Chronic Intestinal Pseudo-obstruction Syndrome Research Articles

Idiopathic chronic intestinal pseudo-obstruction syndrome is strongly associated with low serum levels of vitamin D.

Idiopathic chronic intestinal pseudo-obstruction (CIPO) is associated with intestinal inflammation and malabsorption and may cause serum vitamin D deficiency. We aimed to assess whether there is an association between idiopathic CIPO and serum levels of 25-hydroxy-vitamin D. Consecutive patients with confirmed diagnosis of idiopathic CIPO were prospectively enrolled and matched with healthy controls by gender, age, and BMI. Median serum level of 25-hydroxy-vitamin D of patients with CIPO was compared with that of healthy subjects using the Wilcoxon signed-rank test for matched samples. A total of 35 patients with CIPO and 35 matched healthy subjects were enrolled. All patients with CIPO had a 25-hydroxy-vitamin D deficiency with serum levels <12 ng/ml. The median serum level of vitamin D was significantly lower in patients with CIPO than in healthy controls (5.7 vs. 29.7 ng/ml, P < 0.0001). Serum level of vitamin D was not associated with gender ( P = 0.27), age ( P = 0.22), BMI ( P = 0.95), high (>10 000 × ml) WBC count ( P = 0.08), or high (>5 mg/l) C-reactive protein ( P = 0.87) among patients with CIPO. CIPO seems to be strongly associated with low serum levels of 25-hydroxy-vitamin D.

Pediatric Home Parenteral Nutrition in France: A six years national survey

Home Parenteral Nutrition (HPN) is the cornerstone management for children suffering from chronic intestinal failure (CIF). In France, HPN is organized from a network of 7 certified centers located in University Hospitals spread across the national territory. This study aims to review the data involving children on HPN over a 6-years period in France to outline the global and continuous improvement in care.This cross-sectional study included all children enrolled in any of the 7 French HPN certified centers from January 1st, 2014 to December 31st, 2019. Data was recorded from annual databases provided by each center regarding: age at inclusion, indication and duration of HPN, type of intravenous lipid emulsion (ILE), outcome [PN weaning off, transfer to adult center, death, intestinal transplantation (ITx)], rate of catheter-related bloodstream infections (CRSBIs) for 1000 days of HPN, Taurolidine lock procedure (TLP) use and prevalence of cholestasis defined as conjugated bilirubin ≥20 μmol/l.The number of patients increased by 43.6% from 268 in 2014 to 385 in 2019. According to the year of follow up, the indications for HPN were short bowel syndrome (SBS) (42.3-46.6%), congenital enteropathies (CE) (18.5-22.8%), chronic intestinal pseudo-obstruction syndrome (CIPOS) (13.0-16.3%), long segment Hirschsprung's disease (LSHD) (9.7-13.3%), Crohn's disease (CD) (1.6-2.6%) and other non-primary digestive diseases (NPDD) such as immune deficiency, cancer or metabolic disease (4.0-9.2%). The median age at discharge on HPN decreased from 11.7 months in 2014 to 8.3 months in 2019 (p < .001). By December 31st, 2019, 44.8% of children had left the HPN program after a median duration ranging between 39.9 and 66.4 months. Among these patients, 192 (74.2%) were weaned off PN (94.7% SBS), 41 (15.8%) were transferred to adult centers for CIPOS (42%), SBS (31%) or CE (27%), 21 died (8.1%) - mostly in relation to cancer or immune deficiency - and 5 were transplanted (1.9%): 4 underwent combined liver-intestine transplantation for LSHD (n = 2), SBS, CE and one multivisceral Tx for CIPOS. The use of a composite fish-oil based ILE increased from 67.4% in 2014 to 88.3% in 2019 (p < 0.001). CRBSIs dropped from 1.04 CRSBIs per 1000 days HPN in 2014 to 0.61 in 2019 (p < 0.001) while meantime, the percentage of children receiving TLP increased from 29.4% to 63.0% (p < 0.001). The prevalence of cholestasis (conjugated bilirubin ≥ 20 μmol/l) was low and stable between 4.1 and 5.9% of children during the study period.In France, the number of children enrolled in a HPN program continuously increased over a 6 years period. SBS is the leading cause of CIF requiring HPN. The rate of CRBSIs dropped dramatically as the use of TLP increased. Mortality rate was low and mainly in relation to the underlying disease (cancer, immune deficiency). Cholestasis and intestinal Tx remained very rare.

Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS): Series of 4 Cases Caused by Mutation of ACTG2 (Actin Gamma 2, Smooth Muscle) Gene

MMIHS, also known as Berdon's syndrome, is a rare disease that belongs to primary causes of CIPOS (chronic intestinal pseudoobstruction syndrome). Clinical characteristics of MMIHS are differential, but we come across the following classic symptoms: disorders of intestinal peristalsis, microcolon, and megacystis. In this article, we present a series of 4 patients with Berdon's syndrome, in whom we managed to identify the genetic causes of MMIHS. All infants showed clinical features of bowel obstruction and dysfunction of the urinary system after birth. Two of them also manifested disorders from other systems. The prognosis for these patients is poor, but a constant betterment of management in MMIHS, in which the leading role plays TPN (total parental nutrition), causes improvement of patients' survival.

Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo-obstruction syndrome.

Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo‐obstruction (CIPO) syndrome, a life‐threatening intestinal motility disorder. We showed that CIPO‐SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet‐Derived Growth Factor Receptor‐alpha (PDGFRA) expression. We showed that this modulation occurs without origin‐related differences in CIPO circular and longitudinal‐derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO‐SMC towards an undifferentiated stage. The development of CIPO‐SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO.

Metabolic bone disease in children with intestinal failure is not associated with the level of parenteral nutrition dependency

Children on long-term home parenteral nutrition (HPN) are at increased risk of suboptimal growth and metabolic bone disease (MBD) i.e. decreased bone mineral density (BMD). The aims of this cross-sectional study were to assess growth and bone health in children on long term HPN and to identify risk factors for MBD. Children above the age of 5 years, stable on HPN for more than 2 years were included. Medical files were reviewed retrospectively and included demographics, gestational age, birth weight and height, indication for PN, age at PN start, duration of PN, number of weekly PN infusions, weight-for-age and height-for-age (SD), body mass index (BMI, kg/m2) as well as blood and urine analyses at the time of Dual X-ray absorptiometry (DXA) measurements. All BMD values were adjusted to statural age which corresponds to the 50th percentile of height. Growth failure (height-for-age≤-2SD) and MBD (at least one BMD measurement≤-2SD) were analyzed according to the indication of PN, duration of PN and PN dependency index (PNDI) by comparing means and performing logistic regression analysis. PNDI is the ratio of non-protein energy intake in HPN to resting energy expenditure using Schofield equations. Forty children were assessed at 12.4±4.5 years of age. Mean age at PN start was 1.1±3.6y (median 0.5). The indications for PN were short bowel syndrome (SBS, n=21), chronic intestinal pseudo-obstruction syndrome (CIPOS, n=10) and congenital enteropathies (CE, n=9). The mean number of PN perfusions was 6±1/week. PNDI was 110±30%. The mean serum level of 25-OHD3 was suboptimal at 26.5±9.1ng/mL (66.2±22.8nmol/L). The mean concentrations of calcium, phosphorus, and parathyroid hormone (PTH) were in the normal ranges. Eight children (20%) had PTH levels above normal with low 25-OHD3 levels. The mean weight-for-age and height-for-age Z-scores SDS were 0.4±0.9 and-0.5±1.1 respectively. The actual height was lower than genetic target height (p<0.001). The BMD Z-scores, adjusted to the 50th percentile of height, of the spine, the left femur and the whole body were:-1.1±1.7,-1.2±1.5 and-1.5±1.8 SDS respectively. Children with CE had significantly lower BMD values than those with SBS and CIPOS (p=0.01). Only two children had bone fractures after a mild trauma (5%). All children on long-term PN, are at risk of low BMD. High dependency on PN (PNDI>120%) and very long-term PN (>10 years) do not appear to increase the risk of growth failure nor MBD. PN-related bone fractures were rare. Close follow-up remains mandatory.

Dlx1/2 mice have abnormal enteric nervous system function

Decades ago, investigators reported that mice lacking DLX1 and DLX2, transcription factors expressed in the enteric nervous system (ENS), die with possible bowel motility problems. These problems were never fully elucidated. We found that mice lacking DLX1 and DLX2 (Dlx1/2-/- mice) had slower small bowel transit and reduced or absent neurally mediated contraction complexes. In contrast, small bowel motility seemed normal in adult mice lacking DLX1 (Dlx1-/-). Even with detailed anatomic studies, we found no defects in ENS precursor migration, or neuronal and glial density in Dlx1/2-/- or Dlx1-/- mice. However, RNA sequencing of Dlx1/2-/- ENS revealed dysregulation of many genes, including vasoactive intestinal peptide (Vip). Using immunohistochemistry and reporter mice, we then found that Dlx1/2-/- mice have reduced VIP expression and fewer VIP-lineage neurons in their ENS. Our study reveals what we believe is a novel connection between Dlx genes and Vip and highlights the observation that dangerous bowel motility problems can occur in the absence of easily identifiable ENS structural defects. These findings may be relevant for disorders like chronic intestinal pseudo-obstruction (CIPO) syndrome.

Outcomes of Children With Chronic Intestinal Failure: Experience Over 2 Decades at a Tertiary Paediatric Hospital.

The aim of the study was to aid decisions on prognosis and transplantation; this study describes the outcome of children with intestinal failure managed by the multidisciplinary intestinal rehabilitation program at the Royal Children's Hospital, Melbourne. Retrospective review of children requiring parenteral nutrition (PN) for >3 months who were assessed for home PN between 1991 and 2011. A total of 51 children were included. Forty-two (82%) had short bowel syndrome (SBS), 5 (10%) had chronic intestinal pseudo-obstruction syndrome, and 4 (8%) had congenital enteropathies. Median small bowel length for patients with SBS was 45 cm (interquartile range 30-80) or 23.9% of the expected length for age (interquartile range 17.0%-40.6%). Overall survival rate was 84% (43/51). Mortality in children (n = 7) occurred after a median of 13.2 months (range 6.2-29.2) with intestinal failure-associated liver disease (IFALD) being the only predictor (P = 0.001). Out of 50 children 21 (42%) had IFALD. Children who were premature (P = 0.013), had SBS (P = 0.038), and/or frequent sepsis (P = 0.014) were more likely to develop IFALD. PN weaning occurred in 27 of 35 (77%) SBS survivors, after a median of 10.8 months (up to 8.2 years), with longer residual small bowel (P = 0.025), preservation of the ileocecal valve (P = 0.013) and colon (P = 0.011) being predictors. None of 5 (0%) patients with chronic intestinal pseudo-obstruction syndrome and 2 of 4 (50%) patients with congenital enteropathies weaned off PN. Overall sepsis rate was 7.3 episodes/1000 line days. Frequency of sepsis and longevity of central lines improved with time as patients grew older (both P < 0.001). Long-term PN with intestinal rehabilitation was effective in treating most children with intestinal failure. Children with severe refractory IFALD may have benefited from intestinal transplantation.

Short Bowel Syndrome as the Leading Cause of Intestinal Failure in Early Life: Some Insights into the Management.

Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children.The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting “nutritional failure” which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.

Chronic intestinal pseudo-obstruction syndrome and gastrointestinal malrotation in an infantwith schaaf-yang syndrome - Expanding the phenotypic spectrum

We report a novel patient with the phenotypic characteristics of Schaaf-Yang syndrome. In addition, the patient has a severe chronic digestive malfunction, rendering him dependent on intermittent enteral supplementation. To our knowledge, this is the first report of Schaaf-Yang syndrome associated with severe chronic digestive malfunction manifesting with both a malrotation and signs of a chronic intestinal pseudo-obstruction.

A New Concept to Achieve Optimal Weight Gain in Malnourished Infants on Total Parenteral Nutrition.

Infants with intestinal failure (IF) are at increased risk of malnutrition and require adapted nutrition support. Optimal weight gain during nutrition rehabilitation should occur at the velocity of statural age (adjusted to the 50th percentile of height) and not chronological age. The aim of this study was to assess the relationship between weight gain during catch-up growth, nonprotein energy intake (NPEI) provided by total parenteral nutrition (TPN), and resting energy expenditure (REE) in children with severe malnutrition due to IF. This retrospective study included all infants with severe malnutrition treated with TPN for IF between January 1, 2010, and December 31, 2013. They all had no or minimal oral intake (<10% REE). The REE was calculated using the Schofield equations. Seventeen children were included (11 boys) with a mean age at TPN onset of 5 mo. They were followed for a mean duration of 39 days. On admission, body weight and height were -3.1 ± 0.9 and -3.3 ± 1.3 SD, respectively. The indications for TPN were short bowel syndrome (n = 10), congenital enteropathy (microvillous inclusion disease, n = 6) and chronic intestinal pseudo-obstruction syndrome (n = 1). After 28 days of nutrition rehabilitation with full NPEI from TPN, the observed weight gain was 110 ± 5% of optimal weight gain for statural age. The mean NPEI from TPN was 104.3 ± 8.0 kcal/kg/d. The mean ratio of NPEI over REE was 2.1 ± 0.2. Optimal weight gain was achieved with NPEI from TPN twice the REE in severely malnourished infants with IF. NPEI values were adequate and not excessive for age.

P-029B 青年期に達した慢性特発性仮性腸閉塞症(CIIPS)の一卵性双胎兄弟例(結腸・直腸・肛門, 第44回日本小児外科学会学術集会)

P-029B 青年期に達した慢性特発性仮性腸閉塞症(CIIPS)の一卵性双胎兄弟例(結腸・直腸・肛門, 第44回日本小児外科学会学術集会)

CIIPS(Chronic Idiopathic Intestinal Pseudo-obstruction Syndrome)3例における排尿機能障害

CIIPS(Chronic Idiopathic Intestinal Pseudo-obstruction Syndrome)3例における排尿機能障害

Liver Failure From Ultra-Short Bowel Syndrome on the Intestinal Transplant Waiting List: A Retrospective Study

BackgroundPatients with intestinal failure (IF) are candidates for intestinal transplantation (ITx). In Japan, these patients have few opportunities to undergo cadaveric ITx because of low rates of organ donation. The donor criteria and recipient priority for ITx are still unknown. We reviewed our cases of IF to investigate which patients should be prioritized for ITx. MethodsPatients with IF who were registered as candidates for cadaveric ITx between January 2010 and November 2015 in our institute were included in this retrospective study. Their data were gathered from their charts and analyzed. ResultsFive patients were included. Their primary diseases included total colon aganglionosis (n = 1), chronic idiopathic intestinal pseudo-obstruction syndrome (n = 2), superior mesenteric vein embolization (n = 1), and graft loss after ITx (n = 1). Two patients died of liver failure (LF) during the waiting period. The remaining three are now alive and waiting for transplantation. The lengths of the remaining intestine were more than 20 cm in living cases but less than 20 cm in fatal cases. In the fatal cases, they had several episodes of catheter-related blood stream infection, which caused LF and acute renal failure. ConclusionsWe identified two patients with less than 20 cm residual small bowel who died after acute deterioration of liver function. Patients with ultra-short bowel could have a higher risk of LF. Therefore, they should be referred as soon as possible to a specialized hospital where ITx is a choice of treatment for IF.

Two new mutations of the CLMP gene identified in a newborn presenting congenital short-bowel syndrome

Congenital short-bowel syndrome (CSBS) is a rare neonatal pathology associated with poor prognosis and high mortality rate. We describe a newborn presenting CSBS intestinal malrotation and chronic intestinal pseudo-obstruction syndrome (CIPS), compound heterozygous for two previously unreported heterozygous mutations in Coxsackie and adenovirus receptor-like membrane protein (CLMP) gene, one in intron 1 (c.28+1G>C), the other on exon 4 (c502C>T, p.R168X). Both mutations are predicted to be pathogenic, leading to impaired splicing and the appearance of a premature stop codon, respectively. Our case is remarkable in that it concerns two heterozygous truncating mutations associated with a good clinical prognosis with a favorable cerebral and gastrointestinal outcome and a substantial enteral input at 8 months of age, despite a small intestine measuring only 35cm.

Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center

Parenteral nutrition (PN) is the main treatment for intestinal failure. We aimed to review the indications for home parenteral nutrition (HPN) in children and describe the outcome over a 14-y period from a single center. We conducted a retrospective study that included all children who were referred to our institution and discharged while receiving HPN between 1 January 2000 and 31 December 2013. The indications for HPN were divided into primary digestive diseases (PDDs) and primary nondigestive diseases (PNDDs). We compared our results to a previous study that was performed in our unit from 1980 to 2000 and included 302 patients. A total of 251 patients were included: 217 (86%) had a PDD. The mean ± SD age at HPN onset was 0.7 ± 0.3 y, with a mean duration of 1.9 ± 0.4 y. The indications for HPN were short bowel syndrome (SBS) (59%), PNDD (14%), congenital enteropathies (10%), chronic intestinal pseudo-obstruction syndromes (9%), inflammatory bowel diseases (5%), and other digestive diseases (3%). By 31 December 2013, 52% of children were weaned off of HPN, 9% of the PDD subgroup had intestinal transplantation, and 10% died mostly because of immune deficiency. The major complications of HPN were catheter-related bloodstream infections (CRBSIs) (1.7/1000 d of PN) and intestinal failure-associated liver disease (IFALD) (51 children; 20% of cohort). An increased rate of CRBSIs was observed compared with our previous study, but we saw a decreasing trend since 2012. No noteworthy deceleration of growth was observed in SBS children 6 mo after weaning off HPN. SBS was the major indication for HPN in our cohort. IFALD and CRBSIs were potentially life-threatening problems. Nevertheless, complication rates were low, and deaths resulted mostly from the underlying disease.

Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIPO) syndromes are heterogeneous gastrointestinal disorders, caused by either neuropathy or myopathy, resulting in compromised peristalsis and intestinal obstruction. CIPO can have a profound impact on quality of life, leading the most severely affected individuals to life-long parenteral nutrition and urinary catheterization. To search for disease causing gene(s), we performed the whole exome sequencing (WES) in both eight sporadic and two familial cases, followed by targeted sequencing in additional CIPO patients. After identifying a heterozygous missense variant in the ACTG2 gene in one of 10 patients undergone WES, targeted Sanger sequencing of this gene allowed to detect heterozygous missense variants in 9 of 23 further patients with either megacystis-microcolon-intestinal hypoperistalsis syndrome or intestinal pseudo-obstruction. Variants thus identified, one of which still unreported, affect highly conserved regions of the ACTG2 gene that encodes a protein crucial for correct enteric muscle contraction. These findings provided evidence for a correlation between the clinical phenotype and genotype at the ACTG2 locus, a first step to improve the diagnosis and prognosis of these severe conditions.

Detection of anticonductive tissue autoantibodies in a patient with chronic intestinal pseudo-obstruction and sick sinus syndrome

A 26-year-old patient was diagnosed as having chronic intestinal pseudo-obstruction with manometric and histopathologic features suggestive of an intestinal myopathy. Histology was characterized by smooth muscle degeneration without inflammatory or immune cells. The severe gut dysfunction required full parenteral nutritional support. After a few months, the patient developed symptomatic tachy-brady arrhythmia episodes with syncopes. A thorough diagnostic work-up led to a diagnosis of sick sinus syndrome, which was managed by pacemaker implantation and administration of β-blockers. This led to a partial improvement in tachy-brady arrhythmia episodes. Nonetheless, the patient continued to experience sustained supraventricular tachyarrhythmia runs, poorly responsive to increasing β-blocker doses. To investigate the origin of the cardiologic impairment, the patient was tested for anticonductive tissue autoantibodies, which were positive, thus supporting a possible autoimmune origin of the dysrhythmia. Other autoantibodies were negative. On the basis of these findings, the patient was treated with high-dose steroids, which were then tapered. The patient responded to the steroid treatment and did not experience further episodes of syncope and tachyarrhythmias. The severe gut dysfunction remained unchanged. This case highlights an association between severe gut dysfunction and cardiac conductive tissue abnormalities, with autoantibodies to conductive tissue possibly causing the dysrhythmia. The severe gut and heart (likely autoimmune-mediated) dysfunction presented in this case provides a basis to further assess a link between intestinal and cardiac abnormal rhythmicity.

Mucormycosis as a rare cause of severe gastrointestinal bleeding after multivisceral transplantation

Mucormycosis, an emerging fungal infection in solid organ transplant patients, is mostly located in rhino-orbito-cerebral, pulmonary, and cutaneous areas, or disseminated with poor prognosis. A 4-year-old girl with chronic intestinal pseudo-obstruction syndrome underwent a modified multivisceral transplantation, including half of the stomach, the duodeno-pancreas, the small bowel, and the right colon. On postoperative day 5, a digestive perforation was suspected. Surgical exploration found a small necrotic area on the native stomach, which was externally drained. The next day, massive gastric bleeding occurred. During the emergency laparotomy, 2 hemorrhagic ulcers were found and resected from the transplanted stomach. Pathology and fungal culture showed mucormycosis caused by Lichtheimia (formerly Absidia) ramosa in both the transplanted and native stomach. High-dose intravenous liposomal amphotericin B was immediately started. No other site of fungal infection was found. The child recovered, and 3years after transplantation, is alive and well, off parenteral nutrition. The originality of this case is the very early presentation after transplantation, the unusual site, and the complete recovery after rapid medico-surgical management. The origin of the fungus and treatment are discussed.

Intestinal Failure in Children

Intestinal failure (IF) is a condition in which severe intestinal malabsorption mandates artificial nutrition through a parenteral route. Causes of severe protracted IF include short bowel syndrome, congenital diseases of enterocyte development, and severe motility disorders (total or subtotal aganglionosis or chronic intestinal pseudo-obstruction syndrome). IF can result in nutritional failure, defined as the long-term failure to nourish a child by natural or artificial means. Today, IF-associated liver disease is the most common cause of parenteral nutrition (PN) failure, but catheter-related sepsis and extensive vascular thrombosis may also jeopardize the health of those receiving PN. For a child with nutritional failure, intestinal transplantation, often in the form of a composite visceral graft, offers the only chance for long-term survival. The management of IF requires a multidisciplinary approach. There have been a number of recent advances in both medical and surgical treatments of IF. In particular, new intestinal lengthening techniques and the use of PN formulas rich in fish oil both have resulted in decreased rates of severe complications of IF and its treatments. In addition, better awareness of the risks and benefits of intestinal transplantation have resulted in better patient selection, and ultimately in improved patient survival, hence restricting the indication to transplantation only to patients with nutritional failure and no other chance to survive.

Use of Buprenorphine in Children With Chronic Pseudoobstruction Syndrome

Abdominal pain is the most challenging symptom in chronic intestinal pseudoobstruction (CIPO) syndrome, because of its severity and the limited availability of suitable opioid formulations, especially in pediatric patients with digestive problems. Most of the children with CIPO cannot tolerate oral formulations. We present 4 cases of children with CIPO and severe intractable abdominal pain, and report on the use of a recently available form of opioid, transdermal buprenorphine in a dosage of 5 mcg/h. CIPO and the unique pharmacological profile of buprenorphine are reviewed briefly.