Darlene G. Kelly

Severe Spruelike Enteropathy Associated With Olmesartan

OBJECTIVE To report the response to discontinuation of olmesartan, an angiotensin II receptor antagonist commonly prescribed for treatment of hypertension, in patients with unexplained severe spruelike enteropathy. PATIENTS AND METHODS All 22 patients included in this report were seen at Mayo Clinic in Rochester, Minnesota, between August 1, 2008, and August 1, 2011, for evaluation of unexplained chronic diarrhea and enteropathy while taking olmesartan. Celiac disease was ruled out in all cases. To be included in the study, the patients also had to have clinical improvement after suspension of olmesartan. RESULTS The 22 patients (13 women) had a median age of 69.5 years (range, 47-81 years). Most patients were taking 40 mg/d of olmesartan (range, 10-40 mg/d). The clinical presentation was of chronic diarrhea and weight loss (median, 18 kg; range, 2.5-57 kg), which required hospitalization in 14 patients (64%). Intestinal biopsies showed both villous atrophy and variable degrees of mucosal inflammation in 15 patients, and marked subepithelial collagen deposition (collagenous sprue) in 7. Tissue transglutaminase antibodies were not detected. A gluten-free diet was not helpful. Collagenous or lymphocytic gastritis was documented in 7 patients, and microscopic colitis was documented in 5 patients. Clinical response, with a mean weight gain of 12.2 kg, was demonstrated in all cases. Histologic recovery or improvement of the duodenum after discontinuation of olmesartan was confirmed in all 18 patients who underwent follow-up biopsies. CONCLUSION Olmesartan may be associated with a severe form of spruelike enteropathy. Clinical response and histologic recovery are expected after suspension of the drug.

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.

CLINICAL STAGING AND SURVIVAL IN REFRACTORY CELIAC DISEASE: A SINGLE CENTER EXPERIENCE

BACKGROUND & AIMS Refractory celiac disease (RCD) occurs when both symptoms and intestinal damage persist or recur despite strict adherence to a gluten-free diet. In RCD, the immunophenotype of intraepithelial lymphocytes may be normal and polyclonal (RCD I) or abnormal and monoclonal (RCD II). The aim is to describe the clinical characteristics, treatment, and long-term outcome in a large single-center cohort of patients with RCD. METHODS We compared the clinical characteristics and outcome in 57 patients with RCD: 42 with RCD I and 15 with RCD II. RESULTS Fifteen of 57 patients died during follow-up (n=8 with RCD I and n=7 with RCD II), each within the first 2 years after RCD diagnosis. The overall 5-year cumulative survival is 70%, 80%, and 45% for the entire cohort, RCD I, and RCD II, respectively. The refractory state itself and enteropathy-associated T-cell lymphoma (EATL) were the most common causes of death, respectively. A new staging system is proposed based on the cumulative effect of 5 prognostic factors investigated at the time of the refractory state diagnosis: for patients in stages I, II, and III, the 5-year cumulative survival rate was 96%, 71%, and 19%, respectively (P< .0001). CONCLUSIONS RCD is associated with high mortality with RCD II having an especially poor prognosis because of the development of EATL. A new staging model is proposed that may improve the precision of prognosis in patients with RCD.

Should patients with advanced, incurable cancers ever be sent home with total parenteral nutrition? A single institution's 20-year experience.

Home total parenteral nutrition (TPN) can be lifesaving and life sustaining for some patients. However, in patients with advanced, incurable cancer, its role is controversial. A retrospective study was conducted to explore whether home TPN was associated with long‐term survival (≥ 1 year) in patients with metastatic disease and to identify predictive factors to enable its judicious use.

An open trial of octreotide long-acting release in the management of short bowel syndrome

OBJECTIVES: The aim of this study was to assess the effects of the long-acting release (LAR) depot octreotide preparation Sandostatin LAR Depot on stool water and electrolyte losses, fecal fat excretion, and GI transit in patients with short bowel syndrome. METHODS: We performed a 15-wk, prospective, open-label study of intramuscular (i.m.) Sandostatin LAR Depot, 20 mg, at 0, 3, 7, and 11 wk. Balance studies were performed before and at the end of the 15-wk study. Baseline and posttreatment measurements of body weight, stool fat, sodium and potassium, and gastric and small bowel transit of a radiolabeled egg meal were compared by paired analysis. RESULTS: We studied eight patients with short bowel syndrome (five women and three men; mean age 52 yr, range 37–72 yr) who had been TPN dependent for a mean of 11.8 yr (range 1.5–22 yr). The underlying diagnoses were Crohn’s disease (n = 6), intestinal ischemia (n = 1), and resection for carcinoid tumor (n = 1). Treatment with Sandostatin LAR Depot significantly increased small bowel transit time (p = 0.03). Changes in body weight, urine volume, stool weight, fecal fat excretion, stool sodium and potassium excretion, or gastric emptying rate were highly variable, and no overall significance was observed. CONCLUSIONS: Sandostatin LAR Depot for 15 wk significantly prolonged small bowel transit time. Body weight and stool parameters in response to Sandostatin LAR Depot treatment needs to be assessed further in multicenter studies assessing dose, frequency of administration, and a larger sample size.

Outcome of patients with radiation enteritis treated with home parenteral nutrition

OBJECTIVES:Intestinal failure requiring either surgery or home parenteral nutrition (HPN) develops in approximately 5% of patients treated with radiation. The aim of the study was to determine survival, duration of HPN, and complications associated with HPN in patients with intestinal failure after radiation therapy.METHODS:Fifty-four patients with radiation enteritis who received HPN were studied (39 women and 15 men with a mean age of 57.9 yr). Retrospective data were collected from the patients’ medical records dated between 1975 and 1999. The probability of survival was calculated by the Kaplan-Meier method.RESULTS:HPN was initiated a median of 20 months (range = 2–432) from the start of radiation therapy. The mean number of intestinal operations for radiation-related complications was 2.2/patient (range = 0–6). The causes of intestinal failure resulting from radiation therapy were intestinal obstruction (27 patients), short bowel (17), malabsorption (five), fistula (three), and dysmotility (two). The mean duration of HPN was 20.4 months (range = 2–108). At last follow-up, 37 patients (68%) were dead, most as a result of recurrent cancer. One patient died of catheter sepsis, and no other deaths were directly related to HPN. The overall estimated 5-yr probability of survival on HPN calculated by Kaplan-Meier analysis was 64%.CONCLUSIONS:HPN is a reasonable treatment option in patients with intestinal failure as a result of radiation enteritis. Survival and complications associated with HPN in patients with radiation enteritis seem to be similar to those in other HPN-treated groups.

Giant Hypertrophic Gastropathy (Ménétrier's Disease): Pharmacologic Effects on Protein Leakage and Mucosal Ultrastructure

Seven patients with giant hypertrophic gastropathy participated in a gastric intubation perfusion study to investigate the route and mechanism of protein leakage associated with this disease. All patients had gastric tight junctions wider than those in healthy controls. Acute administration of propantheline bromide reduced gastric albumin leakage (-50.7%, p less than 0.05) and concurrently decreased width of tight junctions (p less than 0.05) in all patients. Another antisecretory agent, cimetidine, had no consistent effect on protein leakage or on the width of tight junctions. Pentagastrin and bethanechol chloride increased protein loss but had no effect on the width of tight junctions. These results are consistent with the hypothesis that proteins may take a paracellular route via the tight junctions as they traverse the gastric mucosa and that this may have a cholinergic mechanism.

Short bowel syndrome: Highlights of patient management, quality of life, and survival

Short bowel syndrome (SBS) occurs as a result of intestinal resection, and in many patients is associated with complications, such as diarrhea, dehydration, weight loss, and nutrition deficiencies. Many individuals with SBS develop intestinal failure and require parenteral nutrition (PN) and/or intravenous (IV) fluids (PN/IV). Although PN is essential for survival, some patients with SBS who require long-term PN experience significant complications that contribute to morbidity and mortality. Consequently, therapies that decrease reliance on PN are of considerable importance. Intestinal adaptation, which results in morphologic and functional changes that increase performance of the remnant bowel, occurs spontaneously after intestinal resection. These effects can be enhanced with nutrition and pharmaceutical approaches. For example, oral or tube-fed nutrients stimulate growth and adaptation of intestinal tissues. In addition, prebiotics support growth of beneficial intestinal microbiota that produce short-chain fatty acids, which have been shown in preclinical studies to enhance intestinal structure and function. Finally, glucagon-like peptide 2 (GLP-2) is an endogenous peptide that promotes intestinal rehabilitation and improves intestinal absorption. Teduglutide, a recombinant human GLP-2 analog, has recently been approved in the United States for the treatment of adults with SBS who are dependent on PN. In pharmacodynamic and clinical studies, teduglutide has been shown to promote changes in intestinal structure, such as increases in villus height and crypt depth, and to improve intestinal absorption, as indicated by reduced PN/IV dependence. This article presents a brief overview of SBS, including effects on survival and quality of life and current treatment options.

How to protect human pancreatic enzyme activities in frozen duodenal juice

We determined whether activity of pancreatic enzymes could be maintained in frozen duodenal juice by diluting the specimens or by adding nutrients or a chymotrypsin inhibitor. Human duodenal juice was obtained during cholecystokinin octapeptide IV administration. Trypsin, chymotrypsin, lipolytic, lipase, and colipase activities were measured in fresh undiluted or diluted (1:4 and 1:16 with saline and T-tube bile) duodenal juice as well as after adding CaCl2, casein, triolein, or a chymotrypsin inhibitor. Subsequently, the samples were frozen at -20 degrees C, and enzyme activities were measured at 1, 2, 3, 7, 14, 28, and 56 days. Activities of chymotrypsin and colipase did not change during freezer storage. Trypsin survival was variable in juice from different subjects. By contrast, in duodenal juice to which no nutrient or only CaCl2 had been added, 90%, 65%, and 40% (P = 0.05 vs. undiluted) of lipolytic activity was lost by 56 days in undiluted and 1:4 or 1:16 diluted duodenal juice samples, respectively. The loss of lipolytic activity was prevented (P less than 0.05) by adding casein or casein and triolein to undiluted and 1:4 diluted samples and turkey egg white to undiluted samples. The loss of lipolytic activity was strongly associated with loss of lipase activity (r = 0.97) but only weakly associated with loss of colipase activity (r = 0.49). In summary, chymotrypsin and colipase are well preserved in frozen duodenal juice and can be used to accurately assess concentrations of pancreatic enzymes after thawing frozen duodenal samples. If it is necessary to measure lipolytic activity after freezing samples, lipase can be maintained by adding casein or a chymotrypsin inhibitor to juice before freezing.

Urinary Oxalate Excretion Increases in Home Parenteral Nutrition Patients on a Higher Intravenous Ascorbic Acid Dose.

BACKGROUND Vitamin C can be metabolized to oxalate. Case reports have suggested an association between IV vitamin C and urinary oxalate excretion. Recently, the US Food and Drug Administration required the dose of vitamin C in IV multivitamin preparations to be increased from 100 mg to 200 mg/d. We compared the urinary oxalate excretion level in stable home total parenteral nutrition (TPN) patients receiving both doses of vitamin C. METHODS Each participant provided a 24-hour urine sample for oxalate determination on the vitamin C dose (100 mg/d), and again after at least 1 month on the increased vitamin C dose (200 mg/d). A 2-day diet diary was completed covering the day before and the day of the urine collection and was analyzed for oxalate and vitamin C content. Comparisons were made using Student paired t test and Wilcoxon signed rank. RESULTS Thirteen patients (7 males/6 females) aged 63.1 ± 12.2 years who had no history of nephrolithiasis and had received TPN for 55.9 ± 78.8 months were enrolled. The most common indication for TPN was short bowel syndrome (38.5%). Eight patients had an intact colon. Urinary oxalate excretion increased on the 200-mg vitamin C dose, from 0.34 ± 0.13 to 0.44± 0.17 mmol/d (mean increase = 0.10 mmol/d; p = .04; 95% confidence interval 0.004 to 0.19 mmol/d). Oral intake of vitamin C and oxalate did not differ between the 2 collection periods. CONCLUSIONS In therapeutically used doses, IV vitamin C increases urinary oxalate excretion, potentially predisposing susceptible individuals to nephrolithiasis. This factor should be considered in patients receiving home TPN.