. In the refractory course of the disease intestinal transplantation.

Vitamin A has an essential role in the maintenance of corneal and conjunctival epithelization, as well as photoreceptor transduction in the retina. A deficiency of vitamin A causes keratinization of the surface epithelium, and night blindness is often the first symptom. This report describes a case of chronic intestinal pseudo-obstruction (CIPO), a rare and potentially fatal disease, diagnosed following detection of a vitamin A deficiency in an ophthalmological examination. A 25-year-old female patient presented with a 3-month history of dryness, a burning sensation, and decreased vision, especially at night, in both eyes. She appeared cachectic and ill, and reported having lost 10 kg in the previous year. An ophthalmological examination revealed conjunctival and corneal keratinization in addition to punctate keratopathy with xerosis in both eyes, which raised the suspicion of a vitamin A deficiency. Her serum vitamin A level confirmed the diagnosis, and she was referred to the gastroenterology clinic, where she was diagnosed with CIPO and treated with parenteral multivitamin supplementation. A vitamin A deficiency should be suspected in patients with malnourishment and xerosis. Rapid diagnosis and treatment can be life-saving in cases with a severe underlying pathology.

The enteric nervous system (ENS) is the third division of the autonomic autonomic nervous system and the largest collection of neurons outside the central nervous system (CNS). The ENS has been referred to as “the brain in the gut” or “the second brain of the human body” because of its highly integrated neural circuits controlling a vast repertoire of gut functions, including absorption/secretion, splanchnic blood vessels, some immunological aspects, intestinal epithelial barrier, and gastrointestinal (GI) motility. The latter function is the result of the ENS fine-tuning over smooth musculature, along with the contribution of other key cells, such as enteric glia (astrocyte like cells supporting and contributing to neuronal activity), interstitial cells of Cajal (the pacemaker cells of the GI tract involved in neuromuscular transmission), and enteroendocrine cells (releasing bioactive substances, which affect gut physiology). Any noxa insult perturbing the ENS complexity may determine a neuropathy with variable degree of neuro-muscular dysfunction. In this review, we aim to cover the most recent update on genetic mechanisms leading to enteric neuropathies ranging from Hirschsprung’s disease (characterized by lack of any enteric neurons in the gut wall) up to more generalized form of dysmotility such as chronic intestinal pseudo-obstruction (CIPO) with a significant reduction of enteric neurons. In this line, we will discuss the role of the RAD21 mutation, which we have demonstrated in a family whose affected members exhibited severe gut dysmotility. Other genes contributing to gut motility abnormalities will also be presented. In conclusion, the knowledge on the molecular mechanisms involved in enteric neuropathy may unveil strategies to better manage patients with neurogenic gut dysmotility and pave the way to targeted therapies.

Background: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. Aim: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. Methods: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. Results: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. Conclusions: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO. [ABSTRACT FROM AUTHOR]

Hollow visceral myopathy (HVM) is described as impaired intestinal function and motility in the absence of mechanical obstruction. In this case report, we describe a unique case of an 18-year-old female who presented to the hospital with complaints of persistent nausea, vomiting, inability to tolerate oral feeds, and substantial weight loss for 2 months. After appropriate investigations, a diagnosis of gastroparesis was established. The patient was started on metoclopramide, which led to significant symptomatic improvement, and she was eventually discharged home. One month after discharge, she presented to the hospital with symptoms similar to her initial presentation. After further laboratory and radiological investigation, she was diagnosed with severe gastroparesis and chronic intestinal pseudo-obstruction. Over the next month, the patient was given an extensive trial of multiple prokinetic agents such as mirtazapine, ondansetron, pyridostigmine, octreotide, and promethazine, but she failed to show clinical improvement. Due to failure of medical therapy, a nasojejunal feeding tube was placed for enteral nutrition. However, the patient reported worsening of her symptoms despite slow feeding rates; hence, a decision was made to start the patient on total parenteral nutrition and transfer her to a larger tertiary center for higher level of care. At the tertiary hospital, the patient was continued on total parenteral nutrition and underwent extensive evaluation. Ultimately, she was diagnosed with HVM after a laparoscopic full-thickness intestinal biopsy showed histopathological evidence of the disease. She underwent isolated small intestine transplant, which led to significant improvement of her symptoms and was eventually discharged home. The patient continues to be symptom-free and follows up with Gastroenterology and Transplant Surgery regularly. This case report highlights a rare clinical condition, HVM, as a potential diagnosis in patients with clinical features of intestinal obstruction without mechanical obstruction. [ABSTRACT FROM AUTHOR]

Colonic inertia is a frustrating motility disorder to patients, clinicians, and pathologists. The pathogenesis is largely unknown. The aims of this study were to: (1) characterize the expression of smoothelin, a novel smooth muscle-specific contractile protein expressed only by terminally differentiated smooth muscle cells, in the normal gastrointestinal (GI) tract; and (2) determine whether smoothelin is aberrantly expressed in patients with colonic inertia. A total of 57 resections of the normal GI tract (distal esophagus to left colon) were obtained from patients without GI motor dysfunction. Sixty-one colon resections were obtained from patients with a clinical diagnosis of colonic inertia. Smoothelin immunostaining was conducted on full-thickness tissue sections. In the nondysmotile controls, strong and diffuse cytoplasmic staining for smoothelin was observed in both the inner circular and outer longitudinal layers of the muscularis propria (MP) throughout the entire GI tract. The muscularis mucosae (MM) and muscular vessel walls were either completely negative or only patchily and weakly stained. The 1 exception to this pattern was observed in the distal esophagus, in which the MM was also diffusely and strongly stained. In cases with colonic inertia, a moderate to marked reduction of smoothelin immunoreactivity was observed in 15 of 61 (24.6%) colon resections, selectively seen in the outer layer of the MP. The data demonstrate that smoothelin is differentially expressed in the MP and MM of the normal GI tract and suggest that defective smoothelin expression may play a role in the pathogenesis of colonic inertia in a subset of patients.

Gastrointestinal inflammatory neuropathy, namely, eosinophilic myenteric ganglioneuronitis (EMG) and lymphocytic ganglioneuronitis (LG), is a form of chronic intestinal pseudo-obstruction and results from the infiltration of the myenteric plexus by eosinophils and lymphocytes, respectively. The literature related to the clinicopathological features of adult inflammatory neuropathy is scarce. We aim to elucidate the clinical and histological details of 7 cases of inflammatory neuropathy (EMG, n = 4, and LG, n = 3) and compare the features of EMG and LG retrospectively. There was no difference between these two entities in terms of clinical, hematological, or biochemical parameters. Histologically, almost all cases (n = 6/7) showed accompanying elements of ganglion cell vacuolization, mesenchymopathy, and partial/complete desmosis in addition to the disease-defining pathology. Besides, all cases of EMG showed infiltration of the inner circular muscle of muscularis propria by eosinophils. Two cases of LG showed additional muscular pathology pertaining to the muscularis propria. Inflammatory infiltration of the myenteric plexus is pathognomonic for the diagnosis of gastrointestinal inflammatory neuropathy although additional features in the form of ganglion cell vacuolization, reduction in the number of ganglia, desmosis, mesenchymopathy, and inflammation of the muscularis propria (eosinophils in EMG) can be seen. The pathologists need proper awareness along with judicious use of special and immunostains for clinching the diagnosis. [ABSTRACT FROM AUTHOR]

Chronic intestinal pseudo-obstruction (CIPO) is a rare, severe, and often debilitating condition that can result in significant morbidity and mortality amongst the pediatric population. Eosinophilic myenteric ganglionitis (EMG) is a rare inflammatory neuropathy of the myenteric plexus with characteristic eosinophilic infiltration with and without hypogangliosis. The disorder has been previously documented as a cause of CIPO. We report the case of a 14-year-old male with no clear obstructive cause who, after multiple visits with a myriad of tests and workups, underwent surgical exploratory laparoscopy with the pathology returning a diagnosis of EMG with unique lymphocytic and eosinophilic cell components., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

[West J Emerg Med. 2012;13(1):106–107.]

Abstract Background MNGIE is a rare and fatal disease in which absence of the enzyme thymidine phosphorylase induces systemic accumulation of thymidine and deoxyuridine and secondary mitochondrial DNA alterations. Gastrointestinal (GI) symptoms are frequently reported in MNGIE patients, however, they are not resolved with the current treatment interventions. Recently, our understanding of the GI pathology has increased, which rationalizes the pursuit of more targeted therapeutic strategies. In particular, interstitial cells of Cajal (ICC) play key roles in GI physiology and are involved in the pathogenesis of the GI dysmotility. However, understanding of the triggers of ICC deficits in MNGIE is lacking. Herein, we review the current knowledge about the pathology of GI dysmotility in MNGIE, discuss potential mechanisms in relation to ICC loss/dysfunction, remark on the limited contribution of the current treatments, and propose intervention strategies to overcome ICC deficits. Finally, we address the advances and new research avenues offered by organoids and tissue engineering technologies, and propose schemes to implement to further our understanding of the GI pathology and utility in regenerative and personalized medicine in MNGIE. Conclusion Interstitial cells of Cajal play key roles in the physiology of the gastrointestinal motility. Evaluation of their status in the GI dysmotility related to MNGIE would be valuable for diagnosis of MNGIE. Understanding the underlying pathological and molecular mechanisms affecting ICC is an asset for the development of targeted prevention and treatment strategies for the GI dysmotility related to MNGIE.

Chronic intestinal pseudo-obstruction (CIPO) is an uncommon disorder characterized by the presence of bowel dilatation and abnormal motility. It is an important cause of chronic intestinal failure in patients with systemic sclerosis (SSc). Although intestinal pseudo-obstruction is an infrequent reason for hospitalization in these patients, it has been correlated with high in-hospital mortality compared to SSc patients hospitalized for other reasons as well as patients with intestinal pseudo-obstruction arising from other causes. Patients present with signs and symptoms of mechanical bowel obstruction, such as nausea, vomiting, constipation, abdominal pain, and abdominal distension, in the absence of an anatomic lesion blocking the movement of intestinal contents. Despite breakthroughs in our understanding of this disorder, these patients continue to be treated largely with organ-based symptomatic therapy. Unfortunately, despite treatment, they often experience decreased quality of life and impairment in their everyday lives. Here, we present an interesting case of an individual with SSc for many years who presented with signs and symptoms of CIPO.

Abstract Background Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome in veterinary medicine characterized by severe intestinal dysmotility without evidence of mechanical occlusion of the intestinal lumen. The exact pathogenesis of CIPO is unknown. Case presentation A 1-year-old male Miniature Bull Terrier dog was presented with a history of chronic weight loss, regurgitation, lethargy, vomiting and diarrhea. The dog was submitted for exploratory laparotomy. A full thickness intestinal biopsy was taken and a CIPO was suspected. The clinical condition deteriorated and the dog was euthanized. At gross examination the small intestine was severely dilated. Histologically severe fibrosis of the submucosa and severe atrophy of the tunica muscularis were present in small intestine and colon. Immunohistochemical examination with a panel of antibodies for gastro-intestinal neuromuscular disease-associated antigens revealed a severely reduced expression of alpha-smooth muscle actin in the tunica muscularis. Conclusions This case report describes the gross, histological and immunohistochemical findings of CIPO affecting a 1-year-old Miniature Bull Terrier; on the basis of these findings a myopathic form of CIPO is hypothesized in this case.

Background: Chronic intestinal pseudo‐obstruction (CIPO) and enteric dysmotility (ED) are small intestinal motility disorders defined by radiological and manometric criteria. In the absence of consensus guidelines, we surveyed opinions on the diagnosis and management of CIPO and ED among experts from different countries. Methods: A survey questionnaire was circulated electronically to members of the European society for Clinical Nutrition and Metabolism, European Society of Neurogastroenterology and Motility, and United European Gastroenterology. Only responses from participants completing all required components were included. Key Results: Of 154 participants, 93% agreed that CIPO and ED should be classified separately. Overall, 73% reported an increasing incidence of CIPO and ED, with hypermobile Ehlers‐Danlos Syndrome the group with the largest increase in referrals (37%), particularly in the UK (P <.0001). The majority (95%) find diagnosing CIPO and ED difficult. Notably, antroduodenal manometry, a test mandated to diagnose ED, is infrequently used (only 21% respondents use in >50% cases) and full thickness biopsies were reported to seldom influence medical treatment, nutritional management, and prognosis. Respondents reported that very few treatments are useful for most patients, with bacterial overgrowth treatment, prucalopride, and psychological therapies felt to be the most useful. While only 23% of clinicians felt that parenteral nutrition (PN) improves gastrointestinal symptoms in >50% of cases, 68% reported PN dependency at 5 years in the majority of cases. Conclusions and Inferences: These data highlight the difficulties with diagnosing and managing CIPO and ED and underscore the urgent need for international, multidisciplinary, clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Vitamin A has an essential role in the maintenance of corneal and conjunctival epithelization, as well as photoreceptor transduction in the retina. A deficiency of vitamin A causes keratinization of the surface epithelium, and night blindness is often the first symptom. This report describes a case of chronic intestinal pseudo-obstruction (CIPO), a rare and potentially fatal disease, diagnosed following detection of a vitamin A deficiency in an ophthalmological examination. A 25-yearold female patient presented with a 3-month history of dryness, a burning sensation, and decreased vision, especially at night, in both eyes. She appeared cachectic and ill, and reported having lost 10 kg in the previous year. An ophthalmological examination revealed conjunctival and corneal keratinization in addition to punctate keratopathy with xerosis in both eyes, which raised the suspicion of a vitamin A deficiency. Her serum vitamin A level confirmed the diagnosis, and she was referred to the gastroenterology clinic, where she was diagnosed with CIPO and treated with parenteral multivitamin supplementation. A vitamin A deficiency should be suspected in patients with malnourishment and xerosis. Rapid diagnosis and treatment can be life-saving in cases with a severe underlying pathology. [ABSTRACT FROM AUTHOR]

Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome characterized by severe impairment of gastrointestinal (GI) motility, and its symptoms are suggestive of partial or complete intestinal obstruction in the absence of any lesion restricting the intestinal lumen. Diagnosis and therapy of CIPO patients still represent a significant challenge for clinicians, despite their efforts to improve diagnostic workup and treatment strategies for this disease. The purpose of this review is to better understand what is currently known about the relationship between CIPO patients and intestinal microbiota, with a focus on the role of the enteric nervous system (ENS) and the intestinal endocrine system (IES) in intestinal motility, underling the importance of further studies to deeply understand the causes of gut motility dysfunction in these patients.

Abstract Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder with significant morbidity and mortality in pediatric patients. The diagnosis of CIPO is difficult, because it is clinically based on the symptoms and signs of bowel obstruction which are similar to the clinical manifestations of other gastrointestinal diseases like short bowel syndrome (SBS). Therefore, it is desirable to identify and establish new laboratory diagnostic markers for CIPO that are reliable and easily accessible. In our study we have identified the ratio of the urinary glutamine and glutamic acid as a promising biomarker for distinguishing suspected CIPO cases and simple SBS cases. The area under ROC curve was 0.83, at cutoff value = 7.04 with sensitivity of 65% and specificity of 92%.