Publications by authors named "Patrizia Zentilin"

72 Publications

Correlation Between Skin and Affected Organs in 52 Sclerodermic Patients Followed in a Diseases Management Team: Development of a Risk Prediction Model of Organ-Specific Complications.

Front Immunol 2021 2;12:588753. Epub 2021 Jun 2.

Dermatologic Unit, University of Genoa, DiSSal, Ospedale-Policlinico San Martino, IRCCS, Genova, Italy.

Objective: To identify the existence of a correlation among the various organs affected, focusing primarily on immuno-dermatological aspects, and to create a risk prediction model of organ-specific complications.

Material And Methods: Fifty-two patients with stable scleroderma, followed between 2015 and 2019, were investigated through an extensive multidisciplinary evaluation in the last year.

Results: Patients with lung involvement presented a worse degree of skin fibrosis than patients without it (p <0.001). No relationship was observed for the heart, kidney, and esophagus. Patients with pulmonary involvement had a lower pressure of the low esophagus sphincter and a higher Warrick score than patients without it (p <0.05). Age was significantly higher in patients with kidney involvement. Diffuse scleroderma patients had a worse pulmonary impairment than limited scleroderma patients (p <0.05). The manometric "sclerodermic" pattern was observed to be the most frequent (55.6%, p <0.05) in dcSSc patients while the sclerodermic and normal pattern were equally represented (41.2 and 32.4% respectively, p <0.05) in lcSSc patients. When compared to the negative serological groups, anti-Scl-70 positive patients presented a worse lung involvement while anti-centromere patients presented a better lung outcome (p <0.05). PM-Scl 100/75 positive patients presented mostly a pulmonary fibrotic pattern (p <0.05) and, also, heart complications were more likely associated with anti PM-Scl 100/75 positivity (p <0.05). The risk prediction model for organ-specific complications had an accuracy of 84.4% (95%CI 78, 89) in complication-site prediction, AUC of 0.871, 86% of sensitivity, and 83% of specificity, Cohen's Kappa (k) of 0.68.

Conclusions: Out of all the organs studied, the skin is the one that correlates with the lung. Patients with a diffuse form of disease presented more frequently the anti Scl-70 antibody and had a worse lung and esophageal involvement (scleroderma pattern) than the negative group. Conversely, patients with limited disease presented all positive for the anti-centromere antibody with a better lung involvement than the negative group, without any difference among the esophageal manometric pattern. Anti PM-Scl 100/75 antibody patients were associated with pulmonary fibrosis and presented cardiac involvement. The model created has demonstrated excellent values of sensitivity, specificity, and accuracy, but further studies are needed for validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.588753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207468PMC
June 2021

Prevention Strategies for Esophageal Cancer-An Expert Review.

Cancers (Basel) 2021 May 1;13(9). Epub 2021 May 1.

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.

In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125297PMC
May 2021

Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art.

Drug Des Devel Ther 2021 19;15:1609-1621. Epub 2021 Apr 19.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.

Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic disorder, whose knowledge remains limited and the management of these patients changes continuously. This review provides a summary of the most recent advancements in the pathogenesis of this disease and the new drugs introduced into the market to overcome some of the unmet needs of traditional therapies. Nowadays, the most fruitful diagnostic examinations are 24-hour impedance-pH monitoring, which allows us to separate true NERD from esophageal functional disorders and high-resolution manometry, which helps to exclude the existence of motility disorders sharing the same symptoms of GERD. Proton pump inhibitors (PPIs) remain the first-choice therapy in the treatment of GERD, but a consistent proportion of these patients continue to experience symptoms despite their intake. These cases pertain mainly to the subpopulation with non-erosive reflux disease (NERD) and represent very challenging clinical situations, because it is mandatory to understand the reasons for PPI failure. The management of these difficult patients requires necessarily to test them and avoid the use of empiric treatments that are often unsuccessful, costly and potentially dangerous. Recently, several new drugs have been used to increase the defensive properties of this mucosa with promising results in randomized clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S306371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064680PMC
April 2021

Nuts and Non-Alcoholic Fatty Liver Disease: Are Nuts Safe for Patients with Fatty Liver Disease?

Nutrients 2020 Nov 1;12(11). Epub 2020 Nov 1.

Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy.

Diet and lifestyle interventions are the recommended treatment for patients with non-alcoholic fatty liver disease (NAFLD), with the aim of achieving a 7-10% weight loss. Several dietary patterns have been suggested for this purpose, however, to date, the best one is represented by the Mediterranean diet (MD) as it is rich in macro- and micro- nutrients known for their effectiveness in health-promotion and cardio-vascular disease prevention. Moreover, MD is characterized by the inclusion of nuts. These foods have shown potential benefits in health-promotion as they are rich in fibers, which have lipid-lowering effects, rich in mono- and poly-unsaturated fatty acids, which help reduce insulin-resistance and serum cholesterol, and contain anti-oxidants which reduce oxidative stress and inflammation. Additionally, nuts are associated with a better control, or reduction, of Body Mass Index (BMI). All these effects are useful targets to achieve in NAFLD, so that nuts have been proposed as a suitable dietary treatment supplement for weight and metabolic control in these patients. In recent years, health authorities raised an alert on nuts consumption as these may be at high risk of aflatoxin (AF) contamination, for which controls and legislations are different among countries. AF is a well-known cancerogenic agent and a recognized risk factor for hepatocellular carcinoma. Patients with NAFLD have an overall, inherent sevenfold increased risk of developing hepatocellular carcinoma as compared with the general population. In this context, one could argue that recommending the inclusion of nuts in the diet of NAFLD patients has to be balanced with the risk of potential chronic exposure to AF, and every effort should be pursued to assure the safety of these nutrients. In this review, we aim to summarize the benefits of nuts consumption, the evidence for AF contamination of nuts and the consequent potential risks in patients with NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12113363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693493PMC
November 2020

Esophageal reflux hypersensitivity: Non-GERD or still GERD?

Dig Liver Dis 2020 12 21;52(12):1413-1420. Epub 2020 Oct 21.

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. Electronic address:

The most recent iteration of the classifications for functional esophageal disorders, Rome IV, proposed relevant modifications of the previous definitions for Rome III. They specifically considered increased esophageal acid exposure as the marker of gastroesophageal reflux disease (GERD), including the remaining part of non-erosive reflux disease patients with normal acid in the group with functional alterations, considering both reflux hypersensitivity and functional heartburn. However, recent pathophysiological and therapeutic data suggest the need for a return to including reflux hypersensitivity in the GERD spectrum. Indeed, physiologic alterations in esophageal mucosal integrity and chemical clearance, the presence of microscopic esophagitis, and strict symptom-reflux association support the concept that reflux hypersensitivity pertains to GERD. Surgical anti-reflux therapy has resulted in positive outcomes, even in the long term, in patients with reflux hypersensitivity and not in those with functional heartburn. Moreover, clinical trials using neuromodulators have been scarce and provided conflicting results. As a result, the real progress of the Rome IV classifications is in dispute. This article aims to summarize the most recent knowledge of non-erosive reflux disease and reflux hypersensitivity to discuss the utility of Rome IV criteria in the identification and management of functional esophageal disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.10.003DOI Listing
December 2020

Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients With Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol 2021 Aug 4;19(8):1554-1563. Epub 2020 Aug 4.

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. Electronic address:

Background: An association has been reported between achalasia and eosinophilic esophagitis (EoE). We performed a retrospective study of high-resolution manometry (HRM) patterns in a large cohort of patients with EoE.

Material And Methods: We collected data from consecutive patients with a new diagnosis of EoE from 2012 through 2019 undergoing HRM during the initial assessment at different centers in Italy. Demographic, clinical, endoscopic and histological characteristics were recorded at baseline and during management. Diagnoses of EoE and esophageal motility disorders were made according to established criteria. Treatments offered included proton pump inhibitors and topical steroids for EoE, and pneumatic dilation and myotomy for achalasia. Response to therapy was defined as less than 15 eosinophils per high power field in esophageal biopsies.

Results: Of 109 consecutive patients (mean age 37 years, 82 male), 68 (62%) had normal findings from HRM. Among 41 patients with motor disorders, 24 (59%) had minor motor disorders and 17 (41%) presented with major motor disorders, including 8 with achalasia (1 with type 1, 4 with type 2, and 3 with type 3). Achalasia and nonachalasia obstructive motor disorders had 14.7% prevalence among patients with EoE. Achalasia was more frequent in women, with longer diagnostic delay and abnormal esophagogram (P < .05) compared with EoE without achalasia or obstructive motor disorders. Clinical features and endoscopic findings did not differ significantly between patients with EoE with vs without achalasia and obstructive motor disorders. A higher proportion of patients without achalasia and obstructive motor disorders responded to topical steroids than patients with these features (P < .005). Invasive achalasia management was required for symptom relief in 50% of patients with achalasia and obstructive motor disorders.

Conclusion: Achalasia and obstructive motor disorders are found in almost 15% of patients with EoE, and esophageal eosinophilia might cause these disorders. Patients with EoE who do not respond to standard treatments might require targeted muscle disruption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2020.07.056DOI Listing
August 2021

A SIGE-SINGEM-AIGO technical review on the clinical use of esophageal reflux monitoring.

Dig Liver Dis 2020 09 6;52(9):966-980. Epub 2020 Jun 6.

Gastrointestinal Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Patients with esophageal symptoms potentially associated with gastroesophageal reflux disease such as heartburn, regurgitation, chest pain, or cough represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal reflux monitoring in clinical practice is: (1) to accurately define reflux burden, (2) to segregate patients according to reflux monitoring results as true GERD, reflux hypersensitivity and functional heartburn, and (3) to establish a treatment plan. With this in mind, in the last decade, investigations and technical advances, with the introduction of impedance-pH monitoring and wireless pH capsule, have enhanced our understanding and management of GERD. The following recommendations were discussed and approved after a comprehensive review of the medical literature pertaining to reflux testing techniques and their recent application. This review created under the auspices of the Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE), Società Italiana di Neuro-Gastro-Enterologia e Motilità (SINGEM) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying reflux studies in the most fruitful manner within the context of their patients with esophageal symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.04.031DOI Listing
September 2020

Latest insights into the hot question of proton pump inhibitor safety - a narrative review.

Dig Liver Dis 2020 08 6;52(8):842-852. Epub 2020 Jun 6.

Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide and their use is continuously increasing. Although they have been shown to combine high therapeutic efficacy and good safety profile in many studies, in last years we have witnessed the publication of many articles reporting the possible association of long-term PPI therapy with important unexpected adverse events and these observations have created alarmism in both patients and physicians. However, the majority of these studies are observational, retrospective and prone to residual confounding. Also, the odds ratio values are generally comprised between 1 and 2 and therefore devoid of strong clinical relevance. As it is unlikely that prospective randomized trials will be ever done to reinforce these associations, we can only attempt to distinguish clear- from unclear-defined adverse events from the available literature. Nowadays we can reasonably exclude cardiovascular diseases, community-acquired pneumonia, all-cause mortality, dementia and bone fractures from PPI-related adverse events. However, physicians should be aware of the existence of possible risks when treating their patients, especially the elderly and frail ones, with long-term PPIs, which should be prescribed only to persons with defined indications and at lowest dose and duration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.04.020DOI Listing
August 2020

Appropriateness of proton pump inhibitors treatment in clinical practice: Prospective evaluation in outpatients and perspective assessment of drug optimisation.

Dig Liver Dis 2020 08 3;52(8):862-868. Epub 2020 Jun 3.

Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy.

Background: High rates of inappropriate proton pump inhibitor (PPI) prescriptions have been reported in retrospective database analyses. Assessing the appropriateness of long-term PPIs in outpatients, with a proactive approach at drug optimisation may enhance treatment adequacy.

Aims: To describe the characteristics of outpatients who are on long-term PPIs, to assess the magnitude of inappropriate PPI prescriptions, and to evaluate the rate of drug optimisation following specialist recommendations.

Methods: Appropriateness of long-term (>8weeks) PPI prescription was prospectively assessed in 249 consecutive patients referred to a Gastroenterology outpatient clinic. We recorded reason for prescription, dose, modality, duration of therapy, and attempts at PPI optimisation.

Results: PPIs were inappropriately prescribed in 96/249 patients (38.6%). Gastro-oesophageal reflux disease (50/143, 35.0%) and prophylaxis of anti-platelet/non-steroidal anti-inflammatory drugs (5/49, 10.2%) were the most common PPI indications and those with the lowest rate of inappropriateness, while the highest rates were observed for treatment of dyspepsia (10/12, 83.3%) and anti-coagulant therapy (21/21, 100%). PPI treatment was optimised in 112 patients (45.0%).

Conclusions: PPIs are inappropriately used in about 40% of outpatients, reflecting scant attention to guidelines. A proactive approach may improve therapeutic adequacy in approximately half of patients. Educational efforts to guide PPI prescription should be further pursued.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.05.005DOI Listing
August 2020

Surveillance for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease: Universal or Selective?

Cancers (Basel) 2020 May 31;12(6). Epub 2020 May 31.

Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy.

Hepatocellular carcinoma (HCC), the most frequent primary liver cancer, is the sixth most common cancer, the fourth leading cause of cancer-related deaths worldwide, and accounts globally for about 800,000 deaths/year. Early detection of HCC is of pivotal importance as it is associated with improved survival and the ability to apply curative treatments. Chronic liver diseases, and in particular cirrhosis, are the main risk factors for HCC, but the etiology of liver disease is rapidly changing due to improvements in the prevention and treatment of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) infections and to the rising incidence of the metabolic syndrome, of which non-alcoholic fatty liver (NAFLD) is a manifestation. NAFLD is now a recognized and rapidly increasing cause of cirrhosis and HCC. Indeed, the most recent guidelines for NAFLD management recommend screening for HCC in patients with established cirrhosis. Screening in NAFLD patients without cirrhosis is not recommended; however, the prevalence of HCC in this group of NAFLD patients has been reported to be as high as 38%, a proportion significantly higher than the one observed in the general population and in non-cirrhotic subjects with other causes of liver disease. Unfortunately, solid data regarding the risk stratification of patients with non-cirrhotic NAFLD who might best benefit from HCC surveillance are scarce, and specific recommendations in this field are urgently needed due to the increasing NAFLD epidemic, at least in Western countries. To further complicate matters, liver ultrasonography, which represents the current standard for HCC surveillance, has a decreased diagnostic accuracy in patients with NAFLD, and therefore disease-specific surveillance tools will be required for the early identification of HCC in this population. In this review, we summarize the most recent evidence on the epidemiology and risk factors for HCC in patients with NAFLD, with and without cirrhosis, and the evidence supporting surveillance for early HCC detection in these patients, reviewing the potential limitations of currently recommended surveillance strategies, and assessing data on the accuracy of potential new screening tools. At this stage it is difficult to propose general recommendations, and best clinical judgement should be exercised, based on the profile of risk factors specific to each patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12061422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352281PMC
May 2020

Risk factors for bleeding following oesophageal band ligation: Providing further evidence to ameliorate clinical practice.

Dig Liver Dis 2020 07 8;52(7):792-793. Epub 2020 May 8.

Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, Viale Benedetto XV, no.6, 16132 Genoa, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.04.007DOI Listing
July 2020

Vonoprazan Fumarate for the Treatment of Gastric Ulcers: A Short Review on Emerging Data.

Clin Exp Gastroenterol 2020 15;13:99-104. Epub 2020 Apr 15.

Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Potassium-competitive acid blockers (P-CABs), such as vonoprazan, represent a novel and heterogeneous class of drugs that competitively block the potassium binding site of gastric H/K ATPase, thus potentially overcoming the limitations of proton-pump inhibitors. Different studies evaluated the efficacy of vonoprazan versus proton-pump inhibitors (PPIs) for the treatment of acid-related disorders, and, therefore, P-CABs present the same indications of PPIs: gastroesophageal reflux disease, gastric and duodenal ulcer healing, management of upper gastrointestinal bleeding, non-steroidal anti-inflammatory drug (NSAID)-associated ulcers and eradication therapy. The aim of this review was to evaluate the role of vonoprazan for the treatment of peptic ulcer disease (PUD) and the management of gastric ulcer occurring after endoscopic submucosal dissection (ESD). Indeed, vonoprazan (at the dose of both 10 and 20mg) showed similar results to PPIs in patients taking long-term NSAIDs, in the absence of severe adverse effects, and provided a more rapid and effective treatment of ulcers induced by ESD. However, studies in medical literature are heterogeneous, mainly performed with a retrospective design, and often carried out in Japan only. For these reasons, further prospective, randomized studies are warranted in order to help physicians, patients, and policymakers regarding the use of vonoprazan in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CEG.S228352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169470PMC
April 2020

Pathophysiology, diagnosis, and pharmacological treatment of gastro-esophageal reflux disease.

Expert Rev Clin Pharmacol 2020 Apr 17;13(4):437-449. Epub 2020 Apr 17.

Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua, Italy.

Introduction: Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic, relapsing disorder, whose knowledge has increased in last years thanks to the advent of new sophisticated techniques, such as 24-h impedance-pH monitoring and high-resolution manometry, for the study of esophageal functions.

Areas Covered: This review provides an overview of our advancements in understanding the complex pathophysiology, improving the diagnosis and defining the modern pharmacological therapeutic approach to GERD.

Expert Opinion: The growing clinical application of impedance-pH testing has allowed us to know the diversity of patients with non-erosive reflux disease (NERD), who nowadays represent about 70% of the whole population with reflux symptoms. We have realized that NERD has to be considered as an umbrella term covering various subgroups with different pathophysiologies. The development of new impedance metrics, in particular mean nocturnal baseline impedance, seems to be promising in the improvement of the diagnostic process of this disease. There are no particularly innovative features in the pharmacological therapy of GERD, unless the interest toward drugs is able to increase the defense properties of esophageal mucosa and/or its protection. These compounds can be of help in combination with proton pump inhibitors in NERD patients with partial response to antisecretory drugs alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17512433.2020.1752664DOI Listing
April 2020

Updates in the field of non-esophageal gastroesophageal reflux disorder.

Expert Rev Gastroenterol Hepatol 2019 Sep 22;13(9):827-838. Epub 2019 Jul 22.

Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy.

: Gastroesophageal reflux disease (GERD) is one of the most prevalent conditions in Western Countries, normally presenting with heartburn and regurgitation. Extra-esophageal (EE) GERD manifestations, such as asthma, laryngitis, chronic cough and dental erosion, represent the most challenging aspects from diagnostic and therapeutic points of view because of their multifactorial pathogenesis and low response to proton pump inhibitors (PPIs). In fact, in the case of EE, other causes must by preventively excluded, but instrumental methods, such as upper gastrointestinal endoscopy and laryngoscopy, have low specificity and sensitivity as diagnostic tools. In the absence of alarm signs and symptoms, empirical therapy with a double-dose of PPIs is recommended as a first diagnostic approach. Subsequently, impedance-pH monitoring could help to define whether the symptoms are GERD-related. : This article reviews the current literature regarding established and proposed EE-GERD, reporting on all available options for its correct diagnosis and therapeutic management. : MII-pH could help to identify a hidden GERD that causes EE. Unfortunately, standard MII-pH analysis results are often unable to define this association. New parameters such as the mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index may have an improved diagnostic yield, but prospective studies using impedance-pH are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17474124.2019.1645593DOI Listing
September 2019

The prevention of NSAID-induced gastric ulcers is a firmly established PPI indication.

Expert Rev Clin Pharmacol 2019 11 17;12(11):1011-1012. Epub 2019 Jul 17.

Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Padova, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17512433.2019.1643199DOI Listing
November 2019

Advancements in the use of manometry and impedance testing for esophageal functional disorders.

Expert Rev Gastroenterol Hepatol 2019 May 21;13(5):425-435. Epub 2019 Mar 21.

b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy.

Introduction: The utilization of high-resolution manometry (HRM) has enhanced our understanding and assessment of esophageal motor disorders. Moreover, the combination of impedance technology with HRM (HRIM) has further improved our knowledge of esophageal physiology and the clinical evaluation of dysmotility, thanks to the addition of accurate measurement of bolus transit. Areas covered. This paper provides an overview of current knowledge in the use of HRIM for the study of esophageal functional disorders by reporting mainly the results of many publications and several systematic reviews in this field. Expert opinion. HRIM has represented a relevant improvement in the assessment of esophageal motility and has required the development of new metrics, such as the esophageal impedance integral ratio, the bolus flow time, the nadir impedance pressure and the impedance bolus height, which increase the evaluation of esophageal bolus transit. An extension of impedance is represented by functional lumen imaging probe (FLIP), which determines the biophysical properties and the distensibility of the esophagus and permits to detect contractility patterns not seen on HRM alone. We eagerly wait for a new and fruitful iteration of the Chicago Classification, now in version 3.0, which can cover the ongoing clinical experience of HRIM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17474124.2019.1595587DOI Listing
May 2019

Improvement in hepatitis C virus patients with advanced, compensated liver disease after sustained virological response to direct acting antivirals.

Eur J Clin Invest 2019 Mar 19;49(3):e13056. Epub 2018 Dec 19.

Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy.

Background: The outcome of patients with chronic hepatitis C virus infection (HCV) and advanced, compensated liver disease after sustained virological response (SVR) to direct-acting antivirals (DAAs) has not yet been completely depicted. We aimed to assess the clinical, biochemical and instrumental outcome of patients with advanced, compensated chronic HCV-related liver disease with DAA-induced SVR to DAAs and who had at least 1-year follow-up.

Materials And Methods: Fifty-two patients with cirrhosis (n = 27) and fibrosis stage F3 (n = 25) followed up for a median of 60 weeks after successful DAA treatment were included. Laboratory work-up, including APRI and FIB-4 scores, liver transient elastography and measurement of the spleen bi-polar diameter were carried out before treatment and at the end of follow-up.

Results: Liver stiffness decreased (P < 0.0001) from a median baseline of 15.2 kPa (12.0-20.0) to 9.3 kPa (7.5-12.0) at follow-up. A liver stiffness value suggestive of the presence (ie, ≥21.0 kPa) of clinically significant portal hypertension was found in 13 patients (25.0%) at baseline and in seven patients (13.5%) at follow-up (P = 0.037). Both APRI (P < 0.0001) and FIB-4 score (P = 0.025) progressively decreased, while platelet count increased (143 × 10 /L [117-176] to 153 × 10 /L [139-186], P = 0.003), and spleen bi-polar diameter decreased (120 mm [112-123] to 110 mm [102-116], P = 0.0009) from baseline to the end of follow-up.

Conclusions: In patients advanced, compensated chronic liver disease, liver stiffness significantly improves in the long-term after SVR, and this improvement is accompanied by an amelioration of indirect indices of liver fibrosis and function, and by a decrease in parameters of portal hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.13056DOI Listing
March 2019

Proton pump inhibitors: use and misuse in the clinical setting.

Expert Rev Clin Pharmacol 2018 Nov 10;11(11):1123-1134. Epub 2018 Oct 10.

b Gastrointestinal Unit, Department of Surgery , Oncology and Gastroenterology, University of Padua , Padua , Italy.

Introduction: The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17512433.2018.1531703DOI Listing
November 2018

Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non-erosive reflux disease.

Aliment Pharmacol Ther 2018 11 7;48(10):1074-1081. Epub 2018 Oct 7.

Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Milan, Italy.

Background: The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing.

Aims: To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated.

Methods: Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring.

Results: Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group.

Conclusions: True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.14986DOI Listing
November 2018

Low Fibrinogen Levels Are Associated with Bleeding After Varices Ligation in Thrombocytopenic Cirrhotic Patients.

Ann Hepatol 2018 Jun;17(5):830-835

Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Ospedale Policlinico San Martino - IRCCS per l'Oncologia, Genoa, Italy.

Introduction And Aim: EVBL is a procedure frequently performed in cirrhotic patients for primary prophylaxis of bleeding. Patients with cirrhosis display various degrees of alteration of common coagulation parameters, and it is not known whether these alterations may predict post-EVBL bleeding. To evaluate factors predictive of post-endoscopic variceal band ligation (EVBL) bleeding in cirrhotic patients with thrombocytopenia.

Methods: We included 109 patients with cirrhosis undergoing EVBL for primary prophylaxis of variceal bleeding. Common coagulation parameters (INR, fibrinogen levels) and complete haemogram were obtained in all patients and evaluated subdividing patients in bleeders and non bleeders following EVBL.

Results: The incidence of post-EVBL bleeding was 5.5% (6 patients). INR and platelet counts, considered as continuous or dichotomous variables according to common cut-offs (i.e., INR>1.5, platelet count <50x109/L) were not predictors of post-EVBL bleeding. Patients who bled had significantly lower fibrinogen levels [146 mg/dL (98 - 262) versus 230 mg/dL (104 - 638), P=0.009], and no other biochemical or clinical predictors of bleeding were identified. A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding.

Conclusion: low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients, and might be used to stratify patients' risk. However, due to their preliminary nature, these findings need to be confirmed in larger populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5604/01.3001.0012.0775DOI Listing
June 2018

A safety review of proton pump inhibitors to treat acid-related digestive diseases.

Expert Opin Drug Saf 2018 08 23;17(8):785-794. Epub 2018 Jul 23.

b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy.

Introduction: Proton pump inhibitors (PPIs) have become the first choice medical treatment of acid-related disease and, as with any pharmacological agent, they have been reported to be associated with some adverse events mainly linked to their chronic use. The most important postulated harms are represented by serum electrolyte alterations, vitamin B12 and iron deficiency, gastric tumors, enteric infections, spontaneous bacterial peritonitis, pneumonia, ischemic heart attacks, bone fractures, chronic kidney disease, dementia, and Alzheimer disease. Specific pathophysiological mechanisms have been identified for some of them and not for other manifestations.

Areas Covered: However, studies on PPIs safety have generally important limitations because of their frequent retrospective design and other methodological drawbacks, such as patients' selection and residual confounders.

Expert Opinion: Obviously, in the vast majority of the cases, adverse drug reactions cannot be assessed by means of randomized clinical trials due to the high costs, ethical reasons, and difficulties in performing prospective observational studies. So far, assessment of retrospective observational investigations remains the only method to evaluate adverse events with any drug in general and, although the weaknesses of these studies are evident, the awareness of the reported associations with the medications analyzed is important for physicians in order to manage adequately their individual patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14740338.2018.1497155DOI Listing
August 2018

The appropriate use of proton-pump inhibitors.

Minerva Med 2018 Oct 31;109(5):386-399. Epub 2018 May 31.

Gastrointestinal Unit, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy.

The introduction of proton-pump inhibitors (PPIs) into clinical practice since about thirty years has greatly improved our therapeutic approach to acid-related diseases for their well recognized efficacy and safety. Accordingly, the role of surgery has been enormously reduced in this field. The main indications for PPI use are universally acknowledged by many scientific societies and are the following: treatment of gastroesophageal reflux disease in its various forms and complications, eradication of H. pylori infection in combination with two or more antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prevention of NSAID-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger-Ellison Syndrome. Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both Western and Eastern countries and this phenomenon poses serious queries about the appropriate prescription of these drugs worldwide. In fact, the endless expansion of PPI market has created important problems for many regulatory authorities for two relevant features: the progressive and irreversible increase of the costs of therapy with this class of drugs and the greater potential harms for the patients. So, there is the need for a reappraisal of PPI correct indications for both general practitioners and various specialists in order to re-establish a correct use of these effective drugs in daily clinical practice, according to the best evidence-based guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4806.18.05705-1DOI Listing
October 2018

Drugs for improving esophageal mucosa defense: where are we now and where are we going?

Ann Gastroenterol 2017 17;30(6):585-591. Epub 2017 Aug 17.

Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa (Patrizia Zentillin, Elisa Marabotto, Gaia Pellegatta, Claudia Coppo, Matteo Brunacci, Pietro Dulbecco, Vincenzo Savarino), Italy.

In the past, the attention of physiologists and doctors has been mainly focused on the key role of acid in the pathogenesis of gastroesophageal reflux disease (GERD), but increasing evidence that 20-40% of reflux patients respond not at all or only partially to proton pump inhibitors (PPIs) has underlined the concept that factors other than acid are implicated in its development and the elicitation of symptoms. Among these, impaired mucosal integrity, particularly in most patients with non-erosive reflux disease, has recently been reincluded and the reinforcement of defensive mechanisms and/or its protection has been reappointed as a renewed therapeutic target for the management of GERD patients. In this review we will summarize the existing knowledge of the old and novel compounds able to produce this therapeutic effect, including sucralfate, alginate-based drugs, and a new medical device consisting of hyaluronic acid and chondroitin sulfate dispersed in a bioadhesive carrier, together with the potential indications for their use. It is to be stressed, however, that, although these compounds may represent a real alternative to PPI therapy in GERD, the combination of mucosal protection with acid suppression may help manage many cases with a partial or unsatisfactory response to PPIs alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20524/aog.2017.0187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670277PMC
August 2017

Esophageal baseline impedance levels allow the identification of esophageal involvement in patients with systemic sclerosis.

Semin Arthritis Rheum 2018 02 9;47(4):569-574. Epub 2017 Aug 9.

Division of Gastroenterology, Departement of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Via Giustiniani 2, 35128 Padova, Italy. Electronic address:

Introduction: Distal esophageal baseline impedance (BI) levels reflect the esophageal mucosal integrity in reflux disease. Systemic sclerosis (SSc) could potentially affect the integrity of esophageal mucosa and consequently impair distal and proximal BI levels, but data in this regard are lacking.

Aim And Methods: We aimed to prospectively investigate and compare BI levels among non-erosive reflux disease (NERD), SSc patients, and healthy controls (HCs). Consecutive patients with reflux symptoms and well-defined diagnosis of SSc underwent upper endoscopy and, in case of no lesions encountered, manometry and impedance-pH testing off-therapy. In addition to traditional impedance-pH parameters, BI values at 3, 5, 7, and 17cm above the lower esophageal sphincter were calculated.

Results: Fifty-two patients with NERD, 50 with SSc, and 50 HCs were enrolled. Nineteen (38%) SSc patients and 22 (42%) NERD patients had abnormal acid exposure. In patients with SSc, median BI values were significantly lower than in NERD patients and HCs (p < 0.0001) at 3, 5, and 7cm; there was no difference between HCs and NERD patients at 17cm in the proximal esophagus, whereas a significant difference was observed at 17cm between SSc and NERD as well as HCs (p < 0.01).

Conclusion: Distal and proximal BI values in SSc patients were lower than in NERD and HCs, thus we speculated that these findings may be related to the deposition of collagen in the connective tissue. Measurement of BI may be used as an indirect, but simple and accurate marker of esophageal involvement in patients with SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2017.08.004DOI Listing
February 2018

A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD).

Expert Opin Pharmacother 2017 Sep 7;18(13):1333-1343. Epub 2017 Aug 7.

b Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties , University of Genoa , Genoa , Italy.

Introduction: Medical therapy of gastroesophageal reflux disease (GERD) is based on the use of proton pump inhibitors (PPIs) as first choice treatment. Despite their effectiveness, about 20-30% of patients report an inadequate response and alternative drugs are required. Areas covered: This review provides an overview of current pharmacotherapy for treating GERD by showing the results of PPIs, reflux inhibitors, antidepressants and mucosa protective medications. Expert opinion: Medical therapy of GERD does not definitely cure the disease, because even PPIs are not able to change the key factors responsible for it. However, they remain the mainstay of medical treatment, allowing us to alleviate symptoms, heal esophagitis and prevent complications in the majority of cases. Nevertheless, many patients do not respond, because acid does not play any pathogenetic role. Prokinetics and reflux inhibitors have the potential to control motor abnormalities, but the results of clinical trials are inconsistent. Antidepressant drugs are effective in specific subgroups of NERD patients with visceral hypersensitivity, but larger, controlled clinical studies are necessary. Protective drugs or medical devices have been recently adopted to reinforce mucosal resistance and preliminary trials have confirmed their efficacy either combined with or as add-on medication to PPIs in refractory patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2017.1361407DOI Listing
September 2017

Complexity and diversity of gastroesophageal reflux disease phenotypes.

Minerva Gastroenterol Dietol 2017 Sep 7;63(3):198-204. Epub 2017 Mar 7.

Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S1121-421X.17.02399-6DOI Listing
September 2017

Relevance of Measuring Substances in Bronchoalveolar Lavage Fluid for Detecting Aspiration-associated Extraesophageal Reflux Disease.

J Neurogastroenterol Motil 2017 Apr;23(2):318-319

Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5056/jnm17027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383128PMC
April 2017

Epidemiology and natural history of gastroesophageal reflux disease.

Minerva Gastroenterol Dietol 2017 Sep 17;63(3):175-183. Epub 2017 Feb 17.

Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries, particularly when considering its most classic symptom that is heartburn. This symptom is very frequent in the community and ranges from 10% to more than 30%, according to the various population-based studies. This disease is much more represented in Europe and USA than in Asiatic countries. It has been shown that GERD prevalence increases in parallel with the remarkable growth of obesity, as this condition is able to favor all the pathogenetic mechanisms leading to it. Current information regarding the phenotypic presentation of GERD shows that there are two main phenotypic manifestations, that are erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter includes the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, a pre-malignant lesion potentially leading to esophageal adenocarcinoma. Data from medical literature on the natural history of this disease are scant and mainly retrospective, so the interpretation of them is very difficult. However, they seem to suggest that both NERD and mild esophagitis tend to remain as such overtime and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur only in a small number of cases, ranging from 0% to 30%, 10-22% and 1-13%, respectively. Future studies should help us in elucidating better the real transition from one category to another and to do this, we have to exclude from the world of GERD all the functional conditions that nowadays can be easily recognized by means of impedance-pH monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S1121-421X.17.02383-2DOI Listing
September 2017

Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity.

Toxicol Appl Pharmacol 2016 09 9;306:113-9. Epub 2016 Jul 9.

ToxStrategies, Mission Viejo, CA 92692, USA. Electronic address:

Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6μgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3μgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8μgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2016.07.004DOI Listing
September 2016
-->