Megacystis-microcolon-intestinal hypoperistalsis syndrome: don't forget the bladder.

PURPOSE: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a well described clinical condition, but reports are focused on microcolon and intestinal hypoperistalsis, while data on bladder management are scant. Aim of the study is to present urological concerns in MMIHS. METHODS: Retrospective evaluation of clinical data on urological management of MMIHS patients treated in the last 10 years. RESULTS: Six patients were enrolled (3 male, 3 female). Three girls had prenatal diagnosis of megacystis (1 vesicoamniotic shunt was placed). All patients had genetic diagnosis: 5 had ACTG2 gene mutations and 1 MYH11 mutation. All patients were addressed to our attention for urinary symptoms, such as urinary retention, urinary tract infections, acute renal injury. Two patients presented frequent stoma prolapses. All children underwent a complete urological evaluation, and then started a bladder management protocol (clean intermittent catheterization, via urethra or cystostomy-tube placement), with improvement of urinary infections, upper urinary tract dilation and stoma prolapses, if present. All patients had good renal function at last follow-up. CONCLUSION: We believe that MMIHS patients must be addressed soon and before onset of symptoms for a multidisciplinary evaluation, including an early assessment by a pediatric urologist expert in functional disorder, to preserve renal function at its best.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS): challenges in diagnosis and management.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare, congenital functional intestinal obstruction, characterised by megacystis (bladder distention in the absence of mechanical obstruction), microcolon and intestinal hypoperistalsis (dysmotility).We are reporting a case of a female child with normal antenatal course who presented with recurrent episodes of abdominal distension since the second day of life and underwent negative exploratory laparotomy on multiple occasions. She also had urinary retention with a grossly distended bladder, requiring drainage by clean intermittent catheterisation. Surgical procedures for bowel decompression, including gastrostomy and ileostomy, were carried out without success. Genetic analysis revealed a mutation in the human smooth muscle (enteric) gamma-actin gene (ACTG2 gene), clinching the diagnosis of MMIHS. The patient was managed with parenteral nutrition and prokinetic medications and tolerated jejunostomy feeds for a brief period before she succumbed to the illness.Female neonates or infants presenting with abdominal distension and dilated urinary tract should be investigated for MMIHS early on. A timely diagnosis will enable the early involvement of a multidisciplinary team to provide the best options available for management.

Chronic intestinal pseudo-obstruction due to adult-onset acquired isolated hypoganglionosis with muscular atrophy in the small intestine: a case report and review of literature.

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.

Acute intestinal pseudo-obstruction secondary to Sjogren's syndrome in pregnancy: a case report and literature review.

BACKGROUND: Intestinal pseudo-obstruction (IPO) is a rare disease, and its clinical manifestations can resemble mechanical intestinal obstruction leading to unnecessary and potentially harmful surgery. Certain autoimmune diseases have been associated with IPO, however, cases secondary to Sjögren's syndrome (SjS) are especially rare. CASE PRESENTATION: We described the first case of SjS-associated acute IPO in pregnancy, which was successfully treated with combined immunosuppressive therapy and resulted in an uneventful caesarean delivery. CONCLUSIONS: Women with SjS is likely to experience more complications during pregnancy, and IPO rather than the classic symptoms could be the first sign of SjS flares. IPO should be suspected in patients with unrelenting symptoms of small bowel obstruction, and a multidisciplinary approach can provide optimal management of such high-risk pregnancies.

Pyridostigmine in chronic intestinal pseudo-obstruction - a systematic review.

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.

Mitochondrial neurogastrointestinal encephalomyopathy in a Pakistani female: a case report.

BACKGROUND: Mitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. Mitochondrial neurogastrointestinal encephalopathy is a progressive degenerative disease characterized by a distinctive tetrad of gastrointestinal dysmotility, peripheral neuropathy, ophthalmoplegia with ptosis, and asymptomatic leukoencephalopathy. It provides a diagnostic dilemma to physicians in regions like Pakistan because of a lack of genetic study availability and associated financial constraints of the population. However, with careful examination and a few basic investigations, mitochondrial neurogastrointestinal encephalopathy can be diagnosed by ruling out most of the close differentials. CASE PRESENTATION: We report the case of a 23-year-old Asian female whose chief complaints were epigastric pain, bilious emesis, weight loss for 3 months, and bilateral lower limb weakness for 20 days. All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. Because of financial constraints, genetic studies could not be performed. The patient was managed with a multidisciplinary approach involving gastroenterology, physiotherapy, and nutrition departments. Currently, therapeutic options for the disease include allogeneic hematopoietic stem cell transplant and carrier erythrocyte entrapped thymidine phosphorylase; however, these could not be provided to the patient owing to certain limitations. CONCLUSIONS: As misdiagnosis and delayed diagnosis are quite common in this disease, the prime objective of this case report is to increase the basic understanding of this disease, especially its signs and symptoms, and address the limitations regarding the diagnostic investigations and management of patients with mitochondrial neurogastrointestinal encephalopathy.

Intestinal Pathology in Patients With Pathogenic ACTG2-Variant Visceral Myopathy: 16 Patients From 12 Families and Review of the Literature.

BACKGROUND: Dominant gamma-smooth muscle actin gene (ACTG2) variants cause clinically diverse forms of visceral myopathy. Many patients undergo intestinal resection or biopsy before identification of their genetic defect. The pathology of ACTG2-variant visceral myopathy has not been evaluated systematically. METHODS: Glass slides, ultrastructural images, molecular genetic reports, and clinical records from 16 patients with pathogenic (15) or likely pathogenic (1) ACTG2 variants were reviewed and compared with surgical specimens from controls (no evidence of a primary myopathy or pseudo-obstruction due to Hirschsprung disease) and published descriptions. RESULTS: The variable clinical manifestations in our cohort matched those in the literature. Only non-specific light and electron microscopic findings observed in non-myopathic controls were encountered in 13 of 16 patients. The remaining 3 patients harbored hyalinized cytoplasmic inclusions in smooth muscle cells and 1 of them had polyglucosan bodies in the muscularis propria. CONCLUSIONS: Apart from hyalinized inclusions, which were only observed in 3/16 patients, intestinal pathology in the majority of patients with ACTG2 variants is not indicative of an underlying visceral myopathy. Molecular testing should be considered even when no diagnostic intestinal pathology is identified.

Hirschsprung disease and Paediatric Intestinal Pseudo-obstruction.

Hirschsprung disease (HSCR) and Paediatric Intestinal Pseudo-obstruction (PIPO) comprise two of the most recognized and severe disorders of gastrointestinal (GI) motility. HSCR is a developmental disorder of the enteric nervous system invariably affecting the large intestine, whereas the majority of PIPO conditions represent congenital disorders of one or more components of the neuromusculature and more diffusely affect the GI tract. Histopathology is deemed the gold standard for the diagnosis of HSCR and, arguably, of PIPO, but, other diagnostic modalities such as manometric and genetic studies have seen recent advances that may increase their utility. Especially for PIPO, management is multidisciplinary and best performed in specialist referral centres. Surgery remains the only viable treatment for HSCR and appears essential to optimize and sustain feeding and viability of intestinal function in PIPO patients. Novel therapies such as neural stem cell transplants show promise for the future.

Small intestine motility disorders: Chronic intestinal pseudo-obstruction.

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.

The Diverse Phenotype of Intestinal Dysmotility Secondary to ACTG2-related Disorders.

BACKGROUND AND AIMS: The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms of intestinal dysmotility disorders. we aimed to describe the diverse phenotype of this newly reported and rare disease. METHODS: Report of 4 new patients, and a systematic review of ACTG2-related disorders. we analyzed the population frequency and used in silico gene damaging predictions. Genotype-phenotype correlations were explored. RESULTS: One hundred three patients (52% girls), from 14 publications, were included. Twenty-eight unique variants were analyzed, all exceedingly rare, and 27 predicted to be highly damaging. The median Combined Annotation Dependent Depletion (CADD) score was 29.2 (Interquartile range 26.3-29.4). Most patients underwent abdominal surgery (66%), about half required intermittent bladder catheterization (48.5%), and more than half were parenteral nutrition (PN)-dependent (53%). One-quarter of the patients died (25.7%), and 6 required transplant (5.8%). Girls had a higher rate of microcolon (P  = 0.009), PN dependency (P = 0.003), and death/transplant (P = 0.029) compared with boys, and early disease onset (<2 years of age) was associated with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) features. There was no statistical association between disease characteristics and CADD scores. CONCLUSIONS: Damaging ACTG2 variants are rare, often associated with MMIHS phenotype, and overall have a wide phenotypic variation. Symptoms usually present in the perinatal period but can also appear at a later age. The course of the disease is marked by frequent need for surgical interventions, PN support, and mortality. Poor outcomes are more common among girls with ACTG2 variants.

Chronic intestinal pseudo-obstruction: diagnostic and prognostic utility of ANNA-1/Anti-Hu onconeural antibodies.

We propose an algorithm for the early detection of cancer from a case of paraneoplastic syndrome.

Chronic Intestinal Pseudo-Obstruction Is Associated with Intestinal Methanogen Overgrowth.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIP) is a rare motility disorder characterized by dilated small bowel in the absence of mechanical obstruction. CIP has a known association with small intestinal bacterial overgrowth (SIBO); however, data regarding association with specific subtypes such as methane-positive (M+) and hydrogen-positive (H+) SIBO are limited. Therefore, we conducted this study to characterize subtypes of SIBO in CIP and compare them with non-CIP patients. AIMS: The aim is to explore the association and prevalence of hydrogen and methane subtypes of SIBO in patients with CIP. METHODS: A retrospective chart review was conducted for 494 patients who underwent glucose breath tests (GBT) in 2019. CIP was diagnosed based on clinical suspicion and after ruling out mechanical obstruction. We also reviewed demographic data, including age, gender, body mass index, tobacco and alcohol history, medical comorbidities, use of proton pump inhibitors, and history of colectomy. RESULTS: Among 494 patients, 7.7% (38) had CIP. The prevalence of M+ GBT in CIP patients was higher compared with non-CIP patients, and it was significant [52.6% (20/38) versus 11.8% (54/456), p < 0.001]. The prevalence of H+ GBT in our cohort of CIP patients was similar to that of non-CIP patients [23.7% (9/38) versus 25.7% (117/456), p = 0.941]. CONCLUSION: The prevalence of methane-positive GBT was higher in CIP patients than in patients without CIP. This finding further strengthens the hypothesis that the relationship between motility disorders and methanogen overgrowth is facilitative.

CHRONIC PSEUDO-OBSTRUCTION OF THE SIGMOID COLON: A CASE REPORT.

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.

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction.

BACKGROUND: Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. METHODS: Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. RESULTS: Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (Ï° = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (Ï° = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p < 0.001). CONCLUSIONS: As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations.

Lower Gastrointestinal Functional and Motility Disorders in Children.

Functional and motility gastrointestinal disorders are the most common complaints to the pediatric gastroenterologist. Disorders affecting the small intestine carry a significant morbidity and mortality due to the severe limitation of therapeutic interventions available and the complications associated with such interventions. Congenital colorectal disorders are rare but also carry significant morbidity and poor quality of life plus the social stigma associated with its complications. In this review, we summarize the clinical presentation, diagnostic evaluations, and the therapeutic interventions available for the most common and severe gastrointestinal functional and motility disorders of the small bowel, colon, and anorectum.

Hollow Visceral Myopathy, a Rare Gastrointestinal Disorder: A Case Report and Short Review.

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.

Chronic intestinal psuedo-obstruction and MIDD, a rare cause of acute abdomen: implications in emergency surgery.

Chronic intestinal pseudo-obstruction (CIPO) is a condition typified by the failure of the small bowel to propel contents in the absence of physical obstruction. CIPO is diagnosed after eliminating other causes, presenting a diagnostic challenge in emergency surgery. We report a case of a 32-year-old man with a rare mitochondrial disorder, Maternally inherited diabetes and deafness (MIDD), who presented to our hospital acutely unwell with peritonitis. Laparotomy revealed distended small bowel with no transition point, and turbid fluid with no macroscopic source. Postoperatively he had severe electrolyte and vitamin deficiencies. The diagnosis of CIPO leading to paralytic ileus and bacterial translocation was established and managed with aggressive electrolyte and vitamin replacement. He was discharged day 12 post operatively after a prolonged ileus with follow-up from a quaternary metabolic unit. We discuss here the challenges and gold standard in the emergency management of CIPO.

Recurrent spontaneous small bowel perforations with a rare pathology: non-familial visceral myopathy.

Visceral myopathy is a rare, often misdiagnosed disease characterised by abnormalities in the gastrointestinal smooth muscle layer. Its clinical presentation includes pseudo-obstruction, intestinal dysmotility and spontaneous perforation. We report an atypical case of a 51-year-old man with a history of recurrent small bowel perforations who presented with an acute abdomen. A laparotomy was performed with identification of a distal jejunal perforation. A small bowel resection with end-to-end anastomosis was done. Minimal adhesions were seen intraoperatively despite the patient's multiple prior surgeries. Pathology showed histiocytic inflammation and patchy loss of the muscle layer reflective of visceral myopathy. Genetic testing revealed a variant of uncertain significance in the myosin light chain kinase gene. It is difficult to make a conclusive diagnosis given the patient's clinical presentation closely mimicking other gastrointestinal disorders. However, it is crucial to consider visceral myopathy in patients with recurrent spontaneous intestinal perforations as a differential diagnosis.

Portal venous gas in a girl with chronic intestinal pseudoobstruction.

Hepatic portal venous gas (HPVG) is associated with various fatal conditions requiring urgent surgical intervention. In patients with chronic intestinal pseudoobstruction (CIPO), HPVG results from intestinal dilation. CIPO is a condition that is generally not surgically remediable; however, in emergency cases, an operative approach is often considered to prevent additional complications or to restore intestinal propulsion. However, surgery in these patients is associated with high postoperative morbidity and mortality rates and frequent reoperation. Intestinal resection and adhesion formation can potentially worsen the underlying dysmotility and are associated with refractory postoperative ileus, which often requires reoperation. Here, we present a case of HPVG in a patient with chronic intestinal pseudoobstruction (CIPO), treated conservatively and discuss the management of patients with HPCG.

Postinfectious T-lymphocytic enteral leiomyositis as a rare cause of chronic intestinal pseudoobstruction.

T-lymphocytic enteral leiomyositis (T-lel) is a rare disorder causing chronic intestinal pseudo-obstruction (CIPO), with cases predominantly being reported in the field of veterinary and pediatric medicine. Here, we present a case of T-lel-associated CIPO in an adult female, who initially presented with a paralytic ileus 2 weeks after a common gastroenteritis. The histological diagnosis was established through full-thickness bowel biopsy, exhibiting a dense lymphocytic infiltrate in the lamina muscularis of the intestinal wall. This case shows that T-lel can be a cause of chronic intestinal pseudo-obstruction not only in children but also in adults. A subsequent induction of an immunosuppressive therapy with steroids, azathioprine, and ultimately TNF-alpha-inhibiting antibodies led to a slow recovery and stable disease.