Chronic Idiopathic Intestinal Pseudo-obstruction Research Articles

Chronic idiopathic intestinal pseudoobstruction in children:a report of two cases

Chronic idiopathic intestinal pseudoobstruction in children:a report of two cases

RECENT ADVANCES IN THE PHARMACOLOGY OF GASTROINTESTINAL PROKINETICS

Gastrointestinal prokinetics promote or increase the coordination of the gut wall contractions leading to enhancement of propulsive motility and, consequently, caudal displacement of luminal contents. Currently, they are considered drugs of choice for the treatment of upper gastrointestinal tract functional motor disorders such as those associated with gastro-oesophageal reflux disease, chronic dyspepsia, gastroparesis (idiopathic or secondary to other diseases) and acute or chronic idiopathic intestinal pseudo-obstruction. The aim of the present review is to give an outline of the pharmacology of currently available prokinetics and of novel drugs endowed with gastrointestinal prokinetic action that require further pharmacological and/or clinical testing. The novel drugs include recent generations of benzamide and non-benzamide 5-HT 4receptor agonists, motilin receptor agonists, and inhibitors of nitric oxide synthase. Furthermore, based on our improved knowledge of the role of 5-HT in emesis and gastrointestinal motility, the therapeutic potential of potent mixed 5-HT 4agonists—5-HT 3antagonists in the control of cytotoxic-drug-induced emesis and associated gut motor disturbances will be discussed. Lastly, a section of this review deals with the colon as a possible target for the action of prokinetics.

Ambulatory 24-Hour Jejunal Motility in Diarrhea-Predominant Irritable Bowel Syndrome

Whether small-bowel motility is abnormal in the irritable bowel syndrome (IBS) is a controversy at present. The aim of our study was to compare ambulatory long-term jejunal motility in 35 IBS patients with predominant diarrhea to normal values obtained in 50 healthy controls. Twenty-four-hour motility was recorded in the proximal jejunum with a portable datalogger and tube-mounted miniature pressure sensors. Fasting motility in the waking (W) and sleeping (S) state and the motor response to a standardized evening meal of 600 kcal underwent visual and computer-aided analysis. Fasting motility in patients showed migrating motor complex (MMC) cycles of normal length and composition. Uninterrupted runs of discrete clustered contractions during phase II (W) occurred in 57% of patients and 52% of controls but had a significantly longer duration in patients (33 +/- 5 versus 19 +/- 7 min; p < 0.005). During phase II (W) IBS patients had an increase in aborally propagated contractions (41 +/- 2% versus 35 +/- 2%; p < 0.01) and higher contraction amplitudes (26.3 +/- 0.8 versus 23.0 +/- 0.5 mm Hg; p < 0.01). Similar differences were obtained during postprandial motility (47 +/- 3% versus 39 +/- 3%; p < 0.01, and 25.9 +/- 0.9 versus 23.8 +/- 0.05 mm Hg; p < 0.02). In three patients (8.6%) disturbed aboral migration of phase III and irregular burst activity, manometric features of chronic idiopathic intestinal pseudo-obstruction, were identified. Whereas 57% of patients had an entirely normal 24-h manometry, 43% had at least one finding not present in any healthy control. Small-intestinal motility is frequently but not universally abnormal in diarrhea-predominant IBS. The abnormal manometric findings are heterogeneous and range from subtle quantitative changes to severe qualitative abnormalities resembling chronic idiopathic intestinal pseudo-obstruction in a small subset of patients.

Plasma somatostatin pattern in patients with chronic idiopathic intestinal pseudo-obstruction

Plasma somatostatin pattern in patients with chronic idiopathic intestinal pseudo-obstruction

A lack of intestinal pacemaker (c- kit) in aganglionic bowel of patients with Hirschsprung's disease

Recent experimental studies in mice have shown that the proto-oncogene c- kit plays a key role in the development of a component of the pacemaker system that is required for generation of autonomic gut motility. These studies further suggest that interaction of the c- kit receptor and its ligand (stem cell factor, SCF) is critical for the development of the enteric nervous system. The authors investigated the presence of c- kit-positive (c- kit + ) cells as well as the expression of SCF in bowel from 12 patients with Hirschsprung's disease (HD), 4 patients with total colonic aganglionosis (TCA), 2 patients with extensive aganglionosis (EA) and 14 controls. Our methods involved the use of immunohistochemistry with antihuman c- kit sera and antihuman SCF sera. A few c- kit + cells were found in the muscle layers of aganglionic bowels from HD, TCA and EA, in contrast to many c- kit + cells in ganglionic bowel segments from control, HD, and TCA patients. Expression of SCF was identified in the muscle layers as well as in myenteric plexus of ganglionic bowel, in contrast to its absence in the muscle layers of aganglionic bowel specimens. A lack of c- kit and SCF might be of significance for autonomic gut dysmotility in aganglionic bowel segments of patients with HD and allied disorders such as chronic idiopathic intestinal pseudo-obstruction.

Aganglionosis and related disorders

Congenital aganglionosis or Hirschsprung's disease (HD) characteristically presents with involvement of the sigmoid colon and rectum. There is an associated increase in cholinergic and adrenergic innervation in the affected bowel wall. Diagnosis of HD in the neonatal period is readily achieved via submucosal rectal biopsy with recognition of the immaturity of ganglion cells within the first year of life, use of a standardized protocol, and supplemental acetylcholinesterase stain. Morbidity and mortality from HD occur caused by Hirsch-sprung's-associated enterocolitis (HAEC); the pathologist can alert the clinician to the presence of HAEC. The HD variant to be aware of is total colonic aganglionosis, which may lack hypertrophic nerves and increased cholinergic nerve endings and contain zonal areas of some ganglion cells. Pseudo HD includes intestinal neuronal dysplasia (IND), chronic idiopathic intestinal pseudo obstruction (CIIP), and chronic constipation in children. Intestinal neuronal dysplasia is characterized by hyperganglionosis, whereas CIIP and chronic constipation in children share a common, newly described myopathic pathology. In this review investigation into peptidergic (VIPergic) innervation in pseudo HD and HD shows increased VIPergic immunostaining in CIIP, chronic constipation, and the ganglionic portion of HD; however, the VIPergic pattern is not diagnostically selective. Until the advent of new molecular biological techniques, histopathology remains the diagnostic gold standard in HD.

Antroduodenojejunal manometry in the diagnosis of chronic idiopathic intestinal pseudoobstruction in children.

We analyzed the antroduodenojejunal (ADJ) manometric patterns in a group of 19 consecutive children (mean age, 53 months; range, 5 months to 14 years) referred for suspected chronic idiopathic intestinal pseudoobstruction. Diagnosis was based on typical symptoms, absence of extraintestinal diseases, and structural lesions of the gut at endoscopy and radiology. Surgical full-thickness intestinal biopsies were evaluated in nine patients. Manometry of the stomach and small bowel was performed in the fasting and fed state with a multilumen perfused probe. All patients showed severe abnormalities of ADJ motor activity that were not seen in the eight controls (mean age, 38.2 months; range, 1-9 years). In 12 patients, manometric patterns suggesting neuropathic disease were detected with fasting and/or fed sustained and incoordinated duodenojejunal phasic waves, aberrant propagation and/or configuration of phase III of the inter-digestive motility complex, inability of a meal to convert a fasting into a fed pattern, and prolonged groups of fasting and fed nonpropagated phasic waves. In seven of these patients, histology revealed marked changes of the intrinsic neurons. In four cases, manometry disclosed features suggestive of a myogenic disease, including severe fasting and fed infrequent low-amplitude contractions, sometimes with some degree of propagation; in two of these cases, histology showed morphological abnormalities of smooth muscle cells of the gut wall. In three patients, manometry revealed signs suggestive of mechanical obstruction of the gut, such as repetitive post-feeding clusters and simultaneous repeated broad-based waves; in these patients, more detailed x-ray studies showed organic obstructive causes (ileal lymphoma, Hirschsprung's disease, and intestinal malrotation).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, laboratory and prognostic features of congenital large intestinal motor dysfunction (pseudo-Hirschsprung's disease).

One hundred and forty-eight cases of congenital large intestinal motor dysfunction (pseudo-Hirschsprung's disease) were reported by members of the Japanese Society of Pediatric Surgeons during the past 20 years. The disorder was defined as a congenital, non-mechanical obstruction of the intestine with the presence of intramural ganglia in the terminal rectum. Intramural ganglia were abnormal in 77 cases, normal in 42, and could not be determined in 29. Of those with abnormal intramural ganglia, 54 had immature ganglia or hypoganglionosis (oligoganglionosis), 15 had neuronal intestinal dysplasia, and eight had a segmental anomaly. Of those with a normal myenteric plexus, 22 had chronic and twelve had suspected idiopathic intestinal pseudo-obstruction syndrome; eight had megacystis-microcolon-intestinal hypoperistalsis syndrome. While cases with both hypoganglionosis and normal intramural ganglia had normal acetylcholine esterase activity, a significantly greater number of patients with hypoganglionosis lacked normal rectoanal reflexes. Patients with hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction syndrome, and megalocystis-microcolon-intestinal hypoperistalsis syndrome had poor prognoses with an overall mortality of 36.9%. These findings indicate that congenital large intestinal motor dysfunction remains a serious disease of childhood.

Biliary tract complications in patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome

The biliary tract system was studied in two patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome (CIIPS) to evaluate manifestations of these diseases, especially as for underlying motility disorder. In a 3-year-old boy with hypoganglionosis, cholelithiasis was diagnosed and the gallbladder specimen showed a markedly hypoplastic neural plexus on histopathology as was found in his total alimentary tract. In a 2-year-old girl with CIIPS, echo-guided gallbladder wall motility testing demonstrated an impaired response to a ceruletide diethylamine stimulation. These clinical experiences in two patients suggest that these pathological entities may be frequently associated with biliary tract complications not only due to a consequence of total parenteral nutrition, but also due to a possible intrinsic involvement of biliary tract dysmotility.

Gastric antral dysrhythmias in children with chronic idiopathic intestinal pseudoobstruction.

Chronic idiopathic intestinal pseudoobstruction is a serious disorder of intestinal neuromuscular function resulting in recurrent episodes of intestinal obstruction, and is caused by primary disease of the enteric nerves or enteric smooth muscle. Gastric electrical control activity detected by the non-invasive technique of surface electrogastrography was investigated in 11 children (0.1-16 years) with proven chronic idiopathic intestinal pseudoobstruction (four with known disease of the enteric nerves, three with disease of smooth muscle cells, and four without defined pathology), to determine whether abnormalities were present and whether these were useful in detecting the underlying pathology. Abnormalities were present in eight of 11 patients. Persistent tachygastria (electrical control activity frequency > 5 cycles/minute) was found in three patients, all with a proven neuropathy. A continuously irregular frequency was found in five patients, three with a proven myopathy and two with undefined pathology. A normal electrical control activity frequency was present in three patients, one with a proven neuropathy and two with undefined pathology. It is suggested that this non-invasive technique may provide a useful screening test of the pathophysiological basis of the functional obstruction in children with chronic idiopathic intestinal pseudoobstruction.

The small intestine and colon: scintigraphic quantitation of motility in health and disease

Radioisotopes allow accurate quantitation of the pattern and effectiveness of the transit of chyme through the small and large intestines. Abnormalities of small bowel transit can be demonstrated in patients with the irritable bowel syndrome, and patients with chronic idiopathic intestinal pseudo-obstruction due to either a visceral myopathy or neuropathy. In the colon, radioisotopic studies of transit have demonstrated the site of delayed transit in some severely constipated patients. In patients with these disorders of transit, functional studies may influence the choice of medical or surgical therapy although there are few prospective studies which have established their worth in this context. Radioisotope studies can also be utilised to study the effectiveness of delivery of drugs to the small and large bowel, and to study the adequacy of rectal evacuation in patients with a defaecatory disturbance. The low radiation dose and possibility of frequent observations make radioisotope studies valuable for clinical and research studies in functional gastrointestinal disorders.

Aerobilia and hypomotility of the sphincter of oddi in a patient with chronic intestinal pseudo-obstruction

A 50-year-old woman with a typical history of chronic idiopathic intestinal pseudo-obstruction was admitted to hospital because of an acute episode of abdominal cramps, nausea, and vomiting. The diagnosis of chronic idiopathic intestinal pseudo-obstruction had been established in this patient who had malnutrition and extreme weight loss as a result of severe malabsorption syndrome. The abdominal roentgenogram showed a typical hypotonic intestine with an enlarged stomach and distended intestinal loops with the radiological signs of an ileus. In addition to former episodes, there was also a transient aerobilia. The patient had not undergone biliary surgery or endoscopic sphincterotomy. To investigate the cause of the findings, endoscopic retrograde cholangiopancreatography and endoscopic manometry of the sphincter of Oddi were performed. The endoscopy showed the stomach and duodenum with a wide and dilated lumen and no spontaneous motility. Endoscopic manometry of the biliary tract and the sphincter of Oddi showed several abnormalities compared with a group of normal volunteers or patients who were examined via biliary manometry for other reasons. There was a low basal pressure (3.5 mm Hg) in the sphincter of Oddi together with low-amplitude phasic contractions (25–30 mm Hg), but the contraction frequency was in the normal range. Further investigations of the motility of the gastrointestinal tract in this patient showed diffuse esophageal spasms and a markedly delayed gastric emptying. The findings of biliary manometry in this patient suggest involvement of the sphincter of Oddi and the biliary system in chronic idiopathic pseudo-obstruction.

Familial visceral neuropathy with neuronal intranuclear inclusions: Diagnosis by rectal biopsy

A family with a visceral neuropathy manifested as chronic idiopathic intestinal pseudo-obstruction is reported. Diagnoses were made histologically by simple rectal biopsy. Discrete eosinophilic intranuclear inclusions, diagnostic of a disease known as neuronal intranuclear inclusion disease, were found in the submucosal ganglion cells. Abnormalities of the autonomic nervous system were identified by pupillary examination and electroretinography. In this family, three of four siblings were affected by the disease, which is apparently transmitted from the paternal side. This pedigree was unique for several reasons: (a) diagnosis in multiple members of two generations indicates that this familial visceral neuropathy was expressed in an autosomal dominant manner, (b) central autonomic nervous system abnormalities were detected by eye examination, and (c) the definitive pathological diagnosis was established antemortem by rectal biopsy in all cases.

Persistent gastrointestinal symptoms after correction of malrotation.

Persistent vomiting, diarrhoea, or intolerance of feeding, are well recognised problems in children after surgical correction of intestinal malrotation. Conversely, intestinal malrotation is a common accompaniment of chronic idiopathic intestinal pseudo-obstruction. We investigated motor activity of the small intestine during fasting in eight children who had persistent vomiting, intolerance of full enteral feeding, or severe diarrhoea after surgical correction of intestinal malrotation. Abnormality of motor function similar to that found in neuropathic pseudo-obstruction was found in seven of the eight patients. Persistence of symptoms after surgical correction of a malrotation is associated with a motility disturbance which seems to be due to a defect of intrinsic enteric innervation. Such a defect may be important in the aetiology of the malrotation.

Idiopathic constipation: any movement?

Severe constipation now attracts considerable research interest. As a consequence, there have been recent advances in most aspects of this disorder. The epidemiology of this condition is now better appreciated, and subgroups of patients with different epidemiologies, symptom complexes, aetiologies, and treatments can now be distinguished. Radioisotopes enable detailed transit studies to be obtained of the entire gastrointestinal tract. Careful psychologic evaluation is an essential part of the evaluation. In young women with severe idiopathic constipation there is a decrease in propulsive mass movements, and specific colonic neurotransmitter abnormalities have been identified. Biofeedback therapy is an effective treatment for many of these patients. The variable results of surgery are now also clearly defined. Patients with chronic idiopathic intestinal pseudoobstruction can be categorized on the basis of their pathologic findings; detailed tissue studies may be required. The recognition that severe constipation encompasses various different conditions is leading to a more precise understanding of pathogenesis and treatment.

Degenerative leiomyopathy in children. A clinico-pathological study

The syndrome of degenerative leiomyopathy (DL) causing intestinal obstruction clinically manifests in young indigenous African children as massive megacolon without aganglionosis. We report on a clinico-pathologic study of 18 children seen over a 15-year period. All patients came from the same geographic area. Mean age at presentation was 9.5 years with mean duration of symptoms 4.3 years. The youngest infant was 6 months old. Eighteen children presented with progressive abdominal distention and infrequent stooling; 11 had intermittent diarrhoea and 9 colicky abdominal pain. Gross colonic gaseous distention was noted with proximal extension into the small bowel in 9 and into the stomach and oesophagus in 4. The rectosphincteric reflex was present in all 7 patients studied with anorectal manometry. The diagnosis, confirmed on full-thickness rectal biopsy, showed characteristic features distinguishing it from chronic idiopathic intestinal pseudo-obstruction, progressive systemic sclerosis, and mixed connective-tissue disease of childhood. The bowel was dilated, thin-walled, and on microscopy showed smooth-muscle degeneration and necrosis with replacement fibrosis of muscular layers, displacement of ganglion cells, mild increase in numbers and thickness of nerve fibres, mild inflammatory change, and medial fibrosis of small muscular arteries. Immunohistochemical studies were within normal limits. One child died; 14 have been maintained with a combination of prokinetic agents, low-residue diet, laxatives, and enemas; and 3 patients did not respond to this medical therapy on short-term follow-up. Nine children required surgical intervention — 2 diagnostic laparotomies, 4 volvulus, and 3 adhesive bowel obstructions. Four of these required subsequent surgical procedures. DL is a distinctive entity with a classical clinical and histologic picture whose exact etiology is still obscure, Exploratory laparotomy should be avoided.

Pneumatosis and pneumoperitoneum in chronic idiopathic intestinal pseudoobstruction

Chronic idiopathic intestinal pseudoobstruction is a diagnosis of exclusion for the rare patient with severe small bowel atony without any demonstrable organic cause. The very poor prognosis associated with this disease has been somewhat improved with the advent of parenteral nutrition; nevertheless, these patients follow a stormy course characterized by malnutrition, recurrent obstruction, infection, hemorrhage, and perforation. We describe a 16-year-old boy with this disease who presented to us with vague abdominal pain and pneumoperitoneum. Laparotomy showed pneumatosis cystoides intestinalis without intestinal perforation. The presence of free air in the abdominal cavity is an almost pathognomonic sign of intestinal perforation. Pneumatosis cystoides intestinalis is one of the very few nonsurgical causes of pneumoperitoneum. Beyond the neonatal period, in which it is the hallmark of necrotizing enterocolitis, it has been described in patients with severe obstructive lung disease, in collagenous disorders, and in the short-bowel syndrome. In the present case, it may have resulted from chronic intestinal distension, allowing air under pressure to dissect through the bowel wall. The challenge of such a unique association of conditions lies in the avoidance of unnecessary surgery in a chronic, essentially nonsurgical disease while avoiding unnecessary delay in a possibly acute surgical event.

Recurrent Pancreatitis in Three Patients with Chronic Idiopathic Intestinal Pseudo-obstruction

Chronic idiopathic intestinal pseudo-obstruction is a syndrome with substantial morbidity and mortality associated both with the syndrome and with its therapy. Standard therapy has included prokinetic agents and intravenous nutritional support when oral feedings are inadequate to maintain nutriture. We report three children with chronic intestinal pseudo-obstruction who experienced one or more attacks of pancreatitis. Two patients developed pseudocysts. One patient died. All three patients underwent cholecystectomy; one had stones, one had acalculous cholecystitis, and one had a normal gallbladder. All patients received prokinetic agents and total parenteral nutrition as therapy for their pseudo-obstruction. Candidate mechanisms to explain the etiology for pancreatitis in chronic intestinal pseudo-obstruction include biliary dysmotility associated with pseudo-obstruction and excessive cholinergic stimulation due to therapy with prokinetic agents.

Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma

Severe gastrointestinal dysmotility is a newly recognized paraneoplastic syndrome that occurs with small-cell lung carcinoma. Thirty-four patients with small-cell carcinoma, of whom 5 had chronic intestinal pseudoobstruction and 29 had no digestive symptoms, were studied serologically. Four of the 5 patients with gut dysmotility had immunoglobulin G antibodies reactive with neurons of the myenteric and submucosal plexuses of jejunum and stomach in an indirect immunofluorescence assay. Antibodies of this type were not found in any of the 29 patients who had no gut dysmotility, nor were they found in patients with chronic idiopathic intestinal pseudoobstruction (n = 8), ovarian cancer (n = 20), or epilepsy (n = 4) or in normal subjects (n = 9). In 4 of the patients with paraneoplastic pseudoobstruction, antibodies in highly diluted serum (1:4000–1:8000) bound selectively to nuclei and cytoplasm of neuronal elements in the gut. This novel autoantibody activity suggests that intestinal pseudoobstruction occurring in patients with small-cell carcinoma may have an autoimmune basis. From a clinical standpoint, serological testing offers a simple means for determining which patients with gut dysmotility syndromes may have associated small-cell carcinoma, thereby enabling earlier diagnosis and treatment of the tumor.

A case of chronic idiopathic intestinal pseudoobstruction and review of literatures in Japan

A case of chronic idiopathic intestinal pseudoobstruction and review of literatures in Japan