Francisca Joly

Tube Feeding Improves Intestinal Absorption in Short Bowel Syndrome 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.

Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide - Analyses from a randomised, placebo-controlled study

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.

Effects of a Multimodal Management Strategy for Acute Mesenteric Ischemia on Survival and Intestinal Failure

BACKGROUND & AIMS Acute mesenteric ischemia (AMI) is an emergency with a high mortality rate; survivors have high rates of intestinal failure. We performed a prospective study to assess a multidisciplinary and multimodal management approach, focused on intestinal viability. METHODS In an Intestinal Stroke Center, we developed a multimodal management strategy involving gastroenterologists, vascular and abdominal surgeons, radiologists, and intensive care specialists; it was tested in a pilot study on 18 consecutive patients with occlusive AMI, admitted to a tertiary center from July 2009 to November 2011. Patients with left ischemic colitis, nonocclusive AMI, chronic mesenteric ischemia, and other emergencies were excluded. Patients received specific medical management: revascularization of viable small bowel and/or resection of nonviable small bowel; 12 patients received arterial revascularization. We evaluated the percentages of patients who survived for 30 days or 2 years, the number with permanent intestinal failure, and morbidity. Lengths and rates of intestinal resection were compared with or without revascularization, and in patients with early or late-stage disease. RESULTS Patients were followed up for a mean of 497 days (range, 7-2085 d); 95% survived for 30 days, 89% survived for 2 years, and 28% had morbidities within 30 days. Intestinal resection was necessary for 7 cases (39%), with mean lengths of intestinal resection of 30 cm and 207 cm, with or without revascularization, respectively (P = .03). Among patients with early or late-stage AMI, rates of resection were 18% and 71%, respectively (P = .049). Patients with early stage disease had shorter lengths of intestinal resection than those with late-stage disease (7 vs 94 cm; P = .02), and spent less time in intensive care (2.5 vs 49.8; P = .02). CONCLUSIONS A multidisciplinary and multimodal management approach might increase survival of patients with AMI and prevent intestinal failure.

Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation

Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability.

Development and validation of the disease-specific Short Bowel Syndrome-Quality of Life (SBS-QoL™) scale.

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 (Cronbachs 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.

Non-transplantation surgical approach for chronic intestinal pseudo-obstruction: analysis of 63 adult consecutive cases

Chronic intestinal pseudo‐obstruction (CIPO) is a recurrent disorder caused by intestinal dysmotility. Although, CIPO is not a surgically remediable condition, surgery is a common issue in CIPO patients. The aim of this study was to assess postoperative morbidity and mortality of patients operated on for CIPO and risk of re‐operation.

Effect of Teduglutide, a Glucagon-like Peptide 2 Analog, on Citrulline Levels in Patients With Short Bowel Syndrome in Two Phase III Randomized Trials

Objectives:In clinical trials, treatment with the glucagon-like peptide 2 analog teduglutide was associated with improved fluid and nutrient absorption and increased intestinal villus height and crypt depth in patients with short bowel syndrome (SBS). Plasma citrulline, an amino acid produced by enterocytes, is considered a measure of enterocyte mass. This analysis assessed changes in plasma citrulline levels in patients with SBS in 2 phase III clinical studies of teduglutide.Methods:Both teduglutide studies (0.05 or 0.10 mg/kg/day in CL0600-004 and 0.05 mg/kg/day in CL0600-020) were phase III, 24-week, double-blind, and placebo controlled. Plasma citrulline levels were analyzed and validated by liquid chromatography coupled to tandem mass spectrometry.Results:In both the CL0600-004 and CL0600-020 studies, change in mean plasma citrulline concentrations at Week 24 vs. baseline was significantly greater with teduglutide compared with placebo (10.9 (0.05-mg/kg/day dose) and 15.7 (0.10-mg/kg/day dose) vs. 2.0 μmol/L and 20.6 vs. 0.7 μmol/L, respectively, for each study (P≤0.0001 for each comparison with placebo)). Teduglutide treatment was associated with reductions from baseline in PS (parenteral support) volume requirements; however, a significant correlation between PS reduction and increase in plasma citrulline at Week 24 was observed in only one out of the three teduglutide treatment groups.Conclusions:In 2 phase III studies, patients receiving teduglutide had significant increases in plasma citrulline at Week 24 compared with patients receiving placebo. Increases in plasma citrulline concentrations likely reflect enterocyte mass expansion, but no clear correlation was detected between change in plasma citrulline and change in weekly PS volume.

Independence From Parenteral Nutrition and Intravenous Fluid Support During Treatment With Teduglutide Among Patients With Intestinal Failure Associated With Short Bowel Syndrome

Background: In phase III clinical studies, treatment with teduglutide was associated with clinically meaningful reductions (≥20% from baseline) in parenteral support (PS; parenteral nutrition and/or intravenous fluids) requirements in adult patients with intestinal failure associated with short bowel syndrome (SBS-IF). This analysis reports clinical characteristics of patients who achieved complete independence from PS during teduglutide treatment. Materials and Methods: Post hoc analysis of adult patients who achieved complete PS independence during treatment with teduglutide 0.05 mg/kg/d. Data were pooled from 5 teduglutide clinical trials (2 phase III placebo-controlled trials [NCT00081458 and NCT00798967] and their respective extension studies [NCT00172185, NCT00930644, NCT01560403]). Descriptive statistics were used; no between-group comparisons were performed because of the small sample size and lack of comparator. Results: Of 134 patients, 16 gained oral or enteral autonomy after a median of 5 years of PS dependence and 89 weeks of teduglutide treatment. Demographic and baseline disease characteristics varied among patients (median age, 55 years; 50% men; median baseline PS volume, 5.1 L/wk; median residual small intestine length, 52.5 cm). Most patients who achieved PS independence had colon-in-continuity; however, there was no significant difference in the frequency of PS independence among patients who maintained colon-in-continuity vs those who did not. Conclusion: Findings from this post hoc analysis suggest that oral or enteral autonomy is possible for some patients with SBS-IF who are treated with teduglutide, regardless of baseline characteristics and despite long-term PS dependence.

Risk of recurrence after surgery for chronic radiation enteritis

Approximately one‐third of patients with chronic radiation enteritis (CRE) require surgery, which is associated with a high morbidity rate and a high risk of reoperation. The aim of this study was to report outcome after surgery for CRE.

Intestinal failure after bariatric surgery.

A 47-year-old woman came to our hospital with malnutrition and liver failure in August, 2011. 28 months earlier, when she had been assessed for a bari atric gastric band, medical history included morbid obesity (height 159 cm, weight 127 kg, BMI 45 kg/m2), arterial hypertension, and moderate restrictive respiratory insuffi ciency; oral food intake was high. The patient had laparoscopic adjustable gastric banding. She was subsequently lost to follow-up. 16 months after banding, she had acute vomiting, abdominal pain, dehydration, and acute renal failure, and was non-responsive to band loosening. On laparotomy, gastric necrosis necessitated subtotal gastrectomy and Roux-en-Y gastric bypass. She recovered with no surgical complications. At follow-up, low oral intake (900 kcal per day), chronic diarrhoea, weight loss, and vitamin defi ciencies were noted. Medications were proton pump inhibitors, oral vitamins, and dietary supplements. 12 months after gastric band removal, the patient had lost 80 kg since before banding (weight 47 kg, BMI 18·6 kg/m2) and came to our clinic with cachexia, liver encephalopathy, hypoglycaemia, sarco penia, oedema, ascites, and diarrhoea. There was no evidence of sepsis, bleeding, chronic hepatocellular insuffi ciency, or portal hypertension, and there were no risk factors for acute or chronic liver disease, except for previous obesity. Laboratory testing showed raised amino transferases, a prothrombin rate of 16% (indicating acute liver failure), hypoalbuminaemia, micronutrient defi ciency, and central pancytopenia (appendix). Ultra sound and CT scans showed a non-dysmorphic steatosic liver and ascites. All biological and morphological tests for infections, intoxi cations, or antitrypsin defi ciency, and gastro intestinal, cardiac, auto-immune, nephrological, haemo lytic, haemato logical, or overload diseases were negative. Trans jugular liver biopsy suggested normal hepatic venous pressure gradient and diff use acute fatty liver with pure microvesicular steatosis aff ecting all hepato cytes, without fi brosis or necrosis (fi gure). Specifi c digestive functions were assessed after parenteral nutri tion refeeding, under stable conditions and with high oral intake (2500 kcal per day) (appendix). Intestinal failure results from obstruction, dysmotility, surgical resection, congenital defect, or disease-associated loss of absorption, and is characterised by the inability to maintain protein-energy, fl uid, electrolyte, or micronutrient balance. Because the patient did not need any nutritional support before surgery, we thought that gastrojejunal bypass had profoundly altered absorptive function. This situation is similar to that seen in short bowel syndrome and is worsened by chronic bacterial overgrowth and pancreatic insuffi ciency (appendix). Intestinal failure contributed to severe malnutrition, microvesicular steatosis, and acute fatty liver failure. A multimodal intestinal failure programme was provided through a central venous line. Oral antidiarrhoeal treatment consisted of pancreatic enzymes, loperamide, and digestive decontamination. After 3 months of digestive and nutritional support, oral intake, nutritional status, liver function, and histology recovered (fi gure), although after 20 months the patient still needed parenteral nutrition. Post-bariatric intestinal failure is an emerging indication for parenteral nutrition or intestinal transplantation encountered in expert centres. Either early or delayed postsurgical chronic diarrhoea, especially combined with low oral intake, should be recognised as a strong indicator of intestinal failure. After optimising digestive functions and nutritional support (including enteral nutrition), some patients still need permanent parenteral nutrition, surgical re hab ilitation, and occasion ally intestinal transplantation.