Publications by authors named "Luca Pastorelli"

61 Publications

Staging esophageal cancer: low EUS accuracy in t2n0 patients.

Endosc Int Open 2021 Mar 18;9(3):E313-E318. Epub 2021 Feb 18.

Bilio-pancreatic Endoscopy and Endoscopic Ultrasound Unit, San Raffaele Hospital, Milan, Italy.

 Esophageal cancer (EC) is one of the most lethal malignancies worldwide. Staging of EC is performed with computed tomography (CT), positron-emission tomography (PET), and endoscopic ultrasonography (EUS). Patient management mostly depends on lymph node status. Compared to histopathology, the accuracy of EUS for T and N parameters is about 85 % and 75 %, respectively. Errors in staging may change prognosis. The aim of this study was to assess the role of EUS in T2-N0 EC considering the experience of two high-volume digestive endoscopic centers.  Two prospectively collected databases were queried to identify all patients with EC, staged as cT2N0 by EUS, with no distant metastases at CT/PET scan and who underwent transthoracic esophagectomy. Preoperative EUS staging (cTNM) was compared to histopathology of the surgical specimen (pTNM) to evaluate accuracy.  Of 729 consecutive patients with EC between January 2011 and September 2018, 72 (49 men) had cT2N0 disease. CT and PET scans confirmed the absence of distant metastasis. In 43 of 72 patients (60 %), the evaluation was correct, 23 of 72 (31,7 %) were understaged, and six of 72 patients (8,3 %) were overstaged. Among the understaged patients, eight were understaged by tumor depth (35 %), seven by nodal involvement (30 %), and eight by both (35 %). All six patients who were overstaged had T1b-N0 disease. EUS accuracy was 77 % in staging for tumor depth and 82 % in staging for nodal metastases. The positive predictive value (PPV) for cT2N0 EC was 60 % (43 pT2N0 /72 cT2N).  The accuracy of EUS staging of T2N0 EC is low, with only 60 % of patients undergoing appropriate therapy based on histopathology.
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http://dx.doi.org/10.1055/a-1336-2505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892275PMC
March 2021

Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.

Dig Liver Dis 2021 03 26;53(3):263-270. Epub 2020 Dec 26.

Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences "L.Sacco" University of Milan, Italy.

Background: It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19.

Objectives: This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders.

Methods: This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed.

Results: 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17).

Conclusion: IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.
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http://dx.doi.org/10.1016/j.dld.2020.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762705PMC
March 2021

An International Multicenter Real-Life Prospective Study of Electronic Chromoendoscopy Score PICaSSO in Ulcerative Colitis.

Gastroenterology 2021 Feb 5. Epub 2021 Feb 5.

Institute of Immunology and Immunotherapy, NIHR Wellcome Trust Clinical Research Facilities, University of Birmingham, and University Hospitals Birmingham NHS Trust, Birmingham, United Kingdom; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Birmingham, United Kingdom; Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Canada.

Background & Aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes.

Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy.

Results: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission.

Conclusion: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC.
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http://dx.doi.org/10.1053/j.gastro.2020.12.024DOI Listing
February 2021

Low prevalence of colorectal neoplasia in microscopic colitis: A large prospective multi-center study.

Dig Liver Dis 2020 Oct 28. Epub 2020 Oct 28.

Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy. Electronic address:

Background And Aims: Microscopic colitis (MC) is the most frequent condition in subjects undergoing ileocolonoscopy for chronic non-bloody diarrhea (CNBD) in Western countries. Emerging evidence has shown a negative association between MC and colorectal cancer. Within this prospective multi-center study we have evaluated the risk of colorectal neoplasia in MC and non-MC patients with CNBD receiving ileocolonoscopy with high-definition plus virtual chromoendoscopic imaging and histopathological assessment.

Methods: Patients with CNBD of unknown origin were prospectively enrolled in 5 referral centers in Northern Italy for ileocolonoscopy with high-definition and digital/optical chromoendoscopy plus multiple biopsies in each segment. The prevalence of colorectal neoplasia (cancer, adenoma, serrated lesion) in MC was compared to that observed in a control group including CNBD patients negative for MC, inflammatory bowel disease or eosinophilic colitis.

Results: From 2014 and 2017, 546 consecutive CNBD patients were recruited. Among the 492 patients (mean age 53±18 years) fulfilling the inclusion criteria against the exclusion critieria, MC was the predominant diagnosis at histopathological assessment (8.7%: N=43, 28 CC, 15 LC). The regression model adjusted for age and gender showed a significant negative association between the diagnosis of CM and colorectal neoplasia (OR=0.39; 95% CI 0.22-0.67, p <0.001) with a 60% decreased risk of adenomatous and neoplastic serrated polyps as compared to the control group (n=412).

Conclusion: This multi-center study confirms MC as a low-risk condition for colorectal neoplasia. No surveillance colonoscopy program is to be performed for MC diagnosis.
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http://dx.doi.org/10.1016/j.dld.2020.09.024DOI Listing
October 2020

Interleukin 33 Triggers Early Eosinophil-Dependent Events Leading to Metaplasia in a Chronic Model of Gastritis-Prone Mice.

Gastroenterology 2021 Jan 1;160(1):302-316.e7. Epub 2020 Oct 1.

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address:

Background & Aims: Interleukin (IL)33/IL1F11 is an important mediator for the development of type 2 T-helper cell (Th2)-driven inflammatory disorders and has also been implicated in the pathogenesis of gastrointestinal (GI)-related cancers, including gastric carcinoma. We therefore sought to mechanistically determine IL33's potential role as a critical factor linking chronic inflammation and gastric carcinogenesis using gastritis-prone SAMP1/YitFc (SAMP) mice.

Methods: SAMP and (parental control) AKR mice were assessed for baseline gastritis and progression to metaplasia. Expression/localization of IL33 and its receptor, ST2/IL1R4, were characterized in corpus tissues, and activation and neutralization studies were both performed targeting the IL33/ST2 axis. Dissection of immune pathways leading to metaplasia was evaluated, including eosinophil depletion studies using anti-IL5/anti-CCR3 treatment.

Results: Progressive gastritis and, ultimately, intestinalized spasmolytic polypeptide-expressing metaplasia (SPEM) was detected in SAMP stomachs, which was absent in AKR but could be moderately induced with exogenous, recombinant IL33. Robust peripheral (bone marrow) expansion of eosinophils and local recruitment of both eosinophils and IL33-expressing M2 macrophages into corpus tissues were evident in SAMP. Interestingly, IL33 blockade did not affect bone marrow-derived expansion and local infiltration of eosinophils, but markedly decreased M2 macrophages and SPEM features, while eosinophil depletion caused a significant reduction in both local IL33-producing M2 macrophages and SPEM in SAMP.

Conclusions: IL33 promotes metaplasia and the sequelae of eosinophil-dependent downstream infiltration of IL33-producing M2 macrophages leading to intestinalized SPEM in SAMP, suggesting that IL33 represents a critical link between chronic gastritis and intestinalizing metaplasia that may serve as a potential therapeutic target for preneoplastic conditions of the GI tract.
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http://dx.doi.org/10.1053/j.gastro.2020.09.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755675PMC
January 2021

Response to "Italian IBD Patients Coping With COVID-19 Emergency: The Mitigating Role of Psychological Readiness to Engage in Self-Care".

Inflamm Bowel Dis 2020 09;26(10):e123

Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.

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http://dx.doi.org/10.1093/ibd/izaa187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454660PMC
September 2020

Impact of COVID-19 outbreak on clinical practice and training of young gastroenterologists: A European survey.

Dig Liver Dis 2020 12 23;52(12):1396-1402. Epub 2020 May 23.

CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Background: SARS-CoV-2 disease (COVID-19) is a major challenge for the healthcare system and physicians, imposing changes in daily clinical activity.

Aims: we aimed to describe what European trainees and young gastroenterologists know about COVID-19 and identify training gaps to implement educational programs.

Methods: A prospective web-based electronic survey was developed and distributed via e-mail to all members of the Italian Young Gastroenterologist and Endoscopist Association and to European representatives.

Results: One hundred and ninety-seven subjects participated in the survey, of whom 14 (7.1%) were excluded. The majority were gastroenterologists in training (123, 67.7%) working in institutions with COVID-19 inpatients (159, 86.9%), aged ≤30 years (113, 61.8%). The activity of Gastroenterology Units was restricted to emergency visits and endoscopy, with reductions of activities of up to 90%. 84.5% of participants felt that the COVID-19 outbreak impacted on their training, due to unavailability of mentors (52.6%) and interruption of trainee's involvement (66.4%). Most participants referred absence of training on the use of personal protective equipment, oxygen ventilation systems and COVID-19 therapies.

Conclusion: COVID-19 outbreak significantly impacted on gastroenterologists' clinical activity. The resources currently deployed are inadequate, and therefore educational interventions to address this gap are warranted in the next future.
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http://dx.doi.org/10.1016/j.dld.2020.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245276PMC
December 2020

Impact of COVID-19 outbreak on the management of patients with severe IBD: a domino effect.

Gastroenterology 2020 May 11. Epub 2020 May 11.

Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1053/j.gastro.2020.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214299PMC
May 2020

Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study.

Gut 2020 07 30;69(7):1213-1217. Epub 2020 Apr 30.

IBD Center, Gastroenterology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy.

Objectives: COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.

Design: This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).

Results: Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.

Conclusions: Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.
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http://dx.doi.org/10.1136/gutjnl-2020-321411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242872PMC
July 2020

Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis.

J Mol Med (Berl) 2020 04 27;98(4):595-612. Epub 2020 Apr 27.

Department of Pharmaceutical Sciences, Università degli Studi di Pavia, 27100, Pavia, Italy.

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNFα therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. KEY MESSAGES: What are the new findings? Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy. The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody. Neutralization of eNAMPT ameliorates acute and chronic experimental colitis. Neutralization of eNAMPT limits the expression of IBD inflammatory signature. Neutralization of eNAMPT impairs immune cell infiltration in lamina propria.
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http://dx.doi.org/10.1007/s00109-020-01892-0DOI Listing
April 2020

Challenges in the Care of IBD Patients During the CoViD-19 Pandemic: Report From a "Red Zone" Area in Northern Italy.

Inflamm Bowel Dis 2020 05;26(6):793-796

Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.

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http://dx.doi.org/10.1093/ibd/izaa084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188155PMC
May 2020

Usefulness of panoramic 344°-viewing in Crohn's disease capsule endoscopy: a proof of concept pilot study with the novel PillCam™ Crohn's system.

BMC Gastroenterol 2020 Apr 7;20(1):97. Epub 2020 Apr 7.

IBD Unit, Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Bologna, Italy.

Background: A new capsule endoscopy (CE) system featuring two advanced optics for 344°-viewing and a prolonged operative time has been recently developed for Crohn's disease (CD) patients. Hence, we evaluated, for the first time, the performance of this novel CE and the add-on value of the 344°-viewing in a multi-center real-life setting.

Methods: Consecutive patients with suspected or established CD received the PillCam™ Crohn's System as supplementary diagnostic work-up focused on the small-bowel between June 2017 and June 2018. Technical and clinical data, including the panenteric CE diagnostic yield, the Lewis score and the impact of small-bowel findings on clinical management during a 6-months follow-up (new diagnosis, staging or treatment upgrade) were collected, thereby evaluating the added value of the 344° panoramic-view (lesions detected by camera A and B) over the standard 172°-view (lesions detected by one camera only).

Results: Among 41 patients (aged 43 ± 20 years), 73% underwent CE for suspected CD and 27% for established CD. The rate of complete enteroscopy was 90%. No technical failure or retention occurred. Compared to the standard 172° view, the panoramic 344°-view revealed a greater number of patients with a relevant lesion (56.1% vs. 39.0%; P = 0.023), resulting in higher Lewis score (222,8 vs. 185.7; P = 0.031), and improved clinical management (48.8% vs. 31.7%, P = 0.023).

Conclusions: The panoramic 344°-view increases small-bowel CE accuracy, thereby improving the clinical management of CD patients with mild small-bowel active disease. This system should be regarded as a new standard for both small-bowel diagnosis and monitoring in inflammatory bowel diseases.
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http://dx.doi.org/10.1186/s12876-020-01231-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140388PMC
April 2020

Hold the Foam: Why Topical Budesonide Remains Relevant for IBD Therapy.

Dig Dis Sci 2020 11;65(11):3066-3068

Gastroenterology Unit, Rho Hospital, ASST Rhodense, Corso Europa 250, 20017, Rho, MI, Italy.

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http://dx.doi.org/10.1007/s10620-020-06199-1DOI Listing
November 2020

Proteomic insights on the metabolism in inflammatory bowel disease.

World J Gastroenterol 2020 Feb;26(7):696-705

Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese 20097, Italy.

Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis. The pathogenesis of IBD is not completely unraveled, IBD are multi-factorial diseases with reported alterations in the gut microbiota, activation of different immune cell types, changes in the vascular endothelium, and alterations in the tight junctions' structure of the colonic epithelial cells. Proteomics represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal specimens. It is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of IBD. Sometimes a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful biomarkers. Although some non-invasive biomarkers have been described, none can be considered as the "gold standard" for IBD diagnosis, disease activity and therapy outcome. For these reason new studies have proposed an "IBD signature", which consists in a panel of biomarkers used to assess IBD. The above described approach characterizes "omics" and in this review we will focus on proteomics.
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http://dx.doi.org/10.3748/wjg.v26.i7.696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039832PMC
February 2020

Corrigendum: Biomarkers and Microscopic Colitis: An Unmet Need in Clinical Practice.

Front Med (Lausanne) 2020;7. Epub 2020 Jan 31.

Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.

[This corrects the article DOI: 10.3389/fmed.2017.00054.].
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http://dx.doi.org/10.3389/fmed.2020.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006028PMC
January 2020

Use, effectiveness and tolerability of budesonide-MMX in ulcerative colitis: A real-life experience.

United European Gastroenterol J 2019 11 17;7(9):1164-1170. Epub 2019 Jul 17.

Gastroenterology Unit, University of Milan, Milan, Italy.

Background: Budesonide-MMX has an established role in the management of relapsing mild-to-moderate ulcerative colitis. Data regarding effectiveness and tolerability in real-life clinical practice are limited.

Aim: The aim of this study was to assess the use of budesonide-MMX in ulcerative colitis, as well as short-term effectiveness and tolerability in real-life practice.

Methods: We conducted a retrospective study of adult patients with mild-to-moderate ulcerative colitis treated with budesonide-MMX at four tertiary inflammatory bowel disease centres in Italy from June 2016 to February 2018. Demographic and clinical features of patients, the use of budesonide-MMX, disease course and concomitant therapy were recorded. The primary outcome assessed was clinical remission at 2 months.

Results: A total of 82 patients with active mild-to-moderate ulcerative colitis were included in the study with a mean age of 45.9 years and a median partial Mayo Score of 4 (interquartile range 3-5). A total of 41 patients were male. Overall, 36 had extensive colitis, 38 left-sided colitis and eight proctitis. Treatments at the time of inclusion included 10 patients receiving biologic therapy, seven azathioprine and 54 mesalazine or salazopyrin. The main reasons for the addition of budesonide-MMX were clinical relapse (47.5%) or inadequate response to current therapy (39.0%). In total, 50% of patients achieved clinical remission, whereas 9.8% had clinical improvement. No response was noted in 40.2% of subjects. Using multivariate binary logistic regression, a moderate degree of activity was the main independent predictor of non-response. Eight significant adverse effects were reported in six patients with three discontinuing treatment.

Conclusion: In real-life clinical practice, budesonide-MMX is commonly used in combination with other therapies, both for acute disease flares and for partial response to therapy.
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http://dx.doi.org/10.1177/2050640619864257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826517PMC
November 2019

Terminal ileum ileoscopy and histology in patients undergoing high-definition colonoscopy with virtual chromoendoscopy for chronic nonbloody diarrhea: A prospective, multicenter study.

United European Gastroenterol J 2019 08 24;7(7):974-981. Epub 2019 Apr 24.

Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.

Background And Aims: Ileo-colonoscopy is the procedure of choice for chronic nonbloody diarrhea (CNBD) of unknown origin. Histological evaluation at different colonic sites is mandatory to assess the presence of microscopic colitis. However, the value of routine ileal biopsy on normal-appearing mucosa as assessed by means of standard-resolution white-light ileoscopy is controversial given its reported low diagnostic yield. Hence, we have assessed for the first time the accuracy of retrograde ileoscopy using high-definition and dyeless chromoendoscopy (HD + DLC), thereby calculating the impact and cost of routine ileal biopsy in CNBD.

Methods: Patients with CNBD of unknown origin were prospectively enrolled for ileo-colonoscopy with HD + DLC at five referral centers. Multiple biopsies were systematically performed on each colorectal segment and in the terminal ileum for histopathological analysis.

Results: Between 2014 and 2017, 546 consecutive patients were recruited. Retrograde ileoscopy success rate was 97.6%. A total of 492 patients (mean age: 53 ± 18 years) fulfilled all the inclusion criteria: Following endoscopic and histopathological work-up, 7% had lymphoid nodular hyperplasia and 3% had isolated ileitis. Compared to the histopathology as the gold standard, retrograde ileoscopy with HD + DLC showed 93% sensitivity, 98% specificity and 99.8% negative predictive value. In patients with normal ileo-colonoscopy, ileum histology had no diagnostic gain and resulted in a cost of US $26.5 per patient.

Conclusions: Retrograde ileoscopy with HD  +  DLC predicts the presence of ileitis in CNBD with excellent performance. The histopathological evaluation of the terminal ileum is the gold standard for the diagnostic assessment of visible lesions but has no added diagnostic value in CNBD patients with negative ileo-colonoscopy inspection using modern endoscopic imaging techniques.
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http://dx.doi.org/10.1177/2050640619847417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683636PMC
August 2019

A rare case of angina bullosa hemorrhagica of the esophagus.

Endoscopy 2019 12 30;51(12):E408-E409. Epub 2019 Jul 30.

Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.

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http://dx.doi.org/10.1055/a-0962-9656DOI Listing
December 2019

Editorial: the increasing burden of microscopic colitis.

Aliment Pharmacol Ther 2019 07;50(2):228-229

Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.

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http://dx.doi.org/10.1111/apt.15363DOI Listing
July 2019

Major duodenal papilla prolapse in Cronkhite-Canada syndrome.

Endoscopy 2019 04 7;51(4):E81-E82. Epub 2019 Feb 7.

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

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http://dx.doi.org/10.1055/a-0800-8148DOI Listing
April 2019

Editorial: Intestinal Inflammation.

Front Med (Lausanne) 2018 13;5:318. Epub 2018 Nov 13.

Internal Medicine, Gastroenterology and Hepatic Diseases Unit, Gastroenterological Area, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.3389/fmed.2018.00318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243125PMC
November 2018

IL-33 promotes recovery from acute colitis by inducing miR-320 to stimulate epithelial restitution and repair.

Proc Natl Acad Sci U S A 2018 10 17;115(40):E9362-E9370. Epub 2018 Sep 17.

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106;

Defective and/or delayed wound healing has been implicated in the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease (IBD). The resolution of inflammation is particularly important in mucosal organs, such as the gut, where restoration of epithelial barrier function is critical to reestablish homeostasis with the interfacing microenvironment. Although IL-33 and its receptor ST2/ILRL1 are known to be increased and associated with IBD, studies using animal models of colitis to address the mechanism have yielded ambiguous results, suggesting both pathogenic and protective functions. Unlike those previously published studies, we focused on the functional role of IL-33/ST2 during an extended (2-wk) recovery period after initial challenge in dextran sodium sulfate (DSS)-induced colitic mice. Our results show that during acute, resolving colitis the normal function of endogenous IL-33 is protection, and the lack of either IL-33 or ST2 impedes the overall recovery process, while exogenous IL-33 administration during recovery dramatically accelerates epithelial restitution and repair, with concomitant improvement of colonic inflammation. Mechanistically, we show that IL-33 stimulates the expression of a network of microRNAs (miRs) in the Caco2 colonic intestinal epithelial cell (IEC) line, especially miR-320, which is increased by >16-fold in IECs isolated from IL-33-treated vs. vehicle-treated DSS colitic mice. Finally, IL-33-dependent in vitro proliferation and wound closure of Caco-2 IECs is significantly abrogated after specific inhibition of miR-320A. Together, our data indicate that during acute, resolving colitis, IL-33/ST2 plays a crucial role in gut mucosal healing by inducing epithelial-derived miR-320 that promotes epithelial repair/restitution and the resolution of inflammation.
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http://dx.doi.org/10.1073/pnas.1803613115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176569PMC
October 2018

Endoscopic full-thickness resection for T1 early rectal cancer: a case series and video report.

Endosc Int Open 2017 Nov 27;5(11):E1081-E1086. Epub 2017 Oct 27.

Division of General Surgery I, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.

Background And Study Aims:  Endoscopic treatment of malignant colorectal polyps is often challenging, especially for early rectal cancer (ERC) localized close to the dentate line. Conversely, the surgical approach may result in temporary or definitive stoma and in frequent post-surgical complications. The Full-Thickness Resection Device (FTRD ) System (Ovesco Endoscopy, Tübingen, Germany) is a novel system that, besides having other indications, appears to be promising for wall-thickness excision of intestinal T1 carcinoma following incomplete endoscopic resection. However, follow-up data on patients treated with this device are scarce, particularly for ERC.

Patients And Methods:  Six consecutive patients with incomplete endoscopic resection of T1-ERC were treated with the FTRD and their long-term outcomes were evaluated based on a detailed clinical and instrumental assessment.

Results:  The endoscopic en bloc full-thickness resection was technically feasible in all patients. The histopathologic analysis showed a complete endoscopic resection in all cases, and a full-thickness excision in four. Neither complications, nor disease recurrence were observed during the 1-year follow-up period.

Conclusions:  The FTRD System is a promising tool for treating ERC featuring a residual risk of disease recurrence after incomplete endoscopic mucosal resection in patients unfit for surgery or refusing a surgical approach.
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http://dx.doi.org/10.1055/s-0043-118657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659870PMC
November 2017

Bowel Sonoelastography in Patients with Crohn's Disease: A Systematic Review.

Ultrasound Med Biol 2018 02 28;44(2):297-302. Epub 2017 Nov 28.

Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; Diagnostica per Immagini con Servizio di Radiologia Interventistica, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

Sonoelastography is an ultrasound-based method for evaluating the biological properties of a target tissue. It is commonly used in the diagnosis of liver and thyroid disease, but recently its use for monitoring the characteristics of bowel wall in patients affected by Crohn's disease (CD) has been proposed. Our aim was a systematic review of the use of sonoelastography in patients with CD. An initial database search retrieved 32 possible articles. On initial screening, 7 articles, concerning a total of 129 patients and 154 lesions of the small and large bowel, were finally included in the review. The age range varied between 6 and 53 y, and disease duration ranged between 1 and 623 mo. We collected data on the examinations performed (type and time), bowel area considered and parameters evaluated. All authors found that elastography correlates well with the degree of fibrosis, as wall strain significantly decreases in segments affected by fibrotic stenosis. Even though the endpoints proposed in the various articles are relatively inhomogeneous and scarcely comparable, we found that sonoelastography is a promising tool in the evaluation of patients with CD as it can differentiate inflammatory and fibrotic strictures in small case series.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.10.004DOI Listing
February 2018

Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study.

Proteomics 2017 Dec 29;17(23-24). Epub 2017 Nov 29.

Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.

This study utilizes 2D-DIGE (difference gel etrophoresis), isotope-coded protein labeling and biochemical assays to characterize protein alteration in ulcerative colitis (UC) and Crohn's disease (CD) in human epithelial cell and mucosal biopsies in inflammatory bowel disease (IBD)-affected patients. The aim of this study is to identify the key molecular signatures involved in epithelial cell structure of IBDs. In non-inflamed UC (QUC) keratins, vimentin, and focal adhesion kinase (7) increased, whereas vinculin and de-tyrosinated α-tubulin decreased; inflammation (IUC) exacerbated molecular changes, being collagen type VI alpha 1 chain (COL6A1), tenascin-C and vimentin increased. In non-inflamed CD (QCD), tenascin C, de-tyrosinated α-tubulin, vinculin, FAK, and Rho-associated protein kinase 1 (ROCK1) decreased while vimentin increased. In inflamed CD (ICD), COL6A1, vimentin and integrin alpha 4 increased. In QUC, cell metabolism is characterized by a decrease of the tricarboxylic acid cycle enzymes and a decrease of short/branched chain specific acyl-CoA dehydrogenase, fatty acid synthase, proliferator-activated receptors alpha, and proliferator-activated receptors gamma. In QCD a metabolic rewiring occurs, as suggested by glycerol-3-phosphate dehydrogenase (GPD2), pyruvate dehydrogenase E1 component subunit beta, NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, and 4-trimethylaminobutyraldehyde dehydrogenase increment, while dihydrolipoyl dehydrogenase decreased. Macroautophagy is activated in QUC and IUC, with increased levels of p62, HSC70, major vault protein, myosin heavy chain 9, whereas it is blunted in QCD and ICD. The differing pattern of extracellular matrix, cytoskeletal derangements, cellular metabolism, and autophagy in UC and CD may contribute to the pathophysiological understanding of these disorders and serve as diagnostic markers in IBD patients.
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http://dx.doi.org/10.1002/pmic.201700164DOI Listing
December 2017

A consumer's guide for probiotics: 10 golden rules for a correct use.

Dig Liver Dis 2017 Nov 1;49(11):1177-1184. Epub 2017 Aug 1.

Laboratory of Clinical Microbiology, Department of Biomedical Science for Health, University of Milan, Milan, Italy; Laboratory of Clinical-Chemistry and Microbiology, IRCCS Galeazzi Institute, University of Milan, Milan, Italy. Electronic address:

Probiotics are used all over the world as their beneficial effects on the human organism have been widely demonstrated. Certain probiotics can down-regulate production of pro-inflammatory cytokines and promote intestinal epithelial barrier functions, increasing an anti-inflammatory response and contributing to the host's overall health. The main mechanisms by which probiotic microorganisms can interact with the host are by modulating the immune system and the epithelial cell functions and interacting with intestinal gut microbiota. To date, hundreds of different microorganisms are used for the formulation of numerous probiotic products; therefore, it is very difficult to choose the best probiotic product for specific or more general needs. Therefore, physicians are getting more and more confused due to the high number of commercial products which are often lacking healthy effects on the host. Therefore, the aim of this paper is to demonstrate the main characteristics that probiotic microorganisms and products should possess to have a positive impact on the host's health. To this purpose, this review suggests "10 golden rules" or "commandments" that clinicians should follow to properly select the optimal probiotic product and avoid misidentifications, mislabelling and "pie in the sky" stories.
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http://dx.doi.org/10.1016/j.dld.2017.07.011DOI Listing
November 2017

MMX technology and its applications in gastrointestinal diseases.

Therap Adv Gastroenterol 2017 Jul 25;10(7):545-552. Epub 2017 May 25.

Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy Department of Biomedical Sciences for Health, Università di Milano, Milan, Italy.

The Multimatrix (MMX) preparation MMX is a recently obtained drug formulation developed to facilitate release of high concentrations of active drugs into the colon, with a homogeneous distribution along all colonic segments, particularly the most distal ones; the distal colonic tracts, indeed, are the most difficult to reach in significant amounts when a drug is given orally. The MMX formulation is characterized by a lipophilic matrix dispersed in a hydrophilic structure. Indeed, in the last few years, MMX technology has been widely used in the development of various drugs for the treatment of inflammatory and infectious gastrointestinal diseases localized in the colon. In particular, MMX mesalamine, budesonide and parnaparin formulations have been investigated in patients with ulcerative colitis, and the first two have reached worldwide registration for the treatment of this disease. Moreover, MMX-rifamycin is being positively tested in the treatment of colonic bacterial infections, including traveler's diarrhea. MMX technology is, thus, proving to be a very effective formulation for the treatment of various colonic diseases. This effectiveness has been related not only to specific colonic delivery, but also to its ability to act in a once-daily dosage, thus favouring patients' adherence to prescribed schedules of treatment. The effective delivery of the active molecule to the site of need in the colon is also associated with very low systemic absorption and very low rates of adverse events (AEs). In this paper, we have reviewed all clinical trials performed with an MMX-bound drug and all possible real-life reports, in order to give an overall evaluation of MMX.
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http://dx.doi.org/10.1177/1756283X17709974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484438PMC
July 2017

experimental study on the Thulium laser system: new horizons for interventional endoscopy (with videos).

Endosc Int Open 2017 Jun 31;5(6):E410-E415. Epub 2017 May 31.

Gastroenterology & Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milano, Italy.

Background And Study Aims:  The Thulium laser system (TLS) is an emerging interventional tool adopted in many surgical specialties. Its 2.0-μm wavelength allows precise coagulation (0.2 - 0.4 mm in depth) and cutting, limiting the possibilities of collateral injuries. We tested the impact of the TLS for gastric endoscopic submucosal dissection (ESD) and per oral endoscopic myotomy (POEM) in pigs.

Materials And Methods:   porcine stomach and esophagus models underwent 2 POEMs, and 3 ESDs (mean diameter 3.5 cm) with TLS using a 272-µm and a 365-µm thick optical fibers. Both continuous and pulsed laser emission were evaluated. Subsequent histopathological analysis was performed by an expert GI pathologist on the whole porcine models.

Results:  Complete POEMs and gastric ESDs were successfully performed in all cases in 30 to 70 and 15 to 20 minutes. Both optical fibers were equally effective and precise. The best power output for mucosal incision was 25 to 30 W during ESD and 25 W for POEM using continuous laser emission. During submucosal dissection and tunneling the favorite power output was 20 W and 15 to 20 W, respectively, operating in continuous mode. No transmural perforation occurred throughout the operations and histopathology confirmed the absence of accidental muscular layer damage.

Conclusions:  The TLS stands out as a precise and manageable instrument in models. This technique appears to be a promising tool for advanced interventional endoscopy.
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http://dx.doi.org/10.1055/s-0043-106738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451280PMC
June 2017

Biomarkers and Microscopic Colitis: An Unmet Need in Clinical Practice.

Front Med (Lausanne) 2017 10;4:54. Epub 2017 May 10.

Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.

One of the most common causes of chronic diarrhea is ascribed to microscopic colitis (MC). MC is classified in subtypes: collagenous colitis (CC) and lymphocytic colitis (LC). Patients with MC report watery, non-bloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient's health-related quality of life. A greater awareness, and concomitantly an increasing number of diagnoses over the last years, has demonstrated that the incidence and prevalence of MC are on the rise. To date, colonoscopy with histological analysis on multiple biopsies collected along the colon represents the unique accepted procedure used to assess the diagnosis of active MC and to evaluate the response to medical therapy. Therefore, the emerging need for less-invasive procedures that are also rapid, convenient, standardized, and reproducible, has encouraged scientists to turn their attention to the identification of inflammatory markers and other molecules in blood or feces and within the colonic tissue that can confirm a MC diagnosis. This review gives an update on the biomarkers that are potentially available for the identification of inflammatory activity, related to CC and LC.
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http://dx.doi.org/10.3389/fmed.2017.00054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423903PMC
May 2017

Interleukin-37: A Peacekeeper at the Intestinal Borders.

Dig Dis Sci 2017 05;62(5):1103-1106

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.

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http://dx.doi.org/10.1007/s10620-017-4523-0DOI Listing
May 2017