[Nutritional therapy in acute pancreatitis]. / Ernährungstherapie bei akuter Pankreatitis.

Acute pancreatitis is a frequent clinical entity in the West. About 80% of patients with acute pancreatitis develop edematous pancreatitis, while 20% develop necrotizing pancreatitis: The latter is a potentially life-threatening disease. In this case, early enteral nutrition has been shown to improve the course of the disease. Usually, gastric enteral nutrition with a polymeric formula via a nasogastric tube is possible; only in a minority of patients is jejunal feeding necessary owing to the high gastric residual volume. An elemental formula is useful for patients with significant intestinal maldigestion. If enteral feeding is not feasible within 5-7 days, (additional) parenteral nutrition has to be considered. Individualized--primary enteral--nutritional support is an essential part of a multimodal therapy in severe acute pancreatitis and it improves clinical outcome.

Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes.

UNLABELLED: Despite treatment with supra-physiological doses of pancreatic enzyme supplements, residual steatorrhoea is a common problem in patients with cystic fibrosis (CF) and pancreatic insufficiency. Strategies to enhance the activity of pancreatic enzymes include decreasing duodenal acidity. The aim of this study was to evaluate the effect of omeprazole (Losec), a proton-pump inhibitor, on fat absorption in CF patients with residual steatorrhoea despite high dose pancreatic enzyme supplements (> or =10,000 U lipase/kg per day). A random cross-over design was chosen. Fat digestion was evaluated with and without omeprazole by means of chemical fat measurements in 3-day stool collections together with 3-day weighed food records for calculation of fat absorption. The results of 15 patients (3 girls and 12 boys) with confirmed steatorrhoea during the control evaluation were analysed. Median age was 8.7 years (range 3.5-15.9 years). Median daily lipase intake was 13,500 U/kg per day (range 10,000-22,000 U/kg per day). During treatment with omeprazole, median faecal fat loss (g fat/day) decreased from 13 g (quartiles 11.5-16.5 g/day) to 5.5 g (quartiles 4.9-8.1 g/day) (P<0.01). The same improvement was noted when fat absorption was calculated: 87% (quartiles 81-89%) without versus 94% (quartiles 90-96%) with omeprazole (P<0.001). CONCLUSION: Omeprazole improves fat digestion and absorption in cystic fibrosis patients with residual faecal fat loss despite maximal pancreatic enzyme substitution.

A pancreatic extract-enriched diet improves the nutritional status of aged rats.

Correction of the malnourished state, particularly common and severe in elderly people, is often unsuccessful. To improve the efficiency of realimentation, we evaluated the nutritional effect of a pancreatic extract (PE)-enriched diet in malnourished aged rats. Sprague-Dawley male rats were randomly assigned to 6 groups as follows: 1 group of control rats had free access to the diet for 12 wk (C group) and 5 groups were 50% food restricted for the same period. One food-restricted group was then killed (R group) and the 4 remaining groups were refed for 1 wk using a standard diet enriched either with two different doses of a pancreatic extract (2.4 or 4.8 g/d in PE1 and PE2 groups, respectively) or with an isonitrogenous casein hydrolysate (CH1 and CH2 groups, respectively). Profound alterations induced by food restriction (FR) were moderately corrected by refeeding, except nitrogen balance, which was reestablished in rats refed all diets (P: < 0.01 vs. R). Supplementation of the food ration with a pancreatic extract clearly improved recovery. Indeed, body weight gain, both jejunal and ileal trophicity [jejunum: total height, PE2: 849 +/- 45 microm vs. CH2: 768 +/- 17 microm (P: < 0.05); protein content, PE2: 69.9 +/- 5.7 mg vs. CH2: 56.4 +/- 4.8 mg (P: < 0.01)] and nonspecific immune response in terms of H2O2 production by polymorphonuclear neutrophils and tumor necrosis factor alpha (TNF-alpha) by macrophages (PE2, 20.7 +/- 4.7 vs. CH2, 8.7 +/- 2.3, P: < 0.05) were improved in rats fed PE2. A pancreatic extract could improve the efficiency of realimentation in malnourished aged rats.

Effects of pancreatic enzyme preparations on erythrocyte glutathione peroxidase activities and plasma selenium concentrations in cystic fibrosis.

To substitute for exocrine pancreatic insufficiency, patients with cystic fibrosis (CF) take pancreatic enzymes (PE) originating from porcine pancreas. Five different pancreatic enzyme preparations used by our patients contained 0.5-1.4 microg selenium per g tablet. In patients taking PE in doses that were gradually increased to improve fat absorption during a 48-month period, the effects of PE dose on erythrocyte selenium-dependent glutathione peroxidase (SeGSH-Px) activities and plasma selenium concentrations were studied. At baseline, erythrocyte SeGSH-Px activities were significantly lower in patients (p=.01), while plasma selenium concentrations did not differ between patients and healthy subjects. When PE dose and, consequently, selenium intake from PE was increased, erythrocyte SeGSH-Px activities (p < .001) and plasma selenium concentrations (p=.02) increased. Changes in SeGSH-Px activities during the initial 8 months correlated with those in selenium intake from PE (r=0.67, p < .001). Plasma selenium concentrations plateaued at 12 months and erythrocyte SeGSH-Px activities did so at 36 months, when patients had reached SeGSH-Px activities similar to those of healthy subjects. At 48 months, patients took an average lipase dose of 17400 U x kg(-1) x d(-1) and selenium dose from PE of 0.53 microg x kg(-1) x d(-1). We conclude that selenium content of PE preparations has a significant effect on SeGSH-Px activity in patients with CF. This form of selenium supply needs to be taken into account when selenium supplements are given to patients with CF.

Response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency.

OBJECTIVE: To study response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency (EPI). DESIGN: Cross-sectional study. ANIMALS: 76 German Shepherd Dogs or rough-coated Collies with EPI and 145 clinically normal dogs of the same breeds. PROCEDURE: Questionnaires were sent to owners of dogs with EPI and owners of clinically normal dogs. Dogs with EPI had been given dietary enzyme supplements for at least 4 months. Relative frequency distributions of gastrointestinal tract and dermatologic signs, prevalences of typical signs of EPI (e.g., weight loss, ravenous appetite, yellow and pulpy feces, high fecal volume), feeding regimens, and dietary intolerances were compared between dogs with EPI and clinically normal dogs. RESULTS: Gastrointestinal tract signs considered typical for dogs with EPI were almost completely controlled with dietary enzyme supplements in half of the dogs with EPI, and their general health was similar to that of clinically normal dogs. A poor treatment response was found in a fifth of dogs with EPI that had several signs that were typical of EPI. Signs most often persisting were high fecal volume, yellow and pulpy feces, and flatulence. Dermatologic problems were common, especially in German Shepherd Dogs with EPI. Treatment response was irrespective of breed. Nonenteric-coated enzyme supplements, powdered enzyme, and raw chopped pancreas were equally effective in controlling clinical signs. Although dietary sensitivities were common, use of adjunctive dietary treatment was minimal. Antibiotics were occasionally administered to half of the dogs with EPI. CLINICAL IMPLICATIONS: Results of this study indicate that, with basically similar treatment regimens, response to long-term enzyme treatment in dogs with EPI varied considerably.

Deficiency of vitamins E and A in cystic fibrosis is independent of pancreatic function and current enzyme and vitamin supplementation.

UNLABELLED: The aim of this study was to evaluate to what extent serum vitamins A and E cystic fibrosis are affected by the underlying disease, pancreatic sufficiency or insufficiency, meconium ileus, nutritional status, age and treatment (enzyme and vitamin supplementation). Serum vitamin A and E levels were determined by high performance liquid chromatography in 210 cystic fibrosis patients, subdivided according to clinical condition into four subgroups (unsupplemented pancreatic insufficiency, supplemented meconium ileus, pancreatic sufficiency, supplemented pancreatic insufficiency) and compared with 42 control subjects. Vitamin A and E levels were generally lower in cystic fibrosis patients than in controls (P < 0.002 and P < 0.001 respectively). Subjects with pancreatic insufficiency regularly receiving enzyme and vitamin supplementation had significantly lower vitamin A (P < 0.05) and vitamin E (P < 0.01) levels than controls. In subjects with pancreatic sufficiency only vitamin A was significantly lower than in controls (P < 0.01). Vitamin levels were not age-dependent in cystic fibrosis, and no significant correlation with standardized body weight (Z-score) was observed. CONCLUSION: Cystic fibrosis patients show a clear tendency to vitamin A and E deficiency, irrespective of pancreatic function, body weight and standardized supplementation with pancreatic extract and liposoluble vitamins. Since the clinical significance of this deficiency is still not clear, longitudinal studies of cystic fibrosis patients with and without adequate vitamin supplementation are required.

Fibrosing colonopathy in cystic fibrosis: results of a case-control study.

Fibrosing colonopathy was first described in cystic fibrosis (CF) children in 1994. We have done a nested case-control study to identify possible associations with this condition. A case ascertainment within the UK CF population to identify any cases that occurred between January, 1984, and April, 1994, found 14 cases, all under 14 years and confirmed by independent histopathological review. All had presented since April, 1993; 12 were boys and six had received some or all of their care in Liverpool. Each case was matched, by date of birth, with four controls from the UK CF Registry. Information was obtained about cases and controls from their case records and by a structured interview with the families. In the 12 months before surgery, there was an association between the occurrence of fibrosing colonopathy and use of high-strength pancreatic enzyme preparations. This association was dose related. Odds ratio per extra 1000 high-strength capsules was 1.45 (95% CI 1.14-1.84). For use of protease, the odds ratio per million extra units per kg was 1.55 (1.19-2.03). For usage of individual high-strength products at any time during the 12 months before surgery some differences were observed; for Creon 25000 the odds ratio was 0.38 (0.10-1.42), for Nutrizym 22 43.4 (2.51-751), and for Pancrease HL 8.4 (1.95-36.1). These last two confidence intervals are extremely wide and compatible with these two products having the same odds ratios. Laxative use was independently predictive (odds ratio 2.42 [1.20-4.94]). We conclude that there is a dose-related association between high-strength pancreatic enzyme preparations and fibrosing colonopathy.

Ulcerative type of colitis associated with the use of high strength pancreatic enzyme supplements in cystic fibrosis.

A 2 1/2-year-old girl with cystic fibrosis, who presented with hematochezia, developed an inflammatory ulcerative type of colitis with mild interstitial fibrosis and colonic narrowing while being treated with high strength pancreatic enzyme supplements. Findings of contrast enema, endoscopy, and colonic biopsy are described. The spectrum of colonic disease associated with the use of high strength pancreatic enzyme supplements in cystic fibrosis patients is discussed.

Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy.

In a double-blind, randomized crossover study, the hypotheses were tested that more powerful inhibition of gastric acid secretion by adjuvant omeprazole further improves the efficacy of pancreatic enzyme replacement therapy compared to adjuvant cimetidine and that excluding the influence of pH-related factors, by virtually complete inhibition of gastric acid secretion with 60 mg omeprazole daily, does not lead to total elimination of steatorrhea. During both adjuvant cimetidine and omeprazole treatment, fecal fat excretion was significantly lower compared to pancreatin monotherapy (P < 0.01). Omeprazole showed a trend towards a more favorable decrease of fecal fat excretion compared to cimetidine but no statistically significant difference. Steatorrhea was almost never abolished, even during 60 mg omeprazole daily. Generally, pH-related factors are considered to explain an inadequate therapeutic response during pancreatic enzyme replacement therapy. However, this study indicates that in vivo other factors also play a significant role.

Benign intracranial hypertension in an older child with cystic fibrosis.

Despite having normal height and weight, a 6-year-old girl had frequent bowel movements and slight recurrent chest infections since the age of 4 years and headache for 1 year. The patient appeared healthy, but examination of the ocular fundus revealed papilledema. Cranial computed tomography appeared normal. Lumbar puncture disclosed an elevated opening cerebrospinal fluid pressure, with normal biochemical, cellular, and bacteriologic findings. Laboratory investigations indicated pathologic steatorrhea, elevated electrolytes in 3 sweat tests, and low serum levels of vitamins A and E. The diagnosis of pseudotumor cerebri in a patient with cystic fibrosis was made. After treatment with prednisone (1 mg/kg/day), pancreatic extracts, and vitamin supplements, headache and papilledema resolved and serum vitamin A and E levels subsequently became normal. Older children with cystic fibrosis rarely have benign intracranial hypertension, but when present it is often due to hypervitaminosis during correction of malnutrition. In this child, pseudotumor cerebri and associated hypovitaminosis improved after combined corticosteroid and vitamin treatment.

Pancreatic enzyme replacement therapy in post-pancreatectomy patients.

The occurrence of malnutrition and maldigestion was studied in nine patients who underwent pancreatoduodenectomy and sclerosis of the residual pancreatic stump with neoprene. The operation causes a complete loss of exocrine pancreatic function, but spares islet cell function. Upon discharge from the hospital, patients received pancreatin powder as a dietary enzyme supplement (18,000 lipase U/meal). Patients were again hospitalized 2 y after surgery for evaluation of nutritional status and digestive function (hospital checkup). Nutritional status was evaluated by measuring serum albumin, total iron binding capacity, and total lymphocytes. Digestive function was assessed by the D-xylose tolerance test and determination of fecal fat excretion. Patients were then discharged with pancrelipase enteric-coated microspheres (ECM) as a dietary enzyme supplement (16,050 lipase U/meal). Malnutrition, defined as the occurrence of at least two abnormal nutritional parameters, was observed in three patients at the time of the hospital checkup. Upon reevaluation of nutritional status after 6 mo on pancrelipase ECM, all patients were well nourished. The mean body weight, which had been 52.8 Kg immediately after surgery, increased to 54.9 Kg at the time of the hospital checkup (p less than 0.01) and to 58.0 Kg after six months of pancrelipase ECM therapy (p less than 0.05). At the hospital checkup, the D-xylose test was normal in all patients and steatorrhea had decreased from a mean of 32.8 g/d without enzyme supplementation to 16.7 g/d with pancrelipase therapy (16,050 lipase U/meal). The complete loss of exocrine pancreatic function following surgery was well tolerated. In fact, when patients were on pancrelipase therapy, much of the original body weight was recovered and the biochemical indices of malnutrition were normalized.

Malabsorption in cystic fibrosis: mechanisms and treatment.

Malabsorption of nutrients in cystic fibrosis (CF) has a multifactorial origin. The factors involved in malabsorption include malfunction of the exocrine pancreas and liver, bile acid metabolism, and disordered intestinal resorptive processes. Therapeutic measures presently employed are only partially effective. Improvement of fat malabsorption is attained by using a pancreatic enzyme supplement consisting of pH-sensitive, enteric-coated microspheres (microsphere preparations) that prevent enzyme degradation in the stomach and travel with the chyme to the small intestine. Microsphere preparations, however, do not improve bile salt deficiency. The detergent Tween-80, given orally to simulate bile salt activity, does not improve fat absorption. The mucus viscosity is probably enhanced in the intestinal epithelium of CF patients and can be decreased by N-acetylcysteine, which breaks down sulfide bonds. However, the addition of a high oral dose of this mucus solvent to pancreatin preparations does not improve fat absorption. Further studies on the disturbed intestinal resorptive mechanism seem warranted since recent investigations point to an abnormal chloride secretion as the primary defect in the intestinal epithelia of CF patients.

Impairment of folic acid absorption by oral pancreatic extracts.

Higher serum folate levels were found among newly diagnosed, untreated patients with pancreatic insufficiency than among treated patients despite greater fat malabsorption in the former group. In vivo folate absorption tests using Tritium-labeled pteroylmonoglutamatic acid showed folate absorption to be enhanced in pancreatic insufficiency patients as compared to control subjects (P less than 0.01). Moreover, pancreatic extract significantly inhibited folate absorption in both normal subjects (P less than 0.05) and pancreatic insufficient patients (P less than 0.001). In vitro testing showed pancreatic extract to form insoluble complexes with folate. Such complex formation may diminish absorption of dietary folate and lead to folate deficiency. Since both pancreatic extract and bicarbonate are used in the treatment of pancreatic insufficiency and both are known to impair folate absorption, folate status should be monitored in patients being treated for pancreatic insufficiency; supplementation may be indicated.

Hyperuricosuria due to high-dose pancreatic extract therapy in cystic fibrosis.

Dysuria, uric acid crystalluria and hyperuricosuria developed in a child with cystic fibrosis and normal serum uric acid. Hyperuricosuria in this patient and two other children was directly related to ingestion of large amounts of pancreatic extract. In these three children, reducing pancreatic extract dosage by 85 percent lowered their purine intake by 307, 225, and 148 mg, respectively; urinary uric acid excretion decreased by 245, 239, and 158 mg. Overmedication resulted from parents' decisions to increase enzyme dosages. In our cystic fibrosis clinic, 15 of 32 patients screened at random were taking higher than the prescribed dose of pancreatic enzymes, and 14 of these 15 children were hyperuricosuric. On the basis of this information, we suggest that the minimal effective dose of pancreatic extract should be determined and adhered to for each child with cystic fibrosis to avoid potential renal injury from hyperuricosuria.