Nicola de Bortoli

Helicobacter pylori Eradication: A Randomized Prospective Study of Triple Therapy Versus Triple Therapy Plus Lactoferrin and Probiotics

OBJECTIVES:Helicobacter pylori is causally associated with gastritis and peptic ulcer diseases. Recent data (meta-analysis) have demonstrated that triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor has an eradication rate of only 74–76% and new therapeutic protocols may be necessary. The aim of this study was to examine whether adding bovine lactoferrin (bLf) and probiotics (Pbs) to the standard triple therapy for H. pylori infection could improve the eradication rate and reduce side effects.METHODS:H. pylori infection was diagnosed in 206 patients: in 107 based on an upper endoscopy exam and a rapid urease test, and in 99 by means of the H. pylori stool antigen-test and the C13 urea breath test (C13 UBT). The patients were randomized into two groups: 101 patients (group A) underwent standard triple eradication therapy (esomeprazole, clarithromycin, amoxicillin), while 105 patients (group B) underwent a modified eradication therapy (standard triple eradication therapy plus bLf and Pb). Successful eradication therapy was defined as a negative C13 UBT 8 wk after completion of the treatment. Results were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis. Data were evaluated and considered positive when P < 0.05.RESULTS:At the end of the study 175/206 patients showed negative C13 UBT results. According to intention-to-treat analysis, the infection was eradicated in 73/101 patients from Group A and in 93/105 from Group B. PP analysis showed 73/96 patients from Group A and 93/101 from Group B to have been successfully treated. More patients from group A than from group B reported side effects from their treatment (P < 0.05).CONCLUSIONS:The results of our study suggest that the addition of bLf and Pbs could improve the standard eradication therapy for H. pylori infection—bLf serving to increase the eradication rate and Pbs to reduce the side effects of antibiotic therapy.

Efficacy of Nissen Fundoplication Versus Medical Therapy in the Regression of Low-Grade Dysplasia in Patients With Barrett Esophagus: A Prospective Study

Objective:The aim of this study is to compare the effect of medical and surgical treatment on the history of patients with Barrett esophagus (BE) and histologic evidence of low-grade dysplasia (LGD). Summary Background Data:BE is a complication of severe gastroesophageal reflux. It is considered a major risk factor for esophageal adenocarcinoma, which may develop through stages from nondysplastic metaplasia to dysplasia (LGD and high-grade dysplasia). Presently, there are no recommended therapeutic guidelines for patients with LGD. Methods:Between 1998 through 2003, 6592 patients underwent upper endoscopy; 327 of 6592 (5%) patients had BE, and 35 of 327 (10.7%) had LGD. Nineteen patients with LGD were treated with high-dose proton pump inhibitors, and 16 patients underwent laparoscopic Nissen fundoplication. Endoscopic and histologic follow-up was available in all patients after 18 months. We used multiple logistic regression to examine the effect of the 2 treatments on regression of LGD. Results:LGD was predominant in men (male-to-female ratio: 1.7:1). Mean age was 58 ± 13.5 years. Sixty percent of patients had no endoscopic evidence of esophagitis. A regression from LGD to BE was observed in 12 of 19 (63.2%) patients in the medical group and in 15 of 16 (93.8%) patients in the surgical group (statistically significant difference). Differences between the 2 groups were statistically significant (P = 0.03). Conclusion:The results of our study suggest that surgical treatment may be more effective than medical therapy to modify the natural history of LGD in patients with BE, perhaps because it not only controls acid but also biliopancreatic reflux into the esophagus.

How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?

AIM To investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR). METHODS Between May 2011 and October 2011, 41 consecutive patients with laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the therapeutic outcome was assessed through validated questionnaires (GERD impact scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose and throat specialists using the reflux finding score (RFS) and reflux symptom index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring. A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD), pathological acid exposure time (AET) in the absence of esophageal erosions (NERD), and a positive correlation between symptoms and refluxes (hypersensitive esophagus, HE). RESULTS The male/female ratio was 0.52 (14/27), the mean age ± SD was 51.5 ± 12.7 years, and the mean body mass index was 25.7 ± 3.4 kg/m(2). All subjects reported one or more LPS. Twenty-five out of 41 patients also had typical GERD symptoms (heartburn and/or regurgitation). The most frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41), linear indentation in the medial edge of the vocal fold (31/41), vocal fold nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy (P < 0.05); conversely, 23/41 did not report any clinical improvement. At the same time, the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand, such result was not recorded for LPS. Esophagitis was detected in 2/41 patients, and ineffective esophageal motility was found in 3/41 patients. The MII-pH analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41 patients had a normal AET and a positive association between symptoms and refluxes (HE), and 25/41 patients had a normal AET and a negative association between symptoms and refluxes (no GERD patients). It is noteworthy that HE patients had a positive association with typical GERD-related symptoms. Gas refluxes were found more frequently in patients with globus (29.7 ± 3.6) and hoarseness (21.5 ± 7.4) than in patients with heartburn or regurgitation (7.8 ± 6.2). Gas refluxes were positively associated with extra-esophageal symptoms (P < 0.05). Overall, no differences were found among the three groups of patients in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in patients with ERD/NERD only. The differences observed by means of MII-pH analysis among the three subgroups of patients (ERD/NERD, HE, no GERD) were not demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was found to have a significant association with the RFS (P = 0.028 and P = 0.026, nominal and numerical correlation, respectively). CONCLUSION MII-pH analysis confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of LPR, most likely because of the low specificity of the laryngoscopic findings.

Association Between Baseline Impedance Values and Response Proton Pump Inhibitors in Patients With Heartburn

BACKGROUND & AIMS Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Influence of the serotonin transporter 5HTTLPR polymorphism on symptom severity in irritable bowel syndrome.

5HTTLPR polymorphism of serotonin transporter yields short (S) and long (L) alleles. SS and LS genotypes are associated with reduced expression of serotonin transporter. This cross-sectional study investigated the association of 5HTTLPR with symptom severity of irritable bowel syndrome (IBS). Patients with IBS (Rome III) and healthy controls were included. Genomic DNA was extracted from saliva, and 5HTTLPR alleles were assessed by polymerase chain reaction. IBS symptom severity was evaluated by means of IBS-SSS questionnaire. Two hundreds and four IBS patients (159 females; mean age: 39.6±12.3 years; 106 with constipation: C-IBS; 98 with diarrhea: D-IBS) and 200 healthy controls (154 females; mean age: 40.4±15.8 years) were enrolled. The overall IBS-SSS value was higher in LS/SS than LL patients (319.0±71.5 versus 283.8±62.3; P = 0.0006). LS/SS patients had also higher values of abdominal pain (59.7±21.0 versus 51.0±18.8; P = 0.020) and bowel dissatisfaction (80.1±23.9 versus 70.5±22.8; P = 0.035). The overall IBS-SSS values in C-IBS and D-IBS patients were 317.2±68.3 and 296.1±71.4, respectively (P = 0.192), with significantly higher values for abdominal distension (65.0±24.4 versus 51.4±24.8; P = 0.0006), but not for bowel dissatisfaction (80.5±21.7 versus 72.9±25.7; P = 0.138). Frequencies of 5HTTLPR genotypes did not differ significantly when comparing IBS patients (overall or upon stratification in C-IBS and D-IBS) with healthy controls. In conclusion, the LS and SS genotypes are significantly correlated with IBS symptom severity, although their possible direct causal role remains to be proven. In addition, the present findings do not support an association of 5HTTLPR with IBS or its clinical presentation in terms of bowel habit predominance.

Alginate controls heartburn in patients with erosive and nonerosive reflux disease

AIM To evaluate the effect of a novel alginate-based compound, Faringel, in modifying reflux characteristics and controlling symptoms. METHODS In this prospective, open-label study, 40 patients reporting heartburn and regurgitation with proven reflux disease (i.e., positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal. They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel. In both sessions, measurements were obtained in right lateral and supine decubitus positions. Patients also completed a validated questionnaire consisting of a 2-item 5-point (0-4) Likert scale and a 10-cm visual analogue scale (VAS) in order to evaluate the efficacy of Faringel in symptom relief. Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good (1) to very poor (6). RESULTS Faringel decreased significantly (P < 0.001), in both the right lateral and supine decubitus positions, esophageal acid exposure time [median 10 (25th-75th percentil 6-16) vs 5.8 (4-10) and 16 (11-19) vs 7.5 (5-11), respectively] and acid refluxes [5 (3-8) vs 1 (1-1) and 6 (4-8) vs 2 (1-2), respectively], but increased significantly (P < 0.01) the number of nonacid reflux events compared with baseline [2 (1-3) vs 3 (2-5) and 3 (2-4) vs 6 (3-8), respectively]. Percentage of proximal migration decreased in both decubitus positions (60% vs 32% and 64% vs 35%, respectively; P < 0.001). Faringel was significantly effective in controlling heartburn, based on both the Likert scale [3.1 (range 1-4) vs 0.9 (0-2); P < 0.001] and VAS score [7.1 (3-9.8) vs 2 (0.1-4.8); P < 0.001], but it had less success against regurgitation, based on both the Likert scale [2.6 (1-4) vs 2.2 (1-4); P = not significant (NS)] and VAS score [5.6 (2-9.6) vs 3.9 (1-8.8); P = NS]. Overall, the tolerability of Faringel was very good 5 (2-6), with only two patients reporting modest adverse events (i.e., nausea and bloating). CONCLUSION Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time, number of acid refluxes and their proximal migration.

Accuracy of b-GGT fraction for the diagnosis of non-alcoholic fatty liver disease

Serum gamma‐glutamyltransferase (GGT) activity is a sensitive but non‐specific marker of non‐alcoholic fatty liver disease (NAFLD). Recently, four GGT fractions (big‐, medium‐, small‐, free‐GGT) were described in humans.

Radionuclide Evaluation of the Lower Gastrointestinal Tract

This review outlines the technical aspects and diagnostic performance parameters of nuclear medicine procedures used on patients with disorders of the lower gastrointestinal tract, with the exclusion of techniques using tumor-seeking radiopharmaceuticals. Chronic disorders of the lower gastrointestinal tract often reduce the quality of life because of discomfort from constipation or diarrhea. Five classes of radionuclide procedures are used to characterize these disorders: transit scintigraphy, searches for ectopic gastric mucosa in Meckels diverticulum, scintigraphy of active inflammatory bowel disease, scintigraphic defecography, and scintigraphy to detect sites of gastrointestinal bleeding. Protocols for these procedures and their relative merit in patient management are discussed, with special emphasis on their potential for semiquantitative assessment of the pathophysiologic parameter investigated. Quantitation is particularly relevant for prognostic purposes and for monitoring the efficacy of therapy.

The appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal

The advent of powerful acid-suppressive drugs, such as proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases and has minimized the role of surgery. The major and universally recognized indications for their use are represented by treatment of gastro-esophageal reflux disease, eradication of Helicobacter pylori infection in combination with antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prophylaxis of non-steroidal anti-inflammatory drug-associated gastric ulcers and control of several acid hypersecretory conditions. However, in the last decade, we have witnessed an almost continuous growth of their use and this phenomenon cannot be only explained by the simple substitution of the previous H2-receptor antagonists, but also by an inappropriate prescription of these drugs. This endless increase of PPI utilization has created an important problem for many regulatory authorities in terms of increased costs and greater potential risk of adverse events. The main reasons for this overuse of PPIs are the prevention of gastro-duodenal ulcers in low-risk patients or the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anticoagulant treatment without risk factors for gastro-duodenal injury, the overtreatment of functional dyspepsia and a wrong diagnosis of acid-related disorder. The cost for this inappropriate use of PPIs has become alarming and requires to be controlled. We believe that gastroenterologists together with the scientific societies and the regulatory authorities should plan educational initiatives to guide both primary care physicians and specialists to the correct use of PPIs in their daily clinical practice, according to the worldwide published guidelines.

Optimal treatment of laryngopharyngeal reflux disease

Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies.