Chronic Idiopathic Intestinal Pseudo-obstruction Research Articles

Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis

A 35-year-old male with an 11-year history of intestinal pseudo-obstruction associated with an idiopathic inflammatory insult of the myenteric plexus and the presence of circulating anti-Hu antibodies developed a neurological syndrome characterized by bilateral hearing loss, deteriorating balance, an unsteady gait and difficulty in estimating distances. A similar neurological syndrome has previously been described in older patients among the paraneoplasic syndromes associated with small-cell lung carcinoma and the presence of circulating anti-Hu antibodies, but never in the rare cancer-free patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction. The patient underwent a steroid treatment. No further episodes of functional intestinal obstruction were observed and, after an initial improvement, the neurological symptoms stabilized, leaving a permanent reduction in hearing function and an unsteady gait. The case shows that an idiopathic inflammatory insult of the myenteric plexus may precede (and perhaps lead to) central nervous system impairment in patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction.

Chronic Intestinal Pseudo‐Obstruction in a Cat Caused by Visceral Myopathy

Chronic Intestinal Pseudo‐Obstruction in a Cat Caused by Visceral Myopathy

TEGASEROD STIMULATES NORMAL BOWEL FUNCTION IN PSEUDOOBSTRUCTION

Chronic Idiopathic Intestinal Pseudoobstruction has been traditionally resistant to medical management. Patients with severe pseudoobstruction often require parenteral nutrition during the phases of bowel dilatation when even enteral feeds cannot be tolerated. We report a child with CIIPO who had a return to normal bowel function when tegaserod was instituted. Tegaserod has been approved for use in women with constipation predominant irritable bowel syndrome. Tegaserod is a partial neuronal 5-HT4 receptor agonist. Its action at the receptor site leads to stimulation of the peristaltic reflex and intestinal secretion, and moderation of visceral hypersensitivity. The time to peak absorption is one hour, and it is recommended that the medication be ingested prior to meals. Due to the effects on peristalsis of the intestines, we became interested in attempting to use this drug in a nine year old boy who had undergone reanastamosis of his small intestine with 30 centimeters of out of circuit colon. The patient had chronic bowel problems, and had undergone resection of a dilated loop of bowel with creation of an ileostomy. Colonic manometry was performed on the defunctionalized colon and demonstrated a high amplitude peristaltic contraction when provocative stimulant laxative was administered through the colon manometry catheter. The patient also stooled some water and secretions during the test. Based on this information, it was decided to reanastamose the large and small intestines. However, the patient could not tolerate feeds, and eventually ended up back on total parenteral nutrition. Within a short time of starting the tegaserod, the child was able to tolerate feeds and began to stool normally. To our knowledge this has not been previously reported. Tegaserod may have a role in treating patients with chronic intestinal pseudoobstruction.

Chronic idiopathic intestinal pseudo-obstruction: the need for a multidisciplinary approach to management.

At the outset of the research programme into irritable bowel syndrome (IBS) it was perceived that there was a need to develop a symptom-based classification for the patients. Four groups of patients were identified, those with spastic colon syndrome, diarrhoea-predominant spastic colon syndrome, functional diarrhoea and midgut dysmotility. While working with outpatients with IBS it was noted how some of them had suffered symptoms for many years; specifically, a group of patients satisfying the criteria for midgut dysmotility had also suffered from particularly severe and intractable intestinal symptoms. These patients underwent 24 h ambulatory studies of small intestinal motility and the majority were found to have manometric features of chronic idiopathic intestinal pseudo-obstruction (CIIP). To characterise the cause, laparoscopic full-thickness small intestine and colonic biopsies have been obtained in forty-five of the latter group of patients. Of these patients 58% have been found to have complete or partial deficiency of alpha-actin epitope staining in the inner circular layer of small intestinal smooth muscle. This deficiency is believed to represent an important biomarker rather than the cause of CIIP, since alpha-actin epitope deficiency has been observed in association with enteric neuropathy and myopathies. In relation to the management of CIIP patients, a multidisciplinary model is proposed incorporating management of co-morbid psychological and psychiatric pathology, abdominal and musculoskeletal pain, fatigue, urological symptoms and nutrition. A six-stage nutritional management plan for these patients is presented.

Intestinal transplantation for gut failure

In recent years, we have witnessed increasing clinical experience with intestinal transplantation at selected centers. Although early results with this therapy were poor, several important advances have led to improved outcomes. These improvements prompted the Centers for Medicare and Medicaid Services to issue a memorandum on October 4, 2000, according federal reimbursement for intestinal transplantation at selected centers and for selected indications.1 The Centers for Medicare and Medicaid Services stipulated that, to qualify for transplantation, patients must meet a specific definition of intestinal failure and have experienced failure of parenteral nutrition (Table 1). In addition, the Centers for Medicare and Medicaid Services set forth centerspecific criteria for reimbursement, including 1-year patient survival rates of at least 65% and minimum center volume of at least 10 transplants performed per year. Only 4 centers in the United States currently meet these criteria (Mount Sinai Medical Center, University of Pittsburgh Medical Center, University of Miami, and University of Nebraska Medical Center). Thus, intestinal transplantation is currently at a crossroads, transitioning from its historical status as an experimental therapy to standard care for patients with appropriate indications. Presently, appropriate indications, timing of referral, and outcomes of intestinal transplantation are not well recognized among physicians caring for patients who may be candidates for this therapy. Definitions of terms such as “intestinal failure” and “failure of parenteral nutrition” are not standard, and there is no accepted algorithm for integrating parenteral nutrition, intestinal rehabilitation, and transplantation for patients with intestinal failure. Herein we review (1) the applicability of intestinal transplantation for patients with intestinal failure, (2) the current state of medical practice in intestinal transplantation with an emphasis on recent improvements, and (3) current results of this therapy. We also offer for the general gastroenterologist or gastrointestinal surgeon a rational approach to managing intestinal failure and integrating intestinal rehabilitation, parenteral nutrition, and transplantation.2 Brief History

Role of interstitial cells of Cajal in motility disorders of the bowel

Objective Idiopathic intestinal pseudo-obstruction is characterized by the failure of the intestinal tract to propel its contents appropriately. This leads to signs and symptoms of bowel obstruction and, in the absence of an associated systemic disorder or the administration of drugs known to result in bowel dysmotility, is termed chronic idiopathic intestinal pseudo-obstruction (CIIP). Histopathologically, patients with CIIP can be characterized as having either myopathic or neuropathic forms, but the large majority of patients do not show any specific histological changes. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the bowel and have been implicated in the pathogenesis of CIIP. The aim of this study was to compare the number and distribution patterns of c-kit+ ICC in CIIP in patients with mechanical bowel obstruction, other bowel motility disorders, and normal controls. Methods Six patients with CIIP, six age-matched normal controls, nine patients with mechanical bowel obstruction, and 18 patients with other motility disorders (non-CIIP), including 10 with secondary intestinal pseudo-obstruction, were studied. Toluidine blue, Masson’s trichrome, and S-100 immunostaining were performed in all subjects. The ICC were identified by an indirect immunoperoxidase method using a polyclonal c-kit antibody. Results All six patients with CIIP showed total absence of c-kit+ ICC. A subject with neonatal meconium ileus in the non-CIIP group showed patchy areas devoid of c-kit+ ICC amid normal areas. The c-kit+ ICC had a normal number and distribution pattern in all patients with mechanical obstruction and in the remaining 17 non-CIIP subjects. Conclusions It seems that CIIP is characterized by a total loss of c-kit+ ICC. ICC may play an important role in the etiopathogenesis of CIIP and transient neonatal meconium syndrome, and staining for c-kit receptor may be very useful in the evaluation of motility disorders of the bowel.

Role of interstitial cells of Cajal in motility disorders of the bowel.

Idiopathic intestinal pseudo-obstruction is characterized by the failure of the intestinal tract to propel its contents appropriately. This leads to signs and symptoms of bowel obstruction and, in the absence of an associated systemic disorder or the administration of drugs known to result in bowel dysmotility, is termed chronic idiopathic intestinal pseudo-obstruction (CIIP). Histopathologically, patients with CIIP can be characterized as having either myopathic or neuropathic forms, but the large majority of patients do not show any specific histological changes. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the bowel and have been implicated in the pathogenesis of CIIP. The aim of this study was to compare the number and distribution patterns of c-kit+ ICC in CIIP in patients with mechanical bowel obstruction, other bowel motility disorders, and normal controls. Six patients with CIIP, six age-matched normal controls, nine patients with mechanical bowel obstruction, and 18 patients with other motility disorders (non-CIIP), including 10 with secondary intestinal pseudo-obstruction, were studied. Toluidine blue, Masson's trichrome, and S-100 immunostaining were performed in all subjects. The ICC were identified by an indirect immunoperoxidase method using a polyclonal c-kit antibody. All six patients with CIIP showed total absence of c-kit+ ICC. A subject with neonatal meconium ileus in the non-CIIP group showed patchy areas devoid of c-kit+ ICC amid normal areas. The c-kit+ ICC had a normal number and distribution pattern in all patients with mechanical obstruction and in the remaining 17 non-CIIP subjects. It seems that CIIP is characterized by a total loss of c-kit+ ICC. ICC may play an important role in the etiopathogenesis of CIIP and transient neonatal meconium syndrome, and staining for c-kit receptor may be very useful in the evaluation of motility disorders of the bowel.

Hyperbaric oxygen therapy for Chronic Idiopathic Intestinal Pseudo-Obstruction?

Hyperbaric oxygen therapy for Chronic Idiopathic Intestinal Pseudo-Obstruction?

A patient with chronic idiopathic intestinal pseudo-obstruction treated with splanchnic nerve block

We report here a patient presenting with long-lasting chronic abdominal pain and constipation that was successfully treated using bilateral splanchnic nerve blocks. Two laparotomies did not reveal the cause the intestinal obstruction and a diagnosis of chronic idiopathic intestinal pseudo-obstruction was made. The splanchnic nerve block is a good option in the treatment of this disease.

Chronic Idiopathic Intestinal Pseudo-obstruction.

The definition of chronic idiopathic intestinal pseudo-obstruction (CIIP) is somewhat vague because it was based on clinical observations that preceded modern advances in the measurement of gut motility and neuromuscular integrity. Appropriate management of patients with CIIP requires an initial consideration, supported by pertinent diagnostic tests, of the tissue affected (muscle, nerves, both), extent and magnitude of gut propulsive failure, and extraintestinal disease.

The striking effect of hyperbaric oxygenation therapy in the management of chronic idiopathic intestinal pseudo-obstruction

Chronic idiopathic intestinal pseudo-obstruction is one of the disorders that is most refractory to medical and surgical treatment. Even when patients are given nutritional support, including total parenteral nutrition, obstructive symptoms seldom disappear. We report a case of chronic idiopathic intestinal pseudo-obstruction, due to myopathy, in which hyperbaric oxygenation therapy was strikingly effective. The presence of myopathy was histologically confirmed on the surgically resected jejunal specimen. Hyperbaric oxygenation resulted not only in relief of the patient’s obstructive symptoms but also in a rapid decrease of abnormally accumulated intestinal gas. At last, he could resume oral intake without any critical adverse effects. These observations strongly suggest that hyperbaric oxygenation can be an effective therapy in the management of chronic idiopathic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction: treatment and long term follow up of 44 patients

AIMSTo document the long term course of chronic idiopathic intestinal pseudo-obstruction syndrome (CIIPS) in children with defined enteric neuromuscular disease, and the place and type of surgery used in their...

Diagnosis and management of small intestinal diseases

Advances in the diagnosis and management of small bowel diseases are the subject of this review. Topics covered include improving the specificity of breath tests for bacterial overgrowth; small bowel enteroscopy; early diagnosis of mesenteric ischemia; the use of polymerase chain reaction for diagnosing central nervous system involvement in Whipple's disease; progress in defining the cause and pathogenesis of chronic idiopathic intestinal pseudoobstruction and the Peutz-Jeghers syndrome; defining the role of gut barrier function in health and disease; the therapeutic role for bile acid-binding resins in diarrhea after refeeding in critically ill patients; use of genetic techniques and topical steroid therapy in treating graft-versus-host disease; and the beneficial effects of combination hormonal therapy in occult gastrointestinal blood loss resulting from angiodysplasia.

Altered contractile proteins and neural innervation in idiopathic megarectum and megacolon.

The aetiology of idiopathic megarectum and idiopathic megacolon is unknown. We postulated that biochemical or ultrastructural abnormalities may be pathologically important, as has been observed in patients with chronic idiopathic intestinal pseudo-obstruction. Resection specimens from five patients with idiopathic megarectum or megacolon were processed for paraffin wax-embedded tissue histology (haematoxylin and eosin, Gomori trichrome and picrosirius stains, phosphatase activity and periodic acid-Schiff staining), and frozen tissue for histochemistry and electron microscopy. The antibodies used in the immunohistochemistry were to myosin light chain kinase, smooth muscle myosin, alpha and beta actins, filamin, tropomyosin, phosphorylated and dephosphorylated neurofilaments and N-CAM. Variable hypertrophy of the muscularis mucosae and externa, no atrophy, and a variable nerve density decrease in longitudinal muscle and increase in the lamina propria was seen. In one patient beta actin and myosin light chain kinase immunoreactivity was reduced. Variable changes in innervation, and an abnormal contractile protein immunoreactivity pattern in one patient, may be of pathogenic importance. These clinically homogeneous conditions are likely to be due to a range of underlying pathogenic abnormalities. A search for further specific biochemical abnormalities is justified.

Evaluation of specific herpes DNA viruses in idiopathic megarectum and idiopathic megacolon.

The aetiology of idiopathic megarectum and idiopathic megacolon is unknown. A previous study in patients with chronic idiopathic intestinal pseudo-obstruction, a condition also associated with a dilated gut, identified the possible involvement of herpes viruses. This study therefore aimed to determine whether these viruses may also be implicated in the pathogenesis of these conditions. Resected large bowel from three patients with idiopathic megarectum and three patients with idiopathic megacolon were studied. Histology for viral inclusions and nested polymerase chain reaction (PCR) using specific primers for cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1 and varicella zoster virus was performed. DNA was extracted from paraffin-embedded blocks by proteinase K and phenol chloroform extraction. Viral inclusions were not seen. PCR failed to identify DNA of the four herpes viruses tested. Patients with idiopathic megarectum or idiopathic megacolon may have subtle abnormalities of the enteric innervation, but these do not appear to be attributable to the neurotropic effects of the herpes viruses studied.

Abnormal distribution of intestinal pacemaker (C-KIT-positive) cells in an infant with chronic idiopathic intestinal pseudoobstruction

Background: Chronic idiopathic intestinal pseudoobstruction (CIIPO) is a rare syndrome with an obscure pathogenesis. The proto-oncogene c- kit encodes a transmembrane tyrosine kinase receptor C-KIT that is critical for the development of the interstitial cells of Cajal, cells that are regarded as being the pacemaker cells of the gut. Thus, C-KIT immunopositive (C-KIT +) cells in the muscle layers of the bowel are considered to be intestinal pacemaker cells. Methods: In this study, the distribution of intestinal pacemaker cells was examined for the first time using C-KIT immunohistochemistry in an infant with CIIPO. Results: C-KIT + cells were found lying on either side of the border between the two muscle layers (longitudinal and circular) of the bowel and dispersed unevenly throughout both muscle layers. Myenteric plexuses were not demarcated by C-KIT + cells. In contrast, in controls, C-KIT + cells were located distinctly between the two muscle layers of the small bowel and dispersed evenly throughout the muscle layers of the colon. Myenteric plexuses were clearly demarcated by C-KIT + cells. Conclusions: This case demonstrates for the first time that there is abnormal distribution of intestinal pacemaker cells in CIIPO and provides new evidence that abnormal c- kit gene expression may be responsible for autonomic gut dysmotility. C-KIT immunohistochemistry may be an indispensable tool for diagnosing CIIPO.

Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults

Background—Chronic idiopathic intestinal pseudo-obstruction, a syndrome of ineffectual motility due to a primary disorder of enteric nerve or muscle, is rare.Aims—To determine the clinical spectrum, underlying pathologies, response to treatments,...

Histological phenotypes of enteric smooth muscle disease causing functional intestinal obstruction in childhood.

Functional intestinal obstruction or chronic idiopathic intestinal pseudo-obstruction is due to defects either in the enteric innervation or in intestinal smooth muscle. We have studied full-thickness intestinal biopsies from 27 patients with functional intestinal obstruction due to enteric smooth muscle disease by routine histology and electron microscopy together with histochemical and immunohistochemical techniques to detect changes in the intestinal smooth muscle. Two patients appeared to have an acquired intestinal myopathy as a result of an autoimmune process. In 25 the disorders were congenital, of these seven had segmental abnormalities limited to the rectum and distal colon and 18 had a diffuse disease affecting both the small and large bowel. We identified five apparent histological phenotypes of enteric muscle disease, three of which represent abnormalities in morphogenesis resulting in alterations in intestinal muscle layering and two exemplify intrinsic myocyte defects and/or changes in the extracellular matrix. Careful phenotyping of these patients is important in devising optimal treatment and in understanding the underlying defect as well as the possible genetic mechanisms resulting in these abnormalities. Recognition of autoimmune smooth muscle disease is helpful, since making the diagnosis influences the patient's management.

Neurogenic chronic idiopathic intestinal pseudo-obstruction, patent ductus arteriosus, and thrombocytopenia segregating as an X linked recessive disorder.

We present a family with three affected males in two generations with congenital neurogenic chronic idiopathic intestinal pseudo-obstruction (CIIP), patent ductus arteriosus, and large platelet thrombocytopenia apparently segregating as an...

DNA viruses in the pathogenesis of sporadic chronic idiopathic intestinal pseudo-obstruction.

BACKGROUND: Hereditary forms of chronic idiopathic intestinal pseudo-obstruction (CIIP) are well described but the aetiology of most cases of sporadic CIIP is unknown. AIM: To determines whether herpes viruses can...