Publications by authors named "Angelo Andriulli"

186 Publications

Circulating levels of cytokines, chemokines and growth factors in patients with achalasia.

Biomed Rep 2021 Nov 10;15(5):92. Epub 2021 Sep 10.

Fondazione IRCCS Casa Sollievo della Sofferenza, Gastroenterology Unit, I-71013 San Giovanni Rotondo, Foggia, Italy.

Idiopathic achalasia is a disease that is characterized by the absence of peristalsis and incomplete relaxation of the lower esophageal sphincter, which is accompanied by dysphagia, regurgitation, chest pain and weight loss. The role of inflammatory infiltrates in the pathogenesis of achalasia remains controversial, although the infiltrating cell profile in the tissue has been previously characterized histologically and immunohistochemically. The present study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with achalasia and the clinical disease characteristics. The cytokine, chemokine and growth factor serum profiles of 68 patients with achalasia and 39 healthy individuals were explored using the 27-Bio-Plex Pro Human Cytokine assay. Reductions in the levels of inflammatory mediators IL-1β, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 (MIP-1)α and MIP-1β, regulated upon activation normal T cell expressed and presumably secreted, TNF-α and VEGF were detected in the serum samples of patients with achalasia compared with those in the control group (P<0.05). However, significant associations between the expression in the levels of inflammatory factors and clinical characteristics of the patients were not found (P>0.05). These results suggest that achalasia is a disease that has a local but not a systemic inflammatory pattern. Further studies are required to improve the current understanding of the mechanism underlying this disease.
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http://dx.doi.org/10.3892/br.2021.1468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461322PMC
November 2021

Germline Alterations in Patients With IBD-associated Colorectal Cancer.

Inflamm Bowel Dis 2021 Aug 4. Epub 2021 Aug 4.

Division of Gastroenterology, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Background: Patients with inflammatory bowel diseases (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), are at risk of developing a colorectal cancer (CRC). No information is available on the contribution of patients' genetic background to CRC occurrence. This study investigates germline alterations in patients with IBD-associated CRC.

Methods: We profiled a panel of 39 genes potentially involved in cancer predisposition and searched for germline variants in IBD patients with CRC or high-grade dysplasia.

Results: After clinical exclusion of genetic cancer syndromes, 25 IBD patients (4 CD and 21 UC) with CRC or high-grade dysplasia were studied. After excluding variants with low likelihood of pathogenicity (classes 1 or 2 according the International Agency for Research on Cancer [IARC]), the panel identified pathogenic variants, likely pathogenic, or variants with unknown significance in 18 patients (72%). Six patients (24%) carried pathogenic or likely variants (IARC class 5 or 4). Of the identified variants, 4 encompassed the APC region, 3 the MLH1 gene, and the remaining ones the MSH2, MSH3, monoallelic MUTYH, EPCAM, BRCA1, CHEK2, POLD1, POLE, CDKN2A, and PDGFRA genes. Four patients carried at least 2 variants in different genes. Duration of IBD was significantly shorter in carriers of 4 or 5 IARC variants (7 years; range 0-21; P = .002) and in those with variants with unknown significance (12 years; range 0-22; P = .005) compared with patients without or with only benign variations (23.5 years; range 15-34).

Conclusions: In silico analysis and sequence-based testing of germline DNA from IBD patients with CRC or high-grade dysplasia detected 24% of variants positioned in pathogenic classes. In patients with type 3, 4, and 5 variants, the onset of high-grade dysplasia or CRC was significantly earlier than in patients with benign or unidentified variants. The screening for these genes could identify IBD patients requiring a more intensive endoscopic surveillance for earlier detection of dysplastic changes.
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http://dx.doi.org/10.1093/ibd/izab195DOI Listing
August 2021

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

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

Carcinogenesis 2021 Aug;42(8):1037-1045

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 tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism 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
August 2021

Inverted colonic diverticulum (ICD): report of two cases and literature review of a not that unusual endoscopic challenge.

Clin Res Hepatol Gastroenterol 2021 Apr 27;45(5):101711. Epub 2021 Apr 27.

Gastroenterology and Endoscopy Units, Fondazione "Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Italy. Electronic address:

Inverted colonic diverticulum (ICD) is a rare intraluminal lesion occurring in about 0.7-1.7% of people, often endoscopically indistinguishable from polyps. Some unspecific endoscopic features may assist to distinguish polypoid ICD from true polyps. This differentiation bears relevance for the therapeutic approach, as colonic polyps require snare polypectomy, a practice which may be associated with colonic perforation in case of true ICD. The endoscopist, therefore, should be aware of the likelihood of detecting these lesions during colonoscopy. A close inspection and a gentle probing could assist in a correct diagnosis and avoid risky procedures such as biopsy or polypectomy. Rarely, a neoplasm arising over an ICD and its treatment has been described. We reported two cases, one of which with dysplasia, and their treatment, and reviewed all the ICD endoscopic cases so far reported in the literature, remarking the possibility of finding pedunculated ICDs or neoplasm arising over an ICD.
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http://dx.doi.org/10.1016/j.clinre.2021.101711DOI Listing
April 2021

Interobserver agreement of the Paris and simplified classifications of superficial colonic lesions: a Western study.

Endosc Int Open 2021 Mar 19;9(3):E388-E394. Epub 2021 Feb 19.

Fondazione "Casa Sollievo della Sofferenza", IRCCS, Gastroenterology and Endoscopy Units, San Giovanni Rotondo, Foggia, Italy.

The Paris classification of superficial colonic lesions has been widely adopted, but a simplified description that subgroups the shape into pedunculated, sessile/flat and depressed lesions has been proposed recently. The aim of this study was to evaluate the accuracy and inter-rater agreement among 13 Western endoscopists for the two classification systems. Seventy video clips of superficial colonic lesions were classified according to the two classifications, and their size estimated. The interobserver agreement for each classification was assessed using both Cohen k and AC1 statistics. Accuracy was taken as the concordance between the standard morphology definition and that made by participants. Sensitivity analyses investigated agreement between trainees (T) and staff members (SM), simple or mixed lesions, distinct lesion phenotypes, and for laterally spreading tumors (LSTs). Overall, the interobserver agreement for the Paris classification was substantial (κ = 0.61; AC1 = 0.66), with 79.3 % accuracy. Between SM and T, the values were superimposable. For size estimation, the agreement was 0.48 by the κ-value, and 0.50 by AC1. For single or mixed lesions, κ-values were 0.60 and 0.43, respectively; corresponding AC1 values were 0.68 and 0.57. Evaluating the several different polyp subtypes separately, agreement differed significantly when analyzed by the k-statistics (0.08-0.12) or the AC1 statistics (0.59-0.71). Analyses of LSTs provided a κ-value of 0.50 and an AC1 score of 0.62, with 77.6 % accuracy. The simplified classification outperformed the Paris classification: κ = 0.68, AC1 = 0.82, accuracy = 91.6 %. Agreement is often measured with Cohen's κ, but we documented higher levels of agreement when analyzed with the AC1 statistic. The level of agreement was substantial for the Paris classification, and almost perfect for the simplified system.
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http://dx.doi.org/10.1055/a-1352-3437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895665PMC
March 2021

Accuracy and inter-observer agreement of the nice and kudo classifications of superficial colonic lesions: a comparative study.

Int J Colorectal Dis 2021 Jul 1;36(7):1561-1568. Epub 2021 Mar 1.

Gastroenterology and Endoscopy Units, Fondazione "Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Italy.

Purpose: For superficial colonic lesions, the NICE and Kudo classifications are used in the in vivo prediction of histology and as guide to therapy. The NICE system derives information from unmagnified NBI endoscopic images. The Kudo one necessitates a magnification, but, as this tool is not commonly available, it is applied also to characterize unmagnified pictures to compare their diagnostic performances.

Methods: We conducted a prospective comparison of the NICE versus the Kudo classification for the differential diagnosis of colonic polyps taking histology as the gold standard. The inter-observer agreement for both classifications among 11 colonoscopists was also evaluated. Short unmagnified NBI videoclips of 64 colonic polyps were sent twice to the participants. In the first round, they classified the lesions according to the NICE classification; 4 months later, the same videos were assessed with the Kudo system. The diagnosis provided by the participants was grouped in non-neoplastic, non-invasive neoplasia, invasive neoplasia.

Results: Overall, the diagnostic accuracy was 82% (95%CI: 79-85) with the NICE system and 81% (95%CI: 78-84) with the Kudo one (ρ = 0.78). The accuracy of the NICE classification for non-neoplastic lesions was greater compared with the Kudo's (ρ = 0.03). Sensitivity sub-analyses revealed a higher ability of the NICE in distinguishing between neoplastic vs. non-neoplastic lesions (ρ = 0.01). The overall inter-rater agreement did not differ when the classifications were compared.

Conclusion: The NICE and the Kudo classifications might be considered comparable. Our data could allow the use of the NBI Kudo classification even in those centers where magnification is not available.
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http://dx.doi.org/10.1007/s00384-021-03897-8DOI Listing
July 2021

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

Int J Cancer 2021 06 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

Transabdominal ultrasound-guided pancreatic biopsy: a neglected but safe, effective and inexpensive procedure that needs to be re-juvinalized.

J Ultrasound 2021 Jun 1;24(2):175-182. Epub 2021 Feb 1.

Division of Gastroenterology and Endoscopy, IRCCS, Fondazione Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71024, San Giovanni Rotondo, Italy.

Background: For solid pancreatic masses, ultrasound endoscopic fine-needle biopsy is suggested as the front-line investigation for tissue achievement, notwithstanding the optimal performance of transabdominal ultrasound (TUS)-guided biopsy.

Purpose: To reassess the efficacy and effectiveness of TUS-guided sampling and to determine the factors predictive of accurate histology.

Methods: In total, 142 patients with an indication for a TUS-guided biopsy of a pancreatic mass were analyzed. A single pass of an 18-gauge Biomol needle was carried out by the Menghini technique. The accuracy, sensitivity, and specificity of the procedure in terms of correctly diagnosing an inflammatory or neoplastic lesion were determined. The patients' characteristics, the size and location of the mass, and the sonographers' experience in performing TUS were recorded.

Results: The sampling was unsuccessful in 24 cases, owing to the deep localization of lesions (57%), bloating (33%), or low patient compliance (10%). The accuracy, sensitivity, and specificity of the 118 successful biopsies were 81%, 79%, and 100%, respectively. A biopsy core was obtained in 90 of the 118 patients (76%) in whom the procedure was attempted. In the multivariate analysis, lesion size (≤ 20 mm vs. > 20 mm) (OR = 5.3 [1.7-17.0]) and operator experience (OR = 4.4 [1.6-12.1]) predicted the acquisition of adequate samples. With an expert sonographer, the accuracy, sensitivity, and specificity were 87%, 85%, and 100%, respectively. Two adverse events were registered: mild abdominal pain and a hypotensive crisis.

Conclusions: The present investigation highlights the optimal performance of a TUS-guided biopsy of a pancreatic mass. Because of its simplicity and safety, the procedure needs to be included among the recommended investigative options.
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http://dx.doi.org/10.1007/s40477-020-00542-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137799PMC
June 2021

Impact of the COVID-19 outbreak and the serum prevalence of SARS-CoV-2 antibodies in patients with inflammatory bowel disease treated with biologic drugs.

Dig Liver Dis 2021 03 6;53(3):277-282. Epub 2021 Jan 6.

Fondazione Casa Sollievo della Sofferenza, Division of Gastroenterology, San Giovanni Rotondo, Italy.

Background: Patients receiving biologic therapies are at risk for viral infections. This study investigated the impact of the SARS-CoV-2 infection and the serum prevalence of SARS-CoV-2 antibodies in patients with inflammatory bowel disease (IBD) treated with biologic drugs.

Methods: Information on demography, co-morbidities, clinical data regarding IBD, symptoms suggestive of the SARS-CoV-2 infection, close contacts with SARS-CoV-2 positive patients, hospitalization, and therapies administered for COVID-19 was collected for all patients who were being treated with biologic drugs. All patients underwent SARS-CoV-2 antibody testing.

Results: Two hundred and fifty-nine patients (27 children) with a mean age of 42.2 ± 16.7 years (range 9 - 88) and a mean duration of disease of 13.4 ± 10 years (range 0.2 - 49) were enrolled. One hundred four patients (40.2%) had ulcerative colitis, and 155 (59.8%) had Crohn's disease. About the therapy: 62 patients were receiving infliximab, 89 adalimumab, 20 golimumab, 57 vedolizumab, 27 ustekinumab, 1 thalidomide, and 3 an experimental compound. The mean Charlson Comorbidity Index was 2. Thirty-two patients (12.3%) reported respiratory symptoms, and 2 of them were hospitalized (0.77%). Two patients resulted positive for IgG against SARS-CoV-2 (0.77%).

Conclusions: In patients with IBD, treatment with biologic drug does not represent a risk factor for the SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.dld.2020.12.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834247PMC
March 2021

Safety and efficacy of switching from infliximab biosimilar CT-P13 to infliximab biosimilar SB2 in patients with inflammatory bowel disease.

Eur J Gastroenterol Hepatol 2021 02;32(2):201-207

Division of Gastroenterology, Department of Medical Science, Fondazione Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.

Introduction: For patients with inflammatory bowel diseases, switching from infliximab originator to biosimilars is effective and safe. Few data on single switch have been published, and data on multiple switches of different infliximab are unavailable.

Methods: A retrospective analysis of patients who switched from CT-P13 to SB2, and of those with multiple switches among different infliximab compounds was conducted. Clinical activity, C reactive protein (CRP), adverse events (AE) and loss of response (LOR) were recorded.

Results: Thirty-six patients (26 males, 14 Crohn's disease and 22 ulcerative colitis) were enrolled and followed up for >6 months. All patients switched from CT-P13 to SB2; 12 of them (33.3%) had already switched from reference Infliximab to CT-P13, and for the remaining patients CT-P13 was the first infliximab. The clinical remission rate six months before and three months after SB2-switch was the same (58.3%) and the rate of mild activity varied from 27.8 to 33.3% (P = 0.68); the percentage of patients with normal CRP values passed from 94.4 to 91.7% (P = 1). Two patients (5.5%) had AE and 11 (30.5%) a LOR. At univariate analysis, patients with a single switch had a non-significant risk of LOR during SB2 [odds ratio (OR) = 7.86; 95% confidence interval (CI) 0.87-71, P = 0.06]. SB2-LOR was associated with previous AE under CT-P13 (OR = 9.1, 95% CI 0.82-100, P = 0.07). None of such factors was significant at multivariate analysis.

Conclusion: Switching from CT-P13 to SB2 seems to be safe and effective either in patients with a single than in those with multiple switches.
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http://dx.doi.org/10.1097/MEG.0000000000001988DOI Listing
February 2021

Correction to: A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies.

Dig Dis Sci 2020 Nov 25. Epub 2020 Nov 25.

Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.

The original version of the article unfortunately contained an error in the first name and the surname of the all authors in the author group. Below is the corrected first name and the surname of the authors.
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http://dx.doi.org/10.1007/s10620-020-06731-3DOI Listing
November 2020

A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies.

Dig Dis Sci 2021 Oct 3;66(10):3352-3358. Epub 2020 Nov 3.

Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.

Background: The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal inflammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by flow cytometry or frozen section immunohistochemistry (IHC), is a specific marker for CD.

Aim: To establish a new IHC assay for γδ-IELs applicable to formalin-fixed paraffin-embedded (FFPE) duodenal biopsies.

Methods: We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis.

Results: Compared to those in non-celiac controls (n = 51), γδ-IEL density was significantly increased in newly diagnosed celiac disease patients (n = 22, p < 0.0001). In ROC-curve analysis, the cutoff of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specificity 95%). γδ-IEL density in CD patients on a gluten-free diet (n = 53) were also higher than in controls (p < 0.0001), but lower than those in newly diagnosed CD (p < 0.0001). The diagnostic value of γδ-IELs outperformed that of CD3 + IELs in both patient groups. γδ-IELs were better than CD3 + IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n = 12).

Conclusions: Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specificity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease.
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http://dx.doi.org/10.1007/s10620-020-06680-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449760PMC
October 2021

Early-Onset Diabetes as Risk Factor for Pancreatic Cancer: miRNA Expression Profiling in Plasma Uncovers a Role for miR-20b-5p, miR-29a, and miR-18a-5p in Diabetes of Recent Diagnosis.

Front Oncol 2020 11;10:1567. Epub 2020 Sep 11.

Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, Italy.

The high prevalence of early-diabetes in patients with pancreatic cancer (PanC) implies that its recognition could help identify people at high risk of developing PanC. Candidate microRNAs (miRNAs) associated with recent diabetes were screened from our previous miRNA expression profiling on 10 pools of plasma from PanC patients and non-PanC controls, both including also subjects with early- and late-diabetes. The droplet digital PCR (ddPCR) was used to re-test candidate miRNAs in a new independent cohort of 69 subjects (40 PanC, 29 non-PanC) with early- (17 PanC, 13 non-PanC) or late-diabetes (23 PanC, 16 non-PanC), and in 100 non-diabetic healthy subjects (HS). miRNA levels were evaluated for differences between subjects enrolled into the study and for their diagnostic performance, also compared to the CA 19-9 determinations. MiR-20b-5p, miR-29a, and miR-18a-5p were selected from the previous miRNA expression profiling. The ddPCR confirmed the increase of miR-20b-5p and miR-29a levels in PanC with early- compared to those with late-diabetes. Conversely, miR-20b-5p, miR-29a, and miR-18a-5p were over-expressed in both PanC and non-PanC with recent diabetes compared to HS, and each miRNA achieved a similar diagnostic performance in distinguishing either PanC or non-PanC with early-diabetes from HS (miR-20b-5p: AUC = 0.877 vs. AUC = 0.873; miR-29a: AUC = 0.838 vs. AUC = 0.810; miR-18a-5p: AUC = 0.824 vs. AUC = 0.875). Despite miR-20b-5p and miR-29a expressions were also higher both in PanC and non-PanC with late-diabetes with respect to HS, the diagnostic accuracy in PanC with late-diabetes vs. HS reached by each miRNA (miR-20b-5p: AUC = 0.760; miR-29a: AUC = 0.630) was lower than the ones achieved in PanC with early-diabetes vs. HS. Furthermore, miR-20b-5p achieved a higher diagnostic accuracy to discriminate non-PanC with early-diabetes from HS (AUC = 0.868; SP = 81%; PPV = 32.1%) compared to the CA 19-9 (AUC = 0.700; SP = 40.0%; PPV = 15.5%), and the joint (miR-20b-5p and CA 19-9) discrimination ability was higher than the one achieved by the CA 19-9 tested alone (AUC = 0.900, = 0.003). Our data highlighted the association between miR-18a-5p and early-diabetes, and suggested for miR-20b-5p and miR-29 a role in identifying early diabetes in PanC, albeit not as an early manifestation of cancer. MiR-20b-5p as more informative marker than CA 19-9 in distinguishing non-PanC with recent diabetes from HS was also uncovered.
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http://dx.doi.org/10.3389/fonc.2020.01567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533599PMC
September 2020

Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer.

Int J Mol Sci 2020 Sep 27;21(19). Epub 2020 Sep 27.

Division of Gastroenterology, IRCCS, Fondazione Casa Sollievo della Sofferenza, viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy.

Fusion genes and epigenetic regulators (i.e., miRNAs and long non-coding RNAs) constitute essential pieces of the puzzle of the tumor genomic landscape, in particular in mechanisms behind the adenoma-to-carcinoma progression of colorectal cancer (CRC). In this work, we aimed to identify molecular signatures of the different steps of sporadic CRC development in eleven patients, of which synchronous samples of adenomas, tumors, and normal tissues were analyzed by RNA-Seq. At a functional level, tumors and adenomas were all characterized by increased activity of the cell cycle, cell development, cell growth, and biological proliferation functions. In contrast, organic survival and apoptosis-related functions were inhibited both in tumors and adenomas at different levels. At a molecular level, we found that three individuals shared a tumor-specific fusion named MRPS31-SUGT1, generated through an intra-chromosomal translocation on chromosome 13, whose sequence resulted in being 100% identical to the long non-coding RNA (lncRNA) MRPS31P5. Our analyses suggest that MRPS31P5 could take part to a competitive endogenous (ce)RNA network by acting as a miRNA sponge or/and as an interactor of other mRNAs, and thus it may be an important gene expression regulatory factor and could be used as a potential biomarker for the detection of early CRC events.
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http://dx.doi.org/10.3390/ijms21197120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582694PMC
September 2020

Landmarks for dual biological therapy in inflammatory bowel disease: lesson from two case reports of vedolizumab in combination with ustekinumab.

Eur J Gastroenterol Hepatol 2020 12;32(12):1579-1582

Department of Gastroenterology and Digestive Endoscopy, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, San Giovanni Rotondo, Foggia.

Inflammatory bowel disease (IBD) is a chronic and disabling disorder. Severity of IBD is prominent among refractory with patients with concomitant immune-mediated disorders. Among those patients, dual biological therapy (DBT) has been suggested as an alternative approach to spare steroids and avoid surgery. However, pieces of evidence on clinical outcomes among patients receiving DBT are still limited. We present two cases of IBD patients, with dermatological comorbidity, treated with a combination of vedolizumab and ustekinumab, identifying possible landmarks to address therapeutic choice. No patient experienced adverse events in the follow-up period and both obtained complete clinical remission. DBT may be an effective approach to consider in selected patients with refractory IBD with concomitant severe immune-mediated diseases taking into account medical history of the patient, presence, and type of concomitant extraintestinal manifestations, safety profile of selected DBT, licensed therapeutic indications, and costs.
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http://dx.doi.org/10.1097/MEG.0000000000001919DOI Listing
December 2020

Endoscopic stenting for colorectal cancer obstruction as a bridge-to-surgery strategy.

Eur J Clin Invest 2020 Apr 22:e13252. Epub 2020 Apr 22.

Unit of Gastroenterology and digestive endoscopy, Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.

Background: Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self-expanding metal stents (SEMS) have been increasingly used as a bridge-to-surgery (BTS) strategy.

Materials And Methods: In an 8-year period, consecutive patients with acute left-sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease-free survival (DFS) of the two therapeutic options.

Results: Forty-five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil-lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43-0.98, P = .04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P = .33) and DFS (36 in SEMS; 35 in ES, P = .35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4-16.6, P = .04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08-50, P = .04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16-0.92, P = .03). At multivariate analysis, no feature retained an independent predictive power.

Conclusion: SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients.
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http://dx.doi.org/10.1111/eci.13252DOI Listing
April 2020

Genome-wide association study identifies an early onset pancreatic cancer risk locus.

Int J Cancer 2020 10 1;147(8):2065-2074. Epub 2020 May 1.

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 × 10 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.
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http://dx.doi.org/10.1002/ijc.33004DOI Listing
October 2020

Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer.

Front Oncol 2020 4;10:44. Epub 2020 Feb 4.

Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della, Foggia, Italy.

The burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients' clinical phenotypes and outcomes. MiRNA expression profiles in plasma were investigated by using a two-stage process. In a discovery phase, miRNAs levels were analyzed using the GeneChip™ miRNA 4.0 Affymetrix assay in 10 pools of plasma samples from PanC patients and HS; in a validation phase, significantly altered miRNAs were re-tested in independent cohorts of cancer patients and controls by droplet digital PCR (ddPCR). The diagnostic performance of the resulting miRNAs was compared to CA 19-9 determinations, and the associations of miRNAs plasma levels with patients' clinical phenotypes and outcomes were also taken into account. Bioinformatics selection of miRNAs differentially expressed in plasma uncovered miR-18a-5p, miR-122-5p, miR-1273g-3p, and miR-6126 as candidate oncogenic miRNAs in PanC. The ddPCR technology confirmed the significant over-expression of miR-122-5p, miR-1273g-3p, and miR-6126 in PanC compared to HS, in line with the trend of the CA 19-9 levels. Plasma levels of miR-1273g-3p, in combination with CA 19-9, showed higher power in distinguishing PanC patients from HS compared to the CA 19-9 tested alone, with a gain in both sensitivity and negative predictive value indicating a low false-negative rate (SE = 90.2% and NPV = 92.3% vs. SE = 82.1% and NPV = 87.9%). None of the oncogenic miRNAs were able to distinguish between a neoplastic and a proliferative/inflammatory disease of the pancreas, and were not able to stratify subjects according to the clinical risk for the disease. The only valuable association in PanC patients was found between miR-1273g-3p and tumor stage, and increased miR-122-5p levels emerged as independent negative prognostic factor for PanC patients (HR = 1.58, 95% CI = 1.03-2.43, = 0.037). Our data highlighted a role for circulating miR-1273g-3p and miR-122-5p as new diagnostic and prognostic biomarkers for PanC.
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http://dx.doi.org/10.3389/fonc.2020.00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010806PMC
February 2020

microRNA-mRNA network model in patients with achalasia.

Neurogastroenterol Motil 2020 03 26;32(3):e13764. Epub 2019 Nov 26.

Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Background: Achalasia is a rare idiopathic disease with a complex etio-pathogenesis still unknown. This study aimed to identify microRNA (miRNA)-mRNA regulatory networks underlying achalasia.

Methods: The investigation was performed in tissue specimens from 11 patients and five controls using the microarray technology followed by an integrated bioinformatics analysis.

Key Results: One hundred and six miRNAs were significantly up-regulated and 64 were down-regulated in achalasia patients. The expression of the most 10 differential expressed miRNAs (miR-122-5p, miR-133a-3p, miR-504-5p, miR-187-3p, miR-133b, miR-200c-3p, miR-375, miR-200b-5p, miR-200b-3p, and miR203a) was confirmed by droplet digital PCR in an independent cohort. The interactions between the significant miRNAs and their targets uncovered 14 miRNA-mRNA interacting pairs with experimentally predicted genes (ie, FN1, ROCK2, DPYSL2), and 35 pairs with not experimentally target genes (ie, SULF1, MRVI1, PRKG1); all genes were involved in immune cell trafficking, skeletal and muscular system development, nervous system development macro-processes.

Conclusion & Inferences: The mRNA-miRNA regulatory networks described in this study provide new insights in the genetic background of the disease, suggesting further investigations in novel pathogenic mechanisms.
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http://dx.doi.org/10.1111/nmo.13764DOI Listing
March 2020

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.

Dig Dis Sci 2020 06 13;65(6):1767-1776. Epub 2019 Nov 13.

Gastroenterology and Artificial Nutrition Department, "San Nicola Pellegrino" Hospital, Trani, Italy.

Background: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis.

Aims: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response.

Methods: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system.

Results: A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2-1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients.

Conclusions: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.
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http://dx.doi.org/10.1007/s10620-019-05904-zDOI Listing
June 2020

Droplet digital PCR quantification of miR-1290 as a circulating biomarker for pancreatic cancer.

Sci Rep 2018 11 6;8(1):16389. Epub 2018 Nov 6.

Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), 71013, Italy.

Droplet digital PCR was used to validate miR-1290 as circulating biomarker for pancreatic cancer (PC). The diagnostic performance of miR-1290 was evaluate in 167 PC patients and 267 healthy subjects at clinical risk of developing the disease (HS). MiR-1290 plasma levels were compared to CA 19-9 determinations, and the combination of the two biomarkers was also taken into account. Plasma levels of miR-1290 were higher in PC patients compared to HS (p = 2.55 × 10). A similar trend was observed for CA 19-9 determinations (p = 1.03 × 10). ROC curve analysis revealed that miR-1290 in combination with CA 19-9 was effective for discriminating between PC patients and HS (AUC = 0.956, 95% CI = 0.933-0.979) than the two biomarkers tested alone (miR-1290: AUC = 0.734, 0.678-0.789; CA 19-9: AUC = 0.914, 0.877-0.951). The discriminating ability was higher when only PC patients with low or slightly increased CA 19-9 levels were compared with HS. MiR-1290 concentrations were not able to differentiate between PC patients with single or multiple risk factors for developing PC. Our data suggest that the absolute quantification of circulating miR-1290 levels does not allow to select patients at clinical risk of PC for entry into a surveillance program, and underline the methodological challenges still existing in utilizing circulating miRNAs as new promising biomarkers for PC.
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http://dx.doi.org/10.1038/s41598-018-34597-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219528PMC
November 2018

The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy.

Dig Liver Dis 2019 03 21;51(3):434-437. Epub 2018 Sep 21.

Biomedical Department of Internal and Specialized Medicine (Di.Bi.M.I.S.), University of Palermo, Italy. Electronic address:

Background: There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs).

Aim: To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking.

Methods: All subjects aged ≥18 years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014.

Results: The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p < 0.01) but not in those positive for other HBV markers.

Conclusions: These findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker.
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http://dx.doi.org/10.1016/j.dld.2018.09.010DOI Listing
March 2019

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

Int J Cancer 2019 03 12;144(6):1275-1283. Epub 2018 Nov 12.

Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University, Rome, Italy.

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10 , p = 3.27 × 10 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10 for highest vs. lowest quintile; p = 1.82 × 10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.
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http://dx.doi.org/10.1002/ijc.31928DOI Listing
March 2019

Forecasting Hepatitis C liver disease burden on real-life data. Does the hidden iceberg matter to reach the elimination goals?

Liver Int 2018 12 10;38(12):2190-2198. Epub 2018 Aug 10.

Internal Medicine, Villa Sofia-Cervello Hospital, Palermo, Italy.

Background & Aims: Advances in direct-acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked-to-care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030.

Methods: Using a modelling approach grounded in Italian real-life data of diagnosed and treated patients, different linkage-to-care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals.

Results: Under the 40% linked-to-care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948-1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0-F3 cases. Under the 60% linked-to-care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958-1978 birth cohorts could capture 55% of F0-F3 individuals. Under the 80% linked-to-care scenario, screening limited in 1968-1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals.

Conclusion: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required.
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http://dx.doi.org/10.1111/liv.13901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282782PMC
December 2018

Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies.

Microbiome 2018 05 22;6(1):92. Epub 2018 May 22.

Division of Gastroenterology, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, 1, 71013, San Giovanni Rotondo, FG, Italy.

Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.
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http://dx.doi.org/10.1186/s40168-018-0483-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964925PMC
May 2018

Exploring the microbiota to better understand gastrointestinal cancers physiology.

Clin Chem Lab Med 2018 08;56(9):1400-1412

Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo (FG), Italy, Phone: +39-0882.416281, Fax: +39-0882.410271.

Gastrointestinal cancers account for around 40% of cancer-related deaths worldwide, representing a global health burden. There is a growing body of evidence highlighting the link between microbiota and gastrointestinal tumorigenesis and/or resistance to therapy. In the present manuscript, we reviewed the published studies on the relationship between the microbiota and the different gastrointestinal tumors, namely, gastric, colorectal and esophageal, including also the cancer of accessory organs such as liver and pancreas. There is an emergent interest in the manipulation of gastrointestinal microflora in order to understand the gastrointestinal tumorigenesis' processes and the establishment of chemoresistance mechanisms.
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http://dx.doi.org/10.1515/cclm-2017-1163DOI Listing
August 2018

Optimization of direct anti-viral agent treatment schedule: Focus on HCV genotype 3.

United European Gastroenterol J 2018 Mar 20;6(2):225-237. Epub 2017 Jun 20.

Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, Italy.

Background And Aim: Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option.

Methods: Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs.

Results: A total of 233 patients with HCV genotype 3 were enrolled. Cirrhotic patients accounted for 83.7%. Overall, the SVR12 rate was achieved by 205 patients (88.0%); the SVR rates were 78.8% after sofosbuvir/ribavirin, 92.5% after sofosbuvir/daclatasvir ± ribavirin, and 100% after sofosbuvir/ledipasvir (seven patients). No difference in rate of SVR was observed in cirrhotic and non-cirrhotic patients (92.2 vs 94.4) using a combination regimen of NS5A and NS5B inhibitors.The systematic review of the literature provided data of 3311 patients: The mean weighted SVR12 rate was 84.4% (CI: 80.4-87.8); the rates varied from 79.0% (CI: 70.9-85.3) with sofosbuvir/ribavirin, to 83.7% (CI: 66.2-93.1) with sofosbuvir/ledispavir, and to 88.2% (CI: 83.3-91.7) with sofosbuvir/daclatasvir.

Conclusions: Our results reinforce the concept that patients with HCV genotype 3 should no longer be considered difficult-to-treat individuals. The optimal therapeutic regimen for these patients appears to be the combination sofosbuvir/daclatasvir, administered for 12 weeks without the use of RBV in non-cirrhotic patients. In cirrhotics the meta-analytic approach suggests extending therapy to 24 weeks.
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http://dx.doi.org/10.1177/2050640617717158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833227PMC
March 2018
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