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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.

Duodenal ulcer due to cytomegalovirus (CMV) is quite infrequent in the inmunocompetent patient. We present an elderly patient with a history of upper urinary infections who was admitted at the hospital because of tarry black stool and coffee ground vomits. Endoscopy revealed duodenal ulcer and the histopathology confirm CMV infection. The workout was negative for human immunodeficient virus (HIV), HTLV-1 and occult cancer. The patient developed a serious infection and died due to urinary septic shock. Key words : Duodenal ulcer, cytomegalovirus, upper gastrointestinal bleeding, immunocompetent.

Perez-Torras S.,University of Barcelona | Perez-Torras S.,Research Center En Red Of Enfermedades Hepaticas gestivas Ciberehd | Vidal-Pla A.,University of Barcelona | Miquel R.,Serveis de Patologia | And 12 more authors.
Cellular Oncology | Year: 2011

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses. © International Society for Cellular Oncology 2011.

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.

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