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.

Survival of home parenteral nutrition-treated patients: 20 years of experience at the Mayo Clinic.

OBJECTIVE: To present the largest single institutional review of demographics, associated primary diseases, and survival of patients receiving home parenteral nutrition (HPN). MATERIAL AND METHODS: We conducted a retrospective review of medical records of all Mayo Clinic patients treated with HPN between 1975 and 1995. The probability of survival was calculated by using Kaplan-Meier analysis. RESULTS: In the 225 study patients requiring HPN (median age, 51 years), the main underlying primary diseases were as follows: inflammatory bowel disease (IBD) (N = 50), nonterminal active cancer (N = 39), ischemic bowel (N = 35), radiation enteritis (N = 32), motility disorder (chronic pseudo-obstruction) (N = 26), and adhesive intestinal obstruction (N = 18). Other conditions included intestinal and pancreatic fistula, refractory sprue, dumping syndrome, and protein-losing enteropathy. The overall probability of 5-year survival during HPN was 60%. The probability of survival at 5 years based on the primary disease was 92% for IBD, 60% for ischemic bowel, 54% for radiation enteritis, 48% for motility disorder, and 38% for cancer. The probability of 5-year survival stratified by age at initiation of HPN was as follows: younger than 40 years, 80%; 40 through 60 years, 62%; and older than 60 years, 30%. Most deaths during therapy with HPN were attributable to the primary disease. Among the 20 patients who died of an HPN-related cause, 11 deaths were from catheter sepsis, 4 from liver failure, 2 from venous thrombosis, and 2 from metabolic abnormalities. CONCLUSION: Survival of HPN-treated patients is best predicted on the basis of the primary disease and the age at initiation of HPN. Patients with IBD and age younger than 40 years have a better 5-year survival in comparison with other groups. Most deaths during treatment with HPN are a result of the primary disease; HPN-related deaths are uncommon.

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.

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.

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.

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.

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.

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.

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.

Short-bowel syndrome.

This article reviews the current literature on the role of diet and trophic factors in the treatment of short-bowel syndrome, focusing on both recent experimental and clinical advances over the past year. The abundance of experimental animal data would suggest that various growth factors and luminal nutrients are of benefit in the treatment of short-bowel syndrome, however there are only a few clinical studies with small numbers of patients that make the same claim.

Nonulcer dyspepsia.

There is considerable confusion in the literature about the entity of nonulcer dyspepsia and its epidemiology, mechanisms, and management. In this review, we discuss the mechanisms and develop a strategy for diagnosis and management of nonulcer dyspepsia in the era of cost-containment. This analysis was based on a computerized literature search on epidemiology, pathophysiology, and management of nonulcer dyspepsia. Inconsistencies in the inclusion criteria of several studies result in disparities in the data from epidemiological and physiology-based studies. We propose that the inclusion criteria need to be unrestricted by the symptom of "pain," and that epidemiological features must be refined further because recent data used pain/discomfort as the dominant feature for identifying "dyspepsia." The interplay between three factors (impaired motor and sensory functions, psychosocial factors, and Helicobacter pylori infection) deserves further study. Advances in this field will follow rigorous reappraisal of the epidemiology using an unrestricted definition of the symptom complex and development of strategies in clinical practice that focus on either the cost-effective investigation of the mechanism and its treatment or an effective sequence of therapeutic trials. An algorithm proposed for patient evaluation needs to be tested, with emphasis on outcome (i.e., symptom control, cost efficacy, and societal costs).

Short bowel syndrome.

This article discusses the causes, prognosis, and management of short bowel syndrome. Attempts to enhance intestinal adaptation with trophic factors and surgical treatment options, including small bowel transplantation, are discussed.

Eosinophilic gastroenteritis presenting as a giant gastric ulcer.

We describe a 43-yr-old female with a giant gastric ulcer, refractory to medical treatment, that ultimately proved to be due to the mural form of eosinophilic gastroenteritis. The patient presented with a 6-month history of abdominal pain, diarrhea, and weight loss. Endoscopy showed a giant gastric ulcer, and biopsies revealed only chronic active ulcerative inflammation. The ulcer progressed on omeprazole therapy; therefore, a distal antrectomy with gastrojejunal anastomosis and bilateral vagotomy was performed. Pathology of the surgical specimen demonstrated the mural form of eosinophilic gastritis. To the best of our knowledge, this case is the first to demonstrate that refractory giant gastric ulcers may be a manifestation of the mural form of eosinophilic gastroenteritis.

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.

Gastrointestinal motility considerations in patients with short-bowel syndrome.

Short-bowel syndrome results from large resections of the small intestine that result in the malabsorption of nutrients and fluids. Following intestinal resection both morphological and functional adaptations of the residual intestine occur. While we have witnessed progress in the understanding of morphological adaptation, little is known about the effects of gastrointestinal motility in short-bowel syndrome. This article reviews what is currently known about gastrointestinal motility in the context of short-bowel syndrome and the motility considerations that impact on clinical management.

Nutritional support for the patient with short-bowel syndrome.

Short-bowel syndrome refers to the clinical consequences that follow extensive resection of the small bowel. As a result of resection, malabsorption of macro- and micronutrients occurs. The prognosis after resection depends on the extent and location of resection, the presence of a colon, the function of the residual intestinal mucosa, and the extent of intestinal adaptation. Intestinal adaptation is influenced by the presence of intraluminal nutrients and various trophic peptides and hormones. This article discusses the dietary management of the patient with short-bowel syndrome and the recent literature on growth factors (ie, growth hormone and glutamine) and small-bowel transplantation.

Ascending colon response to feeding: evidence for a 5-hydroxytryptamine-3 mechanism.

BACKGROUND: The role of serotonergic type-3 receptors in proximal human colon is unclear. Our aims were to assess the postprandial volume and emptying of the ascending colon and to explore the role of 5-hydroxytryptamine-3 (5HT3) mechanisms. METHODS: In healthy subjects with unprepared colons we evaluated in a randomized trial the effects of the 5HT3 antagonist ondansetron (n = 5) or placebo (n = 5) on ascending colon volume and emptying, using a scintigraphic method. RESULTS: Base-line ascending colon volumes were similar and were unaltered by ondansetron. After a 1000-kcal liquid meal the placebo group showed a variable change in volume (P = NS versus base line) during the first 25 min (median, -4%; range, -13% to 135%). Increases in volume during this period coincided with ileal emptying of chyme. During a second phase (30-105 min) there was a significant decrease of ascending colon volume (P = 0.02) relative to the early postprandial volume, but the volume was not significantly different from base line. This second phase was associated with transfer of chyme towards the transverse colon. In the ondansetron group there was an initial modest increase in volume (median, 5%; range, -15% to 14%; P = NS versus base line), and the second phase of contraction was inhibited. CONCLUSIONS: The ascending colon response to a meal in health is characterized by a variable initial change in volume, accommodating ileal chyme in some individuals, and a more consistent reduction in volume from 30 to 105 min postprandially. The latter response is inhibited by ondansetron, suggesting partial control of postprandial colonic motor function by 5HT3 mechanisms.

Acute abdominal pain as a leading symptom for Degos' disease (malignant atrophic papulosis).

We report a case of a 16-yr-old white female patient with acute abdominal pain due to visceral involvement of Degos' disease that required extensive small bowel resection. Skin manifestations of her disease had been present for 2 yr before the correct diagnosis. She died as a result of central nervous system involvement from Degos' disease.

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.