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Background & aims: Subjects with short bowel syndrome (SBS) have impaired quality of life (QoL). No disease-specific instrument has been available to measure treatment-induced changes in QoL over time. Therefore, the aim was to develop and validate an SBS-specific QoL scale. Methods: Classical test theory and Food and Drug Administration (FDA) guidance were applied for development and validation of the SBS-QoL™. Procedures included item generation and raw scale construction. Factor analysis, construct validity and internal consistency were assessed in a non-interventional observation, test re-test reliability and responsiveness in a randomised clinical study. Results: The SBS-QoL™ comprises 17 items including two subscales. Subjects assessed the scale as easy to handle and comprehensible. Good construct validity was shown by comparison with the Home Parenteral Nutrition-Quality Of Life questionnaire as an external scale, which yielded moderately high correlation (r≥0.7). High internal consistency was demonstrated (Cronbach's alpha: 0.94). Also the test re-test reliability was high (r≥0.95), indicating reliable reproducibility of results. The Responsiveness Index (1.84) indicated the ability of the scale to detect changes in QoL over time. Conclusions: The SBS-QoL™ is an easy to handle and comprehensible SBS-specific subject-reported QoL scale. It is valid, reliable and sensitive with excellent psychometric characteristics to measure treatment-induced changes in QoL over time in subjects with SBS. © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Summary Background & aims Short bowel syndrome (SBS) is a rare and severe condition where home parenteral nutrition (HPN) dependence can be either permanent or transient. The timing of HPN discontinuation and the survival, according to SBS characteristics, need to be further reported to help plan pre-emptive intestinal transplantation and reconstructive surgery. Methods 268 Non-malignant SBS patients have been followed in our institution since 1980. HPN dependence and survival rate were studied with univariate and multivariate analysis. Results Median follow-up was 4.4 (0.3–24) years. Actuarial HPN dependence probabilities were 74%, 64% and 48% at 1, 2 and 5 years, respectively. In multivariate analysis, HPN dependence was significantly decreased with an early ( 20 μmol/l, a remaining colon >57% (4/7) and a remnant small bowel length >75 cm. Among the 124 patients who became HPN independent, 26.5% did so more than 2 years after SBS constitution. Conclusions This study indicates that long-term HPN is required in 47% of SBS patients started on this therapy. HPN independence is significantly associated with the remnant small bowel length, remaining colon and early plasma citrulline concentration. Noteworthy, HPN dependence could be reversed until 5 years after SBS constitution.

Introduction Management of chronic radiation enteritis is often controversial, particularly due to the risk of short bowel syndrome. Methods One hundred and seven chronic radiation enteritis patients with short bowel syndrome were studied retrospectively between 1980 and 2009. Survival and home parenteral nutrition dependence rates were evaluated with univariate and multivariate analysis. Results The survival probabilities were 93%, 67% and 44.5% at 1, 5 and 10 years, respectively. On multivariate analysis, survival was significantly decreased with residual neoplastic disease (HR = 0.21 [0.11–0.38], p 3 (HR = 0.38 [0.20–0.73], p = 0.004) and an age of chronic radiation enteritis diagnosis >60 years (HR = 0.45 [0.22–0.89], p = 0.02). The actuarial home parenteral nutrition dependence probabilities were 66%, 55% and 43% at 1, 2 and 3 years, respectively. On multivariate analysis, this dependence was significantly decreased when there was a residual small bowel length >100 cm (HR = 0.35 [0.18–0.68], p = 0.002), adaptive hyperphagia (HR = 0.39 [0.17–0.87], p = 0.02) and the absence of a definitive stoma (HR = 0.48 [0.27–0.84], p = 0.01). Conclusion The survival of patients with diffuse chronic radiation enteritis after extensive intestinal resection was good and was mainly influenced by underlying comorbidities. Almost two-thirds of patients were able to be weaned off home parenteral nutrition.

BACKGROUND Segmental reversal of the small bowel (SRSB) is proposed in patients with short-bowel syndrome (SBS) as a rehabilitative therapy, but its effects on absorption have not been studied. OBJECTIVE We aimed to determine intestinal macronutrient absorption and home parenteral nutrition (HPN) dependence in SBS patients with intestinal failure. DESIGN We included in a retrospective study all consecutive patients who had an SRSB between 1985 and 2010 and underwent a study of macronutrient absorption. Patients were matched to SBS controls with the same digestive characteristics. Energy and macronutrient absorption were measured. The dependence on HPN was expressed by the number of infusions per week and by the calories infused daily divided by the basal energy expenditure multiplied by 1.5. RESULTS Seventeen patients who had an SRSB were matched to 17 control patients. Intestinal absorption was higher in the SRSB group for total calories (69.5% compared with 58.0%), fat (48.4% compared with 33.2%), and protein (62.7% compared with 53.4%) (P < 0.05). Median oral autonomy was 100% ± 38.4% in the SRSB group, whereas it was 79% ± 39.6% in the control group (P < 0.05). The number of calories infused was lower in the SRSB group (500 ± 283 compared with 684 ± 541; P < 0.05), as was HPN dependence (33% ± 20% compared with 48% ± 38%; P < 0.05) at the time of the study. CONCLUSION SRSB allows a gain in macronutrient absorption, which is associated with a lower HPN dependence. To our view, SRSB should be integrated in intestinal rehabilitative adult programs.

Teduglutide was discontinued after being tested for ≥ 24 weeks in patients with parenteral nutrition (PN) -dependent short bowel syndrome in a clinical trial for efficacy to reduce PN volume. This study was describes change in body mass index (BMI) and PN volume over 12 months in patients who stopped drug after the clinical trial.Prescribed PN volume, weight, and complications were reported. Patients with stable (NEUT, n = 15) or decreased (DEC, n = 7) PN volume by 12 months after stopping drug (NEUT/DEC, n = 22) were compared to those who had increased PN volume (INC, n = 15). With drug response defined by ≥ 20% reduction from pre-drug PN volume to end of drug therapy, 12 INC and 13 NEUT/DEC patients were drug responders.Eleven of 20 eligible sites reported data for 39 of 53 eligible study participants, with follow-up data for 37. INC patients had shorter colon and less frequently had colon in continuity than NEUT/DEC. BMI was decreased at 3, 6, and 12 months relative to the first off-drug visit in INC patients (P = .001), but not in NEUT/DEC patients. Change in BMI off-drug was predicted by colon and small bowel length, baseline BMI, and on-drug change in PN volume (adjusted R2 = 0.708).Gastrointestinal anatomy, baseline BMI, and PN volume reduction on-drug predicted change in BMI off-drug. Whether this response would be maintained for a longer time or in the context of a challenging clinical situation has not been evaluated.

Background and aims Teduglutide, a GLP-2 analogue, may restore intestinal structural and functional integrity by promoting repair and growth of the mucosa and reducing gastric emptying and secretion, thereby increasing fluid and nutrient absorption in patients with short bowel syndrome (SBS). This 24-week placebo-controlled study evaluated the ability of teduglutide to reduce parenteral support in patients with SBS with intestinal failure. Methods In 83 patients randomised to receive subcutaneous teduglutide 0.10 mg/kg/day (n=32), 0.05 mg/kg/day (n=35) or placebo (n=16) once daily, parenteral fluids were reduced at 4-week intervals if intestinal fluid absorption (48 h urine volumes) increased ≥10%. Responders were subjects who demonstrated reductions of ≥20% in parenteral volumes from baseline at weeks 20 and 24. The primary efficacy end point, a graded response score (GRS), took into account higher levels and earlier onset of response, leading to longer duration of response. The intensity of the response was defined as a reduction from baseline in parenteral volume (from 20% to 100%), and the duration of the response was considered the response at weeks 16, 20 and 24. The results were tested according to a step-down procedure starting with the 0.10 mg/kg/day dose. Results Using the GRS criteria, teduglutide in a dose of 0.10 mg/kg/day did not have a statistically significant effect compared with placebo (8/32 vs 1/16, p=0.16), while teduglutide in a dose of 0.05 mg/kg/day had a significant effect (16/35, p=0.007). Since parenteral volume reductions were equal (353±475 and 354±334 ml/day), the trend towards higher baseline parenteral volume (1816±1008 vs 1374±639 ml/day, p=0.11) in the 0.10 mg/kg/day group compared with the 0.05 mg/kg/day group may have accounted for this discrepancy. Three teduglutide-treated patients were completely weaned off parenteral support. Serious adverse events were distributed similarly between active treatment groups and placebo. Villus height, plasma citrulline concentration and lean body mass were significantly increased with teduglutide compared with placebo. Conclusions Teduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure. ClinicalTrials.gov number NCT00172185.

Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

Undernutrition as well as specific nutrient deficiencies has been described in patients with Crohn's disease (CD), ulcerative colitis (UC) and short bowel syndrome. In the latter, water and electrolytes disturbances may be a major problem. The present guidelines provide evidence-based recommendations for the indications, application and type of parenteral formula to be used in acute and chronic phases of illness. Parenteral nutrition is not recommended as a primary treatment in CD and UC. The use of parenteral nutrition is however reliable when oral/enteral feeding is not possible. There is a lack of data supporting specific nutrients in these conditions. Parenteral nutrition is mandatory in case of intestinal failure, at least in the acute period. In patients with short bowel, specific attention should be paid to water and electrolyte supplementation. Currently, the use of growth hormone, glutamine and GLP-2 cannot be recommended in patients with short bowel.

In short bowel syndrome (SBS), although a remaining colon improves patient outcome, there is no direct evidence of a mucosal colonic adaptation in humans. This prospective study evaluates morphology, proliferation status, and transporter expression level in the epithelium of the remaining colon of adult patients compared with controls. The targeted transporters were Na+/H+exchangers (NHE2 and 3) and oligopeptide transporter (PepT1). Twelve adult patients with a jejuno-colonic anastomosis were studied at least 2 yr after the last surgery and compared with 11 healthy controls. The depth of crypts and number of epithelial cells per crypt were quantified. The proliferating and apoptotic cell contents were evaluated by revealing Ki67, PCNA, and caspase-3. NHE2, NHE3, PepT1 mRNAs, and PepT1 protein were quantified by quantitative RT-PCR and Western blot, respectively. In patients with SBS compared with controls, 1) hyperphagia and severe malabsorption were documented, 2) crypt depth and number of cells per crypt were 35% and 22% higher, respectively ( P < 0.005), whereas the proliferation and apoptotic levels per crypt were unchanged, and 3) NHE2 mRNA was unmodified; NHE3 mRNA was downregulated near the anastomosis and unmodified distally, and PepT1 mRNA and protein were unmodified. We concluded that, in hyperphagic patients with SBS with severe malabsorption, adaptive colonic changes include an increased absorptive surface with an unchanged proliferative/apoptotic ratio and well-preserved absorptive NHE2, NHE3, and PepT1 transporters. This is the first study showing a controlled nonpharmacological hyperplasia in the colon of patients with SBS.

Chronic intestinal pseudoobstruction (CIPO) is classified into enteric visceral myopathies, neuropathies, and/or mesenchymopathies. Although the histology usually permits to highlight pathologic abnormalities of CIPO, it fails in almost a third of cases. The yield of a systematic immunohistochemistry needs to be evaluating.Twenty-one adult patients with idiopathic CIPO [11 females/10 males, median age 23.1 (0.3 to 57) y] were included and compared with 27 control and 10 with mechanical obstruction patients. Comparison between standard histology (hematoxylin and eosin-stained sections) and systematic immunohistochemistry using muscular (smooth muscle alpha-actin, desmin, and smoothelin-A/B), nervous (Hu C/D, Bcl-2, and S100 protein), and mesenchymal (CD117) markers was carried out.Histology showed neuromuscular abnormalities in 13 out of 21 (62%) patients, consisting of enteric visceral myopathy in 9 (43%) patients, enteric visceral neuropathy in 2 (9.5%), and mixed neuromyopathy in 2 (9.5%). Among the 8 patients who had no histologic structural abnormality, 6 patients (75%) had underlying abnormalities detected with immunohistochemistry: immunostain with Hu C/D detected a hypoganglionosis (50 ganglion cells/cm) in 6 out of 21 (29%) patients, 4 of them undiagnosed on standard histology; CD117 (c-kit) detected a interstitial cells of Cajal defect in 10 out of 21 (48%) patients, 2 of them with no histologic structural abnormality. Smoothelin-A/B and desmin were useless as normally expressed in all patients with no myopathy; although it was not relevant in ileal samples (86% of abnormal expression in control patients), smooth muscle alpha-actin showed an abnormal expression in 2 CIPO patients (2/21).Immunohistochemistry using Hu C/D and CD117 antibodies combined to the standard histology increased the yield of detection of neuromuscular abnormalities in idiopathic CIPO patients.

Background & Aims: Tube feeding, recommended for patients with short bowel syndrome in only the postoperative period, has not been compared with oral feeding for absorption. We studied whether tube feeding increased absorption in patients with short bowel syndrome following the postoperative period. Methods: A randomized crossover study compared absorption between isocaloric tube feeding and oral feeding in 15 short bowel syndrome patients more than 3 months after short bowel constitution. An oral feeding period combined with enriched (1000 kcal ● day 1 ) tube feeding was also tested. We measured the net intestinal absorption rates of proteins, lipids, and total calories using elemental nitrogen, Van de Kamer, and bomb calorimetry methods, respectively. Results: Tube feeding increased the mean (SD) percent absorption (P < .001) of proteins (72% 13% vs 57% 18%), lipids (69% 25% vs 41% 27%), and energy (82% 12% vs 65% 16%) compared with oral feeding. In the group given the combined feedings (n 9), the total enteral intake and net percent absorption increased (P < .001) for proteins (67% 10%), lipids (59% 19%), and total energy (75% 8%) compared with oral feeding. Absorption (kcal ● day 1 ) was greater (P < .001) with tube (2225 457) and combined feedings (2323 491) than with oral feeding (1638 458). Conclusions: In patients with short bowel syndrome, continuous tube feeding (exclusively or in conjunction with oral feeding) following the postoperative period significantly increased net absorption of lipids, proteins, and energy compared with oral feeding.

Background & Aims: The US Medicare indications for intestinal transplantation are based on failure of home parenteral nutrition. The American Society of Transplantation also includes patients at high risk of death from their primary disease or with high morbidity intestinal failure. A 3-year prospective study evaluated the appropriateness of these indications. Methods: Survival on home parenteral nutrition or after transplantation was analyzed in 153 (97 adult, 56 pediatric) candidates for transplantation and 320 (262 adult, 58 pediatric) noncandidates, enrolled through a European multicenter cross-sectional survey performed in 2004. Kaplan–Meier and chi-square test statistics were used. Results: The 3-year survival was 94% (95% CI, 92%–97%) in noncandidates and 87% (95% CI, 81%–93%) in candidates not receiving transplants (P = .007). Survival was 80% (95% CI, 70%–89%), 93% (95% CI, 86%–100%), and 100% in parenteral nutrition failure, high-risk primary disease, and high-morbidity intestinal failure, respectively (P = .034). Fifteen candidates underwent transplantation. Six died, including all 3 of those who were in hospital, and 25% of those who were at home at time of transplantation (P = .086). Survival in the 10 patients receiving a first isolated small bowel transplant was 89% (95% CI, 70%–100%), compared with 85% (95% CI, 74%–96%) in the candidates with parenteral nutrition failure not receiving transplants because of central venous catheter complications, or 70% (95% CI, 53%–88%) in those with parenteral nutrition–related liver failure (P = .364). Conclusions: The results confirm home parenteral nutrition as the primary therapeutic option for intestinal failure and support the appropriateness and potential life-saving role of timely intestinal transplantation for patients with parenteral nutrition failure.

In human, citrulline (plasma concentration about 40 micromol/L) is an amino acid involved in intermediary metabolism and that is not incorporated in proteins. Circulating citrulline is mainly produced by enterocytes of the small bowel. For this reason plasma or serum citrulline concentration has been proposed as a biomarker of remnant small bowel mass and function. This article reviews this concept and its metabolic basis.Conditions in which there is a significantly reduced small bowel enterocyte mass and function and a plasma or serum citrulline were measured in adults and children. These studies included patients with a short bowel syndrome, villous atrophy states, Crohn's disease, during monitoring of digestive toxicity of chemotherapy and radiotherapy or follow-up of patients after small bowel transplantation.In all these situations, with more than 500 studied patients a decreased level of plasma citrulline correlated with the reduced enterocyte mass independently of nutritional and inflammatory status. A close correlation between small bowel remnant length and citrullinemia was found. In addition, diagnosis of intestinal failure was assessed through plasma citrulline levels in severe small bowel diseases in which there is a marked enterocyte mass reduction.The threshold for establishing a diagnosis of intestinal failure is lower in villous atrophy disease (10mumol/L) than in short bowel syndrome (20mumol/L). Compromised renal function is an important factor when considering plasma citrulline levels as a marker of intestinal failure as this potentially can increase circulating citrulline values.Reduced plasma citrulline levels are an innovative quantitative biomarker of significantly reduced enterocyte mass and function in different disease states in humans.

In addition to non-digested nutrients, human stools contain endogenous substrates, among which bacteria are a major component, whose growth may be stimulated when more dietary nutrients are available for bacterial fermentation, as in patients with malabsorption syndrome. We assessed the energy content and composition of both stools and faecal bacteria in healthy volunteers and patients with a short bowel and colon in continuity (SBC). Our goal was to clarify the magnitude of error introduced by the faecal bacteria in the measurement of the digestibility of ingested energy and nutrients. We studied six healthy volunteers and six patients with a SBC under free oral intake. The bacterial mass of stools was isolated. In the bacterial fractions and fresh stools, calorie, fat, nitrogen and short-chain fatty acid contents were determined. The Wilcoxon signed rank or the Mann–Whitney tests were used for comparison. In healthy volunteers and patients with SBC, faecal bacterial mass accounted for 44 and 35% of faecal dry weight, and contained 50 and 34% of total faecal energy. In healthy volunteers, the apparent digestibilities when corrected by bacterial constituents (88–97% according to nutrients) were significantly higher than the apparent non-corrected digestibilities (84–94%). In patients with SBC, the corrected apparent digestibilities (69–89% according to nutrients) were significantly higher than the apparent non-corrected digestibilities (54–83%). The error introduced by the faecal bacterial fraction when assessing the extent of nutrient digestibility is small in healthy volunteers; it is more pronounced in patients with SBC, reaching 18% for the digestibility of ingested fat.

The development of parenteral nutrition (PN) was an important, life-saving advance in the care of patients with short bowel syndrome (SBS). Nevertheless, its long-term use is often associated with complications. Therefore, it is desirable, when possible, to wean SBS patients to an oral diet. Given the complexity of PN weaning and the lack of published guidelines, the purpose of this article is to describe strategies of PN weaning and illustrate important clinical considerations during the weaning process. Patient education and motivation are key factors in successful PN weaning. The patient should have clearly defined care protocols and understand the importance of each aspect of the weaning program. Other factors likely to influence weaning success include the length and health of the remnant bowel, the presence of a colon, and the degree to which bowel adaptation has occurred. It is imperative that daily oral fluid and caloric intake goals are met prior to initiating PN weaning and that the patient receives an optimized dietary and medication plan. During weaning, the most practical measures for assessing adequate hydration and nutritional status are oral intake, stool and urine output, serum electrolytes and visceral proteins, and body weight. PN reductions can be made by either decreasing the days of PN infusion per week or decreasing the PN infusion volume equally across all days of the week. Use of recombinant human growth hormone, with or without glutamine, may play a role in facilitating the PN weaning process.

We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy.

Background and aims: Intestinal adaptation after small bowel resection in humans is debated. We have quantified in adult short bowel (remnant small bowel length 1.5×resting energy expenditure), independently and negatively related to fat absorption (p

To assess the dynamics of taurine metabolism in vivo, two sets of studies were carried out in healthy volunteers. First, pilot studies were carried in a single human subject to determine the time course of plasma and whole blood isotope enrichment over the course of an 8-h, unprimed continuous infusion of [1,2-13C2]taurine. Second, five healthy adult males received two tracer infusions on separate days and in randomized order: 1) a 6-h continuous infusion of [1,2-13C2]taurine (3.1 ± 0.2 μmol·kg−1·h−1) and 2) a bolus injection of [13C2]taurine (3.0 ± 0.1 μmol/kg). Isotope enrichments in plasma and whole blood taurine were determined by gas chromatography-mass spectrometry. The pilot experiments allowed us to establish that steady-state isotope enrichment was reached in plasma and whole blood by the 5th h of tracer infusion. The plateau enrichment reached in whole blood was lower than that obtained in plasma taurine ( P < 0.02). In the second set of studies, the appearance rate (Ra) of plasma taurine, determined from continuous infusion studies was 31.8 ± 3.1 μmol·kg−1·h−1. After a bolus injection of tracer, the enrichment decay over the subsequent 2 h was best fitted by a two-exponential curve. Taurine Ra was ≈85% higher when determined using the bolus injection technique compared with continuous infusion of tracer. We conclude that 1) taurine Ra into plasma is very low in healthy postabsorptive humans, and, due to taurine compartmentation between the extra- and intracellular milieus, may represent only interorgan taurine transfer and merely a small fraction of whole body taurine turnover; and 2) the bolus injection technique may overestimate taurine appearance into plasma. Further studies are warranted to determine whether alterations in bile taurine dynamics affect taurine Ra.

Background: Long-term home parenteral nutrition (HPN) may induce liver disorders. Transient elastography (TE) has been proposed as a noninvasive alternative to liver biopsy analysis for assessment of the progression of hepatic fibrosis to cirrhosis. The goal of this study was to compare values from TE measurements to biopsy-determined stages of histologic fibrosis in patients receiving HPN. Methods: In this multicenter prospective study, patients receiving long-term HPN (‰6 months) who required a liver biopsy for clinical reasons were included. TE (FibroScan) values for each patient were compared with the degree of hepatic fibrosis measured from biopsy specimens based on the Brunt classification. TE values were also correlated to biochemical and histologic cholestasis. Two noninvasive indices for predicting liver fibrosis (APRI and FIB-4) were also evaluated. Results: Thirty patients were included in this study (mean age, 42.1 years; 63% male). The mean duration of HPN was 100.7 months; 25 patients had a short bowel and 13 had an intestinal stoma. Biochemical cholestasis was described in 22 patients. Liver histologic features varied among these patients. There was no correlation between the values of TE and the stages of histologic fibrosis, but TE values were significantly correlated to serum bilirubin level and the severity of histologic cholestasis as well as APRI and FIB-4 scores. Conclusions: In patients with long-term HPN, TE failed to assess the degree of hepatic fibrosis. This could be due to the heterogeneity of liver histologic features observed in these patients and the presence of chronic cholestasis.

For the assessment of colonic Crohn's disease (CCD) attacks, no clinicobiological and/or morphological (endoscopic, radiological) criteria of severity have been validated in relation to anatomical criteria of severity (ACS) as a gold standard obtained from colectomy specimen examination. Our objective was to assess the accuracy of colonoscopy in predicting the anatomical severity grading of CCD.Colectomy specimens from 78 consecutive patients operated between 1982 and 1996 for CCD resistant to medical treatment were analyzed and classified into two groups according to the presence (ACS+) or absence (ACS-) of ACS. These were defined as either deep ulcerations eroding the muscle layer, or mucosal detachments or ulcerations limited to the submucosa but extending to more than one third of one defined colonic segment (right, transverse, left colon). Three endoscopic criteria of severity (ECS) were then defined: 1) deep ulcerations eroding the muscle layer (ECS1), 2) deep ulcerations not eroding the muscle layer but involving more than one third of the mucosal area (ECS2), and 3) mucosal detachment on the edge of ulcerations (ECS3).According to colectomy specimen examination, 68 and 10 patients belonged to ACS+ and ACS- groups, respectively. ECS1, ECS2, and/or ECS3 were found in 70 patients. Positive predictive values of ECS1, ECS2, and ECS3 for the presence of ACS were 90%, 98%, and 92%, respectively. Negative predictive values were 43%, 72%, and 23% respectively. However, at least one ECS (ECS1, ECS2, or ECS3) was found in 95% of patients with ACS. The extent of ulcerations at colonoscopy was correlated to the results of colectomy specimen examination (p0.001). Taking into account only patients with ACS, 88% of those with at least one ECS were diagnosed through left side colonoscopy. Usual clinical and biological severity criteria were not different in ACS + and ACS- groups. Two cases of toxic megacolon and toxic shocks were observed after the colonoscopy.In experienced hands, colonoscopy can be useful in severe CCD attacks. When at least one ECS is found, colonoscopy predicts the anatomical severity of the colitis with a high probability. Conversely, when none of the three ECSs is found, colonoscopy can reasonably exclude the diagnosis of severe anatomical CCD.

BACKGROUND Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial. OBJECTIVE We explored effects of rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action. DESIGN Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg⁻¹ · d⁻¹) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment. RESULTS rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states. CONCLUSIONS In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.

Background: Home parenteral nutrition (HPN) is a lifesaving treatment in patients with intestinal failure. Dependency of nutritional support becomes permanent for the majority of patients who had received HPN for at least 2 years. The alternative to long term HPN in selected patients is intestinal transplantation. Aims: To study some of the clinical, social and rehabilitation aspects of long-term HPN treatment. Methods: A survey was performed in nine European HPN centres. The questionnaire covered epidemiologic data, underlying diseases, intestinal anatomy, nutritional support and status, marital status, rehospitalization rate, HPN complications, rehabilitation score, drugs use, coexistent diseases and interest in intestinal transplantation. For some items, data were collected within 12 months prior to the evaluation. Results: This survey included 228 patients with a median age of 49 years. The median duration of HPN was 7 years (range 2–24 years). Short bowel length less than 100 cm was reported in 65% of patients with a predominance of end-jejunostomy or jejuno-colonic anastomosis. Global subjective nutritional status was normal in 79% of the patients, who were supplied with a mean number of 5.6 bags of parenteral nutrition weekly. Rehospitalizations within the 12 months prior to evaluation accounted for a mean period of 23 days and were due to HPN complications in half of the cases. Catheter-related sepsis was the most frequent HPN-complication. Bone metabolism disorders, which seemed to be more common than liver diseases, were directly related to HPN duration. One-third of the HPN patients was regularly consuming analgesics or opiates. HPN impair complete rehabilitation status but may improve the status of patients who had a very low rehabilitation score before starting HPN. An interest of intestinal transplantation was noted in only 10% of medical teams and in 8% of HPN patients. Conclusions: This study is the largest European survey on long-term HPN patients with long standing or permanent intestinal failure. Data enlighten clinical, social and rehabilitation aspects of patients who could face the option of intestinal transplantation in the future.

Background & Aims: No blood marker assessing the functional absorptive bowel length has been identified. Plasma citrulline, a nonprotein amino acid produced by intestinal mucosa, is one candidate. We tested this hypothesis in adult patients with the short-bowel syndrome, whose condition can lead to intestinal failure. Methods: In 57 patients, after a minimal follow-up of 2 years subsequent to final digestive circuit modification, postabsorptive citrulline concentration was measured and parenteral nutrition dependence was used to define permanent (n = 37) and transient (n = 20) intestinal failure. Absorptive function, studied over a 3-day period, was evaluated by net digestive absorption for protein and fat (n = 51). Relations between quantitative values were assessed by linear regression analysis and cutoff citrulline threshold, for a diagnosis of intestinal failure by linear discriminant analysis. Cox model was used to compare citrulline threshold and anatomic variables of the short bowel as indicators of transient as opposed to permanent intestinal failure. Results: In patients with short-bowel syndrome, citrulline levels were lower than in controls (n = 51): 20 ± 13 vs. 40 ± 10 μmol/L (mean ± SD), respectively ( P P r = 0.86) and to net digestive absorption of fat, but to neither body mass index nor creatinine clearance. A 20-μmol/L threshold citrullinemia, (1) classified short bowel patients with permanent intestinal failure with high sensitivity (92%), specificity (90%), positive predictive value (95%), and negative value (86%); and (2) was a more reliable indicator (odds ratio, 20.0; 95% confidence interval, 1.9–206.1) than anatomic variables (odds ratio, 2.9; 95% confidence interval, 0.5–15.8) to separate transient as opposed to permanent intestinal failure. Conclusions: In patients with short-bowel syndrome, postabsorptive plasma citrulline concentration is a marker of functional absorptive bowel length and, past the 2-year adaptive period, a powerful independent indicator allowing distinction of transient from permanent intestinal failure. GASTROENTEROLOGY 2000;119:1496-1505

BACKGROUND Breath tests are currently used to qualitatively assess colonic fermentation; no quantitative estimations are available for healthy subjects. OBJECTIVE This study describes a stable-isotope-dilution method to measure acetate production quantitatively from colonic bacterial fermentation. DESIGN Six volunteers received a primed, constant, intravenous infusion of [1-13C]acetate at a rate of 1.01 +/- 0.04 micromol x kg(-1) x min(-1) for 7 h. They ingested 20 g pure lactulose after 1 h of the tracer infusion. Expired air and arterialized venous blood were sampled every 15 min. RESULTS Before lactulose intake, the breath-hydrogen concentration was 7 +/- 2 ppm and the plasma acetate concentration and isotopic enrichment were 141 +/- 14 micromol/L and 14.8 +/- 1.4 moles percent excess, respectively. Whole-body acetate turnover was 6.0 +/- 0.7 micromol x kg(-1) x min(-1). After lactulose ingestion, maximum breath hydrogen and acetate concentrations reached 63 +/- 15 ppm (P = 0.004) and 313 +/- 25 micromol/L (P = 0.002), respectively, whereas [13C]acetate enrichment decreased to 9.9 +/- 1.3 moles percent excess (P = 0.03). Whole-body acetate turnover increased to 9.8 +/- 1.5 micromol x kg(-1) x min(-1) and later decreased almost to baseline values. Colonic lactulose fermentation yielded 140 +/- 12 mmol acetate over 6 h, representing 86% of the production based on stoichiometric equations. CONCLUSION This new method provides a quantitative estimate of colonic carbohydrate fermentation via evaluation of acetate production.

The Leiden factor V mutation is observed in 20% of unexplained lower limb venous thromboses and involves substitution of the arginine residue at position 506 by glutamine (R506Q). It is known to decrease the anticoagulant activity of activated protein C. This case report describes 4 cases of small bowel infarction (SBI) associated with the presence of this mutation. Two cases of arterial and 2 cases of venous SBI were observed. Extensive assessment excluded the usual causes of SBI and plasma hypercoagulation syndrome (antithrombin III, protein C, and protein S deficiency and myeloproliferative syndrome). An abnormal resistance to activated protein C was observed. Molecular analysis consisting of polymerase chain reaction amplification and digestion with MnlI showed that 2 patients were heterozygous and 2 were homozygous for the R506Q mutation. Despite familial history of thrombosis in only 1 patient, first- and second-degree relatives of 2 patients also had the presence of the mutation. Examination for the presence of abnormal resistance to activated protein C should be part of the etiological assessment of SBI. Its presence may warrant consideration of long-term anticoagulant therapy, especially for patients with shortened small bowel who are treated by home parenteral nutrition with deep venous access.

We compared the tolerance of a diet providing 20 g/d lactose and a lactose-free diet in 14 patients with short-bowel syndrome with either the colon in continuity (group A, n = 8) or a terminal jejunostomy (group B, n = 6). Lactose tolerance was studied after a single 20-g lactose load in the fasting state, and during two 3-d periods during which the subjects consumed their usual diet plus either 20 g/d lactose, with no more than 4 g/d as milk, or no lactose. Records and measurements included symptoms, fecal weight, and during the 8 h after the lactose load, breath-hydrogen excretion (group A) or lactose and hexoses flow rates in stomal effluents (group B). Results are expressed as medians with ranges in parentheses. Lactose absorption was 61% (0-90) in group A and 53% (18-84) in group B, and no symptoms of intolerance were noticed. During the lactose-rich diet as compared to the lactose-free diet, no symptoms were noticed nor was there any worsening of diarrhea: 1534 g/d (240-4760) versus 1466 (1590-7030) in group A, and 4122 g/d (1730-6830) versus 3496 (1590-7030) in group B. We conclude that a diet providing 20 g/d lactose with no more than 4 g/d as milk is well tolerated in the majority of patients with short-bowel syndrome, and that a lactose-free diet has usually no benefit in these subjects.

Summary Background & aims Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. Methods QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05 mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. Results PS reductions were associated with QoL improvements (ANCOVA, p = 0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100 cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. Conclusions Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo. ClinicalTrials.gov identifier: NCT00798967.

To assess the effect of colonic fermentation on respiratory gas exchanges, six methane-nonproducing healthy volunteers ingested in the postabsorptive state 1 wk apart either 90 mL lactulose syrup containing 60 g lactulose, 4 g lactose, and 7 g galactose or the same solution but without lactulose (control solution). Six patients with short bowel and remnant colon (SBS) also ingested 90 mL lactulose syrup. Carbon dioxide production (VCO 2 ), oxygen consumption (VO 2 ), respiratory quotient (RQ), and hydrogen excreted in breath were measured basally and for 4 h after the ingestion of solutions. In healthy volunteers within 4 h after ingestion of the control solution, VCO 2 and the RQ decreased whereas VO 2 remained unchanged. In contrast, in healthy volunteers and patients with SBS, VCO 2 and the RQ increased after lactulose ingestion, whereas VO 2 did not change. The increase in VCO 2 appeared to be accounted for mainly by bacterial production of carbon dioxide and was significantly related to breath-hydrogen concentration (r = 0.56, P < 0.02 for healthy subjects ; r = 0.59, P < 0.01 for SBS subjects). A breath-hydrogen test should be performed in conjunction with indirect calorimetry to determine whether colonic fermentation is taking place and, if so, to correct appropriately the VCO 2 value in calorimetric xequations.

Background/Aims: Long-term survival of patients with intestinal failure requiring home parenteral nutrition (HPN) has been only partly shown. Therefore, we described the survival of these patients and explored prognosis factors. Methods: Two hundred seventeen noncancer non-acquired immunodeficiency syndrome adult patients presenting with chronic intestinal failure enrolled from January 1980 to December 1989 in approved HPN programs in Belgium and France; prognosis factors of survival were explored using multivariate analysis. Data were updated in March 1991; not one of the patients was lost to follow-up. Results: Seventy-three patients died during the survey, and the mortality rate related to HPN complications accounted for 11% of deaths. Probabilities of survival at 1, 3, and 5 years were 91%, 70%, and 62%, respectively. Three independent variables were associated with a decreased risk of death: age of patients younger than 40 years, start of HPN after 1987, and absence of chronic intestinal obstruction. In patients younger than 60 years of age included after 1983 with a very short bowel, who could represent suitable candidates for small bowel transplantation, the 2-year survival rate was 90%, a prognosis that compared favorably with recent reports of survival after small bowel transplantation. Conclusions: HPN prognosis compares favorably with recent reports of survival after small bowel transplantation.

Background & Aims Although home parenteral nutrition (PN) can save the lives of patients with massive bowel loss that results in short-bowel syndrome and intestinal failure, quality of life is impaired by PN and its complications. We examined the 12-month tolerability and efficacy of teduglutide to reduce PN dependency. Methods Patients who received teduglutide (0.05 or 0.10 mg/kg/d) for 24 weeks in a randomized controlled trial were eligible for a 28-week double-blind extension study; 52 patients were given 52 weeks of the same doses of teduglutide. We investigated the safety, tolerability, and clinical efficacy (defined as a clinically meaningful ≥20% reduction in weekly PN volume from baseline) at week 52. Results The most common adverse events reported included headache (35%), nausea (31%), and abdominal pain (25%); 7 patients withdrew because of adverse events (gastrointestinal disorders in 4). Both groups had progressive reduction in PN. At week 52, 68% of the 0.05-mg/kg/d and 52% of the 0.10-mg/kg/d dose group had a ≥20% reduction in PN, with a reduction of 1 or more days of PN dependency in 68% and 37%, respectively. Four patients achieved complete independence from PN. Conclusions For patients with short-bowel syndrome intestinal failure, the efficacy of teduglutide was maintained over 52 weeks and the safety profile was sufficient for it to be considered for long-term use. Further studies are needed to determine whether these effects will translate into improved quality of life and reduced PN complications. ClinicalTrials.gov number, NCT00172185.

Teduglutide, a glucagon-like peptide 2 analogue, might restore intestinal structural and functional integrity by promoting growth of the mucosa and reducing gastric emptying and secretion. These factors could increase fluid and nutrient absorption in patients with short bowel syndrome with intestinal failure (SBS-IF). We performed a prospective study to determine whether teduglutide reduces parenteral support in patients with SBS-IF.We performed a 24-week study of patients with SBS-IF who were given subcutaneous teduglutide (0.05 mg/kg/d; n = 43) or placebo (n = 43) once daily. Parenteral support was reduced if 48-hour urine volumes exceeded baseline values by ≥ 10%. The primary efficacy end point was number of responders (patients with20% reduction in parenteral support volume from baseline at weeks 20 and 24).There were significantly more responders in the teduglutide group (27/43 [63%]) than the placebo group (13/43 [30%]; P = .002). At week 24, the mean reduction in parenteral support volume in the teduglutide group was 4.4 ± 3.8 L/wk (baseline 12.9 ± 7.8 L/wk) compared with 2.3 ± 2.7 L/wk (baseline 13.2 ± 7.4 L/wk) in the placebo group (P.001). The percentage of patients with a 1-day or more reduction in the weekly need for parenteral support was greater in the teduglutide group (21/39 [54%]) than in the placebo group (9/39 [23%]; P = .005). Teduglutide increased plasma concentrations of citrulline, a biomarker of mucosal mass. The distribution of treatment-emergent adverse events that led to study discontinuation was similar between patients given teduglutide (n = 2) and placebo (n = 3).Twenty-four weeks of teduglutide treatment was generally well tolerated in patients with SBS-IF. Treatment with teduglutide reduced volumes and numbers of days of parenteral support for patients with SBS-IF; ClinicalTrials.gov Number, NCT00798967.

This study aimed to compare the absorption and tolerance of 20-g lactose loads as milk and yogurt in 17 patients with short-bowel syndrome with either a terminal jejunostomy (group A, n = 6) or a jejunocolic anastomosis (group B, n = 11). Records and measurements during the 8 h after the meals included fecal weight, symptoms, lactose and hexose flow rates in stomal effluents (group A), and breath-hydrogen excretion (group B). In group A lactose was better absorbed in the form of yogurt than in the form of milk (mean +/- SE: 76 +/- 6% vs 50 +/- 9%, P < 0.05), whereas no significant difference could be detected by using the breath-hydrogen test in group B. The excellent tolerance to 20 g lactose from milk and yogurt suggests that lactose should not be excluded from the diet of these subjects.

To assess the effect of feeding on glutamine kinetics, six healthy men received 4-h intravenous infusions of L-[2-15N]glutamine and L-[1-13C]leucine on 3 separate days: 1) in the postabsorptive state, 2) over the course of an 8-h nasogastric infusion of a small peptide-based nutrient mixture, and 3) during an 8-h isonitrogenous, isoenergetic intravenous infusion (1.5 g amino acid.kg-1.d-1; 130 kJ.kg-1.d-1, or 31 kcal.kg-1.d-1; 58% carbohydrate and 42% fat). Regardless of the route, nutrition increased leucine appearance rate (Ra) and oxidation, stimulated protein synthesis, and improved leucine balance; apparent rates of protein breakdown decreased during enteral nutrition only. Glutamine Ra increased 16.8% (NS) and 26.2% (P < 0.01) with parenteral and enteral feeding, respectively, over postabsorptive values. The present findings are consistent with a major role of glutamine in interorgan nitrogen transport in the fed state and further suggest that increased availability of precursors may stimulate glutamine synthesis de novo, and enteral infusion of peptide-bound amino acids may be an effective route to provide free glutamine to the rest of the body.

This study describes three adults with coeliac disease and hepatic vein obstruction, an association which has not been reported so far. Similarities were found with the cases of five children with Budd-Chiari syndrome and intestinal villous atrophy recently reported in the literature. All subjects had North African origin. Coeliac disease and Budd-Chiari syndrome are uncommon conditions, and it is postulated that this is probably not a chance association, although no link between these diseases and the ethnic origin of the subjects could be elucidated.

Background & aims: Indications and timing for referral for intestinal transplantation (ITx) were investigated through a review of the literature on home parenteral nutrition (HPN) for benign intestinal failure and a benchmarking to the results of a prospective European survey which evaluated the appropriateness of the current indications for ITx. Methods: Manuscripts reporting outcomes of adults and children on HPN were retrieved through a PubMed search. Data from the European survey were compared with those on HPN reported in the literature, and with those on ITx reported by the USA registry and by the Pittsburgh center. Results: HPN is a safe treatment with a high probability of survival. The risk of death during HPN is increased by the absence of a specialist team, and appears greater during the early period of treatment. Survival probability is decreased in patients with: age >40 or

The management of CIPO remains difficult and requires a multidisciplinary approach. In adult patients with CIPO on HPN, the 10-year survival rate was 68%. Long-term HPN dependence does not seem to be associated with a significant increase in mortality and morbidity. HPN could be a safe and efficient approach to the management of intestinal failure caused by CIPO, with restoring oral intake and lowering hospitalization frequency as major goals of treatment.

Background The indications for intestinal transplantation (ITx) are still debated. Knowing survival rates and causes of death on home parenteral nutrition (HPN) will improve decisions. Methods A prospective 5-year study compared 389 non-candidates (no indication, no contraindication) and 156 candidates (indication, no contraindication) for ITx. Indications were: HPN failure (liver failure; multiple episodes of catheter-related venous thrombosis or sepsis; severe dehydration), high-risk underlying disease (intra-abdominal desmoids; congenital mucosal disorders; ultra-short bowel), high morbidity intestinal failure. Causes of death were defined as: HPN-related, underlying disease, or other cause. Results The survival rate was 87% in non-candidates, 73% in candidates with HPN failure, 84% in those with high-risk underlying disease, 100% in those with high morbidity intestinal failure and 54%, in ITx recipients (one non-candidate and 21 candidates) (p2 years (p¼0.006). In candidates, the death HRs were increased in those with desmoids (7.1; 95% CI 2.5 to 20.5; p¼0.003) or liver failure (3.4; 95% CI 1.6 to 7.3; p¼0.002) compared to non-candidates. In deceased candidates, the indications for ITx were the causes of death in 92% of those with desmoids or liver failure, and in 38% of those with other indications (p¼0.041). In candidates with catheter-related complications or ultra-short bowel, the survival rate was 83% in those who remained on HPN and 78% after ITx (p¼0.767). Conclusions HPN is confirmed as the primary treatment for intestinal failure. Desmoids and HPN-related liver failure constitute indications for life-saving ITx. Catheter-related complications and ultra-short bowel might be indications for pre-emptive/rehabilitative ITx. In the early years after commencing HPN a life-saving ITx could be required for some patients at higher risk of death from their underlying disease.

Short bowel syndrome; Lactobacillus; Microbiota; Nutrition; Gut; Dysbiosis; International audience; Short bowel syndrome (SBS) is observed in Humans after a large resection of gut. Since the remnant colon and its associated microbiota play a major role in the outcome of patients with SBS, we studied the overall qualitative and quantitative microbiota composition of SBS adult patients compared to controls. The population was composed of 11 SBS type II patients (with a jejuno-colonic anastomosis) and 8 controls without intestinal pathology. SBS patients had 38 +/- 30 cm remnant small bowel length and 66 +/- 19% of residual colon. The repartition of proteins, lipids, carbohydrates and fibres was expressed as % of total oral intake in patients and controls. The microbiota was profiled from stool and biopsy samples with temporal temperature gradient gel electrophoresis and quantitative PCR. We show here that microbiota of SBS patients is unbalanced with a high prevalence of Lactobacillus along with a sub-dominant presence and poor diversity of Clostridium leptum, Clostridium coccoides and Bacteroidetes. In addition, Lactobacillus mucosae was detected within the fecal and mucosa-associated microbiota of SBS patients, whereas it remained undetectable in controls. Thus, in SBS the microbial composition was deeply altered in fecal and mucosal samples, with a shift between dominant and sub-dominant microbial groups and the prevalence of L. mucosae.

Chronic intestinal pseudo-obstruction (CIPO) is a rare, disabling disorder responsible for motility-related intestinal failure. Because it induces malnutrition, CIPO is a significant indication for home parenteral nutrition (HPN). The objective of the study was to evaluate long-term outcome of CIPO patients requiring HPN during adulthood.In total, 51 adult CIPO patients (18 men/33 women, median age at symptom occurrence 20 (0-74) years, 34/17 primary/secondary CIPO) followed up at our institution for HPN management between 1980 and 2006 were retrospectively studied for survival and HPN dependence rates using univariate and multivariate analysis.Follow-up after diagnosis was 8.3 (0-29) years. Surgery was required in 84% of patients. The number of interventions was 3 +/- 3 per patient (mean +/- s.d.), leading to short bowel syndrome in 19 (37%) patients. Actuarial survival probability was 94, 78, 75, and 68% at 1, 5, 10, and 15 years, respectively. Multivariate analysis showed that lower mortality was associated with the ability to restore oral feeding at baseline (hazard ratio (HR) = 0.2 (0.06-0.65), P = 0.008) and symptom occurrence before the age of 20 years (HR=0.18 (0.04-0.88), P = 0.03). Higher mortality was associated with systemic sclerosis (HR=10.4 (1.6-67.9), P = 0.01). Actuarial HPN dependence was 94, 75, and 72% at 1, 2, and 5 years, respectively.In this large cohort of CIPO adult patients with severe intestinal failure, i.e., those requiring HPN, we found a higher survival probability than previously reported. These results should be taken into account when considering intestinal transplantation.

Ten adult ambulatory patients with the nonactive digestive disease short bowel syndrome were prospectively studied to quantitatively assess their free oral intake and their net digestive absorption of total calories, fat, protein, and carbohydrate during a 3-day period at least 6 months after a resection. The remaining portions of small bowel had a mean length of 75 cm (range, 0-200 cm); the remaining colon lengths had a mean of 67% of normal (range, 0%-100%). The experimental diets were formulated according to a home dietary inquiry. During the study period, pooled intakes and digestive losses were measured for total calories, fat, and protein using the bomb calorimetry, Van de Kamer, and Kjeldahl techniques, respectively. The ingested diet provided 58 +/- 14 kcal.kg-1.day-1 (mean +/- SD) and consisted of 46% carbohydrate, 31% fat, and 23% protein. Net digestive absorption was 67% +/- 12% for total calories, 79% +/- 15% for carbohydrate, 52% +/- 16% for fat, and 61% +/- 19% for protein. The larger net digestive absorption of carbohydrate (P less than or equal to 0.004) compared with fat and protein suggests salvage of colonic cholesterol in short bowel syndrome patients. It is concluded that these patients with the short bowel syndrome adapted to a hypercaloric, hyperprotein diet to compensate for increased fecal losses and that this hyperphagia does not seem to have impaired their net digestive absorption.

Rates of oxidation of infused 13C-labeled substrates are calculated from CO2 production and 13C enrichment in breath CO2. Breath sampling through a mouthpiece is not appropriate in severely ill patients; the authors therefore validated the use of direct air sampling from the ventilated canopy of an indirect calorimeter for measuring the oxidation of 13C-labeled substrates. Infusions of H13CO3Na or L-[1-13C]leucine were performed in four healthy postabsorptive adults and six malnourished patients receiving total parenteral nutrition (TPN). At each sampling point, air was collected from the canopy to compare with breath air sampled through a mouthpiece and 13CO2 enrichment determined by isotope ratio mass spectrometry. Despite five-fold dilution of expired air by room air within the canopy (a dilution required to maintain safe CO2 levels in inspired air): (1) Breath 13CO2 enrichment was accurately predicted using samples from the canopy, with a correction taking into account the measured CO2 fractions in canopy and room air; (2) the precision in isotopic determination was similar with both methods (SD/mean of 12 determinations = 2.5 +/- 1.0% vs 3.0 +/- 1.0%). These data demonstrate that the use of a ventilated canopy allows for combined assessment of energy expenditure and rates of oxidation of 13C-labeled substrates even in sick, debilitated patients receiving total parenteral nutrition.

Background & Aims 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. Methods 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-γ were analyzed for mutations. Results 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-γ 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). Conclusion 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.

Objective To determine an association between magnesium (Mg) depletion and chondrocalcinosis, which has been reported but not investigated in a cross-sectional study. Methods Prevalence of chondrocalcinosis was investigated in 144 individuals: 72 patients receiving home parenteral nutrition (HPN) compared with 72 age- and sex-matched controls. Presence of chondrocalcinosis was assessed by knee radiographs. Blood serum and globular Mg levels and 24-hour urinary Mg content were compared. Results Mean ± SD age for both patients and controls was 51 ± 17 years, and 51% in both groups were women. Mean duration of HPN was 6.4 years. Prevalence of chondrocalcinosis was markedly higher in patients receiving HPN than controls (16.6% versus 2.7%; P = 0.006, odds ratio [OR] 7.0, 95% confidence interval [95% CI] 1.45–66.1). Mean ± SD serum and globular Mg levels were significantly lower in patients than controls (serum: 0.75 ± 0.09 mmoles/liter versus 0.81 ± 0.08 mmoles/liter, P = 0.0006; globular Mg: 1.8 ± 0.31 mmoles/liter versus 2.0 ± 0.35 mmoles/liter, P = 0.0003). Twenty-four-hour urinary Mg level was lower in patients than controls (mean ± SD 3.85 ± 1.50 mmoles versus 5.37 ± 3.71 mmoles; P = 0.001). Prevalence of chondrocalcinosis was significantly higher in patients with a low serum Mg level (OR 13.5, 95% CI 2.76–127.3, P < 0.0001), with a similarly high but not significant occurrence of chondrocalcinosis in patients with a low globular Mg level (OR 4.09, 95% CI 0.603–20.26, P = 0.08) and in patients with a low 24-hour urinary Mg level (OR 3.9, 95% CI 0.77–16.34, P = 0.05). Conclusion Long-lasting Mg depletion is strongly associated with chondrocalcinosis.

Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

Taurine deficiency in patients on long-term parenteral nutrition may be involved in cholestasis. We aimed to assess plasma taurine and tauro-conjugated bile acids in adults with short-bowel syndrome and their response to intravenous taurine. Thirty-two adult patients, who had been on taurine-free parenteral nutrition for a mean of 59(SE14) months for short-bowel syndrome, were studied retrospectively. In a second study, a subgroup of ten patients with chronic cholestasis received taurine-enriched (6·0(SE0·6)mg/kg per d) parenteral nutrition for 55(SE13) months. Post-absorptive plasma taurine and bile acid concentrations were measured and liver function tests routinely sampled. At baseline, plasma taurine was lower in patients with a jejunal length of less than 35cm (group A,n16) than in those with a jejunal length of 35cm or more (group B,n16): 43(SE3)v. 58(SE4)μmol/l (P=0·01). The groups were no different in terms of chronic cholestasis (1/6v.1/6 patients), total bile acids (26(SE13)v.14(SE5)μmol/l) or the ratio of tauro-conjugated:glyco-conjugated bile acids (5(SE2)v.8(SE 4)%, usual range 30–60%). After supplementation, there was an increase in plasma taurine level (63(SE8)v. 43(SE4),P=0·007) but was no change in either total bile acids or the ratio of tauro-conjugated: glyco-conjugated bile acids. There was a significant decrease in aspartate aminotransferase level. Long-term parenteral nutrition for short-bowel syndrome is associated with an impaired tauro-conjugation of bile acids (enterohepatic pool), irrespective of plasma taurine level (systemic pool) and despite long-term taurine intravenous supplementation.

Given the lack of published guidelines regarding the use of trophic factors to treat patients with short bowel syndrome (SBS), a group of experts in the field convened to discuss best-practice strategies. Trophic factors, such as recombinant human growth hormone (r-hGH) and glucagon-like peptide-2 (GLP-2), may enhance intestinal adaptation and decrease parenteral nutrition (PN) requirements; therefore, their utility in treating SBS patients was evaluated. Available clinical data on use of r-hGH therapy in SBS patients were discussed, as were the utility of r-hGH in the PN weaning process, the optimal timing of r-hGH therapy, and how to select appropriate patients for r-hGH therapy. In addition, contraindications and precautions as well as adverse effects of r-hGH treatment were discussed. The meeting culminated with the development of a treatment algorithm to summarize best-practice recommendations for the management of SBS in adult patients. This algorithm involves attempting to wean patients off PN without the use of trophic factors. If this is unsuccessful, it is recommended that patients be treated with an r-hGH regimen or participate in investigational studies using other trophic factors.

Background Previous studies showed high prevalence rates of cholelithiasis in patients with home parenteral nutrition (HPN). Our aim was to determine, in an HPN population, the incidence and risk factors for gallstones and sludge and their complications. Study design Retrospective chart review was conducted in a tertiary care center. One hundred fifty-three consecutive patients who received HPN for longer than 2 months (range 2 to 204 months; median 15 months) between 1985 and 1997 were followed with ultrasonography. Kaplan-Meier curves and log-rank tests were calculated to assess risk factors for gallbladder lithiasis and complications. Results Thirty-four patients (22%) underwent cholecystectomy before HPN. Of the 119 remaining patients with gallbladder in situ, cholelithiasis appeared during HPN in 45 (38%). The probability of cholelithiasis developing during HPN was estimated to be 6.2%, 21.2%, and 38.7% at 6, 12, and 24 months, respectively. Biliary complications developed in eight patients (7%) during followup. Therapy consisted of endoscopic sphincterotomy (three patients) or operation (five patients) with uncomplicated outcomes except for one patient; no death was observed. Incidence rates of biliary complication during HPN were estimated to be 0.0%, 4.7%, and 10.1% at 6, 12, and 24 months, respectively. Nil or negligible ingesta was the only factor notably associated with incidence of cholelithiasis (p Conclusions This first incidence study shows a high rate of cholelithiasis and a low rate of complications during HPN. Both events were notably related to nil or negligible ingesta.

OBJECTIVES: Epidemiology of candidacy for intestinal transplantation (ITx) and timing for referral for ITx are unknown. Patient candidacy and physician attitudes toward ITx were investigated among centers that participated in previous European surveys on home parenteral nutrition (HPN). METHODS: Patients on HPN for benign intestinal failure (IF) were evaluated by a structured questionnaire. Candidacy was assessed by USA Medicare and American Transplantation Society criteria, categorized as: (1) life-threatening HPN complications; (2) high risk of death because of the gastrointestinal disease; (3) IF with high morbidity or patient HPN refusal. Physicians judged candidacy as immediate or potential. RESULTS: Forty-one centers from nine countries enrolled 688 adults (> 18 yr) and 166 pediatric patients; 70% of patients were from five countries which collected 60-100% of their HPN patients. Candidacy was 15.7% in adults and 34.3% in pediatrics (HPN failure, 62.1% and 28.1%; gastrointestinal disease, 25.9% and 59.6%; high morbidity IF or HPN refusal, 12.0% and 12.3%, respectively). Immediate candidacy was required for 14.8% of adult and 15.8% of pediatric candidates (< 50% of candidates because of HPN-related liver failure). Among centers, the candidacy rate ranged 0-100% and was negatively associated with the number of patients enrolled in the survey (R = -0.463, p = 0.002). Among the major contributing countries, candidacy ranged 0.3-0.8/million inhabitants for adults and 0.9-2/million inhabitants < or = 18 yr for pediatric candidates. CONCLUSIONS: The rate of candidacy and the indications for ITx candidacy differed greatly among age groups and HPN centers; within countries candidacy was more homogeneous; physicians had a generally reserved attitude toward ITx.