Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

BACKGROUND: Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). METHODS: Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). KEY RESULTS: Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). CONCLUSIONS & INFERENCES: This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis.

BACKGROUND: The consensus statements for eosinophilic oesophagitis recommend that ambulatory pH monitoring is one means of determining if gastro-oesophageal reflux is the cause of oesophageal eosinophilia and should guide pharmacological therapy. AIM: To evaluate prospectively the accuracy of pH monitoring as a predictor of endoscopic, histological and symptomatic response in patients with oesophageal eosinophilia. METHODS: We conducted a prospective trial in which patients with oesophageal eosinophilic infiltration with ≥15 eos/hpf underwent a 24-h pH study and were placed in one of two treatment arms for 6 weeks based on positive or negative results. Patients with abnormal acid exposure were treated with esomeprazole 40 mg twice daily and others were treated with oral viscous budesonide 1 g twice daily. Response to treatment was assessed by oesophageal histology (<5 eos/hpf) and symptoms. RESULTS: A total of 51 patients were enrolled in the study. The average patient age was 39 years and 31 patients (61%) were male. The average number of eosinophils per hpf, prior to study enrolment was 41.2 (range 15-140, s.d. 27.7). Nineteen (37%) had positive pH studies and 32 (63%) had negative pH studies. Eighteen patients completed treatment with esomeprazole. Only eleven (61%) had histological response and, of these eleven, five (46%) had symptomatic improvement. A total of 28 patients with normal acid exposure completed treatment with budesonide. Only 16 (57%) had histological and 11 (69%) had symptomatic improvement. CONCLUSION: In this prospective trial of pH-guided treatment, neither positive nor negative results of initial pH monitoring accurately predicted response to therapy.

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.

INTRODUCTION: Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. METHODS: MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. RESULTS: 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (chi(2)=28.3, p=0.001, I(2)=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=-0.34; 95% CI -0.60 to -0.07). There was statistically significant heterogeneity (chi(2)=67.04, p<0.001, I(2)=79%), but this was explained by one outlying trial. CONCLUSION: Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

Does co-administration of a non-selective opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipation-predominant irritable bowel syndrome? A randomized controlled trial.

Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5-HT4 agonist alone. We hypothesized that the combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation-predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C-IBS. Forty-eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit.

Eosinophilic esophagitis: an update.

Eosinophilic esophagitis (EE) is a disease that is being recognized with increasing frequency. In children it is responsible for feeding disorders, vomiting, reflux symptoms and abdominal pain and in adults it causes dysphagia and esophageal food impactions. The diagnosis requires the histologic finding of > 20 eosinophils per high powered field in esophageal squamous mucosa. The most common treatment regimens in children and adults involve the ingestion of topical corticosteroids. Symptomatic relapse after one treatment course is common, and many patients require repeated courses of treatment. The long-term prognosis of EE is largely unknown.

Comparison of gastric volumes in response to isocaloric liquid and mixed meals in humans.

AIMS: To compare gastric volume responses to ingestion of isocaloric liquid or mixed (solid-liquid) meals and document the intra- and interindividual reproducibility of gastric volume measurement using single photon emission computed tomography (SPECT) imaging after i.v. 99mTc-pertechnetate. METHODS: Eight healthy volunteers performed two studies at least 9 months apart. Gastric volumes were measured after a 317 kcal liquid nutrient meal. Within 2 weeks of the second liquid meal study, participants performed a third study, ingesting an isocaloric mixed meal. The order of the mixed and second liquid meals was randomized; Bland-Altman plot displayed data on repeated studies with liquid meal and paired t-test compared gastric volumes after mixed or liquid isocaloric meals. RESULTS: Fasting and postprandial gastric volumes associated with the two liquid meals were not significantly different; inter- and intra-individual coefficients of variation were 13 and 13.8%. In response to the mixed meal, there was a lower absolute postprandial volume and lower change in gastric volume over fasting volume compared with the response to the liquid meal (P = 0.0001). CONCLUSION: The SPECT measurement of gastric volumes in response to a nutrient liquid meal is reproducible. The magnitude of the volume response is greater after the liquid meal compared with the isocaloric mixed meal.

Effect of a somatostatin analogue on gastric motor and sensory functions in healthy humans.

BACKGROUND: Pharmacological approaches to alter satiation may have an impact on functional upper gastrointestinal disorders and potentially change food intake in obesity. AIM: Our aim was to compare the effects of two doses of octreotide and placebo on postprandial symptoms, gastric accommodation, and gastric emptying using validated non-invasive techniques. METHODS: In a randomised, parallel group, two dose, double blind, placebo controlled study, 39 healthy participants (13 per group) were randomised to 30 or 100 micro g octreotide or placebo, administered subcutaneously, 30 minutes before each study. Studies were performed on three separate days and included scintigraphic gastric emptying of solids and liquids, (99m)Tc SPECT imaging to measure fasting stomach volume and gastric accommodation following a 300 ml Ensure meal, and a standardised nutrient drink test to measure maximum tolerated volume and postprandial symptoms. RESULTS: Relative to placebo, both doses of octreotide delayed gastric emptying of solids (not liquids), increased fasting gastric volume, reduced the change in gastric volume post meal, and decreased the sensation of fullness after a satiating meal. CONCLUSION: The somatostatin analogue octreotide significantly alters human gastric functions, including inhibition of the normal reflex responses of gastric volume increase and emptying of the meal. These pharmacological effects suggest studies of the medication in disorders of satiation, including obesity and dyspepsia, are warranted.

The microenvironment of human Peyer's patches inhibits the increase in CD38 expression associated with the germinal center reaction.

Analysis of B cells in the human tonsils identified CD38 expression as a hallmark of germinal center (GC) B cells. However, the signals responsible for the in vivo induction of CD38 have not been determined. The primary site for generation of memory and plasma cells in the gastrointestinal tract is the GCs of Peyer's patches (PP). PP and intestinal mucosa, but not tonsils or oral mucosa, express mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The ligand for MAdCAM-1, integrin alpha(4)beta(7), is expressed on naive B cells and memory B cells that traffic to the gastrointestinal tract. In this study we determine that, unlike tonsil, human PP GC B cells do not express significant levels of CD38. PP B cells can be induced to express CD38 upon culture with CD40 ligand, anti-B cell receptor, and IFN-gamma. However, coculture of tonsil naive B cells with an Ab directed against integrin beta(7) inhibits IFN-gamma-induced CD38 hyperexpression. The absence of CD38 on PP GCs suggests that there are tissue-specific pathways of B cell development that differ between tonsil and PP. The differential expression pattern of MAdCAM-1, together with the observation that ligation of beta(7) can inhibit the induction of CD38 expression, suggests that ligation of alpha(4)beta(7) in vivo may contribute to a PP-specific GC phenotype.

Irritable bowel syndrome in women: the physician-patient relationship evolving.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders seen by primary care physicians and specialists. The disorder affects approximately 15% to 20% of the world's population and is predominately found in women. Despite the high prevalence of IBS in the general population, our understanding of the disorder's diagnosis, etiology, and treatment options are limited. This deficiency in our understanding is the foundation to the distressed physician-patient relationships that are commonly found with this disorder. By becoming familiar with the diagnostic criteria for IBS and gaining a stronger understanding of the biopsychosocial factors of IBS symptomatology as well as the available treatment methods, the primary care physician or specialist can ensure greater confidence in making a correct diagnosis and in making other professional decisions with patients with IBS. Improvements in these areas will foster a supportive environment for a therapeutic relationship between physician and patient, thereby optimizing quality patient care and treatment outcome.

Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors.

Previous studies have shown that the intestinal peristaltic reflex initiated by mucosal stimulation is mediated by release of 5-hydroxytryptamine (HT) from enterochromaffin cells; 5-HT acts via 5-HT4 receptors in rat and human, and via both 5-HT4 and 5-HT3 receptors in guinea pig to activate intramural sensory neurons that release calcitonin gene-related peptide. In this study, selective agonists and antagonists were used to examine the involvement of 5-HT4 and 5-HT3 receptors in colonic propulsion. The velocity of propulsion was measured with artificial fecal pellets introduced into the orad end of an isolated guinea pig colonic segment. Control velocity ranged from 0.5 to 3.3 mm/s; mean +/- S.E.M., 1.3 +/- 0.1 mm/s. The 5-HT4 antagonist, GR 113808A, and the 5-HT3 antagonist, LY 278584, decreased the velocity of pellet propulsion in a concentration-dependent fashion (39 +/- 2% and 47 +/- 1% decrease at 10 microM, respectively). A combination of both antagonists (10 microM each) was additive, decreasing the velocity by 82 +/- 3% to 84 +/- 4%. The selective 5-HT4 agonists, HTF 919 and R093877, as well as 5-HT in the presence of the 5-HT2a antagonist, ketanserin, increased the velocity of propulsion in a concentration-dependent fashion with EC50s of 6.9 +/- 0.1 nM, 37.4 +/- 1.0 nM, and 3.9 +/- 0. 1 nM, respectively. Compared with HTF 919, R093877 was less potent and appeared to be a partial agonist. All three agonists were effective at submicromolar concentrations; at concentrations above 1 microM, there was no increase in the velocity of propulsion. We conclude that the presence of fecal pellets triggers the release of 5-HT, which acts via both 5-HT3 and 5-HT4 receptors to regulate propulsive activity in guinea pig colon.

Mediators and regulation of peristalsis.

Peristalsis is the main postprandial propulsive activity of the gut. It is mediated by neurons of the enteric nervous system, which form an integrated circuit composed of sensory neurons, modulatory interneurons, and motor neurons to the circular and longitudinal muscle layers. Work outlined in this review has identified, by anatomic, physiologic, and pharmacologic techniques, the myenteric neurons and neurotransmitters involved in the regulation of this reflex. Of particular note are studies identifying the role of 5-hydroxytryptamine4 (5-HT4) receptors in the initiation of the peristaltic reflex and the development of selective 5-HT4 agonists as potential therapeutic agents.

5-HT4 receptor agonists and delta-opioid receptor antagonists act synergistically to stimulate colonic propulsion.

Opioid neurons exert a tonic restraint on inhibitory VIP/PACAP/NOS motoneurons of the enteric nervous system. A decrease in opioid peptide release during the descending phase of the peristaltic reflex, which underlies propulsive activity, leads to an increase in vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and nitric oxide (NO) release and circular muscle relaxation. These effects are accentuated by opioid receptor antagonists. Endogenous opioid peptides and selective opioid delta-, kappa- and mu-receptor agonists decreased the velocity of pellet propulsion in isolated segments of guinea pig colon, whereas selective antagonists increased velocity in a concentration-dependent fashion with an order of potency indicating preferential involvement of delta-receptors. 5-HT4 agonists (HTF-919 and R-093877), which also increase the velocity of propulsion, acted synergistically with the delta-receptor antagonist naltrindole; a threshold concentration of naltrindole (10 nM) shifted the concentration-response curve to HTF-919 to the left by 70-fold. A combination of 10 nM naltrindole with threshold concentrations of the 5-HT4 agonists caused significant increases in the velocity of propulsion (50 +/- 7 to 77 +/- 8%). We conclude that 5-HT4 agonists and opioid delta-receptor antagonists act synergistically to facilitate propulsive activity in isolated colonic segments.

5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine.

BACKGROUND & AIMS: The peristaltic reflex induced by mucosal stimuli is mediated by intrinsic sensory calcitonin gene-related peptide (CGRP) neurons activated by 5-hydroxytryptamine (5-HT) released from enterochromaffin cells. The involvement of 5-HT4 receptors was examined with selective 5-HT4 agonists. METHODS: Compartmented intestinal segments were used to measure neurotransmitter release and the mechanical components of the reflex. RESULTS: In human jejunal and rat and guinea pig colonic segments, addition of the 5-HT4 agonist HTF 919 elicited release of CGRP only into the compartment where the 5-HT4 agonist was added; vasoactive intestinal peptide (VIP) was released only into the compartment where descending relaxation was measured, and substance P (SP) was released only into the compartment where ascending contraction was measured. The CGRP antagonist hCGRP8-37 inhibited both mechanical responses by 75%-80%. Release of CGRP, VIP, and SP as well as ascending and descending responses were inhibited by selective 5-HT4 but not by selective 5-HT3 antagonists. Similar results were obtained with a different 5-HT4 agonist, R093877. However, HTF 919 was 10-30 times more potent (median effective concentration, approximately 10 nmol/L for peptide release and 5 nmol/L for mechanical responses) than R093877. CONCLUSIONS: Selective 5-HT4 agonists applied to the mucosa in nanomolar concentrations trigger the peristaltic reflex in human, rat, and guinea pig intestine.

Assessment of human colon cancer protein kinetics in vivo.

BACKGROUND: Malignancies enlarge because protein synthesis exceeds the rate of breakdown; however, the specific protein kinetic pattern remains unknown. Determining in vivo protein kinetic rates for a tumor may be useful for quantifying individual responses to a specific therapy. The aim of this study was to assess whether the growth of tumors is related to an increase in protein synthesis or an inhibition of protein breakdown. METHODS: Five patients (age, 59 +/- 3 years) with adenocarcinoma of the colon undergoing colonoscopy were studied. Tissue protein synthesis and breakdown rates were measured in vivo for both segments of colon cancer and adjacent normal-appearing colonic mucosa by using a primed, continuous infusion of 1(13)C leucine with tissue biopsy and quantitation of regional blood flow by laser Doppler flowmetry. RESULTS: Segments of colon cancer had a significantly (p < 0.05) greater rate of protein synthesis as quantitated by both the fractional rate of protein synthesis (Ca 45.4% +/- 5.0%/day versus nl mucosa 35.7% +/- 3.1%/day; mean +/- SEM) and by the tissue synthesis rate (Ca 69.4 +/- 9.0 versus nl mucosa 51.6 +/- 5.2 mumol/L leucine/day/100 gm tissue). Regional blood flow was significantly elevated in the cancer (Ca 110.9 +/- 5.8 versus nl mucosa 91.2 +/- 2.9 ml/min/100 gm), which contributed to commensurate rates of tissue breakdown (Ca 28.6 +/- 2.0 versus nl mucosa 28.2 +/- 2.4 mumol/L leucine/day/100 gm). CONCLUSIONS: These results illustrate that human colon cancers grow in vivo as a result of increases in protein synthesis. Furthermore, increases in regional blood flow limit the rate of tissue protein breakdown of colon cancer, thereby contributing to growth of the malignancy. These findings support the contention that therapeutic strategies aimed at negating this inherent increase in protein synthesis or limiting blood flow may effectively limit the growth of malignancies. This methodology may also provide an index for evaluating the effectiveness of future therapies aimed at reducing tumor growth for individual patients.

Antibiotics and pancreatitis.

Despite improvements in the general supportive care of patients with acute pancreatitis, the morbidity of infectious complications remains high and bacterial infections account for most deaths. The role of antibiotics in reducing infectious morbidity and mortality has been debated for decades because of a lack of supportive clinical data. Research completed over the past decade has helped to define the microbiology, establish the risk factors, and improve the understanding of the pathogenesis of infectious complications in patients with acute pancreatitis. Patients with acute necrotizing pancreatitis are at the greatest risk of developing an infection with enteric gram-negative or gram-positive bacteria translocated from the bowel lumen into the necrotic pancreatic tissue. The most effective antimicrobial agents are the fluoroquinolones, imipenem-cilastatin, and metronidazole, which achieve adequate penetration into pancreatic juice and necrotic tissue and inhibit the growth of enteric bacteria. Animal and human studies support the use of antibiotics for the prevention of infectious morbidity and mortality in severe acute pancreatitis. Recent clinical trials have assessed the role of both systemic antibiotic prophylaxis and selective bowel decontamination with nonabsorbable oral antimicrobials in high-risk patients with acute necrotizing pancreatitis. This article provides an overview of our current knowledge of pancreatic infections and a critical analysis of studies on the role of antibiotics in this disease.

Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine.

BACKGROUND & AIMS: The role of 5-hydroxytryptamine (5-HT) in regulating the peristaltic reflex in humans is unknown. The neural pathways subserving peristalsis induced by mucosal stimulation were characterized in human jejunum and guinea pig colon. METHODS: Compartmented flat-sheet preparations that enable measurement of 5-HT and sensory transmitter release into one compartment and mechanical responses in adjacent compartments were used. RESULTS: Mucosal stimuli (2-8 brush strokes) caused concomitant release of 5-HT and calcitonin gene-related peptide (CGRP) into the compartment where stimulation was applied in both species; in contrast, muscle stretch caused release of CGRP only. CGRP release as well as ascending contraction and descending relaxation of circular muscle induced by mucosal stimulation were inhibited by a selective 5-HT4 antagonist in human jejunum and by selective 5-HT4 and 5-HT3 antagonists in guinea pig colon. The effects of the 5-HT3 and 5-HT4 antagonists in guinea pig colon were additive. A selective 5-HT1P antagonist mimicked the effect of the 5-HT4 antagonist. The CGRP antagonist human CGRP8-37 inhibited ascending and descending responses in both species. CONCLUSIONS: 5-HT released by mucosal stimulation initiates a peristaltic reflex by activating 5-HT4/5-HT1P receptors on sensory CGRP neurons in human intestine and 5-HT4/5-HT1P and 5-HT3 receptors in guinea pig colon.

Regulation of colonic propulsion by enteric excitatory and inhibitory neurotransmitters.

The contribution of excitatory and inhibitory motor neurotransmitters to colonic propulsion was examined in isolated segments of guinea pig colon. Synthetic fecal pellets were inserted at the proximal end of the segment, and the velocity of pellet propulsion across a fixed distance was measured in the presence and absence of selective neurotransmitter antagonists. The control velocity (0.97 +/- 0.02 mm/s) was inhibited in a concentration-dependent fashion by atropine and the neurokinin (NK)-2a antagonist MEN-10,376 [half-maximal inhibitory concentration (IC50), 1 microM; maximal inhibition, 98 +/- 1%]. The NK-1 antagonist GR-82,334 (10 microM) also inhibited velocity by 65 +/- 9%, consistent with involvement of acetylcholine, neurokinin A (NK-2 agonist), and substance P (NK-1 agonist) in the contractile components of the peristaltic reflex. Velocity was also inhibited in a concentration-dependent fashion by the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA; IC50, 1 microM; maximal inhibition, 96 +/- 2%) and by the vasoactive intestinal peptide (VIP) antagonist VIP-(10-28) (IC50, 30 nM; maximal inhibition, 64 +/- 6%), consistent with involvement of both nitric oxide and VIP in descending relaxation of circular muscle and contraction of longitudinal muscle. A combination of threshold concentrations of L-NNA and the NK-2a antagonist was synergistic (53 +/- 7% inhibition). The potentiation implied that the ascending and descending phases were functionally coupled in series. We conclude that blockade of neurotransmitters that mediate either phase of the peristaltic reflex inhibits colonic propulsive activity. Serial coupling of the phases leads to synergism between inhibitors, a condition of potential therapeutic importance.

Percutaneous endoscopic gastrojejunostomy: a dual center safety and efficacy trial.

Although jejunal tube placement through a percutaneous endoscopic gastrostomy (PEG) has not been proven to be preferable to PEG feeding, it would be theoretically advantageous for those patients prone to gastrointestinal aspiration. However, reliable placement of a small bowel feeding tube through a PEG has been technically difficult. We have previously reported successful placement of a percutaneous endoscopic gastrojejunostomy (PEG/J) with minimal complications. These results are in contrast to other series that report technical difficulty, frequent tube dysfunction and gastric aspiration. We describe an over-the-wire PEG/J technique performed by multiple operators at two medical centers. Gastrostomy tube placement was successful in 94% of patients. Initial placement of the jejunal tube was successful in 88% of patients. Second attempts were 100% successful. The average procedure time was 36 minutes. The distal duodenal and jejunal placement of the jejunal tube resulted in no episodes of gastroduodenal reflux. Complications included jejunal tube migration (6%), clogging (18%), and unintentional removal (11%). The majority of patients were ultimately converted to either oral or intragastric feedings. We conclude that the PEG/J system is a reliable, reproducible method of small bowel feeding and is associated with no episodes of tube feeding reflux when the jejunal tube is positioned in the distal duodenum or beyond. Furthermore, it provides a temporary nutritional bridge for those patients who are later transitioned to either PEG or oral feeding.