Publications by authors named "Gabriele Capurso"

194 Publications

Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis.

Pancreatology 2021 Jul 3. Epub 2021 Jul 3.

Division of Pancreatic Surgery and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment.

Methods: The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates.

Results: Seven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5-93.9) with no heterogeneity (I = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5-40.3) with moderate heterogeneity (I = 51%). A higher rate of relapse (35.9%, 95%CI 17.3-60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8-53) with substantial heterogeneity (I = 73.6%). No publication bias was observed.

Conclusion: Treatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.pan.2021.06.009DOI Listing
July 2021

Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma.

Carcinogenesis 2021 Jul 3. Epub 2021 Jul 3.

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P=7.14×10 -10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumor cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P=3.56×10 -6). This SNP is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
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http://dx.doi.org/10.1093/carcin/bgab057DOI Listing
July 2021

Utility of the "2019 ACR/EULAR classification criteria" for the management of patients with IgG4-related disease.

Semin Arthritis Rheum 2021 May 8;51(4):761-765. Epub 2021 May 8.

Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.

Background: The 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown.

Objective: To validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management.

Methods: Four experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab.

Results: Among the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p<0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes.

Conclusions: The ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.
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http://dx.doi.org/10.1016/j.semarthrit.2021.04.021DOI Listing
May 2021

Does chronic consumption of angiotensin-converting enzyme inhibitors affect survival after surgical resection of pancreatic ductal adenocarcinoma?

Dig Liver Dis 2021 May 16. Epub 2021 May 16.

Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Via Olgettina 60, Milan, Italy.

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http://dx.doi.org/10.1016/j.dld.2021.04.027DOI Listing
May 2021

Screening for pancreatic cancer-a compelling challenge.

Hepatobiliary Surg Nutr 2021 Apr;10(2):264-266

Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Università Vita-Salute, Milan, Italy.

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http://dx.doi.org/10.21037/hbsn-20-861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050588PMC
April 2021

Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected.

United European Gastroenterol J 2021 Mar;9(2):139-149

Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF.

Objective: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF.

Methods: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders.

Results: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality.

Conclusion: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.
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http://dx.doi.org/10.1002/ueg2.12057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259236PMC
March 2021

A tug-of-war in intraductal papillary mucinous neoplasms management: Comparison between 2017 International and 2018 European guidelines.

Dig Liver Dis 2021 Apr 9. Epub 2021 Apr 9.

Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden; Division of Surgical Oncology, Department of Surgery - University of Colorado, Anschutz Medical Campus, Denver, United States.

Background: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management.

Aim: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN.

Methods: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated.

Results: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN.

Conclusions: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features.
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http://dx.doi.org/10.1016/j.dld.2021.03.009DOI Listing
April 2021

Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival.

Sci Rep 2021 Apr 7;11(1):7570. Epub 2021 Apr 7.

Department of Biology, University of Pisa, Via Derna 1, 56126, Pisa, Italy.

Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients' response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58-15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.
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http://dx.doi.org/10.1038/s41598-021-87130-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027406PMC
April 2021

Factors associated with risk of COVID-19 contagion for endoscopy healthcare workers: A survey from the Italian society of digestive endoscopy.

Dig Liver Dis 2021 05 20;53(5):534-539. Epub 2021 Mar 20.

Department of Medical and Surgical Sciences, University of Bologna, Italy.

Background And Aims: The present study was aimed to assess the risk of SARS-CoV-2 infection and associated factors among HCWs in endoscopy centers in Italy.

Methods: All members of the Italian Society of Digestive Endoscopy (SIED) were invited to participate to a questionnaire-based survey during the first months of the COVID-19 outbreak in Italy.

Results: 314/1306 (24%) SIED members accounting for 201/502 (40%) endoscopic centers completed the survey. Personal Protection Equipment (PPE) were available in most centers, but filtering face-piece masks (FFP2 or FFP3) and negative pressure room were not in 10.9 and 75.1%. Training courses on PPE use were provided in 57.2% of centers only; there was at least one positive HCW in 17.4% of centers globally, 107/3308 (3.2%) HCWs were diagnosed with COVID-19 with similar rates of physicians (2.9%), nurses (3.5%) and other health operators (3.5%). Involvement in a COVID-19 care team (OR: 4.96) and the lack of training courses for PPE, (OR: 2.65) were associated with increased risk.

Conclusions: The risk of COVID-19 among endoscopy HCWs was not negligible and was associated with work in a COVID-19 care team and lack of education on proper PPE use. These data deserve attention during the subsequent waves.
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http://dx.doi.org/10.1016/j.dld.2021.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980179PMC
May 2021

High sensitivity of ROSE-supported ERCP-guided brushing for biliary strictures.

Endosc Int Open 2021 Mar 19;9(3):E363-E370. Epub 2021 Feb 19.

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, Vita-Salute San Raffaele University, Milan, Italy, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in biliary strictures, with brushing being a cheap and fast method to acquire a cytological specimen, despite a sensitivity around 45 %. Rapid on-site evaluation (ROSE) is widely used for endoscopic ultrasound-acquired cytological specimen adequacy, improving its sensitivity and specificity. Nevertheless, no study has evaluated its role for ERCP-guided brushing. Our aim was to assess the diagnostic yield of ERCP-guided brushing of biliary strictures when supported by ROSE.  This was a retrospective single-center study that included patients undergoing ERCP-guided brush cytology supported by ROSE for biliary strictures. Recorded data included patient clinical-radiological and ERCP features. Final diagnosis was determined after surgery, intraductal biopsy or adequate follow-up. The diagnostic yield was calculated and a subgroup analysis for factors associated with false-negative or true-positive results was performed. Two hundred six patients were included, 57.3 % males, median age 72 years, 77.2 % having extrahepatic biliary strictures. Of the patients, 99 % had an adequate sample at ROSE after a mean of 2.6 passages. The diagnostic yield was accuracy 83 %, sensitivity 74.6 %, and specificity 98 %, positive and negative predictive values 98 % and 71 % respectively, with an area under the curve of 0.86. A diagnosis of cholangiocarcinoma was significantly more frequent among true-positive cases (68 % vs 46.8 %;  = 0.04). This is the first study evaluating the use of ROSE as support for ERCP-guided brushing of biliary strictures, with a sensitivity far higher than those reported for brushing alone and at least comparable to those of more expensive and invasive techniques.
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http://dx.doi.org/10.1055/a-1322-2638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895655PMC
March 2021

Gastrointestinal mucosal damage in patients with COVID-19 undergoing endoscopy: an international multicentre study.

BMJ Open Gastroenterol 2021 02;8(1)

Department of Gastroenterology, Newcastle upon Tyne hospitals NHS Trust, Newcastle upon Tyne, UK.

Background: Although evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported.

Aims: We aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19.

Methods: All consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ or Fisher's exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors.

Results: Between February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58-74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69-86.87)) and presence of GI symptoms (OR=6.17 (1.13-33.67)) were independently associated with major abnormalities at multivariate analysis.

Conclusion: In this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy.

Trial Registration Number: ClinicalTrial.gov (ID: NCT04318366).
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http://dx.doi.org/10.1136/bmjgast-2020-000578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907837PMC
February 2021

Artificial intelligence in EUS for autoimmune pancreatitis: bias and real life.

Gut 2021 Feb 22. Epub 2021 Feb 22.

Pancreato-Biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy.

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http://dx.doi.org/10.1136/gutjnl-2021-324338DOI Listing
February 2021

Time for Change? The Why, What and How of Promoting Innovation to Tackle Rare Diseases - Is It Time to Update the EU's Orphan Regulation? And if so, What Should be Changed?

Biomed Hub 2020 May-Aug;5(2):1-11. Epub 2020 Jul 17.

Imperial College London, London, United Kingdom.

Since developments are global in the healthcare arena, more should be done to align EU and other big markets' regulatory practices for rare disease patients. Notwithstanding efforts and cooperation between the US and EU aimed to harmonize their strategic plans in the field of orphan drugs, regulatory criteria and procedures to gain the designation, terms and classifications should be still harmonised. Aligning the criteria of prevalence and support to orphan medicines in the various jurisdictions internationally, would facilitate patient recruitment eventually at global level, so as to gain the data and the biological insights required to identify biomarkers and appropriate endpoints needed for progressing clinical development. A conducive regulatory environment can further support the development of medicines to treat rare diseases. Overall there is a need for joined-up regulatory process coordination. Better integration of regulatory pathways and better integration of regulatory systems, such as scientific tools and methods to generate evidence, would be helpful. There is a need to revise and agree the current frameworks to be improved which will take into account the considerations and challenges to diagnose and treat different rare diseases and improve quality of life. Deliberative processes with multi-stakeholders' involvement for reimbursement should be considered. This paper explores the successes and limitation of both the regulation and its implementation mechanisms in the current regulatory context, and suggests some improvements that could maximise its benefits and boost rare disease research even further.
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http://dx.doi.org/10.1159/000509272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841717PMC
July 2020

Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Int J Cancer 2021 Jun 3;148(11):2779-2788. Epub 2021 Feb 3.

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
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http://dx.doi.org/10.1002/ijc.33475DOI Listing
June 2021

Association of Serum Triglyceride Levels with Severity in Acute Pancreatitis: Results from an International, Multicenter Cohort Study.

Digestion 2021 Jan 21:1-5. Epub 2021 Jan 21.

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA,

Background: Hypertriglyceridemia (HTG) is considered within the top 5 etiologies in acute pancreatitis (AP), but the association of serum triglyceride (TG) levels with the clinical course of AP remains controversial.

Objectives: This study aims to examine the effect of TG levels on severity of AP.

Methods: Patients were enrolled prospectively through APPRENTICE. High TG levels were defined based on the Endocrine Society Clinical Practice Guidelines. HTG was categorized as mild (serum TG levels 150-199 mg/dL), moderate (200-999 mg/dL), severe (1,000-1,999 mg/dL), and very severe (≥2,000 mg/dL). Severity of AP was based on the revised Atlanta classification criteria.

Results: Early TG levels were measured in 764 subjects and found elevated in 342 (120 with mild; 176, moderate; and 46, severe/very severe HTG). Patients with increased TG levels were younger (age ≥60, 16.7 vs. 30.3%), more likely to be male (66.1 vs. 51.2%), with more frequent alcohol use (62.8 vs. 50.7%), and diabetes mellitus (30.2 vs. 12.3%; all p ≤ 0.005). Severe AP (24.9 vs. 10.0%), ICU admission (32.5 vs. 19.7%), and mortality (5.3 vs. 1.7%; all p ≤ 0.005) were more frequently seen in patients with elevated TG levels. Based on multivariable analysis, elevated TG levels were independently associated with severe AP (p < 0.05).

Conclusion: This large multicenter study confirms that elevated TG levels are associated with severe disease regardless of AP etiology.
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http://dx.doi.org/10.1159/000512682DOI Listing
January 2021

Efficacy and safety of rituximab biosimilar (CT-P10) in IgG4-related disease: an observational prospective open-label cohort study.

Eur J Intern Med 2021 Feb 29;84:63-67. Epub 2020 Dec 29.

Università Vita-Salute San Raffaele, All at IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), All at IRCCS San Raffaele Scientific Institute, Milan, Italy.

Objective: Rituximab is increasingly used in IgG4-related disease (IgG4-RD) but high costs limit its wide off-label administration. European and US regulatory agencies have recently approved rituximab biosimilars for the treatment of different rheumatologic and hematological conditions. No data are available, yet, on the efficacy and safety of rituximab biosimilars for the treatment of IgG4-RD. Scope of the present work is to evaluate the efficacy and safety of the rituximab biosimilar CT-P10 (RTX-B) in patients with IgG4-RD.

Methods: Patients with active IgG4-RD, naïve to rituximab or switched from the originator (RTX-O) to the biosimilar were treated with RTX-B and prospectively followed-up for 18 months. Safety and efficacy were assessed at six months. Relapse rate was assessed at 18 months. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI).

Results: Thirty-eight patients were included in this study. Thirty-three patients (87%) were naïve to RTX. Five patients (13%) relapsed after RTX-O and were switched to RTX-B. After six months, 21 patients (60%) achieved disease remission. The median serum IgG4 concentration decreased from 1344 to 575 mg/L (p < 0.01), and the median IgG4-RD RI decreased from 7.5 to 0 (p < 0.01). B-cell depletion was observed in all patients. Eight patients (36%) relapsed within 18 months. Side effects related to RTX-B administration were observed in 14 patients (37%). These results are in line with our previous experience with RTX-O.

Conclusions: The (Truxima) rituximab biosimilar CT-P10 represents a safe and effective alternative to rituximab originator for the treatment of IgG4-RD.
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http://dx.doi.org/10.1016/j.ejim.2020.12.006DOI Listing
February 2021

Factors associated with the risk of patients and healthcare workers to develop COVID-19 during digestive endoscopy in a high-incidence area.

Gastrointest Endosc 2021 01;93(1):274-275

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy.

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http://dx.doi.org/10.1016/j.gie.2020.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833546PMC
January 2021

IgG4-related autoimmune liver disease.

Minerva Gastroenterol Dietol 2020 Dec 3. Epub 2020 Dec 3.

Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy -

The term IgG4-related autoimmune liver disease (AILD) refers to hepato-biliary manifestations of IgG4-related disease (IgG4-RD) including IgG4-related sclerosing cholangitis and IgG4-related pseudotumors. The association of some forms of autoimmune hepatitis to IgG4-RD remains controversial. Although autoimmune phenomena have not been clearly observed in IgG4-AILD, perturbation of the adaptive immune system and activation of the humoral response represent established pathophysiological hallmarks and potential therapeutic targets. Clinical manifestations of IgG4-AILD are virtually indistinguishable from bile duct cancer or primary sclerosing cholangitis, and are due to mass forming lesions and thickening of the biliary tract that progressively lead to biliary ducts obstruction. There are no current reliable biomarkers for IgG4-AILD and diagnosis should rely on the integration of clinical, serological, radiological, and histological findings. In analogy to most IgG4-RD manifestations, and in contrast to its major mimickers, IgG4-AILD promptly responds to glucocorticoids but frequently relapses, thus requiring long-term maintenance therapy to avoid progressive fibrosclerotic disease and liver cirrhosis. Accumulating evidence on the efficacy of B-cell depletion therapy in patients with systemic IgG4-RD is gradually changing the treatment paradigm of IgG4-AILD and biologics will be increasingly used also for gastroenterological manifestations of IgG4-RD to spare glucocorticoids and traditional immunosuppressive agents. Looking ahead, identification of reliable biomarkers and of miniinvasive strategies to obtain informative biopsies from the biliary tree represent unavoidable priorities to optimize diagnosis and management of IgG4-AILD.
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http://dx.doi.org/10.23736/S1121-421X.20.02794-4DOI Listing
December 2020

RNA Extraction from Endoscopic Ultrasound-Acquired Tissue of Pancreatic Cancer Is Feasible and Allows Investigation of Molecular Features.

Cells 2020 11 30;9(12). Epub 2020 Nov 30.

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Transcriptome analyses allow the distinguishing of pancreatic ductal adenocarcinoma (PDAC) subtypes, exhibiting different prognoses and chemotherapy responses. However, RNA extraction from pancreatic tissue is cumbersome and has been performed mainly from surgical samples, which are representative of < 20% of cases. The majority of PDAC patients undergo endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA), but RNA has been rarely extracted from EUS-TA with scanty results. Herein, we aimed to determine the best conditions for RNA extraction and analysis from PDAC EUS-TA samples in order to carry out molecular analyses. PDAC cases underwent diagnostic EUS-TA, with needles being a 25G fine needle aspiration (FNA) in all patients and then either a 20G lateral core-trap fine needle biopsy (FNB) or a 25G Franseen FNB; the conservation methods were either snap freezing, RNALater or Trizol. RNA concentration and quality (RNA integrity index; RIN) were analyzed and a panel of genes was investigated for tissue contamination and markers of molecular subtype and aggressivity through qRT-PCR. Seventy-four samples from 37 patients were collected. The median RNA concentration was significantly higher in Trizol samples (10.33 ng/uL) compared with snap frozen (0.64 ng/uL; < 0.0001) and RNALater (0.19 ng/uL; < 0.0001). The RIN was similar between Trizol (5.15) and snap frozen samples (5.85), while for both methods it was higher compared with RNALater (2.7). Among the needles, no substantial difference was seen in terms of RNA concentration and quality. qRT-PCR analyses revealed that samples from all needles were suitable for the detection of PDAC subtype markers (GATA6 and ZEB1) and splice variants associated with mutational status (GAP17) as well as for the detection of contaminating tissue around PDAC cells. This is the first study that specifically investigates the best methodology for RNA extraction from EUS-TA. A higher amount of good quality RNA is obtainable with conservation in Trizol with a clear superiority of neither FNA nor FNB needles. RNA samples from EUS-TA are suitable for transcriptome analysis including the investigation of molecular subtype and splice variants expression.
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http://dx.doi.org/10.3390/cells9122561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761443PMC
November 2020

A four-step method to centralize pancreatic surgery, accounting for volume, performance and access to care.

HPB (Oxford) 2021 Jul 27;23(7):1095-1104. Epub 2020 Nov 27.

Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Background: Adequate criteria for pancreatic surgery centralization are debated. This retrospective study aimed to define a reproducible method for complex care centralization, accounting for hospital performance and access to care.

Methods: The method consisted in: 1. Analysis of overall outcome and mortality-related factors. 2. Assessment of volume and adjusted mortality of each hospital. 3. Definition of different centralization models. 4. Final adjustments to guarantee access to care, evaluating travel times and waiting lists. This method was tested on Lombardy, the most populous Italian region (about 10 million inhabitants, 24 000 km).

Results: According to Ministry of Health data, 79 hospitals performed 3037 resections in 2014-2016. Mean overall mortality was 5.0%, increasing from 2.3%, of seven high-volume facilities (>30 resections/year) to 10.7% of 56 low-volume facilities (<10 resections/year). Five centralization models were tested (range: 7-23 hospitals): the best performing model included seven high-volume facilities, providing both low mortality (<2%), and easy access to care, namely reasonable travel time (≤60 min for >90% of the population), and limited impact on waiting list (1.1 extra-resection/hospital/week).

Conclusion: The four-step method appears as a flexible tool to centralize pancreatic surgery, allowing regulatory institutions to estimate the effect of different models.
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http://dx.doi.org/10.1016/j.hpb.2020.11.006DOI Listing
July 2021

Factors Associated With the Risk of Progression of Low-Risk Branch-Duct Intraductal Papillary Mucinous Neoplasms.

JAMA Netw Open 2020 11 2;3(11):e2022933. Epub 2020 Nov 2.

Pancreato-biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.

Importance: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are common pancreatic preneoplastic lesions, but their surveillance is not personalized.

Objective: To investigate patient- and cyst-related factors associated with progression into worrisome features (WFs) or high-risk stigmata (HRS) categories of BD-IPMNs.

Design, Setting, And Participants: Cyst- and patient-related factors of consecutive BD-IPMNs without WFs or HRS in 540 patients diagnosed from 2009 to 2018 with at least 12 months' surveillance until February 28, 2020, were registered in a 2-center ambispective cohort study in Italy. In a subgroup, the ABO blood group was studied for the first time in this setting.

Exposure: Cyst-related and patients-related factors and ABO blood group.

Main Outcomes And Measures: The study outcome was the appearance of WFs or HRS according to the 2017 International Association of Pancreatology guidelines. Survival probability was calculated using Kaplan-Meier curve and risk factors identified by Cox proportional hazards regression. ABO blood group was inferred through genotypes with DNA extraction.

Results: Of 540 patients with BD-IPMNs (median age, 66 years [interquartile range, 58.5-72.0 years]; 337 women [62.4%]) undergoing surveillance for a median of 51.5 months (interquartile range, 28-84 months) for 2758 person-years, 130 patients (24.1%) experienced progression. Probability of progression was 3.7% at 1 year, 23.4% at 5 years, and 43.3% at 10 years; 15 patients (2.8%) underwent surgery, 7 patients (1.3%) had malignant histologic findings, and 3 patients (0.56%) died of pancreatic-associated disease. Initial cyst size greater than 15 mm (hazard ratio [HR], 2.05; 95% CI, 1.44-2.91), body mass index greater than 26.4 (HR, 1.72; 95% CI, 1.19-2.50), and heavy smoking (HR, 1.81; 95% CI, 1.14-2.86) were significant independent factors associated with progression risk. The AA blood genotype was also associated with progression risk (HR, 3.49; 95% CI, 1.04-11.71) compared with the OO genotype in the investigated subgroup.

Conclusions And Relevance: This analysis of factors associated with progression of BD-IPMNs according to recent guidelines suggests that cyst size alone is not a reliable factor for estimation of progression risk; however, along with other readily available data, size is helpful for planning personalized surveillance of BD-IPMNs.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.22933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705592PMC
November 2020

COVID-19 and acute pancreatitis: examining the causality.

Nat Rev Gastroenterol Hepatol 2021 01;18(1):3-4

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy.

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http://dx.doi.org/10.1038/s41575-020-00389-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670484PMC
January 2021

The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma.

Mol Oncol 2021 02 24;15(2):579-595. Epub 2020 Nov 24.

Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, Rome, Italy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Most patients present with advanced disease at diagnosis, which only permits palliative chemotherapeutic treatments. RNA dysregulation is a hallmark of most human cancers, including PDAC. To test the impact of RNA processing dysregulation on PDAC pathology, we performed a bioinformatics analysis to identify RNA-binding proteins (RBPs) associated with prognosis. Among the 12 RBPs associated with progression-free survival, we focused on MEX3A because it was recently shown to mark an intestinal stem cell population that is refractory to chemotherapeutic treatments, a typical feature of PDAC. Increased expression of MEX3A was correlated with higher disease stage in PDAC patients and with tumor development in a mouse model of PDAC. Depletion of MEX3A in PDAC cells enhanced sensitivity to chemotherapeutic treatment with gemcitabine, whereas its expression was increased in PDAC cells selected upon chronic exposure to the drug. RNA-sequencing analyses highlighted hundreds of genes whose expression is sensitive to MEX3A expression, with significant enrichment in cell cycle genes. MEX3A binds to its target mRNAs, like cyclin-dependent kinase 6 (CDK6), and promotes their stability. Accordingly, knockdown of MEX3A caused a significant reduction in PDAC cell proliferation and in progression to the S phase of the cell cycle. These findings uncover a novel role for MEX3A in the acquisition and maintenance of chemoresistance by PDAC cells, suggesting that it may represent a novel therapeutic target for PDAC.
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http://dx.doi.org/10.1002/1878-0261.12847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858117PMC
February 2021

Patient-reported experience measure in pancreatobiliary endoscopy: a systematic review to highlight areas for improvement.

Eur J Gastroenterol Hepatol 2021 Jun;33(6):832-838

Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy.

Objective: Increasing attention is paid to measure patient's experience using specific patient-reported experience measures (PREMs) as tool to assess the overall quality of care provided. The European Society of Gastrointestinal Endoscopy and the United European Gastroenterology have recognized the measure of quality of endoscopy facilities as a priority to provide an adequate service. However, although some studies included patient satisfaction measurement, specific PREMs for gastrointestinal endoscopy are limited, especially in the field of pancreatobiliary endoscopy, with heterogeneous methods and results. This study is aimed at systematically reviewing the literature to summarize the available PREMs for pancreatobiliary endoscopy and to highlight areas of implementation.

Methods: PubMed, Embase and Scopus were searched until February 2020.

Results: The search initially retrieved 1064 articles, but only six were includable. The identified studies employed several methods to measure patient's experience, with the most frequently used questionnaires being Gastrointestinal Endoscopy Satisfaction Questionnaire and Group Health Association of America-9. The following areas that need implementation were identified: (a) evaluation of pain is one of the most investigated areas but seems marginal, as most pancreatobiliary endoscopic procedures are performed under deep sedation; (b) endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography are considered as a whole, but they have very different indication and contexts (e.g. inpatients or outpatients); (c) 'experience' and 'satisfaction' are wrongly considered as synonyms; (d) the optimal modality and timing of questionnaire administration are unclear.

Conclusion: There are few tools to measure PREMS in pancreatobiliary endoscopy with several limitations. We have, therefore, started the process of building a specific PREM tool for pancreatobiliary EUS.
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http://dx.doi.org/10.1097/MEG.0000000000001957DOI Listing
June 2021

How to get away with COVID-19: endoscopy during post-peak pandemic. A perspective review.

Therap Adv Gastroenterol 2020 8;13:1756284820965070. Epub 2020 Oct 8.

Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS. Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, Roma, 00168, Italy.

The SARS-CoV-2 pandemic has changed the way we work, and health care services have to adapt. The use of personal protective equipment (PPE) and the delay of non-urgent procedures were the immediate measures adopted by Gastrointestinal (GI) Endoscopy Units at the time of crisis. As the peak has now passed in most countries, GI facilities are facing the next challenge of this pandemic: service providers must adapt their routine work to a 'new normal'. Routine casework must resume, and waiting lists must be addressed: all in the awareness of the ongoing potential risks of COVID-19, and the threat of a second wave. In this review, we discuss strategies to manage the workload by improving procedure appropriateness and prioritization, whilst maintaining a 'COVID-free' environment. This includes monitoring of an adequate stock of PPE and the implications for the staff's workload, and the GI trainees' need of training.
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http://dx.doi.org/10.1177/1756284820965070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548539PMC
October 2020

Infection Control Practices and Outcomes of Endoscopy Units in the Lombardy Region of Italy: A Survey From the Italian Society of Digestive Endoscopy During COVID-19 Spread.

J Clin Gastroenterol 2020 Nov 17. Epub 2020 Nov 17.

Department of Gastroenterology, ASST Rhodense, Rho and Garbagnate Milanese Hospital.

Goals: The present survey from the Italian Society of Digestive Endoscopy (SIED-Società Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area.

Background: Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy.

Methods: A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak.

Results: In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found.

Conclusions: Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.
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http://dx.doi.org/10.1097/MCG.0000000000001440DOI Listing
November 2020

Necrosis volume and Choi criteria predict the response to endoscopic ultrasonography-guided HybridTherm ablation of locally advanced pancreatic cancer.

Endosc Int Open 2020 Oct 7;8(10):E1511-E1519. Epub 2020 Oct 7.

Pancreatico-Biliary Endoscopy & Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy.

 Endoscopic ultrasound (EUS)-guided ablation of pancreatic ductal adenocarcinoma (PDAC) with HybridTherm-Probe (EUS-HTP) is feasible and safe, but the radiological response and ideal tool to measure it have not been investigated yet. The aims of this study were to: 1) assess the radiological response to EUS-HTP evaluating the vital tumor volume reduction rate, Response Evaluation Criteria in Solid Tumors (RECIST1.1) and Choi criteria; 2) determine the prognostic predictive yield of these criteria.  A retrospective analysis was performed of patients with locally advanced PDAC after primary treatment or unfit for chemotherapy prospectively treated by EUS-HTP. Computed tomography scan was performed 1 month after EUS-HTP to evaluate: 1) vital tumor volume reduction rate (VTVRR) by measuring necrosis and tumor volumes through a computer-aided detection system; and 2) RECIST1.1 and Choi criteria.  EUS-HTP was feasible in 22 of 31 patients (71 %), with no severe adverse events. Median post-HTP survival was 7 months (1 - 35). Compared to pre-HTP tumor volume, a significant 1-month VTVRR (mean 21.4 %) was observed after EUS-HTP (  = 0.005). We identified through ROC analysis a VTVRR > 11.46 % as the best cut-off to determine post-HTP 6-month survival outcome (AUC = 0.733; sensitivity = 70.0 %, specificity = 83.3 %). This cut-off was significantly associated with longer overall survival (HR = 0.372;  = 0.039). According to RECIST1.1 and Choi criteria, good responders to EUS-HTP were 60 % and 46.7 %, respectively. Good responders according to Choi, but not to RECIST1.1, had longer survival (HR = 0.407;  = 0.04).  EUS-HTP induces a significant 1-month VTVRR. This effect is assessed accurately by evaluation of necrosis and tumor volumes. Use of VTVRR and Choi criteria, but not RECIST 1.1 criteria, might identify patients who could benefit clinically from EUS-HTP.
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http://dx.doi.org/10.1055/a-1221-9879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541180PMC
October 2020

Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis.

Dig Liver Dis 2020 12 16;52(12):1383-1389. Epub 2020 Sep 16.

Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, Rome 00185, Italy.

The microbiota-gut-liver-lung axis plays a bidirectional role in the pathophysiology of a number of infectious diseases. During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity. Intestinal damage due to SARS-CoV-2 infection, systemic inflammation-induced dysfunction, and IL-6-mediated diffuse vascular damage may increase intestinal permeability and precipitate bacterial translocation. The systemic release of damage- and pathogen-associated molecular patterns (e.g. lipopolysaccharides) and consequent immune-activation may in turn auto-fuel vicious cycles of systemic inflammation and tissue damage. Thus, intestinal bacterial translocation may play an additive/synergistic role in the cytokine release syndrome in Covid-19. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Moreover, it presents an overview of readily applicable measures for the modulation of the gut-liver axis and microbiota in clinical practice.
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http://dx.doi.org/10.1016/j.dld.2020.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494274PMC
December 2020

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer.

Front Med (Lausanne) 2020 3;7:495. Epub 2020 Sep 3.

Gastroenterology and Interventional Endoscopy Department, Clinical Emergency Hospital Bucharest, Bucharest, Romania.

Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels.

Main Outcome: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered."

Secondary Outcomes: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations.

Analysis: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients.

Sample Size: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.
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http://dx.doi.org/10.3389/fmed.2020.00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509408PMC
September 2020

ASO Author Reflections: Chemopreventive Agents After Pancreatic Resection for Ductal Adenocarcinoma.

Ann Surg Oncol 2021 Apr 14;28(4):2323-2324. Epub 2020 Sep 14.

Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.

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http://dx.doi.org/10.1245/s10434-020-09139-5DOI Listing
April 2021