Papers by Nicola de Bortoli
World Journal of Gastrointestinal Pathophysiology, 2016
Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the... more Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic
World journal of gastroenterology, Jan 28, 2015
Irritable bowel syndrome (IBS) and functional constipation (FC) are the most common functional ga... more Irritable bowel syndrome (IBS) and functional constipation (FC) are the most common functional gastrointestinal disorders. According to the Rome III Criteria these two disorders should be theoretically separated mainly by the presence of abdominal pain or discomfort relieved by defecation (typical of IBS) and they should be mutually exclusive. However, many gastroenterologists have serious doubts as regards a clear separation. Both IBS-C and FC, often associated with many other functional digestive and non digestive disorders, are responsible for a low quality of life. The impact of the media on patients' perception of these topics is sometimes disruptive, often suggesting a distorted view of pathophysiology, diagnosis and therapy. These messages frequently overlap with previous subjective opinions and are further processed on the basis of the different culture and the previous experience of the constipated patients, often producing odd, useless or even dangerous behaviors. The ...
Su1085 Patients Who Respond to PPI Therapy are Always Considered GERD Patients? a MII-pH Study
Gastroenterology, 2012
Analyses of the Post-reflux Swallow-induced Peristaltic Wave Index and Nocturnal Baseline Impedance Parameters Increase the Diagnostic Yield of Impedance-pH Monitoring of Patients With Reflux Disease
Clinical Gastroenterology and Hepatology, 2016
Analyses of impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) ... more Analyses of impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI) have been proposed to increase the accuracy of diagnosis of reflux disease. We assessed whether these improve the diagnostic yield of impedance pH monitoring of reflux disease. We performed a prospective study of consecutive patients with proton pump inhibitor-responsive heartburn who underwent 24hr impedance pH monitoring at hospitals in Italy from January 2011 through December 2013. Reviewers blindly analyzed off-therapy impedance pH tracings from 289 patients with proton pump inhibitor-responsive heartburn, 68 with erosive (ERD), and 221 with non-erosive (NERD) reflux disease, along with 50 healthy individuals (controls). The PSPW index, the MNBI, the esophageal acid exposure time, the number of total refluxes, and the bolus exposure were calculated, as well as the symptom association probability (SAP) and the symptom index (SI). In receiver operating characteristic analysis, the area under curve of the PSPW index (0.977; 95% confidence interval, 0.961-0.993) was significantly greater than that of the other impedance pH parameters in identifying patients with reflux disease (P<.001). The PSPW index and the MNBI identified patients with ERD with the highest level of sensitivity (100% and 91%, respectively), as well as the 118 pH-positive (99% and 86%) and 103 pH-negative (77% and 56%) cases of NERD. The PSPW index and the MNBI identified pH-negative NERD with the highest level of sensitivity: values were 82% and 52% for the 65 SAP- and/or SI-positive cases, and 68% and 63% for the 38 SAP- and SI-negative cases. Diagnoses of NERD were confirmed by pH-only criteria, including those that were positive based on the SAP or SI, for 165/221 cases (75%), and by impedance pH criteria for 216/221 cases (98%) (P=.001). The PSPW index and the MNBI increase the diagnostic yield of impedance pH monitoring of patients with reflux disease. Analysis of impedance pH data, by calculating the PSPW index and the MNBI, can increase the accuracy of diagnosis of patients with reflux disease, compared with pH-only data.
Gastroenterology, 2012
Background/Aims: Gastroesophageal reflux (GER) and subsequent aspiration events are hypothesized ... more Background/Aims: Gastroesophageal reflux (GER) and subsequent aspiration events are hypothesized to be potential contributors to chronic allograft dysfunction in lung transplant recipients. There are limited data on changes in GER or esophageal motility post-transplantation. We hypothesized that patients who had undergone lung transplantation would be predisposed to increased reflux events. Methods: Prospective comparative series of 19 pretransplant patients (47% female) and 13 post-transplant patients (23% female) being evaluated for GER. All patients were on regular acid suppression. After informed consent, patients filled out a detailed GER symptom questionnaire. Thereafter, both groups underwent esophageal manometry and 24hour catheter pH monitoring. Results: Mean age was similar between groups (Pre: 55yrs, 95% CI: 49-60; Post: 53yrs, 95% CI: 47-58. p= 0.65) . Cause of lung disease was also similar between groups (interstitial lung disease: 9/19 patients pre, 4/13 post. COPD: 7/19 patients pre, 4/13 post). No differences in esophageal manometry, including baseline lower esophageal sphincter (LES) pressures (Pre-transplantation: 12.5 mmHg, 95% CI: 9.5-16.0. Post transplant: 9.0, 95% CI: 5.0-12.9. p=0.13) and percent LES relaxation (Pre-transplant: 76%, 95% CI: 63-88. Post transplant: 70%, 95% CI: 58-83, p= 0.28) were observed between the two groups. Patients post-lung transplantation had a significantly increased total time spent in reflux over the 24 hour study period, as well as a significantly increased number of reflux episodes over five minutes (Table ). There was a trend towards an increase in the DeMeester score in patients post-lung transplantation. Conclusion: This hypothesis-generating study suggests that post-lung transplant patients have more prolonged reflux episodes and total time spent in reflux compared to pretransplant candidates, via a mechanism independent of altered esophageal motility.
Gastroenterology, 2013
Background: Gastroesophageal reflux (GER) and microaspiration of gastric contents has been propos... more Background: Gastroesophageal reflux (GER) and microaspiration of gastric contents has been proposed as an important mechanism in the pathogenesis of ventilator associated pneumonia (VAP) but properties of GER in patients receiving acid suppresive therapy in intensive care unit (ICU) and its effect on VAP and respiratory function in these patients is not elucidated. Aim: This study aims to assess the association between GER and VAP by defining the differences between VAP and non-VAP patients in ICU in terms of proximal extension and chemical properties of GER assessed by 24 hour combined esophageal intraluminal electrical impedance/pH measurements. We also aimed to study the association of impedance/pH values with respiratory function (PaO2/FiO2 ratio) and gastropulmonary microaspiration assessed by pepsin measurements in deep tracheal aspirates(DTA). Methods: 20 intubated patients on acid suppressive medication for stress ulcer prophylaxis in a neurological and medical ICU were included in this study. Patients who had pneumonia at the time of intubation or who were diagnosed with pneumonia during the first 48 hours after intubation were excluded. Pepsin measurements were made on DTA samples on the third day. Afterwards esophageal impedance/pHmetry catheters were placed and 24 hour recordings were analyzed. Patients were followed throughout their stay in ICU for VAP and daily PaO2/FiO2 ratios were recorded for one week. Impedance/pH values and pepsin levels were compared between VAP and nonVAP patients. Results: 8 patients were diagnosed with VAP. VAP patients had more proximal reflux compared to non-VAP patients (7(2-14) vs. 3,5(0-8))(p=0,003). Proximal weakly acidic reflux was again more common in VAP patients (4,5(2-9) vs 2(0-4)(p=0,006). Pepsin levels in DTA samples were correlated with the number of weakly acidic reflux episodes(r=0,615;p=0,004). Pepsin levels were also correlated with the number of proximal reflux episodes, especially with proximal weakly acidic reflux(r=0,489;p=0,029 ; r=0,651,p=0,002 ). PaO2/FiO2 ratios were negatively correlated with both pepsin levels and proximal weakly acidic reflux (r=-0,585,p=0,007 ; r=-0,620;p=0,004). Conclusion: Proximal extension of GER, especially proximal weakly acidic reflux is associated with microaspiration, VAP and worsening of respiratory function in intubated ICU patients on acid suppressive therapy.
Gastroenterology, 2013
Forty-six subjects had biopsy to "rule out EoE"; 29 (63%) of these had normal WEPM. The maximum e... more Forty-six subjects had biopsy to "rule out EoE"; 29 (63%) of these had normal WEPM. The maximum eos/hpf ranged between 1 and 75 with 19 patients having between 1-15 eos/hpf (mean ± sd: 4.5 ± 4.5) and 6 having .15 eos/hpf (mean ± sd: 41.3 ± 21.3). Of these, 2 patients, 4.3% (95% CI: 0.5, 14.8%) proved to have EoE and one had eosinophilic gastroenteritis with eosinophilic esophagitis. These 46 patients were significantly younger, more commonly female, more likely to have dysphagia, less likely to have abnormal EGD, BE, subepithelial tissue and lamina propia fibrosis than patients who had EB done for other reasons. Patients with abnormal WEPM were significantly more likely to have basal cell hyperplasia (57% vs. 23%; p=0.004). Abnormal histology was significantly more common in patients with abnormal WEPM than in those with normal WEPM (73% vs. 44%; p=0.011). Patients with abnormal histology were more likely to have heartburn and/or regurgitation than those with normal histology (p=0.019). CONCLUSION: Nearly 45% of patients with normal pH study have histologic findings that may affect patient management. EoE is an uncommon finding in patients undergoing WEPM for evaluation of atypical or refractory gastroesophageal reflux symptoms.
Gastroenterology, 2012
ROC for SI as predictor of PPI response. Error bars show standard error. ROC with crossvalidation... more ROC for SI as predictor of PPI response. Error bars show standard error. ROC with crossvalidation is black line, without cross-validation is gray line (~10% greater AUC). Development of a Mobile Phone Application to Diagnose GERD Jerry D. Gardner Introduction. Physicians typically base the diagnosis of GERD on medical history or a symptom-focused questionnaire. Sometimes, measurements of 24-hour esophageal pH are also used to confirm or exclude the diagnosis. Physicians, however, are often faced with two challenges. First, values for 24-hour esophageal pH above a particular cut-point, such as 5%, are defined as positive whereas values below this cut-point are defined as negative. Intuitively, however, physicians know that there is little clinical difference between values of 5.1% and 4.9%, even though only the former would be positive for GERD. Second, there is no convenient way for physicians to combine information from the medical history or questionnaire with the results from esophageal pH measurements to arrive at a diagnosis of GERD. Methods. Values for time pH<4 from 24-hour esophageal pH recordings from 26 healthy subjects, each of whom was studied twice, and 56 GERD subjects who experienced heartburn at least 4 times/week for at least 6 months were used to determine the sensitivity and specificity for GERD for each value of time esophageal pH<4 using receiver-operator characteristic (ROC) analysis. A nonlinear curve-fitting program (GraphPad Prism 5) was then used to develop equations that best fit the relationships between time esophageal pH<4 and sensitivity or specificity. Results. The area (95% CI) under the ROC curve was 0.90 (0.83, 0.97). The value of R2 for the equation for time esophageal pH<4 and sensitivity was 0.99 and for the equation for specificity was 0.98. The equations for sensitivity and specificity were then used to calculate the Bayesian Likelihood for any value of time esophageal pH<4. This Likelihood was used to calculate the posterior probability of GERD for any initial estimate that a patient might have GERD based on clinical history or a questionnaire. Finally, this process was incorporated into an application for a mobile phone. The application returns the probability that a patient actually has GERD after the user enters an initial estimate that the patient might have GERD based on clinical history followed by the value for time 24hour esophageal pH<4. Conclusion. A Bayesian model that employs information from a patient's clinical history plus the patient's 24-hour esophageal acid exposure can calculate the probability that a patient actually has GERD. This model has been incorporated into an application for mobile phone and will be available for demonstration.
Therapeutics and Clinical Risk Management, 2015
Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal tr... more Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal tract, meanly characterized by recurrent abdominal pain or discomfort and altered bowel habit. It is a complex disorder involving biological, environmental, and psychosocial factors. The diagnosis is achieved according to the Rome III criteria provided that organic causes have been excluded. Although IBS does not constitute a life-threatening condition, it has a remarkable prevalence and profoundly reduces the quality of life with burdening socioeconomic costs. One of the principal concerns about IBS is the lack of effective therapeutic options. Up to 40% of patients are not satisfied with any available medications, especially those suffering from chronic constipation. A correct management of IBS with constipation should evolve through a global approach focused on the patient, starting with careful history taking in order to assess the presence of organic diseases that might trigger the disorder. Therefore, the second step is to examine lifestyle, dietary habits, and psychological status. On these bases, a step-up management of disease is recommended: from fiber and bulking agents, to osmotic laxative drugs, to new molecules like lubiprostone and linaclotide. Although new promising tools for relief of bowel-movement-related symptoms are being discovered, a dedicated doctor-patient relationship still seems to be the key for success.
Gastroenterology, 2015
G12V mutation. There was no G12V mutation in both healthy serum controls and chronic pancreatitis... more G12V mutation. There was no G12V mutation in both healthy serum controls and chronic pancreatitis serum controls, although the rates of K-ras mutations in healthy and in chronic pancreatitis were 1/20 (5%) and 4/20 (20%), respectively. Conclusion: Analysis of ctDNA is a new useful procedure to detect genetic mutations in pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as to predict patients' survival.
Gastroenterology, 2015
test for H. pylori, 3. cardiothrombotic diseases, and 4. anticipated regular use of NSAIDs for th... more test for H. pylori, 3. cardiothrombotic diseases, and 4. anticipated regular use of NSAIDs for the duration of the trial. We excluded patients who used concomitant anticoagulants, had a history of gastroduodenal surgery other than a patch repair, gastric outlet obstruction, renal failure (serum creatinine level >200 µmol/L), pregnancy, terminal illness, or cancer. After providing written informed consent, all eligible patients received esomeprazole 20 mg once daily. They were randomized to receive either celecoxib 100 mg twice daily or naproxen 500 mg twice daily for up to 18 months. Patients were prescribed or asked to continue low-dose aspirin 80 mg once daily. The primary endpoint was recurrent ulcer bleeding within 18 months, which was defined as hematemesis, melena, or a decrease in the hemoglobin level of at least 2.0 g per deciliter with ulcers or bleeding erosions as adjudicated by an independent committee. Results: The intention-to treat population included 512 patients (256 celecoxib, 256 naproxen) who took at least one dose of study drug; 368 patients received concomitant low-dose aspirin (72.3% in the celecoxib group, 71.5% in the naproxen group). The demographic characteristics such as sex, age, type of arthritis, smoking, alcohol use, hemoglobin and creatinine levels were comparable between two groups. Fifteen patients (7.2%) receiving celecoxib and 31 (15.9%) receiving naproxen met the criteria for the primary endpoint (adjusted hazard ratio, 0.45; 95% CI, 0.26-0.84; p=0.01). Conclusion: Among patients with cardiothrombotic disease and a history of ulcer bleeding, combination of a COX-2 selective NSAID and a PPI is superior to a nonselective NSAID plus a PPI in preventing recurrent ulcer bleeding. Acknowledgment: This study was supported by a competitive grant from the Research Grant Council of Hong Kong (RGC project references: 460909 and 460910) Cumulative incidence of recurrent ulcer bleeding of naproxen+aspirin+esomeprazole (upper curve) vs. celecoxib+aspirin+esomeprazole (lower curve) p=0.01
Pharmacogenomics, 2015
Functional gastrointestinal disorders (FGIDs) are highly prevalent syndromes, without evident und... more Functional gastrointestinal disorders (FGIDs) are highly prevalent syndromes, without evident underlying organic causes. Their pathogenesis is multifactorial in nature, with a combination of environmental and genetic factors contributing to their clinical manifestations, for which most of current treatments are not satisfactory. It is acknowledged that amine mediators (noradrenaline, dopamine and serotonin) play pivotal regulatory actions on gut functions and visceral sensation. In addition, drugs of therapeutic interest for FGIDs act on these transmitter pathways. The present article reviews current knowledge on the impact of genetics and pharmacogenetics of aminergic pathways on FGID pathophysiology, clinical presentations, symptom severity and medical management, in an attempt of highlighting the most relevant evidence and point out issues that should be addressed in future investigations.
Gastroenterology, 2015
Background: In the last decade combined impedance-pH monitoring has become the gold standard for ... more Background: In the last decade combined impedance-pH monitoring has become the gold standard for the detection of reflux episodes with several studies demonstrating its increased diagnostic yield in gastro-esophageal reflux disease (GERD). This is mainly due to the capability of impedance-pH to correlate symptoms to both acid and non-acid reflux episodes. However, despite its large use in clinical practice, limited data about its clinical usefulness for the management of GERD patients are present. Aim&Methods: We aimed to assess whether patients with non-acid reflux disease (NARD) may benefit from anti-reflux surgery as those with erosive and non-erosive reflux disease (ERD and NERD). Consecutive refractory patients with heartburn and/or regurgitation lasting more than 6 months and with at least three episodes per week, were prospectively enrolled in this open label, multicenter trial. All patients underwent upper endoscopy and, within 3 days, manometry and impedance-pH testing off-therapy. We measured 24-hour distal esophageal acid exposure time (AET), characteristics of reflux episodes (acid/weakly acidic) and symptom-reflux association using both symptom association probability (SAP+ if ≥95%) and symptom index (SI+ if ≥50%). Then, patients with ERD (endoscopy+), NERD (endoscopy-, AET>4.2% and/or SAP/SI+ for acid reflux) and NARD (endoscopy-, AET<4.2% and SAP/SI+ for non-acid reflux or both kind of reflux) underwent laparoscopic fundoplication (LF). Before LF and at 1, 6 and 12 months after surgery patients were assessed by clinically validated questionnaires. Upper endoscopy, esophageal manometry, and impedance-pH monitoring was repeated at 1 year. Quality of life was also assessed. Results: Forty-eight refractory patients (24F/24M; mean age 49; 14 ERD, 22 NERD and 12 NARD) reporting at least 3 symptoms during the impedance-pH monitoring were included. Fundoplication had a similar effect in all groups, as shown in the Figure . At 1 year, esophageal AET and number of total, acid and non-acid refluxes significantly decreased after surgery (in all cases, p<0.01), whereas mean lower esophageal pressure increased (p<0.05). The percentage of patients with resolved or markedly improved typical symptoms at 12 months after surgery was similar among the groups (ERD 93% vs. NERD 82% vs NARD 83%, p=ns). Quality of life similarly improved in all groups (p=ns). Finally, the percentage of failure or adverse events did not differ among the groups (ERD 21% vs. NERD 23% vs NARD 17%, p=ns). Conclusion: Our data show that laparoscopic fundoplication was a safe and effective procedure in relieving typical reflux symptoms in patients with NARD as well as in patients with ERD and NERD, thus markedly improving their quality of life. Therefore, impedance-pH monitoring facilitated a more focused therapeutical approach to patients with PPI-resistant GERD.
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E, Jan 17, 2014
A wide variety of pieces of evidence has suggested that obesity is associated with a significant ... more A wide variety of pieces of evidence has suggested that obesity is associated with a significant increase in the risk for gastroesophageal reflux disease (GERD) symptoms and its complications. The aim of this study was to evaluate the effect of weight loss on reflux symptoms in overweight/obese patients with proven GERD. We enrolled overweight/obese patients with typical GERD symptoms and erosive esophagitis. At baseline, patients underwent detailed reflux symptoms evaluation and anthropometric assessment, and were divided into two treatment groups: group A received proton pump inhibitor (PPI) and a personalized hypocaloric diet and aerobic exercise; and group B received PPI and a 'standard of care diet'. The dietetic treatment was considered effective if at least 10% of weight loss was achieved within 6 months. All patients were evaluated in terms of anthropometric data, GERD symptoms, and PPI use. In group A, mean body mass index (BMI) decreased from 30.3 ± 4.1 to 25.7 ± 3...
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E, Jan 12, 2014
Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate h... more Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physi...
World journal of gastrointestinal pharmacology and therapeutics, Jan 6, 2014
Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of ga... more Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have...
Therapeutic advances in chronic disease, 2013
Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A l... more 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...
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Papers by Nicola de Bortoli