M. Staun

Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European cooperative Crohn's disease study VI

BACKGROUND & AIMS This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohns disease after surgical resection. METHODS In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohns Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohns disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

ESPEN Guidelines on Parenteral Nutrition: Home Parenteral Nutrition (HPN) in adult patients

Home parenteral nutrition (HPN) was introduced as a treatment modality in the early 1970s primarily for the treatment of chronic intestinal failure in patients with benign disease. The relatively low morbidity and mortality associated with HPN has encouraged its widespread use in western countries. Thus there is huge clinical experience, but there are still few controlled clinical studies of treatment effects and management of complications. The purpose of these guidelines is to highlight areas of good practice and promote the use of standardized treatment protocols between centers. The guidelines may serve as a framework for development of policies and procedures.

Home parenteral nutrition in adults: a Europeanmulticentre survey in 1997

Abstract A retrospective survey on home parenteral nutrition (HPN) in Europe was performed fromJanuary to December 1997. Data were compared to a similar study performed in 1993. A questionnaire of HPN practice was designed by the members of the ESPEN-HAN group. This involvedadult patients (older than 16 years) newly registered in an HPN program between 1 January and 31 December 1997 and included: number of patients, underlying diseases and a 6–12 month outcome. Incidence and prevalence (at 1.1.1998) of adult HPN were calculated according to the estimated total population in 1997 for the countries in which more than 80% of HPN patients were reported. A total of 494 patients were registered in 73 centres from nine countries (Belgium (B), Denmark (D), France (F), Poland (P), Spain (S), Sweden (Sw), United Kingdom (UK), The Netherlands (N) and Germany (G). The underlying diseases for HPN in 494 patients were cancer (39%), Crohns (19%), vascular diseases (15%), radiation enteritis (7%), AIDS (2%), other diseases with intestinal failure (18%). Incidence (patients/million inhabitants/year) were in N (3), F. (2.9), D. (2.8), B. (2.6), UK (1.2), S (0.7) and P (0.36), respectively. Prevalence were in D. (12.7). U.K. (3.7), N. (33), F (3.6), B (3.0), P (1.1), S (0.65). After this 6–12 months follow-up (n=284), the mortality was respectively 4% in Crohns disease, 13% in vascular diseases, 16% in others, 21% in radiators enteritis, 34% in AIDS, 74% in cancer. Incidences and prevalences modestly increased in these seven European countries in 1997 in comparison to 1993. The percentages of underlying diseases in these countries remained similar except for ADS that significantly decreased (from 7% to 2%). Outcomes did not significantly differ in the 4-year period except for AIDS (34% instead of 88% mortality) and could have been related to newer, more efficacious therapy.

Long-term follow-up of patients on home parenteral nutrition in Europe: implications for intestinal transplantation

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) (p<0.001). The primary cause of death on HPN was underlying disease-related in patients with HPN duration ≤2 years, and HPN-related in those on HPN duration >2 years (p=0.006). In candidates, the death HRs were increased in those with desmoids (7.1; 95% CI 2.5 to 20.5; p=0.003) or liver failure (3.4; 95% CI 1.6 to 7.3; p=0.002) 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 (p=0.041). 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 (p=0.767). 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.

Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection.

Background—H2 receptor blockers and proton pump inhibitors reduce intestinal output in patients with short bowel syndrome. Aims—To evaluate the effect of intravenous omeprazole and ranitidine on water, electrolyte, macronutrient, and energy absorption in patients with intestinal resection. Methods—Thirteen patients with a faecal weight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowel length of 100 cm were studied. Omeprazole 40 mg twice daily or ranitidine 150 mg twice daily were administered for five days in a randomised, double blind, crossover design followed by a three day control period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had no influence on the results. Results—Omeprazole increased median intestinal wet weight absorption compared with no treatment and ranitidine (p<0.03). The effect of ranitidine was not significant. Four patients with faecal volumes below 2.6 kg/day did not respond to omeprazole; in two absorption increased by 0.5-1 kg/day; and in five absorption increased by 1−2 kg/day. Absorption of sodium, calcium, magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged. Four high responders continued on omeprazole for 12–15 months, but none could be weaned from parenteral nutrition. Conclusion—Omeprazole increased water absorption in patients with faecal output above 2.50 kg/day. The effect varied significantly and was greater in patients with a high output, but did not allow parenteral nutrition to be discontinued. Absorption of energy, macronutrients, electrolytes, and divalent cations was not improved. The effect of ranitidine was not significant, possibly because the dose was too low.

ESPEN guidelines on chronic intestinal failure in adults

BACKGROUND & AIMS Chronic Intestinal Failure (CIF) is the long-lasting reduction of gut function, below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. CIF is the rarest organ failure. Home parenteral nutrition (HPN) is the primary treatment for CIF. No guidelines (GLs) have been developed that address the global management of CIF. These GLs have been devised to generate comprehensive recommendations for safe and effective management of adult patients with CIF. METHODS The GLs were developed by the Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds, and accepted in an online survey of ESPEN members. RESULTS The following topics were addressed: management of HPN; parenteral nutrition formulation; intestinal rehabilitation, medical therapies, and non-transplant surgery, for short bowel syndrome, chronic intestinal pseudo-obstruction, and radiation enteritis; intestinal transplantation; prevention/treatment of CVC-related infection, CVC-related occlusion/thrombosis; intestinal failure-associated liver disease, gallbladder sludge and stones, renal failure and metabolic bone disease. Literature search provided 623 full papers. Only 12% were controlled studies or meta-analyses. A total of 112 recommendations are given: grade of evidence, very low for 51%, low for 39%, moderate for 8%, and high for 2%; strength of recommendation: strong for 63%, weak for 37%. CONCLUSIONS CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for both the underlying gastrointestinal disease and to provide HPN support. The rarity of the condition impairs the development of RCTs. As a consequence, most of the recommendations have a low or very low grade of evidence. However, two-thirds of the recommendations are considered strong. Specialized management and organization underpin these recommendations.

Candidates for Intestinal Transplantation: A Multicenter Survey in Europe

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 ≤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.

Clinical nutrition in Danish hospitals: a questionnaire-basednutrition among doctors and nurses

Abstract Specific nutrition standards are now developed by the Joint Commission on Accreditation ofHealthcare Organizations (JCAHO) in order to improve the nutritional status in hospitalized patients. We investigated the use of clinical nutrition in Danish hospitals and compared itwith the standards of JCAHO by doing a questionnaire-based investigation among doctors and nurses randomly selected in 40 hospitals including internal medicine, gastroenterology, oncology, orthopedic departments and intensive care units (ICU). Overall, 857 (43.4%) responded to the questionnaire (doctors: 395, nurses: 462). Seventy-seven percent stated that nutritional assessment ought to be performed on admission, but only 24% stated that it was a routine procedure. Forty percent found it difficult to identify risk-patients, and 52% needed specific screening tools. Twenty-two percent registered body weight in all patients, end 18% registered nutrient intake routinely. Eighty-four percent found that a nutrition plan should be described in the patient record, but 39% found it difficult to set up on individual plan, and 79% expressed a need for specific guidelines. Eighty-four percent would only accept a patient being on isotonic glucose and/or electrolyte infusion for The use of clinical nutrition in Danish hospitals did not fulfill the standards for nutrition supportaccording to the criteria established by JCAHO. Special efforts should be aimed at education, specific screening tools and introduction of guidelines in clinical nutrition.

Short-term Administration of Glucagon-like Peptide-2. Effects on Bone Mineral Density and Markers of Bone Turnover in Short-Bowel Patients with No Colon

Background: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of shortbowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. Methods: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 μg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. Results: Mean ± s x (SEM) percent changes in spinal and hip BMD were 1.1 ± 0.4% ( P < 0.05) and 1.9 ± 0.8% ( P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% ( P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. Conclusion: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Home enteral nutrition in adults: a European multicentre survey

AIMS This study was undertaken to report indications and practice of home enteral nutrition (HEN) in Europe. METHODS A questionnaire on HEN practice was sent to 23 centres from Belgium (B), Denmark (D), France (F), Germany (G), Italy (I), Poland (P), Spain (S) and the United Kingdom (UK). This involved adult patients newly registered in HEN programme from 1 January 1998 to 31 December 1998. RESULTS A total of 1397 patients (532 women, 865 men) were registered. The median incidence of HEN was 163 patients/million inhabitants/year (range: 62-457). Age distribution was 7.5%, 16-40 years; 37.1%, 41-65 years; 34.5%, 66-80 years and 20.9% >80 years. The chief underlying diseases were a neurological disorder (49.1%), or head and neck cancer (26.5%); the main reason for HEN was dysphagia (84.6%). A percutaneous endoscopic gastrostomy (58.2%) or a naso-gastric tube (29.3%) were used to infuse commercial standard or high energy diets (65.3%), or fibre diets (24.5%); infusion was cyclical (61.5%) or bolus (34.1%). Indications and feeds were quite similar throughout the different centres but some differences exist concerning the underlying disease. There was greater variation in the choice of tubes and mode of infusion. In F, G, I, S, and UK, costs of HEN are fully funded. In B, D, and P patients have to pay part or all of the charges. CONCLUSIONS In Europe, HEN was utilised mainly in dysphagic patients with neurological disorders or cancer, using a standard feed via a PEG. However, there were important differences among the countries in the underlying diseases treated, the routes used, the mode of administration and the funding.