Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients.

BACKGROUND AND AIMS: Glucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity. METHODS: Teduglutide was given subcutaneously for 21 days once or twice daily to 16 SBS patients in the per protocol investigational group, 10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3) mg/kg/day), one with <50% colon in continuity (dose 0.03 mg/kg/day), and five with > or = 50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance studies, D-xylose tests, and intestinal mucosa biopsies were performed at baseline, on the last three days of treatment, and after three weeks of follow up. Pre-study fasting native GLP-2 levels were determined for the five patients with > or = 50% colon in continuity. RESULTS: Pooled across groups and compared with baseline, teduglutide increased absolute (+743 (477) g/day; p<0.001) and relative (+22 (16)%; p<0.001) wet weight absorption, urine weight (+555 (485) g/day; p<0.001), and urine sodium excretion (+53 (40) mmol/day; p<0.001). Teduglutide decreased faecal wet weight (-711 (734) g/day; p = 0.001) and faecal energy excretion (-808 (1453) kJ/day (-193 (347) kcal/day); p = 0.040). In SBS patients with end jejunostomy, teduglutide significantly increased villus height (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema. The improvements in intestinal absorption and decreases in faecal excretion noted after treatment had reversed after the drug free follow up period. A controlled study with a more robust design is ongoing in order to determine the optimal dosage of teduglutide for SBS patients to achieve the maximal effect and utility of this drug in clinical practice. CONCLUSION: Teduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.

Treatment of short-bowel syndrome.

The present article reviews the current literature on the role of diet and other trophic factors in the treatment of short-bowel syndrome. Results using glutamine, growth hormone and glucagon-like peptide 2 are reviewed. Although experimental animal data would suggest that various growth factors are of benefit in the treatment of short-bowel syndrome, only a few clinical studies have made the same claim.

Metastasis of head and neck carcinoma to the site of percutaneous endoscopic gastrostomy: case report and literature review.

BACKGROUND: Patients with head and neck cancer often need a percutaneous endoscopic gastrostomy to provide adequate nutrition because of inability to swallow after tumor radiation therapy. However, metastasis of the original tumor to the gastrostomy exit site may occur. METHODS: We describe the case of a 61-year-old man with stage III (T2 N1) squamous cell carcinoma of the tongue in whom a PEG tube was placed to circumvent anticipated difficulties in swallowing after radiation therapy. We also compare this case with similar cases in the literature. RESULTS: Soreness and erythema near the gastrostomy site reported by the patient were diagnosed as cellulitis, and two courses of antibiotic treatment were prescribed. However, a biopsy showed that the original squamous cell carcinoma had metastasized to the gastrostomy exit site. The "pull" method of tube placement had been used in this patient and in all 19 cases of metastasis reported in the literature. CONCLUSIONS: Metastatic cancer should be considered in patients with head and neck cancer who have unexplained skin changes at the gastrostomy site. Our experience with this case and review of the literature indicate that, in patients with head and neck cancer, "pull" procedures for placement of gastrostomy tubes may induce metastasis by direct implantation of tumor cells because of contact between the gastrostomy tube and tumor cells. Methods of tube insertion that avoid such contact are preferred.

Rational approach to patients with unintentional weight loss.

Unintentional weight loss is a problem encountered frequently in clinical practice. Weight loss and low body weight have potentially serious clinical implications. Although a nonspecific observation, weight loss is often of concern to both patients and physicians. There are multiple potential etiologies and special factors to consider in selected groups, such as older adults. A rational approach to these patients is based on an understanding of the relevant biologic, psychological, and social factors identified during a thorough history and physical examination. The goal of this article is to discuss the clinical importance, review potential pathophysiology, and discuss specific etiologies of unintentional weight loss that will enable the clinician to formulate a practical stepwise approach to patient evaluation and management.

Prophylactic placement of gastrostomy feeding tubes before radiotherapy in patients with head and neck cancer: is it worthwhile?

BACKGROUND: After radiation treatment of head and neck cancer, placement of gastrostomy feeding tubes can be technically difficult. The practice of placing tubes before treatment is probably justified if the tube is used for more than 4 weeks and if complications are infrequent. The aim of this study was to determine the outcome of prophylactically placed gastrostomy tubes in patients with head and neck cancer at our institution from 1995 to 1999. STUDY: Data collected retrospectively from the patients' medical records included demographics, duration of tube use, and complications associated with placement. RESULTS: A total of 54 patients (40 men, 14 women) with a mean age of 68.5 years (range, 49-88 years) were studied. Thirty-one patients were treated with both surgery and radiotherapy; 17, with only radiotherapy; and 6, with chemotherapy, radiation, and surgery. The gastrostomy tube was placed before initiation of radiation treatment in 41 patients and after treatment in 13. The method of placement included pull technique (n = 41), introducer technique (n = 10), and surgical (n = 3). Four patients who had a tube placed after treatment required hospitalization for dehydration, whereas no hospitalizations were needed in the prophylactic group. The median duration of tube use was 165 days (range, 0-1,105 days). Only three patients had a complication directly related to placement. CONCLUSION: Gastrostomy tube placement before treatment is appropriate, given the median number of days required for use and limited complications associated with placement.

Effect of glutamine in short-bowel syndrome.

BACKGROUND AND AIMS: Animal studies have reported positive effects of glutamine on intestinal absorption and morphology; human studies have been less convincing. The aim of this study was to evaluate the effects of glutamine and diet on intestinal morphology, motility, and absorption. METHODS: A randomized, double blind, placebo-controlled crossover study in 8 patients with short-bowel on a high carbohydrate, low fat (HCLF) diet, was performed. Active treatment was oral glutamine (0.45 g kg(-1)day(-1)) for eight weeks. Intestinal morphology was evaluated by light microscopy. Gastrointestinal transit was measured by dual gamma camera scintigraphy. D-xylose and fecal fat collection was used to evaluate intestinal absorption. Results of active treatment versus placebo were compared by the signed-rank test. RESULTS: Morphology analysis, reported as median active treatment versus placebo, was villus height: 0.48 mm versus 0.50 mm, P=1.0, and crypt depth: 0.11 mm versus 0.10 mm, P=0.469. Percent D-xylose absorption, reported as median active treatment versus placebo, was 7% versus 10.5%, P=0.109. There was not a significant difference in wet weight or fat absorption compared to placebo, P>0.05. Likewise, gastrointestinal transit was not different compared to placebo. CONCLUSIONS: The results of this controlled study would support that 8 weeks of treatment with oral glutamine and a HCLF diet does not significantly improve intestinal morphology, gastrointestinal transit, D-xylose absorption and stool losses in short bowel patients.

Influence of tacrolimus and prednisone on serum lipids after liver transplantation.

BACKGROUND: Hyperlipidemia after orthotopic liver transplant is thought to be the result of the immunosuppression therapy given postoperatively. The purpose of this study was to evaluate serum lipid levels pretransplant, 4 months, and 12 months posttransplant. METHODS: A retrospective chart review of 50 patients after liver transplantation was completed. Pretransplant serum lipid levels (triglyceride, cholesterol, and high-density lipoprotein [HDL]) were compared with values at 4 months and 12 months posttransplantation. Pretransplant serum lipid levels were compared using one factor analysis of variance (ANOVA) model. Values between the viral, alcohol, and cholestatic groups were compared using two-factor ANOVA model. RESULTS: Of the 50 patients (22 females, 28 males) with a mean age of 52 years (range, 16 to 69 years), all 50 had completed their 12-month follow-up at the time of this study. The etiology of liver disease included: viral hepatitis (21), alcohol (8), primary biliary cirrhosis and sclerosing cholangitis (7), and others (14). The protocol for immunosuppression included tacrolimus and prednisone. Mean serum triglyceride levels included: 134 mg/dL pretransplant, 155 mg/dL at 4 months, and 169 mg/dL at 12 months posttransplant (p = .117). Mean total serum cholesterol levels included: 174 mg/dL pretransplant, 165 mg/dL at 4 months, and 163 mg/dL at 12 months posttransplant (p = .654). Mean HDL levels included: 39 mg/dL pretransplant, 45 mg/dL at 4 months and 44 mg/dL at 12 months posttransplant (p = .032). There was not a significant difference in serum lipids between the different categories of liver diseases. CONCLUSIONS: Although a significant positive effect was observed with HDL, the present data show that total serum cholesterol and triglyceride did not change significantly over time after orthotopic transplantation. This is most likely related to the type of immunosuppressive therapy given posthepatic transplantation.

Dysphagia without endoscopically evident disease: to dilate or not?

OBJECTIVES: It is not known whether patients with symptoms of dysphagia but normal upper endoscopy benefit from empiric esophageal dilation. The aim of this prospective study was to determine whether patients with solid food dysphagia and normal upper endoscopy have symptomatic benefit from empiric dilation using a through-the-scope balloon. METHODS: Patients who were seen for complaints of solid food dysphagia and who had normal endoscopic examinations at our institution from 1998 through 1999 were identified. Those patients who had agreed before sedation to participate in the study, if eligible, were randomized to either sham or balloon dilation using an 18-mm through-the-scope balloon at the time of esophagogastroduodenoscopy. All potentially eligible patients who had given provisional consent completed a dysphagia questionnaire and a 10-cm visual analog dysphagia scale before endoscopy. Follow-up questionnaires were completed on day 1 and at 3 months and 6 months after the procedure. The primary endpoint of the study was the patient's self-assessment of difficulty swallowing, based on the questionnaires. RESULTS: A total of 83 patients met the study criteria and were randomized to balloon dilation (n = 43) or sham (n = 40). The two groups were comparable in age, sex, severity of baseline dysphagia. and use of antireflux medication. Improvement in dysphagia comparing sham to balloon on day 1 was 66% versus 67% (p = 0.99); at 3 months it was 82% versus 76% (p = 0.56); and at 6 months it was 84% versus 73% (p = 0.38). There were no reported complications in either group. CONCLUSION: The data from this prospective randomized, controlled study do not support the practice of empiric dilation in patients with symptoms of dysphagia without an endoscopically evident cause of dysphagia.

Endoscopic YAG laser treatment of watermelon stomach (gastric antral vascular ectasia) in patients with systemic sclerosis.

OBJECTIVE: Gastric antral vascular ectasia (GAVE) has been recognized as a rare but important cause of chronic iron deficiency anemia. A number of reported patients were found to have evidence of autoimmune disorders or connective tissue diseases. We carried out this study in order to determine the clinical, endoscopic, and pathologic features in a large series of patients with systemic sclerosis (SSc) who were diagnosed with GAVE. We also determined the response to YAG laser treatment for chronic blood loss in these patients. METHODS: A retrospective chart review of 20 cases diagnosed over an 11-year period, with diagnoses of both SSc and GAVE. RESULTS: Twenty patients with SSc presented with prominent anemia and were diagnosed with GAVE. Treatment with endoscopic laser therapy was successful in preventing surgery for bleeding in GAVE in 85% of cases. CONCLUSIONS: GAVE should be considered in patients with SSc who develop chronic iron deficiency anemia. YAG laser treatment can be useful in the treatment of chronic blood loss anemia in SSc patients with GAVE.

Substrate oxidation in patients with cirrhosis: comparison with other nutritional markers.

BACKGROUND: Malnutrition in patients with hepatic cirrhosis is associated with abnormal fuel metabolism marked by reduced glucose oxidation and increased lipid oxidation. A low respiratory quotient (R/Q) indicates reduced glucose and increased lipid oxidation. The aim of this study was to determine if there is an association between substrate oxidation, using indirect calorimetry, and other markers of malnutrition in patients with cirrhosis awaiting liver transplantation. METHODS: Indirect calorimetry (MedGraphics) was used to determine resting energy expenditure and R/Q after an overnight fast. Anthropometric measurements including tricep skinfold thickness (TSF) and midarm muscle circumference (MAMC) were performed and expressed as a percentage of standard values. A 24-hour urinary creatinine excretion was collected to calculate creatinine height index (CHI) and serum albumin. A subjective global assessment (SGA) score was completed on each patient by a dietitian and physician. Spearman rank correlation was used for statistical comparison of R/Q to other nutritional markers. RESULTS: Fifteen patients (7 men, 8 women; mean age, 52 years) were studied. Mean values include: body mass index (BMI) 27.7 kg/m2 +/- 7.3, R/Q 0.78 +/- 0.04, serum albumin 2.97 g/dL +/- 0.56, TSF 71% +/- 27%, MAMC 85% +/- 13%, CHI 75% +/- 18%, and SGA median score A. There was a significant correlation (p < .05) between R/Q and serum albumin, CHI, and SGA score. There was a greater than 90% correlation of SGA estimation by a physician and dietitian. CONCLUSIONS: There is good correlation between R/Q values and serum albumin, CHI, and SGA score. BMI and anthropometric measurements may suggest normal nutrition when, in fact, indirect calorimetry (R/Q) suggests changes consistent with abnormal fuel metabolism and poor nutrition. R/Q can be a useful adjunct in the nutrition assessment of patients with hepatic cirrhosis.

Success with intestinal failure: from adaptation to transplantation.

Intestinal failure can result from large resections of small intestine (short bowel syndrome) and from failure of normal intestinal motility. The medical management of short bowel syndrome centers around appropriate diet and use of specific medications including experimental trophic factors. Enteral tubes and prokinetic medications can be successfully used to treat patients with intestinal failure as a result of abnormal intestinal motility. Small bowel transplantation may be a treatment option in certain patients with intestinal failure. This article reviews the management of intestinal failure with a recent update on small bowel transplantation.

Effect of growth hormone, glutamine, and diet on body composition in short bowel syndrome: a randomized, controlled study.

BACKGROUND: A previous controlled study of ten patients with short bowel syndrome (SBS) reported human recombinant growth hormone resulted in a significant increase in body weight and lean body mass (LBM) without clinical edema. The aim of this study was to assess the effect of growth hormone, glutamine, and diet on body composition. METHODS: A randomized, 6-week, double-blind, placebo-controlled, crossover study was performed in eight patients. Active treatment was 21 days of growth hormone, oral glutamine, and a high-carbohydrate-low-fat (HCLF) diet. Body composition was determined by dual-energy x-ray absorptiometry (DEXA) scan. Treatments were compared by paired t test. RESULTS: Active treatment resulted in significant increases in body weight (mean 3.02 +/- 0.7 kg, p < .05) and lean body mass, (mean 3.96 +/- 0.5 kg, p < .001). Percent body fat was significantly reduced in the actively treated group (mean -2.51% +/- 0.4, p < .001). Body weight returned to base-line within 2 weeks of discontinuing active treatment. Macronutrient and fluid absorption did not increase with active treatment. CONCLUSIONS: Treatment with growth hormone, glutamine, and HCLF diet resulted in decreased percent body fat and increased body weight and LBM in patients with SBS, without an increase in macronutrient or fluid absorption. The positive findings are most likely a reflection of increased extracellular fluid because all eight patients developed peripheral edema on active treatment. Furthermore, the positive effect of active treatment does not appear to be sustained once discontinued.

Nutrition supplementation in patients with acute and chronic pancreatitis.

Acute pancreatitis is a hypermetabolic state characterized by increased protein catabolism, lipolysis, and glucose intolerance. Most patients presenting with acute pancreatitis are better within 5 to 7 days and can be resume a regular diet. Patients with severe pancreatitis and who are unable to eat within 7 to 10 days should receive nutritional support. The decision to use parenteral or enteral nutrition is controversial. More recent data suggest that jejunal feedings are just as beneficial, if not better, than parenteral nutrition. Marked weight loss and abdominal pain are the features of chronic pancreatitis. Steatorrhea develops when greater than 90% of pancreatic exocrine dysfunction occurs. Treatment focuses on pain control and pancreatic enzyme replacement. Pancreatic enzymes should be given with meals. Patients with refractory steatorrhea may benefit from the addition of an H2 antagonist or proton-pump inhibitor with pancreatic enzyme replacement. Micronutrients, including antioxidants, should be replaced if serum levels suggest a deficiency.

A randomized prospective study comparing rigid to balloon dilators for benign esophageal strictures and rings.

BACKGROUND: The optimum choice of dilator (rigid vs. balloon) for benign esophageal strictures has not been well studied. The aim of this study was to compare the immediate relief of dysphagia and the incidence of repeat dilatation within the first year with the use of either a rigid (Savary) dilator or balloon dilator for benign lower esophageal strictures. METHODS: Patients with dysphagia found to have benign esophageal strictures during endoscopy were randomized to undergo dilation with a rigid (Savary) or a balloon dilator (Microvasive or Bard). The 1-year incidence of repeat dilatation was estimated by the Kaplan-Meier method. RESULTS: A total of 251 subjects were stratified at entry according to the type of stricture (peptic vs. Schatzki ring) and severity of stricture (mild vs. moderate/severe) and then randomized to either a Savary (n = 88), Microvasive (n = 81), or Bard (n = 82) dilator. There were no significant differences between the rigid dilator or the two balloons with regard to immediate relief of dysphagia or the need for repeat dilatation at one year. Patients with moderate/severe strictures required repeat dilatation at one year twice as often as those with mild strictures. There were no significant complications reported in these patients. CONCLUSIONS: Both rigid and balloon dilators are equally effective and safe in the treatment of benign lower esophageal strictures caused by acid reflux and Schatzki rings.

Nutritional management of chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIP) is a gastrointestinal motility disturbance characterized by recurrent episodes of postprandial nausea and bloating in the absence of mechanical obstruction of the small bowel or colon. Weight loss and severe malnutrition are often seen in advanced stages of the disorder. This article discusses the nutritional management of patients with CIP, focusing on general dietary as well as enternal and parenternal nutritional support. Enteral access methods and various enteral formulas used in CIP are also discussed.