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Article ; Online: Strictures in Crohn's Disease: From Pathophysiology to Treatment.

Crespi, Mattia / Dulbecco, Pietro / De Ceglie, Antonella / Conio, Massimo

2020 Volume 65, Issue 7, Page(s) 1904–1916

Abstract: Despite recent advances aimed to treat transmural inflammation in Crohn's disease (CD) patients, the progression to a structuring behavior still represents an issue for clinicians. As inflammation becomes chronic and severe, the attempt to repair damaged ...

Abstract	Despite recent advances aimed to treat transmural inflammation in Crohn's disease (CD) patients, the progression to a structuring behavior still represents an issue for clinicians. As inflammation becomes chronic and severe, the attempt to repair damaged tissue can result in an excessive production of extracellular matrix components and deposition of connective tissue, thus favoring the formation of strictures. No specific and accurate clinical predictors or diagnostic tools for intestinal fibrosis exist, and to date, no genetic or serological marker is in routine clinical use. Therefore, intestinal fibrosis is usually diagnosed when it becomes clinically evident and strictures have already occurred. Anti-fibrotic agents such as tranilast, peroxisome proliferator-activated receptor gamma agonists, rho kinase inhibitors, and especially mesenchymal stem cell therapy have provided interesting results, but most of the evidence has been derived from studies performed in vitro. Therefore, current therapy of fibrotic strictures relies mainly on endoscopic and surgical procedures. Although its long-term outcomes may be debated, endoscopic balloon dilation appears to be the safest and most effective approach to treat appropriately selected strictures. The use of endoscopic stricturotomy is currently limited by the expertise needed to perform it and by the few data available in the literature. Some good results have been achieved by the positioning of self-expandable metal stents (SEMS). However, there is no concordance regarding the type of stent to use and for how long it should be left in place. The development of new specific SEMS may lead to better outcomes and to an increased use of this alternative in CD-related strictures.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Constriction, Pathologic/etiology ; Constriction, Pathologic/metabolism ; Constriction, Pathologic/physiopathology ; Constriction, Pathologic/therapy ; Crohn Disease/complications ; Crohn Disease/metabolism ; Crohn Disease/physiopathology ; Crohn Disease/therapy ; Dilatation ; Endoscopy, Gastrointestinal ; Extracellular Matrix/metabolism ; Fibroblasts/metabolism ; Fibrosis/metabolism ; Fibrosis/physiopathology ; Gastrointestinal Agents/therapeutic use ; Humans ; Inflammation/metabolism ; Inflammation/physiopathology ; Intestines/pathology ; PPAR gamma/agonists ; Protein Kinase Inhibitors/therapeutic use ; Self Expandable Metallic Stents ; Tumor Necrosis Factor Inhibitors/therapeutic use ; ortho-Aminobenzoates/therapeutic use ; rho-Associated Kinases/antagonists & inhibitors
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Gastrointestinal Agents ; PPAR gamma ; Protein Kinase Inhibitors ; Tumor Necrosis Factor Inhibitors ; ortho-Aminobenzoates ; rho-Associated Kinases (EC 2.7.11.1) ; tranilast (HVF50SMY6E)
Language	English
Publishing date	2020-04-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-020-06227-0
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Article ; Online: Therapeutic potential of curcumin in digestive diseases.

Dulbecco, Pietro / Savarino, Vincenzo

World journal of gastroenterology

2014 Volume 19, Issue 48, Page(s) 9256–9270

Abstract: Curcumin is a low-molecular-weight hydrophobic polyphenol that is extracted from turmeric, which possesses a wide range of biological properties including anti-inflammatory, anti-oxidant, anti-proliferative and anti-microbial activities. Despite its ... ...

Abstract	Curcumin is a low-molecular-weight hydrophobic polyphenol that is extracted from turmeric, which possesses a wide range of biological properties including anti-inflammatory, anti-oxidant, anti-proliferative and anti-microbial activities. Despite its diverse targets and substantial safety, clinical applications of this molecule for digestive disorders have been largely limited to case series or small clinical trials. The poor bioavailability of curcumin is likely the major hurdle for its more widespread use in humans. However, complexation of curcumin into phytosomes has recently helped to bypass this problem, as it has been demonstrated that this new lecithin formulation enables increased absorption to a level 29-fold higher than that of traditional curcuminoid products. This allows us to achieve much greater tissue substance delivery using significantly lower doses of curcumin than have been used in past clinical studies. As curcumin has already been shown to provide good therapeutic results in some small studies of both inflammatory and neoplastic bowel disorders, it is reasonable to anticipate an even greater efficacy with the advent of this new technology, which remarkably improves its bioavailability. These features are very promising and may represent a novel and effective therapeutic approach to both functional and organic digestive diseases.
MeSH term(s)	Animals ; Biological Availability ; Biotransformation ; Chemistry, Pharmaceutical ; Curcuma ; Curcumin/adverse effects ; Curcumin/pharmacokinetics ; Curcumin/therapeutic use ; Digestive System Diseases/diagnosis ; Digestive System Diseases/drug therapy ; Gastrointestinal Agents/adverse effects ; Gastrointestinal Agents/pharmacokinetics ; Gastrointestinal Agents/therapeutic use ; Humans ; Phytotherapy ; Plant Extracts/adverse effects ; Plant Extracts/pharmacokinetics ; Plant Extracts/therapeutic use ; Plants, Medicinal ; Treatment Outcome
Chemical Substances	Gastrointestinal Agents ; Plant Extracts ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2014-01-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v19.i48.9256
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Article ; Online: Are proton pump inhibitors really so dangerous?

Savarino, Vincenzo / Dulbecco, Pietro / Savarino, Edoardo

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

2016 Volume 48, Issue 8, Page(s) 851–859

Abstract: For decades, millions of patients with acid-related disorders have had their acid inhibited effectively and safely first with H2-receptor antagonists (H2RAs) and then with proton pump inhibitors (PPI). As with any pharmacological agent, PPIs have been ... ...

Abstract	For decades, millions of patients with acid-related disorders have had their acid inhibited effectively and safely first with H2-receptor antagonists (H2RAs) and then with proton pump inhibitors (PPI). As with any pharmacological agent, PPIs have been reported to be associated with some adverse events, but several recent large-scale observational studies have evidenced new and serious abnormalities generally linked to their chronic use. However, these studies have often important limitations for their frequent retrospective design and other methodological drawbacks, such as selection biases of the analyzed populations and the presence of various confounding factors. Overall, although the conclusions of these pharmacovigilant investigations must be taken into account and can generate important hypotheses for future research, they do not have to create panic among patients and alarmism among physicians. On considering the weakness of these studies, we suggest physicians should not refrain from continuing to use PPIs, if these drugs are given for medical indications clearly established in the literature and, more importantly, they should not be induced to shift to H2RAs, a class of antisecretory agents that are much less effective than PPIs. A return to the past is potentially dangerous for the patients, taking into account the well-known success of PPIs in the wide spectrum of all acid-related conditions.
MeSH term(s)	Bacterial Infections/etiology ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Gastroesophageal Reflux/drug therapy ; Hip Fractures/etiology ; Histamine H2 Antagonists/therapeutic use ; Humans ; Malnutrition/etiology ; Myocardial Ischemia/etiology ; Pneumonia/etiology ; Proton Pump Inhibitors/adverse effects ; Proton Pump Inhibitors/therapeutic use ; Renal Insufficiency, Chronic/etiology ; Vitamin B 12 Deficiency/etiology
Chemical Substances	Histamine H2 Antagonists ; Proton Pump Inhibitors
Language	English
Publishing date	2016-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1459373-7
ISSN	1878-3562 ; 1125-8055
ISSN (online)	1878-3562
ISSN	1125-8055
DOI	10.1016/j.dld.2016.05.018
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Article ; Online: Ilaprazole for the treatment of gastro-esophageal reflux.

Savarino, Edoardo / Ottonello, Andrea / Martinucci, Irene / Dulbecco, Pietro / Savarino, Vincenzo

Expert opinion on pharmacotherapy

2016 Volume 17, Issue 15, Page(s) 2107–2113

Abstract: Introduction: Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new ... ...

Abstract	Introduction: Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new PPI, ilaprazole, has been developed and used in GERD patients. Areas covered: The present review provides an update on the following points: current knowledge of GERD mechanisms; limitations of actual therapies; pharmacokinetic profile and metabolism of ilaprazole; initial studies on the therapeutic efficacy of ilaprazole in GERD. Expert opinion: Compared with all other approved PPIs, ilaprazole has shown an extended plasma half-life, a metabolism not significantly influenced by CYP2C19 genetic polymorphism and similar safety. This characteristics account for a low inter-individual variability, particularly in Asian populations, a higher suppression of gastric acid secretion, a more rapid acid control and consequent quicker symptom relief and a better effect on nocturnal acidity. However, clinical investigations assessing the efficacy of ilaprazole in the management of GERD are lacking and therefore the potential improvements achievable with ilaprazole in the current standard of care for acid-suppressing treatment must be confirmed in large and randomly controlled clinical trials enrolling patients with both erosive and non-erosive reflux disease.
MeSH term(s)	2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use ; Gastroesophageal Reflux/drug therapy ; Half-Life ; Humans ; Proton Pump Inhibitors/therapeutic use
Chemical Substances	2-Pyridinylmethylsulfinylbenzimidazoles ; Proton Pump Inhibitors ; ilaprazole (776Q6XX45J)
Language	English
Publishing date	2016-10
Publishing country	England
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2016.1232389
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Article ; Online: Observational studies on prescription practices: interpret with caution.

Savarino, Vincenzo / Dulbecco, Pietro

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

2010 Volume 42, Issue 5, Page(s) 348–349

MeSH term(s)	Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Gastrointestinal Hemorrhage/chemically induced ; Gastrointestinal Hemorrhage/prevention & control ; Helicobacter Infections/complications ; Helicobacter Infections/epidemiology ; Helicobacter pylori/isolation & purification ; Humans ; Italy/epidemiology ; Middle Aged ; Observation ; Peptic Ulcer/chemically induced ; Peptic Ulcer/microbiology ; Peptic Ulcer/prevention & control ; Practice Patterns, Physicians' ; Prevalence ; Proton Pump Inhibitors/therapeutic use
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Proton Pump Inhibitors
Language	English
Publishing date	2010-05
Publishing country	Netherlands
Document type	Comment ; Editorial
ZDB-ID	1459373-7
ISSN	1878-3562 ; 1125-8055
ISSN (online)	1878-3562
ISSN	1125-8055
DOI	10.1016/j.dld.2010.02.017
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Article ; Online: The appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal.

Savarino, Vincenzo / Dulbecco, Pietro / de Bortoli, Nicola / Ottonello, Andrea / Savarino, Edoardo

European journal of internal medicine

2017 Volume 37, Page(s) 19–24

Abstract: The advent of powerful acid-suppressive drugs, such as proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases and has minimized the role of surgery. The major and universally recognized indications for their use are ... ...

Abstract	The advent of powerful acid-suppressive drugs, such as proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases and has minimized the role of surgery. The major and universally recognized indications for their use are represented by treatment of gastro-esophageal reflux disease, eradication of Helicobacter pylori infection in combination with antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prophylaxis of non-steroidal anti-inflammatory drug-associated gastric ulcers and control of several acid hypersecretory conditions. However, in the last decade, we have witnessed an almost continuous growth of their use and this phenomenon cannot be only explained by the simple substitution of the previous H2-receptor antagonists, but also by an inappropriate prescription of these drugs. This endless increase of PPI utilization has created an important problem for many regulatory authorities in terms of increased costs and greater potential risk of adverse events. The main reasons for this overuse of PPIs are the prevention of gastro-duodenal ulcers in low-risk patients or the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anticoagulant treatment without risk factors for gastro-duodenal injury, the overtreatment of functional dyspepsia and a wrong diagnosis of acid-related disorder. The cost for this inappropriate use of PPIs has become alarming and requires to be controlled. We believe that gastroenterologists together with the scientific societies and the regulatory authorities should plan educational initiatives to guide both primary care physicians and specialists to the correct use of PPIs in their daily clinical practice, according to the worldwide published guidelines.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Critical Care ; Critical Illness ; Duodenal Ulcer/drug therapy ; Dyspepsia/drug therapy ; Gastroesophageal Reflux/drug therapy ; Helicobacter Infections/drug therapy ; Helicobacter pylori ; Humans ; Inappropriate Prescribing ; Peptic Ulcer/chemically induced ; Peptic Ulcer/prevention & control ; Proton Pump Inhibitors/therapeutic use ; Respiration, Artificial ; Zollinger-Ellison Syndrome/drug therapy
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Proton Pump Inhibitors
Language	English
Publishing date	2017-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2016.10.007
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Article: Can artificial neural networks be beneficial in diagnosing gastro-oesophageal reflux disease?

Savarino, Vincenzo / Dulbecco, Pietro

European journal of gastroenterology & hepatology

2005 Volume 17, Issue 6, Page(s) 599–601

MeSH term(s)	Diagnosis, Computer-Assisted/methods ; Gastroesophageal Reflux/diagnosis ; Humans ; Neural Networks (Computer)
Language	English
Publishing date	2005-03-30
Publishing country	England
Document type	Comment ; Editorial
ZDB-ID	1034239-4
ISSN	1473-5687 ; 0954-691X
ISSN (online)	1473-5687
ISSN	0954-691X
DOI	10.1097/00042737-200506000-00001
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Article: Drugs for improving esophageal mucosa defense: where are we now and where are we going?

Savarino, Edoardo / Zentilin, Patrizia / Marabotto, Elisa / Pellegatta, Gaia / Coppo, Claudia / Brunacci, Matteo / Dulbecco, Pietro / Savarino, Vincenzo

Annals of gastroenterology

2017 Volume 30, Issue 6, Page(s) 585–591

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2017-08-17
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	2032850-3
ISSN	1108-7471
ISSN	1108-7471
DOI	10.20524/aog.2017.0187
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Article ; Online: Anti-TNF therapy is able to stabilize bowel damage progression in patients with Crohn's disease. A study performed using the Lémann Index.

Bodini, Giorgia / Giannini, Edoardo G / De Maria, Costanza / Dulbecco, Pietro / Furnari, Manuele / Marabotto, Elisa / Savarino, Vincenzo / Savarino, Edoardo

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

2017 Volume 49, Issue 2, Page(s) 175–180

Abstract: Aims: The Lémann Index (LI) was developed to assess the cumulative structural damage of the intestinal tract in patients with Crohn's Disease (CD) independently of clinical and biochemical activity. Recently, the goal of CD focused on obtaining mucosal ... ...

Abstract	Aims: The Lémann Index (LI) was developed to assess the cumulative structural damage of the intestinal tract in patients with Crohn's Disease (CD) independently of clinical and biochemical activity. Recently, the goal of CD focused on obtaining mucosal healing and deep remission rather than simple symptom control. These new therapeutic aims emphasize the need to prevent progression of bowel damage. In this study we aimed to evaluate the influence of different treatments on structural damage progression, assessed by means of LI in a series of CD patients consistently treated with various drugs. Methods: The LI was calculated at inclusion and at the end of follow-up in 104 CD patients subdivided according to treatments received: biological drugs (n=40, 38.4%), azathioprine (n=19, 18.3%), and mesalazine (n=45, 43.3%). Results: The median follow-up was 29 months, with no difference among groups. During follow-up, the median LI was stable in the biological group [from 6.3 (range, 0.6-37.3) to 6.4 (range, 0.6-37.6), P=0.543], whereas it significantly increased from 4.1 (range, 0.6-30) to 8.3 (range, 0.6-31.8) in the azathioprine group (P=0.0006), and from 2.4 (range, 0.6-25.8) to 4.1 (range, 0.6-28.8) in the mesalazine group (P<0.0001). Also during follow-up the LI increased significantly (P=0.004) in the azathioprine (68.4%) and mesalazine (60.0%) groups as compared with the biological therapy group (30.0%). Conclusions: In CD patients the LI tends to increase over time, although the use of biological drugs rather than azathioprine or mesalazine seems to be able to reduce the progressive bowel damage.
MeSH term(s)	Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Azathioprine/therapeutic use ; Colonoscopy ; Crohn Disease/drug therapy ; Crohn Disease/pathology ; Disease Progression ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Intestines/pathology ; Italy ; Magnetic Resonance Imaging ; Male ; Mesalamine/therapeutic use ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Tomography, X-Ray Computed ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Young Adult
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Immunosuppressive Agents ; Tumor Necrosis Factor-alpha ; Mesalamine (4Q81I59GXC) ; Azathioprine (MRK240IY2L)
Language	English
Publishing date	2017-02
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	1459373-7
ISSN	1878-3562 ; 1125-8055
ISSN (online)	1878-3562
ISSN	1125-8055
DOI	10.1016/j.dld.2016.10.014
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Article ; Online: Prevention of postoperative recurrence of Crohn's disease by Adalimumab: a case series.

Savarino, Edoardo / Dulbecco, Pietro / Bodini, Giorgia / Assandri, Lorenzo / Savarino, Vincenzo

European journal of gastroenterology & hepatology

2012 Volume 24, Issue 4, Page(s) 468–470

Abstract: Adalimumab, an anti-TNF-α monoclonal antibody, was found to be effective for the treatment of luminal Crohn's disease (CD), but its efficacy for the prevention of postoperative recurrence of CD is still unknown. Here, we present a case series of six ... ...

Abstract	Adalimumab, an anti-TNF-α monoclonal antibody, was found to be effective for the treatment of luminal Crohn's disease (CD), but its efficacy for the prevention of postoperative recurrence of CD is still unknown. Here, we present a case series of six patients who underwent resection for an ileocecal stricture caused by CD. Surgery removed the involved ileocolon, and pathology confirmed the presence of a fibrotic stricture. Two weeks after the operation, they were given Adalimumab at the dose of 160/80/40 mg every 2 weeks and were followed up. Since then, they have been disease-free for ≈ 3 years after surgery on clinical, radiological, and endoscopic/histological grounds (Crohn's Disease Activity Index ≤ 110 in all occasions). Up to now, they have had no anemia, no increase in inflammatory indices, and no abnormal blood tests. These are the first cases, to our knowledge, in which Adalimumab has been successfully used to prevent the postsurgical recurrence of CD, an event so far considered to be mandatory. Further large placebo-controlled studies are necessary to show the therapeutic advantage and the economic implications of these observations.
MeSH term(s)	Adalimumab ; Adult ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/therapeutic use ; Cecum/surgery ; Combined Modality Therapy ; Crohn Disease/prevention & control ; Crohn Disease/surgery ; Drug Administration Schedule ; Female ; Humans ; Ileum/surgery ; Male ; Middle Aged ; Secondary Prevention ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Young Adult
Chemical Substances	Anti-Inflammatory Agents ; Antibodies, Monoclonal, Humanized ; Tumor Necrosis Factor-alpha ; Adalimumab (FYS6T7F842)
Language	English
Publishing date	2012-04
Publishing country	England
Document type	Clinical Trial ; Journal Article
ZDB-ID	1034239-4
ISSN	1473-5687 ; 0954-691X
ISSN (online)	1473-5687
ISSN	0954-691X
DOI	10.1097/MEG.0b013e3283500849
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