Cause Of Chronic Intestinal Pseudo-obstruction Research Articles

S2466 Pelvic Floor Dysfunction as a Cause of Chronic Intestinal Pseudo Obstruction

Introduction: Chronic intestinal pseudo-obstruction (CIPO) is a rare motility disorder with a variety of secondary causes, including genetics, metabolic disease, paraneoplastic syndromes, inflammatory disorders, and neurologic disorders. We present a case of CIPO secondary to pelvic floor dyssynergia. Case Description/Methods: A 64 year-old male with a past medical history of hypertension, atrial tachycardia, and heavy alcohol use was referred for further GI workup by his primary care physician following a 5 month history of worsening constipation after a viral infection. Prior to the infection, he had a bowel movement 2-3 times per week. However, he now describes one Bristol 4 or 7 bowel movement with straining per month. Symptoms were refractory to Dulcolax and Colace. Initial workup included a normal extended electrolyte panel, normal TSH, and negative Celiac disease serologies. A CT abdomen and pelvis revealed extensive dilation of proximal colon, compression of descending and sigmoid colon, and small bowel fecalization. A representative coronal image is shown in Figure 1. Subsequent colonoscopy did not reveal any evidence of obstruction. Anorectal manometry (ARM) findings included elevated resting pressure (74.94 mmHg), decreased sensation, paradoxical contraction with Valsalva, and inability to pass the balloon catheter after 2.5 minutes. Normal rectal capacity (280 mL) and excellent squeeze pressure but paradoxical contraction with Valsalva is consistent with pelvic floor dyssynergia. Biofeedback therapy was recommended. Discussion: Evaluating for secondary causes of CIPO (i.e., obstruction, metabolic disturbances, autoimmune disorders, neurologic disorders, and musculoskeletal disorders) is an important diagnostic step. Key tests include imaging, colonoscopy, electrolytes and autoimmune panels, and anorectal manometry. This case highlights long-standing pelvic floor dyssynergia as an underlying cause of CIPO.Figure 1.: CT abdomen and pelvis with extensive dilation of proximal colon and small bowel fecalization.

Hollow Visceral Myopathy: Diagnosis and Management

Abstract: The aetiology of hollow visceral myopathy remains poorly understood despite the review of histology and is often misdiagnosed. It is characterized by impaired intestinal function and motility in absence of mechanical obstruction, which may be familial (transmitted by a dominant or recessive gene) or sporadic. Familial visceral myopathy is a rare hereditary myopathic degeneration of both gastrointestinal (and urinary tracts) that causes chronic intestinal obstruction. Typically, it presents after the first decade of life with symptoms of abdominal distension, abdominal pain, vomiting, constipation, and diarrhoea. It is, therefore, a rare cause of chronic intestinal pseudo-obstruction. Secondary chronic intestinal pseudo-obstruction is typically managed by treating the underlying condition, however, decompression by colostomy or tube gastrostomy/enterostomy/caecostomy may be performed; this also allows for feeding and irrigation of the alimentary tract. This case study emphasizes the atypical presentation of hollow visceral myopathy and the importance of thorough investigations, the various findings during surgery (including a para-duodenal volvulus), and the different approaches to decompression of the intestinal tract that may be considered for such a patient.

Pediatric Intestinal Pseudo-obstruction in the Era of Genetic Sequencing.

The purpose of this review is to discuss current knowledge on pediatric intestinal pseudo-obstruction. We will also review new mutations that have been identified through advancement in genetic testing, allowing for a better understanding of the underlying mechanisms of intestinal dysmotility and potential etiologies. With the advancements in genetic testing, new mutations have been identified in the diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), a disorder leading to pediatric pseudo-obstruction. MYLK, LMOD1, MYL9, and MYH11 encode for various proteins within smooth muscle cells; abnormalities within these proteins lead to abnormal intestinal smooth muscle contractions. Chronic intestinal pseudo-obstruction (CIPO) is defined by symptoms of bowel obstruction in the absence of a lumen-occluding lesion. CIPO is a heterogeneous group of disorders caused by abnormalities in the enteric neurons, intestinal smooth muscle, and/or the interstitial cells of Cajal (ICC). Symptoms can be non-specific and etiologies include both primary and secondary causes of CIPO that contribute to the delay in recognizing this condition and making the correct diagnosis. Chronic intestinal pseudo-obstruction has been recognized in both adults and children with fundamental differences in the etiology, symptom onset, clinical features and natural history of this disorder. For this reason, it has been considered a separate entity referred to as pediatric intestinal pseudo-obstruction (PIPO).

Unusual Histology of Eosinophilic Myenteric Ganglionitis: A Case Report.

Eosinophilic myenteric ganglionitis is a disorder characterized by infiltration of the Auerbach myenteric plexus by eosinophils. As a cause of chronic intestinal pseudo-obstruction (CIPO), eosinophilic myenteric ganglionitis has been rarely reported and the majority of the reported cases in the literature were children. We experienced a case of eosinophilic myenteric ganglionitis associated with CIPO in a 53-year-old female patient. Histologic examination of the resected descending colon showed moderate eosinophilic infiltrates with hypogangliosis in the myenteric plexus. Immunohistochemical study revealed increased number of CD4-positive lymphocytes and stronger but scantier glial fibillary acid protein expression in the inflamed myenteric plexus.

Chronic Intestinal Pseudo-obstruction: A Rare Paraneoplastic Syndrome

Chronic Intestinal Pseudo-obstruction (CIPO) is a rare digestive disorder that is a disruption in gut motility mimicking obstruction but not associated with a mechanical obstruction. CIPO can be secondary to an underlying pathology or idiopathic. Secondary causes of CIPO are numerous including paraneoplastic process. This case highlights the challenging evaluation of CIPO presenting as a paraneoplastic neurologic syndrome (PNS). A 57-year-old black male with a history of tobacco use presented with symptoms and imaging consistent with a partial small bowel obstruction (pSBO). He underwent an exploratory laparotomy that was unrevealing for the cause of his pSBO and therefore was transferred to a tertiary care center for further evaluation. His initial work-up including ileocolonoscopy was concerning for Crohn's Disease. Due to lack of clinical response with steroids, he underwent an ileocecal resection with pathology negative for Crohn's Disease. His imaging continued to show dilated loops of small bowel with air fluid levels, and he was subsequently diagnosed with CIPO (Figure 1). CT scans of the chest, abdomen, and pelvis showed no signs of malignancy. Work-up for secondary causes of CIPO with a Mayo Clinic Paraneoplastic Autoantibody Evaluation of serum was positive for anti-ganglionic neuronal acetylcholine receptors (ganglionic AchR) and acetyl receptor striational (StrAbs). Two years later, respiratory complaints prompted a repeat CT chest that revealed a pleural effusion, and the pathology was consistent with lung adenocarcinoma (Figure 2). PNS is a rare paraneoplastic process that causes gut dysmotily, most commonly CIPO. Certain onconeural antibodies are specific for gut dysmotility such as type 1 anti-neuronal nuclear antibody (ANNA-1), which has the strongest correlation between gut dysmotility and malignancy. Surprisingly, our patient was negative for ANNA-1. Ganglionic AchR and StrAbs are associated with gut dysmotility and lung cancer, which correlates with the patient's findings. His initial imaging did not show signs of malignancy, which can be expected as symptoms of gut dysmotility due to PNS may occur months prior to diagnosis of the malignancy. No definitive features differentiate paraneoplastic and non-paraneoplastic CIPO, therefore it is important to investigate and continue surveillance for malignancies especially in those who smoke.Figure 1Figure 2

Chronic intestinal pseudo-obstruction: systematic histopathological approach can clinch vital clues

The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is critical, and the findings are often missed by the histopathologists for lack of awareness and nonavailability of standard criteria. We aimed to describe a detailed histopathological approach for working-up cases of CIP by citing our experience. Eight suspected cases of CIP were included in the study to determine and describe an approach for reaching the histopathological diagnosis collected over a period of the last 1.5 years. The Hirschsprung's disease was put apart from the scope of this study. A detailed light microscopic analysis was performed along with special and immunohistochemical stains. Transmission electron microscopy was carried out on tissue retrieved from paraffin embedded tissue blocks. Among the eight cases, three were neonates, one in the pediatric age group, two adolescent, and two adults. After following the described critical approach, we achieved the histological diagnoses in all the cases. The causes of CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4), mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in all of them along with other primary pathologies. One of the IND patients also had visceral myopathy, type IV. Histopathologists need to follow a systematic approach comprising of diligent histological examination and use of immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup. Therapy and prognosis vary depending on lesions identified by pathologists. These lesions can be seen in isolation or in combinations.

Intestinal pseudo-obstruction due to small bowel α-actin deficiency in a child with Ehlers–Danlos syndrome

Chronic intestinal pseudo-obstruction (CIPO) is a syndrome characterized by signs and symptoms of intestinal obstruction without a mechanical cause. In children, two main subtypes, the neuropathic and myopathic forms, are found [1]. A variety of pathological findings of the smooth muscle can result in clinical syndromes involving a motility disorder of the small or large intestine. Moreover, abnormalities of enteric innervation or intestinal muscle defects may be diffuse or involve limited tracts [1]. Deficiency of one of the isoforms of the cytoskeletal smooth muscle protein actin, aactin, involving the circular muscle of the jejunum, is known to induce CIPO both in adults and in children [2]. We report a unique case of a-actin deficiency associated with Ehlers– Danlos syndrome. A 14-year-old girl was urgently admitted because of shock with abdominal distension and severe dehydration. On plain abdominal X-rays, severe small and large bowel dilatation was noted. The patient’s history was negative for any previous medical or surgical condition. She had mandibular prognathism causing aerophagia and affecting speech and mastication. An urgent exploratory laparoscopy was carried out; dilatation of the ascending colon and terminal ileum were found. No perforation or necrosis was detected on inspection of the whole intestine. Two weeks later, persistent bowel dilatation necessitated ileostomy. The patient developed intestinal obstruction following ileostomy closure. Subsequently, several surgical intestinal deviation procedures were performed and after every attempt at reversal immediate reoperation was required. Ten months later, a definitive end ileostomy had to be fashioned 10 months later. Full-thickness biopsies of the ileum and colon were obtained. Histological examination with conventional (hematoxylin and eosin, H&E) staining appeared basically normal (Fig. 1a). Immunohistochemical assessment (NSE, S100, CD117) showed normal features of the enteric nervous system in both the small intestine and the colon, whereas immunohistochemistry for a-actin revealed decreased expression in the circular layer of the small bowel (Fig. 1b– d) and normal features in the colon. Skin biopsy performed after abdominal surgery, revealed hallmarks of disturbed fibrillogenesis and led to the diagnosis of Ehlers–Danlos syndrome, classical type (old type I) [3]. Abnormal intestinal findings often leading to intestinal perforation, especially in the colon, are observed in Ehlers– Danlos syndrome, although almost exclusively in patients with subtype IV [4]. As far as we know, no previous association has been described between Ehlers–Danlos syndrome and a-actin deficiency. The latter was probably the cause of CIPO in our patient (since the enteric nervous system appeared normal), causing impaired propulsion in the small bowel and pseudo-obstructive symptoms. The diagnosis of CIPO, in both adults and children, is often delayed, due a low index of suspicion and the fact G. Pelizzo ! G. Nakib ! V. Calcaterra Pediatric Surgery Unit, Department of Mother and Child Health, IRCSS Polyclinic S. Matteo Foundation, University of Pavia, Pavia, Italy

Visceral Smooth Muscle α-Actin Deficiency Associated With Chronic Intestinal Pseudo-obstruction in a Bengal Cat (Felis catus × Prionailurus bengalensis)

An adult Bengal cat (Felis catus × Prionailurus bengalensis) with a prolonged history of partial anorexia, regurgitation, and weight loss and a clinical, radiographic, and ultrasonographic diagnosis of persistent megaesophagus and gastrointestinal ileus was submitted for necropsy. The intestinal tract was diffusely distended by gas and fluid with appreciable loss of muscle tone and an absence of luminal obstruction, consistent with the clinical history of chronic intestinal pseudo-obstruction. Histologically, the autonomic nervous system was intact, but the smooth muscle within the gastrointestinal wall exhibited a marked basophilia that was most pronounced in the jejunum. Immunohistochemistry for neurofilament, synaptophysin, CD117, and desmin demonstrated that the number of myenteric ganglia, number of interstitial cells, and leiomyocyte desmin content were similar when compared with the unaffected age- and species-matched control. Immunohistochemistry for smooth muscle α-actin demonstrated a striking loss of immunoreactivity, predominantly in the circular layer of the jejunum, that corresponded with the tinctorial change in leiomyocytes. Transmission electron microscopy revealed loss of myofibrils, loss of organelle polarity, and significantly larger central mitochondria (megamitochondria) in affected leiomyocytes, as well as nonspecific degenerative changes. Although the presence of a primary leiomyopathy and a causal relationship could not be confirmed in this case, leiomyopathies are considered a cause of chronic intestinal pseudo-obstruction in human medicine, and loss of smooth muscle α-actin immunoreactivity is one recognized marker for intestinal dysmotility.

Eosinophilic myenteric ganglionitis as a cause of chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIPO) represents a rare and severe condition characterized by failure of the intestinal tract to propel its contents normally [1, 2]. The condition presents with clinical features such as abdominal pain, vomiting, distended abdomen, constipation, and diarrhea [1, 2]. These symptoms resemble an intestinal mechanical obstruction in the absence of a demonstrable lesion occluding the gut. It is thought that this can result from disturbance of the intestinal motor function, supplied by the enteric nervous system (ENS). The neurons of the ENS are contained in two groups of ganglia: the myenteric (Auerbach's) and the submucosal (Meissner's) plexuses. The ENS has the unique ability to control most gut functions, such as regulating vascular tone, secretion/absorption, and gut motility [3, 4]. Given these important functions of the ENS, it is not surprising that damage to the ENS results in digestive disorders and reduced quality of life. Human and experimental evidence indicates that inflammation can occur in the ENS, resulting in severe intestinal motor impairment. Inflammation of the ENS has indeed been observed in some cases of CIPO [3, 5, 6]. Many efforts have been made to classify CIPO. Based on histological examination, CIPO may be categorized as primary, secondary, or idiopathic in nature [1]. Primary CIPO can be classified into three major categories of gastrointestinal neuromuscular disorders (GINMD): mesenchymopathies, myopathies, and neuropathies, depending on the predominant involvement of interstitial cells, smooth muscle cells, or enteric neurons, respectively [1, 7]. The enteric neuropathies underlying CIPO can be subdivided into two major entities: (a) degenerative neuropathies, without any evident inflammatory response and (b) inflammatory neuropathies, referred to as myenteric ganglionitis [3, 8]. Inflammation within the myenteric ganglia is a recognized primary cause of CIPO, but the mechanisms through which the dysfunction occurs and the mechanisms leading to enteric neuropathies remain poorly understood [3, 4]. In this case report, we present the first male neonate with eosinophilic myenteric ganglionitis underlying CIPO and report his successful recovery following steroid treatment.

Frequency of Mitochondrial Defects in Patients With Chronic Intestinal Pseudo-Obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder caused by intestinal dysmotility and characterized by chronic symptoms suggesting bowel obstruction in the absence of fixed, occluding lesions. CIPO has been associated with primary defects of the mitochondrial oxidative phosphorylation pathway, although the frequency of mitochondrial disorders in patients with CIPO is unknown. This study evaluates mitochondrial function in patients with CIPO. A retrospective study was performed of data collected from 80 CIPO patients at a tertiary centre over a 25-year period. Mitochondrial disorders were detected by analysis of serum lactate and thymidine phosphorylase activities, brain magnetic resonance images, and muscle biopsies. Genes encoding thymidine phosphorylase, mitochondrial DNA tRNA(leu(UUR)) or tRNA(lys), and DNA polymerase-gamma were analyzed for mutations. Mitochondrial defects were identified in 15 patients (10 women; median age at diagnosis 32 years), representing 19% of the study cohort. All 15 patients had extra-digestive symptoms, 5 had mutations in the thymidine phosphorylase gene, 2 had mutations in tRNA(leu(UUR)), and 5 had mutations in the DNA polymerase-gamma gene. No genetic defect was detected in 3 of the patients with mitochondrial disorders. Patients with mitochondrial CIPO differed from patients without mitochondrial defects in their very severe nutritional status (frequent and long-term requirement for parenteral nutrition) and poor prognosis (frequent digestive and neurologic complications that led to a high incidence of premature death). Mitochondrial disorders seem to be an important cause of CIPO. Patients with CIPO, especially severe cases with associated neurologic symptoms, should be tested for mitochondrial defects.

Mitochondrial DNA A3243G mutation involved in familial diabetes, chronic intestinal pseudo-obstruction and recurrent pancreatitis

Aims To report on a family with five members who carry the A3243G mutation in mitochondrial tRNA for leucine 1 ( MTTL1) and present with diabetes, chronic intestinal pseudo-obstruction (CIPO) and recurrent pancreatitis, and to screen for this mutation in a cohort of 36 unrelated patients with recurrent pancreatitis. Methods The mutation was quantified in several tissue samples from patients. Respiratory chain activity was studied in muscle biopsies and fibroblast cultures. In addition, the thymidine phosphorylase gene ( TP) involved in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and three genes involved in chronic pancreatitis – PRSS1, SPINK1 and CFTR – were sequenced in affected patients. Finally, the MTTL1 gene was examined in 36 unrelated patients who had recurrent pancreatitis, but no mutations in the PRSS1 and SPINK1 genes. Results Heteroplasmy for the mtDNA A3243G mutation was found in all tissue samples from these patients, but no mutations were found in the genes coding for thymidine phosphorylase, PRSS1, SPINK1 and CFTR. Also, none of the 36 unrelated patients with recurrent pancreatitis were carrying any MTTL1 mutations. Conclusion The mtDNA A3243G mutation associated with the gastrointestinal manifestations observed in the affected family should be regarded as a possible cause of CIPO and unexplained recurrent pancreatitis. However, the mutation is probably only weakly involved in cases of isolated recurrent pancreatitis.

Autoimmune enteric leiomyositis: A rare cause of chronic intestinal pseudo-obstruction with specific morphological features

Autoimmune enteric leiomyositis is an extraordinary rare cause of acquired chronic intestinal pseudo-obstruction in children. We report a 5-year-old girl who developed chronic intestinal pseudo-obstruction 3 years after an autoimmune hepatitis. Mucosal biopsies of the upper gastrointestinal tract and colon showed minimal inflammatory changes. On full-thickness biopsies of the small intestine, a dense lymphocytic infiltrate of the muscularis propria was seen, mainly consisting of cytotoxic T lymphocytes. Smooth muscle fibers were degenerated and diminished, but the myenteric plexus was intact. The coexistence of an autoimmune hepatitis in our case indicates an expansion of autoreactive T cells to homologous self-antigens. It is of practical importance for histopathological diagnosis that inflammation in autoimmune enteric leiomyositis affects the muscularis propria of the small intestine, whereas mucosa and submucosa do not show severe inflammatory changes. Therefore, correct diagnosis may be missed in peroral and peranal mucosal biopsies, but full-thickness biopsies are required.

Neuronal dysplasia and chronic intestinal pseudoobstruction: Rectal biopsy as a possible aid to diagnosis

We report a patient with an unusual cause of chronic intestinal pseudoobstruction, i.e., neuronal intestinal dysplasia. This disorder is characterized by hyperplasia of the nerve plexuses of the intestine or colon, or both. Detailed morphologic and manometric studies are provided. The discussion emphasizes the various motor abnormalities that may be found in chronic intestinal pseudoobstruction. We propose that rectal biopsy may be of value in the diagnosis of this unusual form of pseudoobstruction.