Randomised clinical trial: oesophageal radiofrequency energy delivery versus sham for PPI-refractory heartburn.

BACKGROUND: Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs. AIM: To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn. METHODS: A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient. RESULTS: Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2 weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups. CONCLUSION: This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.

Pyloric distensibility measurement after gastric surgery: Which surgeries are associated with pylorospasm?

BACKGROUND AND STUDY AIMS: History of gastric surgery is found in 10% of patients with gastroparesis, and vagal lesion is often suspected to be the cause of pylorospasm. Recently, pyloric distensibility measurement using the EndoFLIP® system showed that pylorospasm was present in 30%-50% of gastroparetic patients. Our objective was to assess whether pylorospasm, diagnosed using EndoFLIP® system was observed in three different types of gastric surgeries: antireflux surgery, sleeve gastrectomy, and esophagectomy. PATIENTS AND METHODS: Pyloric distensibility and pressure were measured using the EndoFLIP® system in 43 patients from two centers (18 antireflux surgery, 16 sleeve gastrectomy, and nine esophagectomy) with dyspeptic symptoms after gastric surgery, and in 21 healthy volunteers. Altered pyloric distensibility was defined as distensibility below 10 mm2 /mm Hg as previously reported. RESULTS: Compared to healthy volunteers (distensibility: 25.2 ± 2.4 mm2 /mm Hg; pressure: 9.7 ± 4.4 mm Hg), pyloric distensibility was decreased in 61.1% of patients in the antireflux surgery group (14.5 ± 3.4 mm2 /mm Hg; P < .01) and 75.0% of patients in the esophagectomy group (10.8 ± 2.1 mm2 /mm Hg; P < .05), while pyloric pressure was only increased in the antireflux surgery group (18.9 ± 2.2 mm Hg; P < .01). Pyloric distensibility and pressure were similar in healthy volunteers and in sleeve gastrectomy (distensibility: 20.3 ± 3.8 mm2 /mm Hg; pressure: 15.8 ± 1.6 mm Hg) groups, with decreased pyloric distensibility affecting 18.7% of sleeve gastrectomy patients. CONCLUSION: Antireflux surgery and esophagectomy were associated with pylorospasm although pylorospasm was not found in all patients. Sleeve gastrectomy was not associated with altered pyloric distensibility nor altered pyloric pressure.

Pyloric distensibility measurement predicts symptomatic response to intrapyloric botulinum toxin injection.

BACKGROUND AND AIMS: Recent studies have reported that pyloric distensibility was altered in 30% to 50% of patients with gastroparesis, and this was correlated with gastric emptying and symptom severity. The aim of this study was to assess whether pyloric distensibility measurement was predictive of symptomatic response after intrapyloric botulinum toxin (BT) injection. METHODS: Pyloric distensibility was measured using the EndoFLIP system (Crospon, Galway, Ireland) before intrapyloric BT injection. Altered pyloric distensibility was defined as distensibility below 10 mm2/mm Hg. Total symptomatic score (TSS), dyspeptic symptoms, Gastrointestinal Quality of Life Index (GIQLI), and gastric emptying were investigated prospectively before and 3 months after BT injection. RESULTS: Nineteen of 35 patients had altered pyloric distensibility. In those patients, TSS decreased at 3 months from 13.5 to 10.5 (P < .01), whereas it remained unchanged in patients with normal pyloric distensibility (P = .7). Gastric fullness (from 3.5 to 2.5; P = .03) and bloating (from 3.0 to 2.0; P = .01) were the only symptoms that improved in patients with altered pyloric distensibility, whereas none of them was improved in patients with normal pyloric distensibility. GIQLI score increased from 59.5 to 76.5 in patients with altered pyloric distensibility (P = .02), whereas there was no statistical difference (P = .43) in patients with normal pyloric distensibility. In patients with altered pyloric distensibility, gastric emptying half time was 223 minutes before and 190 minutes 3 months after injection (P = .02), whereas it remained unchanged in patients with normal pyloric distensibility (P = .6). CONCLUSIONS: Pyloric distensibility measurement before intrapyloric BT injection predicted symptomatic and quality of life response 3 months after injection in patients with gastroparesis.

Does calprotectin level identify a subgroup among patients suffering from irritable bowel syndrome? Results of a prospective study.

BACKGROUND: Irritable bowel syndrome is a multifactorial disease. Although faecal calprotectin has been shown to be a reliable marker of intestinal inflammation, its role in irritable bowel syndrome remains debated. OBJECTIVE: The aims of this prospective study were to select a subgroup of irritable bowel syndrome patients and to characterise those patients with high faecal calprotectin by systematic work-up. METHODS: Calprotectin levels were determined by enzyme-linked immunosorbent assay test in consecutive irritable bowel syndrome patients fulfilling Rome III criteria in whom normal colonoscopy and appropriate tests had excluded organic disease. Calprotectin levels were compared in irritable bowel syndrome patients, healthy controls and patients with active and quiescent Crohn's disease. When the calprotectin level was higher than 50 µg/g, the absence of ANCA/ASCA antibodies and a normal small bowel examination were required to confirm irritable bowel syndrome diagnosis. Additional explorations included assessment of irritable bowel syndrome severity, anxiety and depression, impact on quality of life, glucose and fructose breath tests, rectal distension test by barostat and quantitative and qualitative assessment of inflammation on colonic biopsies. RESULTS: Among the 93 irritable bowel syndrome patients (73% women; 66.7% with diarrhoea) recruited, 34 (36.6%) had reproducibly elevated calprotectin. Although they tended to be older than those with normal calprotectin (P = 0.06), there were no other differences between the two groups. When elevated, calprotectin was correlated with age (P = 0.03, r = 0.22). CONCLUSIONS: Elevated faecal calprotectin was observed in one third of patients in this series, without any significant association with a specific clinical phenotype (except age) or specific abnormalities.

Lack of correlation between morbid obesity and severe gastroesophageal reflux disease in candidates for bariatric surgery: results of a large prospective study.

The relationship between obesity and gastroesophageal reflux disease (GERD) is a subject of debate. In this large series of 250 morbidly obese patients, all candidates for bariatric surgery, we have shown the very low prevalence of severe GERD and neither Barrett's esophagus nor esophageal adenocarcinoma was detected. Moreover, no relationship was found between GERD and not only BMI but also abdominal diameter.

Role of toll like receptors in irritable bowel syndrome: differential mucosal immune activation according to the disease subtype.

BACKGROUND: The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. METHODOLOGY AND FINDINGS: In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1ß. CONCLUSIONS: Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.

Macrophage HIV-1 infection in duodenal tissue of patients on long term HAART.

Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. Since the role of intestinal macrophages as viral reservoirs during chronic HIV-1 infection has not been elucidated, we investigated the effects of successful therapy on intestinal HIV-1 persistence. Intestinal macrophage infection was demonstrated by the expression of p24 antigen by flow cytometry and by the presence of proviral DNA, assessed by PCR. Proviral DNA was detected in duodenal mucosa of HIV-infected patients under treatment with undetectable plasma viral load. These findings confirm that intestinal macrophages can act as viral reservoirs and permit HIV-1 production even after viral suppression following antiretroviral therapy.

[Percutaneous endoscopic gastrostomy in patients with neurological diseases. Results of a prospective multicenter and international study]. / La gastrostomía endoscópica percutánea en pacientes con trastornos deglutorios de origen neurologico. Resultados de un estu- dio prospectivo multicéntrico internacional.

AIM: To determine prospectively the long-term evolution of patients with neurological diseases after insertion of percutaneous endoscopic gastrostomy (PEG). METHODS: 109 PEG were performed in 99 consecutive patients (49 females, 50 males), mean age 75 years (range: 20-97 years) as an alternative to a nasogastric tube. Patients were enterally fed because of chronic neurological swallowing difficulties: cerebrovascular disease 38, dementia 27, disordered swallowing mechanisms in elderly patients 10, motor neurona disease and multiple sclerosis 10, neuro-surgical disease 6, Parkinson's disease 3, brain tumor 3, neo-natal encephalopathy 1, HIV encephalopathy 1. The procedure took place in a dedicated endoscopy room. In all cases, prophylatic antibiotics were given and the PEG tube was inserted by the "pull" technique. RESULTS: PEG insertion was technically succesful in all cases. After PEG insertion, all patients were subsequently discharged to local nursing home facilities. 85/99 patients were long-term followed-up on an outpatient basis, 25% of them were followed for more than a year. The mean follow-up time was 3 months (range: 1-24 months). The most frequent complication were minor: local wound infection 6, ostomy leakage 8, silicon degradation 16, leading to the removal of the PEG and the placement of a new PEG tubes in 10 cases. Two major complications were observed : one gastric perforation and death 2 months after the PEG placement and one gastrocolic fistula. No aspiration pneumonia was reported. In one patient, PEG was removed after recuperation of a normal swallowing. All patients had a nutritional improvement. A total of 11 deaths occurred during the follow-up, related to the neurological disorder in 10/11 cases. Nursing home team, patient's physicians and patient's families found PEG manipulations easier than naso-gastric tube. CONCLUSION: Our study suggests that PEG is a method of choice for enteral feeding of patients with chronic neurological disorders. PEG is well-tolerated, leading to an improvement in nutritional status and offering good facilities for home nursing.

La gastrostomía endoscópica percutánea en pacientes con trastornos deglutorios de origen neurologico. Resultados de un estu- dio prospectivo multicéntrico internacional. / [Percutaneous endoscopic gastrostomy in patients with neurological diseases. Results of a prospective multicenter and international study]

AIM: To determine prospectively the long-term evolution of patients with neurological diseases after insertion of percutaneous endoscopic gastrostomy (PEG). METHODS: 109 PEG were performed in 99 consecutive patients (49 females, 50 males), mean age 75 years (range: 20-97 years) as an alternative to a nasogastric tube. Patients were enterally fed because of chronic neurological swallowing difficulties: cerebrovascular disease 38, dementia 27, disordered swallowing mechanisms in elderly patients 10, motor neurona disease and multiple sclerosis 10, neuro-surgical disease 6, Parkinsons disease 3, brain tumor 3, neo-natal encephalopathy 1, HIV encephalopathy 1. The procedure took place in a dedicated endoscopy room. In all cases, prophylatic antibiotics were given and the PEG tube was inserted by the [quot ]pull[quot ] technique. RESULTS: PEG insertion was technically succesful in all cases. After PEG insertion, all patients were subsequently discharged to local nursing home facilities. 85/99 patients were long-term followed-up on an outpatient basis, 25

of them were followed for more than a year. The mean follow-up time was 3 months (range: 1-24 months). The most frequent complication were minor: local wound infection 6, ostomy leakage 8, silicon degradation 16, leading to the removal of the PEG and the placement of a new PEG tubes in 10 cases. Two major complications were observed : one gastric perforation and death 2 months after the PEG placement and one gastrocolic fistula. No aspiration pneumonia was reported. In one patient, PEG was removed after recuperation of a normal swallowing. All patients had a nutritional improvement. A total of 11 deaths occurred during the follow-up, related to the neurological disorder in 10/11 cases. Nursing home team, patients physicians and patients families found PEG manipulations easier than naso-gastric tube. CONCLUSION: Our study suggests that PEG is a method of choice for enteral feeding of patients with chronic neurological disorders. PEG is well-tolerated, leading to an improvement in nutritional status and offering good facilities for home nursing.

Esophageal motility disorders in HIV patients.

Opportunistic esophageal infections (Candida, cytomegalovirus, herpes simplex virus) and idiophatic esophageal ulcerations are commonly found in HIV patients. However, motility disorders of the esophagus have seldom been investigated in this population. The aim of this prospective study was to determine the presence of motility disorders in HIV patients with esophageal symptoms (with or without associated lesions detected by endoscopy) and in HIV patients without esophageal symptoms and normal esophagoscopy. Eigthteen consecutive HIV patients (10 male, 8 female, ages 20-44 years, mean age 33.5; 8 HIV positive and 10 AIDS) were studied prospectively. Nine patients complained of esophageal symptoms, e.g, dysphagia/odynophagia (group 1) and 9 had symptoms not related to esophageal disease, such as diarrhea, abdominal pain, or gastrointestinal bleeding (group 2). All patients underwent upper endoscopy; mucosal biopsies were taken when macroscopic esophageal lesions were identified or when the patients were symptomatic even if the esophageal mucosa was normal. Esophageal manometry was performed in the 18 patients, using a 4-channel water-perfused system according to a standardized technique. Sixteen of the 18 patients (88.8%) had baseline manometric abnormalities. In group 1, 8/9 patients had esophageal motility disorders: nutcrackeresophagus in 1, hypertensive lower esophageal sphincter (LES) with incomplete relaxation in 2, nonspecific esophageal motility disorders (NEMD) in 3, diffuse esophageal spasm in 1, esophageal hypocontraction with low LES pressure in 1. Six of these 9 patients had lesions detected by endoscopy: CMV ulcers in 2, idiopathic ulcers in 1, candidiasis in 1, idiopathic ulcer + candidiasis in 1, nonspecific esophagitis in 1; and 3/9 had normal endoscopy and normal esophageal biopsies. In group 2, 8/9 patients had abnormal motility: hypertensive LES with incomplete relaxation in 1, nutcracker esophagus in 2, esophageal hypocontraction in 3, and NEMD in 2. All these patients had a normal esophageal mucosa at endoscopy. In conclusion, our findings suggest that HIV patients have esophageal motility disorders independent of esophageal symptoms and/or the presence of mucosal esophageal lesions.

Enfermedad por reflujo gastroesofágico y epitelio de Barrett / Gastroesophageal reflux disease and Barrett's esophagus

La enfermedad por reflujo gastroesofágico es una de las situaciones clínicas más comunes. El esófago de Barrett(EB) es su consecuencia evolutiva más importante y está asociado con un riesgo incrementado de adenocarcinoma. Ultimamente se han desarrollado nuevos marcadores para detectar la psobilidad de malignización. La cirugía antirreflujo es la alternativa del tratamiento médico. No se han podido establecer si se consigue la regresión del epitelio columnar especializado y displasia para evitar la progresión al cáncer. Por consiguiente, debe realizarse la vigilancia endoscópica por el riesgo de adenocarcinoma. La ablación endoscópica de la mucosa con metaplasia intestinal parece ser una técnica prometedora en este grupo de pacientes

Enfermedad por reflujo gastroesofágico y epitelio de Barrett / Gastroesophageal reflux disease and Barretts esophagus

La enfermedad por reflujo gastroesofágico es una de las situaciones clínicas más comunes. El esófago de Barrett(EB) es su consecuencia evolutiva más importante y está asociado con un riesgo incrementado de adenocarcinoma. Ultimamente se han desarrollado nuevos marcadores para detectar la psobilidad de malignización. La cirugía antirreflujo es la alternativa del tratamiento médico. No se han podido establecer si se consigue la regresión del epitelio columnar especializado y displasia para evitar la progresión al cáncer. Por consiguiente, debe realizarse la vigilancia endoscópica por el riesgo de adenocarcinoma. La ablación endoscópica de la mucosa con metaplasia intestinal parece ser una técnica prometedora en este grupo de pacientes