Fisiopatologia Digestiva

Modena, Italy

Fisiopatologia Digestiva

Modena, Italy

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Krarup A.L.,University of Aalborg | Liao D.,University of Aalborg | Gregersen H.,University of Aalborg | Drewes A.M.,University of Aalborg | And 7 more authors.
Annals of the New York Academy of Sciences | Year: 2013

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high-resolution manometry in noncardiac chest pain; whether pH-impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain. © 2013 New York Academy of Sciences.


Frazzoni M.,Fisiopatologia Digestiva | Conigliaro R.,Gastroenterologia | Mirante V.G.,Fisiopatologia Digestiva | Melotti G.,Chirurgia Generale
Neurogastroenterology and Motility | Year: 2012

Background By analysis of symptom-reflux association, endoscopy-negative refractory heartburn can be related to acid/non-acid refluxes with impedance-pH monitoring. Unfortunately, patients frequently do not report symptoms during the test. We aimed to assess the contribution of quantitative analysis of impedance-pH parameters added to symptom-reflux association in evaluating patients with endoscopy-negative heartburn refractory to high-dose proton pump inhibitor therapy. Methods The symptom association probability (SAP), the symptom index (SI), the esophageal acid exposure time and the number of distal and proximal refluxes were assessed at on-therapy impedance-pH monitoring. Relationships with hiatal hernia and manometric findings were also evaluated. Key Results Eighty patients were prospectively studied. Refractory heartburn was more frequently related to reflux by a positive SAP/SI and/or abnormal impedance-pH parameters (52/80 cases) (65%) than by a positive SAP/SI only (38/80 cases) (47%) (P=0.038). In patients with refractory non-erosive reflux disease (NERD) defined by a positive SAP/SI and/or abnormal impedance-pH parameters, the prevalence of hiatal hernia was significantly higher (56%vs 21%, P=0.007) and the mean lower esophageal sphincter tone was significantly lower (18.7 vs 25.8mmHg, P=0.005) than in those (35%) with reflux-unrelated, i.e., functional heartburn (FH). On the contrary, no significant difference was observed subdividing patients according to a positive SAP/SI only. Conclusions & Inferences Quantitative analysis of impedance-pH parameters added to symptom-reflux association allows a subdivision of refractory-heartburn patients into refractory NERD and FH which is substantiated by pathophysiological findings and which restricts the diagnosis of FH to one third of cases. © 2011 Blackwell Publishing Ltd.


Frazzoni M.,Fisiopatologia Digestiva | Conigliaro R.,Gastroenterologia | Manta R.,Gastroenterologia | Melotti G.,Chirurgia Generale
Alimentary Pharmacology and Therapeutics | Year: 2011

Aliment Pharmacol Ther 2011; 34: 67-75 Summary Background EsophyX is a novel transoral incisionless fundoplication device developed to mimic surgical fundoplication. EsophyX fundoplication improves acid reflux parameters in proton pump inhibitor (PPI)-responsive GERD patients but its efficacy in refractory GERD has been scarcely studied. Aim To assess reflux parameters before and after EsophyX or laparoscopic fundoplication and their relationship with symptoms in refractory GERD. Methods In an open-label study, we enrolled prospectively patients with heartburn/regurgitation persisting despite high-dose PPI therapy. Impedance-pH monitoring was performed on PPI therapy before intervention and off PPI therapy 3 months after intervention. Results Ten patients chose to undergo EsophyX (EndoGastric Solutions, Redmond, WA, USA) fundoplication while ten chose laparoscopic fundoplication, and the baseline characteristics were comparable. Distal and proximal refluxes were significantly reduced post-operatively in the surgical but not in the endoscopic group and the median values were significantly lower in the former than in the latter. The oesophageal acid exposure time was normal in 50% of cases after EsophyX and in 100% of cases after surgery (P = 0.033); the number of distal refluxes was normal in 20% and 90% of cases (P = 0.005) and the number of proximal refluxes was normal in 40% and 100% of cases (P = 0.011), respectively. A positive persisting symptom-reflux association was found post-operatively in 6/10 patients in the EsophyX group and in 0/10 patients in the surgical group (P = 0.011). Conclusions In patients with refractory GERD, EsophyX fundoplication is significantly less effective than laparoscopic fundoplication in improving reflux parameters and accordingly, in inducing symptom remission. © 2011 Blackwell Publishing Ltd.


Frazzoni M.,Fisiopatologia Digestiva | Conigliaro R.,Gastroenterologia | Melotti G.,Chirurgia Generale
Digestive Diseases and Sciences | Year: 2011

Background: Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied. Aims: The aim of this study was to assess reflux parameters and their relationship with symptoms before and after laparoscopic fundoplication, on and off PPI therapy, respectively, in patients with PPI-unresponsive heartburn/regurgitation and with a positive symptom-reflux association and/or abnormal reflux parameters detected on PPI therapy. Methods: Impedance-pH monitoring was performed on high-dose PPI therapy and 3 months after laparoscopic fundoplication, off PPI therapy, in 40 patients with PPI-unresponsive heartburn/regurgitation. Symptoms were scored by a validated questionnaire. Results: Esophageal acid exposure time as well as the number of total and proximal reflux events and of acid and weakly acidic refluxes decreased significantly after surgery: normal values were found in 100, 77, 95, 92 and 65% of cases, respectively. Weakly alkaline refluxes increased significantly postoperatively but neither before nor after intervention were associated with symptoms. All patients reported total/subtotal remission of heartburn/regurgitation 3 months after surgery. Conclusions: Laparoscopic fundoplication improves acid and weakly acidic reflux parameters when compared with PPI therapy. This improvement justifies the very high post-surgical symptom remission rate that we observed. Prolonged follow-up is warranted but our findings strongly support the surgical option in PPI failures. © 2010 Springer Science+Business Media, LLC.


Frazzoni M.,Fisiopatologia Digestiva | Conigliaro R.,Gastroenterologia | Melotti G.,Chirurgia Generale
Alimentary Pharmacology and Therapeutics | Year: 2011

Background In patients with heartburn that persists despite proton pump inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its pathogenesis has been scarcely studied. Aim To assess reflux parameters by impedance-pH monitoring in PPI-resistant reflux oesophagitis. Methods Impedance-pH monitoring was performed on PPI therapy in patients with symptomatic reflux oesophagitis detected despite standard or high-dose PPI therapy of at least 8-week duration. Results Twenty patients, ten on once daily and ten on twice daily PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4) ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid exposure time (per cent time pH <4) was abnormal in 20% of patients only. The number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%, 100% and 15% of patients, respectively. Conclusions Weakly acidic refluxes were above the normal range in all cases, whereas acid reflux parameters and weakly alkaline refluxes were normal in the vast majority of cases. Gastric acid secretion, with consequent intra-gastric pepsins activation, persists despite ongoing PPI therapy and activated pepsins may well be present in weakly acidic refluxes. As activated pepsins maintain their proteolytic activity in a weakly acidic environment, they may be responsible for mucosal damage. We conclude that weakly acidic refluxes have a major role in the pathogenesis of PPI-resistant reflux oesophagitis. Therapeutic interventions in patients with PPI-resistant reflux oesophagitis should be tailored on the basis of impedance-pH-monitoring results. © 2010 Blackwell Publishing Ltd.


Bertani H.,Endoscopia Digestiva | Frazzoni M.,Fisiopatologia Digestiva | Dabizzi E.,Endoscopia Digestiva | Pigo F.,Endoscopia Digestiva | And 5 more authors.
Digestive Diseases and Sciences | Year: 2013

Background: Probe-based confocal laser endomicroscopy (pCLE) is a new technique allowing in vivo detection of neoplastic tissue using a standard endoscope. Aims: Our aim was to compare the incident dysplasia detection rate of biopsies obtained by high-definition white light endoscopy (HD-WLE) or by pCLE in a cohort of patients with Barrett's esophagus (BE) participating in a surveillance program. Methods: Fifty of 100 patients underwent pCLE in addition to HD-WLE. Four-quadrant biopsy specimens according to the Seattle biopsy protocol were obtained in all patients to ensure standard-of-care. Diagnosis of dysplasia/neoplasia was made by a blinded gastrointestinal pathologist. Results: Incident high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were diagnosed in 3/100 and in 16/100 cases. In the HD-WLE group, areas suspicious for neoplasia were not observed and dysplasia was diagnosed in 5/50 (10 %) patients (one with HGD). In the pCLE group, areas suspicious for neoplasia were observed by pCLE in 21/50 (42 %) patients; dysplasia was confirmed in 14 cases (28 %) (two with HGD). The dysplasia detection rate was significantly higher in the pCLE group than in the HD-WLE group (P = 0.04). The sensitivity, specificity, positive and negative predictive values of pCLE for dysplasia were 100, 83, 67, and 100 %, respectively. Conclusions: Incident dysplasia can be more frequently detected by pCLE than by HD-WLE in BE. The higher dysplasia detection rate provided by pCLE could improve the efficacy of BE surveillance programs. © 2012 Springer Science+Business Media, LLC.


Frazzoni M.,Fisiopatologia Digestiva | Conigliaro R.,Endoscopia Digestiva | Colli G.,Chirurgia Generale | Melotti G.,Chirurgia Generale
Surgical Endoscopy and Other Interventional Techniques | Year: 2012

Background Laparoscopic Nissen fundoplication (LNF) is a technically demanding surgical procedure designed to cure gastroesophageal reflux disease (GERD). It represents an alternative to life-long medical therapy and the only recommended treatment modality to overcome refractoriness to proton pump inhibitor (PPI) therapy. The recent development of robotic systems prompted evaluation of their use in antireflux surgery. Between 1997 and 2000, in a PPI-responsive series we found postoperative normalization of esophageal acid exposure time (EAET) in most but not all cases. Between 2007 and 2009, in a PPI-refractory series we found postoperative normalization of EAET in all cases. We decided to analyze retrospectively our prospectively collected data to evaluate whether differences other than the conventional or robot-assisted technique could justify postoperative differences in acid reflux parameters. Methods Baseline demographic, endoscopic, and manometric parameters were compared between the two series of patients, as well as postoperative manometric and acid reflux parameters. Results There were no significant differences in the baseline demographic, endoscopic, and manometric characteristics between the two groups of patients. The median lower esophageal sphincter tone increased significantly, and the median EAET decreased significantly after conventional as well as after robot-assisted LNF. The median postoperative EAET was significantly lower in the robot-assisted (0.2%) than in the conventional LNF group (1%; P = 0.001). Abnormal EAET values were found in 6 of 44 (14%) and in 0 of 44 cases after conventional and robot-assisted LNF, respectively (P = 0.026). Conclusions Robot-assisted LNF provided a significant gain in postoperative acid reflux parameters compared with the conventional technique. In a challenging clinical setting, such as PPI-refractoriness, inwhich the efficacy of endoscopic or pharmacological treatment modalities is only moderate, even a small therapeutic gain can be clinically relevant. In centers where robot-assisted LNF is available, it should be preferred to conventional LNF in PPI-refractory GERD. © 2011 Springer Science+Business Media, LLC.


Manta R.,Gastroenterologia Ed Endoscopia Digestiva | Frazzoni M.,Fisiopatologia Digestiva | Conigliaro R.,Gastroenterologia Ed Endoscopia Digestiva | Maccio L.,University of Modena and Reggio Emilia | And 7 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2013

Background: SpyGlass® single-operator peroral cholangioscopy appears to be a promising technique to overcome some limitations of conventional peroral cholangioscopy. We aimed to prospectively evaluate the SpyGlass system in a cohort of patients with indeterminate biliary lesions. Methods: Patients with indeterminate strictures or filling defects at endoscopic retrograde cholangiopancreatography (ERCP) were consecutively enrolled. After SpyGlass visual evaluation, targeted biopsies were taken with the SpyBite ® and histopathological assessment was made by two experienced gastrointestinal pathologists. SpyBite-targeted biopsy results were evaluated by assessing agreement with surgical specimens and by evaluation of final, clinical follow-up-based diagnosis. Results: Fifty-two patients participated in the study. In 7 cases, definite diagnosis (stones, varices) was made by SpyGlass endoscopic evaluation. In 42 of the remaining 45 cases, material suitable for histopathology assessment was provided by the SpyBite. Overall, a definite diagnosis was made in 49 (7 + 42; 94 %) cases. Agreement of SpyBite biopsy results with surgical specimen diagnosis was found in 38/42 (90 %) cases; sensitivity, specificity, and positive and negative predictive values were 88, 94, 96, and 85 %, respectively. Procedure-related complications consisted of one case of mild cholangitis and one case of mild pancreatitis. Conclusions: In our series, the SpyGlass system allowed adequate biopsy sampling and definite diagnosis with high accuracy in the vast majority of patients with indeterminate biliary lesions. Its use was associated with a low complication rate. Further refinements of the technique are warranted, but the SpyGlass system has the potential to become a diagnostic standard for the assessment of indeterminate biliary lesions. © 2012 Springer Science+Business Media New York.


Frazzoni M.,Fisiopatologia Digestiva | Manta R.,Endoscopia Digestiva | Mirante V.G.,Endoscopia Digestiva | Conigliaro R.,Endoscopia Digestiva | And 2 more authors.
Neurogastroenterology and Motility | Year: 2013

Background: Impedance-pH monitoring allows assessment of retrograde and antegrade intra-esophageal movement of fluids and gas. Reflux is followed by volume clearance and chemical clearance, elicited by secondary and swallow-induced peristalsis, respectively. We aimed to assess whether chemical clearance is impaired in gastro-esophageal reflux disease (GERD). Methods: Blinded retrospective review of impedance-pH tracings from patients with erosive reflux disease (ERD) and non-erosive reflux disease (NERD), and from proton pump inhibitor (PPI)-refractory patients before and after laparoscopic fundoplication. The number of refluxes followed within 30 s by swallow-induced peristaltic waves was divided by the number of total refluxes to obtain a parameter representing chemical clearance namely the postreflux swallow-induced peristaltic wave (PSPW) index. Key Results: The PSPW index was significantly lower in 31 ERD (15%) and in 44 NERD (33%) off-PPI patients than in 30 controls (75%), as well as in 18 ERD (16%) and in 48 NERD (31%) on-PPI patients than in 26 on-PPI functional heartburn (FH) cases (67%) (P < 0.05 for all comparisons). In 29 PPI-refractory patients, the median PSPW index was unaltered by otherwise effective antireflux surgery (20% postoperatively, 21% preoperatively). The overall sensitivity, specificity, positive, and negative predictive values of the PSPW index in identifying GERD patients were 97%, 89%, 96%, and 93%. Conclusions & Inferences: Impairment of chemical clearance is a primary pathophysiological mechanism specific to GERD: it is unaffected by medical/surgical therapy, is not found in FH, and is more pronounced in ERD than in NERD. Using the PSPW index could improve the diagnostic efficacy of impedance-pH monitoring. © 2013 Blackwell Publishing Ltd.


Frazzoni M.,Fisiopatologia Digestiva | Piccoli M.,Chirurgia Generale | Conigliaro R.,Endoscopia Digestiva | Manta R.,Endoscopia Digestiva | And 2 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2013

Background: Some patients with typical (heartburn/regurgitation) symptoms of gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) therapy. Impedance-pH monitoring can identify PPI-refractory patients who could benefit from laparoscopic fundoplication, but outcome data are scarce. We aimed to assess whether PPI-refractory GERD as diagnosed by impedance-pH monitoring can be cured by laparoscopic fundoplication. Methods: Forty-four consecutive GERD patients with heartburn/regurgitation refractory to high-dose PPI therapy entered a 3-year outcome assessment following robot-assisted laparoscopic fundoplication. Preoperative on-PPI impedance-pH diagnostic criteria consisted of positive symptom association probability (SAP)/symptom index (SI), and/or abnormal percentage esophageal acid exposure time (%EAET), and/or abnormal number of total refluxes. GERD cure was defined by 3-year postoperative off-PPI normal impedance-pH findings with persistent symptom remission. Results: Preoperatively, 24 of 38 (63 %) patients who completed the outcome assessment had a positive SAP/SI, 20 of 38 (53 %) for weakly acidic refluxes; 3 of 38 (8 %) patients had an abnormal %EAET, 11 of 38 (29 %) an abnormal number of total refluxes only. Postoperatively, heartburn/regurgitation recurred in 3 patients; abnormal impedance-pH findings were found in two of them, and they responded to PPI therapy. GERD cure was achieved in 34 of 38 (89 %) patients, 11 of 11 with an abnormal number of total refluxes as the only preoperative abnormal impedance-pH finding. Postoperatively, there was a significant decrease of the %EAET (1 vs. 0.1 %, P = 0.002) and of the number of total refluxes (68 vs. 8, P = 0.001), with the latter finding mainly due to a decrease in the number of weakly acidic refluxes. Conclusions: Normal reflux parameters and persistent symptom remission at 3-year follow-up can be achieved with laparoscopic fundoplication in the majority of patients with PPI-refractory GERD as diagnosed by impedance-pH monitoring. On-PPI impedance-pH diagnostic criteria should include SAP/SI positivity, an abnormal %EAET, and an abnormal number of total refluxes. Weakly acidic refluxes have a major role in the pathogenesis of PPI-refractory GERD. © 2013 Springer Science+Business Media New York.

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