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Background Abdominal ultrasound (US) is a reliable method for visualizing gastric wall layers and measuring their thickness. The objective of this study is to characterize the ultrasound features of H. pylori -induced gastritis and assess its predictive potential role for this condition. Methods A cohort of 119 patients underwent gastroscopy with biopsy and abdominal US to evaluate antral wall thickness (AWT), submucosal wall thickness (SLT), mucosal wall thickness (MLT), gastric motility, and the presence of ingested material. They were divided into three groups: group A (normal mucosa without H. pylori infection), group B (gastritis H. pylori negative) and group C (gastritis H. pylori positive). Results : SLT and reduced gastric motility were significantly increased in the H. pylori gastritis group ( p < 0.001). Multivariate analysis identified SLT as the only significant independent predictor of H. pylori gastritis ( p < 0.001). An SLT threshold of 1.55 mm was determined as optimal for differentiating H. pylori -positive patients from -negative, yielding a sensitivity of 77% and a specificity of 72%. Conclusions These findings suggest that H. pylori gastritis is characterized by submucosal layer thickening and impaired gastric motility.

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.

Objective: From September 2020, a second wave of COVID-19 pandemic started. We aimed at exploring the impact of SARS-CoV-2 infection in IBD patients during the two waves., Patients and Methods: All IBD patients with a confirmed diagnosis of SARS-CoV-2 infection were enrolled. They were sorted into two groups (those infected before September 2020, and those from September 2020 to January 2021) and compared by demographic and clinical data., Results: Twenty-five patients (out of about 600 with a follow-up visit) were infected with SARS-CoV-2 (4.1%). Sixteen were male and the mean age was 46.5 ± 14.3 years (range 24-74). Six were smokers and 11 had comorbidities; 2 were on steroids and 17 on immunosuppressants or biologics. Three patients (12%) needed hospitalization and other three patients were treated with azithromycin, steroids and LMWH, all of them during the second wave. No patient died or developed any sequelae. Two subjects were infected during the first wave (0.3 vs. 3.83, p<0.0001). Non-significant differences were found between the two groups., Conclusions: A higher number of IBD patients were infected during the second wave. No patient developed a severe form of pneumonia, even those treated with immunosuppressants or biologics. No risk factor for hospitalization was found.

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.

Aim: The rates of post-operative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) are between 5% and 30%. Nowadays, pancreaticojejunostomy (PJ) represents the most common type of reconstruction after PD, but the ideal technique is still debated. Our randomized trial was conceived with the intent to evaluate if two variants of PJ could influence the post-operative outcome in term of early complications., Material and Methods: Forty-eight consecutive patients treated with PD were randomized into 2 groups (Group 1 or Large Jejunal Incision or LJI group and Group 2 or Small Jejunal Incision or SJI group). Outcome measures were the operative time, postoperative complications, length of postoperative hospital stay, amylase content in drains., Results: wenty-two patients were enrolled in the LJI and 26 in the SJI group. Median operative times did not differ between the 2 groups. The groups were homogeneous in respect to the median age of patients, the clinical presentation of jaundice and the presence of percutaneous biliary drainage (PBD). POPF developed in 3/22 (13.6%) and 1/26 (4%) patients among the LJI and SJI group respectively (3 grade B and 1 grade C respectively) (p=0.341). PPH occurred in 8/22 (36%) and 2/26 (8%) patients among the LJI and SJI group, respectively (p=0.018). The Amylase content in the drainage fluid measured at the 5th postoperative day showed a higher value in patients who underwent LJI anastomosis compared to those with SJI anastomosis [LJI group: 26.5 (6-254) U/l vs SJI group: 7 (0-38) U/l; p=0.051]. Delayed Gastric Emptying (DGE) was not different. The multivariate logistic regression analysis demonstrated both LJI anastomosis and DGE as independent predictors for pancreatic fistula (DGE: OR=20.04, CI 95%=1.92-208.83, P=0.012; LJI anastomosis: OR=24.58, CI 95%=1.71-354.32, P=0.019) and PPH (DGE: 30.5, CI 95%=3.02-308.16, P=0.004; LJI anastomosis: OR=12.71, CI 95%=1.23-131.55, P=0.033)., Conclusions: Based on the present results, we suggest to adopt what a "pancreas duct-oriented" approach: if pancreas duct is large a SJI-PJ is recommended; if the duct is < than 3 mm, a LJI must be preferred. Our conclusion is that the association of some surgeons to perform always the techniques with them are more confident is a concept of the past: recent data suggest that the pancreatic surgeon must have the different techniques in his "armamentarium" and varying the technique depending on local characteristic of the pancreas to allow a tailored approach to the patient., Key Words: Pancreaticojejunostomy, Pancreatic fistula, Surgical Sutcome.

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 -16 ). A similar trend was observed for CA 19-9 determinations (p = 1.03 × 10 -47 ). 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.

Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology., Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features., Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P = .021), larger tumours (P = .038), better liver function (higher percentage of Child-Pugh class A [P = .007] and MELD < 10 [P = .003]), higher percentage of metastasis (P = .024) and lower percentage of portal vein thrombosis (P = .010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco-regional therapies for BCLC stage B patients with 3-5 features (P = .012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P = .046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead-time adjusted survival., Conclusions: Our "real world" study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Data on the prevalence of hepatitis C virus (HCV) infection in Italy are outdated and usually derived from studying residents in small towns., Methods: To assess prevalence of and risk factors for HCV infection among Italian residents in 5 metropolitan areas, subjects ≥20 years of age were randomly selected from the list of the general practitioners' registers in 2015. Anti-HCV was tested by a salivary test; HCV-RNA, HCV genotypes, and ALT were determined in positive individuals. Logistic regression analysis evaluated independent risk factors for HCV., Results: Of the 4907 enrolled subjects, 112 (2.3%) tested anti-HCV positive. The prevalence of HCV increased with age, from 0.2% in subjects born after the year 1984, to 4.2% in those born before the year 1935 (P < 0.01). The birth-cohort prevalence peaked (7.0%) in elderly. Serum HCV-RNA was detected in 1.7% of the whole population. Nearly 80% of anti-HCV subjects were aware of their status. Age > 70 years, low education level, past use of glass syringes, blood transfusion, intravenous drug use, and cohabitation with an anti-HCV positive subject predicted the HCV positivity., Interpretation: In metropolitan areas in Italy, HCV is prevalent in elderly, reflecting a cohort effect determined by modalities of viral transmission no longer operative. The impact of the infection will further diminish in the years to come due to the natural depletion of the reservoir of the virus. This age pattern and the high proportion of subjects aware of their status do not warrant a policy of screening., (Copyright © 2018. Published by Elsevier B.V.)

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.

Objectives: To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy., Participants: Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis)., Measurements: We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered., Results: Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14 ± 4 months (range 5-23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk., Conclusion: In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Background: Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D'Amico might provide new insights on timing for antiviral therapy., Methods: We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n=575) or cirrhosis (n=2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines., Results: The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients., Conclusion: Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3-5) who are at greatest risk and have the most to gain from therapy., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis., Aim: To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection., Methods: A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate., Results: Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6-82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8-80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4-89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4-89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients., Conclusion: The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents., (© 2017 John Wiley & Sons Ltd.)

Background: In cirrhotics with low circulating platelets (PLT), restoration of normal cell counts has been traditionally recommended before invasive procedures. However, there is neither consensus on the PLT transfusion threshold nor evidence of its clinical efficacy., Patients: In order to fill this gap of knowledge, we prospectively collected and analyzed data on circulating PLT counts [and International Normalized Ratio (INR)] values in a case series of 363 cirrhotics scheduled to undergo invasive investigations. PLT and/or fresh-frozen plasma (FFP) units were infused at the discretion of the attending physician, and the occurrence of post-procedural bleeding was related to pre-and post-infusion results., Results: 852 Procedures were carried out in 363 cirrhotics sub-grouped according to the Child-Pugh-Turcotte (CPT) classification (class A/B/C: 124/154/85). The infusion of PLT and/or FFP improved only marginally circulating PLT counts and INR values. Ten post-procedural bleeds occurred in the whole case series, i.e. 1 episode every 85 procedures or every 36 patients. Post-procedural bleeding was unrelated to the PLT counts, to the degree of INR abnormalities, nor to the CPT classes, but was more frequent in patients who underwent repeated investigations. In the 10 patients with the most profound alterations in PLT and/or INR values, no post-procedural bleeding occurred., Conclusions: In cirrhotic patients with low PLT and/or abnormal INR values undergoing invasive investigations, post-procedural bleeding was rare and unpredicted by PLT counts or abnormal INR values. In particular, the recommendation to infuse platelets when counts are <50×10 3 /L is not substantiated by this case series of cirrhotic patients., (Copyright © 2016. Published by Elsevier B.V.)

Background: Crohn's disease (CD) is a pathologic condition with different clinical expressions that may reflect an interplay between genetics and environmental factors. Recently, it has been highlighted that three genetic markers, NOD2, MHC and MST1, were associated to distinct CD sites, supporting the concept that genetic variations may contribute to localize CD. Genetic markers, previously shown to be associated with inflammatory bowel disease (IBD), were tested in CD patients with the aim to better dissect the genetic relationship between ileal, ileocolonic and colonic CD and ascertain whether a different genetic background would support the three disease sites as independent entities., Methods: A panel of 29 SNPs of 19 IBD loci were analyzed by TaqMan SNP allelic discrimination method both evaluating their distinct contribute and analyzing all markers jointly., Results: Seven hundred and eight CD patients and 537 healthy controls were included in the study. Of the overall population of patients, 237 patients had an ileal involvement (L1), 171 a colonic localization (L2), and the 300 remaining an ileocolon location (L3). We confirmed the association for 23 of 29 variations (P < 0.05). Compared to healthy controls, 16 variations emerged as associated to an ileum disease, 7 with a colonic disease and 14 with an ileocolonic site (P < 0.05). Comparing ileum to colonic CD, 5 SNPs (17%) were differentially associated (P < 0.05). A genetic model score that aggregated the risks of 23 SNPs and their odds ratios (ORs), yielded an Area Under the Curve (AUC) of 0.70 for the overall CD patients. By analyzing each CD location, the AUC remained at the same level for the ileal and ileocolonic sites (0.73 and 0.72, respectively), but dropped to a 0,66 value in patients with colon localization., Conclusions: Our findings reaffirm the existence of at least three different subgroups of CD patients, with a genetic signature distinctive for the three main CD sites., Competing Interests: The authors have declared that no competing interests exist.

Background: Therapy of chronic hepatitis D with Interferon is successful when testing for HDV-RNA turns negative. This end-point is disputed., Aim: To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV-RNA in pegylated interferon (Peg-IFN)-treated chronic hepatitis D (CHD)., Methods: Sixty-two patients with CHD, treated with Peg-IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV-RNA (responders, R), 12 cleared the HDV-RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV-RNA (nonresponders, NR)., Results: In responders, at baseline the median value (mv) of HBsAg and HDV-RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV-RNA was undetectable in 12 patients. In NR, the pre-therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV-RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV-RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV-RNA from baseline to month 6 predicted the clearance of this marker., Conclusions: A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV-RNA. Quantitative HBsAg may predict the long-term response to Peg-IFN therapy and provide a guide to prolong or stop treatment., (© 2016 John Wiley & Sons Ltd.)

Background: A pelvic magnetic resonance imaging (MRI) represents the front-line method for evaluating perianal disease in patients with inflammatory bowel disease (IBD). Recently, transperineal ultrasonography (TPUS) has been proposed as a simple, safe, time-sparing and useful diagnostic technique to assess different pathological conditions of the pelvic floor., Aim: The aim of this prospective single centre study was to evaluate the accuracy of TPUS versus MRI for the detection and classification of perineal disease in IBD patients., Methods: From November 2013 to November 2014, 28 IBD patients underwent either TPUS or MRI. Fistulae and abscesses were classified according to Parks' and AGA's classification methods. A concordance was assessed by k statistics., Results: Overall, 33 fistulae and 8 abscesses were recognized by TPUS (30 and 7 by MRI, respectively). The agreement between TPUS and MRI was 75% according to Parks' classification (k=0.67) and 86% according to AGA classification (k=0.83), while it was 36% (k=0.34) for classifying abscesses., Conclusions: TPUS proved to be as accurate as MRI for detecting superficial and small abscesses and for classifying perianal disease. Both examinations may be performed at the initial presentation of the patient, but TPUS is a cheaper, time-sparing procedure. The optimal use of TPUS might be in follow-up patients., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Altered functioning of the biological clock is involved in cancer onset and progression. MicroRNAs (miRNAs) interact with the clock genes modulating the function of genetically encoded molecular clockworks. Collaborative interactions may take place within the coding-noncoding RNA regulatory networks. We aimed to evaluate the cross-talk among miRNAs and clock genes in colorectal cancer (CRC). We performed an integrative analysis of miRNA-miRNA and miRNA-mRNA interactions on high-throughput molecular profiling of matched human CRC tissue and non-tumor mucosa, pinpointing core clock genes and their targeting miRNAs. Data obtained in silico were validated in CRC patients and human colon cancer cell lines. In silico we found severe alterations of clock gene-related coding-noncoding RNA regulatory networks in tumor tissues, which were later corroborated by the analysis of human CRC specimens and experiments performed in vitro. In conclusion, specific miRNAs target and regulate the transcription/translation of clock genes and clock gene-related miRNA-miRNA as well as mRNA-miRNA interactions are altered in colorectal cancer. Exploration of the interplay between specific miRNAs and genes, which are critically involved in the functioning of the biological clock, provides a better understanding of the importance of the miRNA-clock genes axis and its derangement in colorectal cancer., Competing Interests: The authors declare that there are no conflicts of interest with respect to the authorship and/or publication of this article.

Aim: To evaluate similarities and differences in HCV-1 subtypes 1a and 1b in the presenting clinical features and the response to peg-interferon and ribavirin (Peg/RIBA)., Patients and Methods: A total of 1,233 naïve patients with HCV genotype-1 infection, 159 (13%) with subtype 1a and 1,074 (87%) with subtype 1b were treated with Peg-IFN/RIBA at 12 Italian centers. Covariates included in the logistic model were age, gender, BMI, serum alanine aminotransferase, serum gamma-glutamiltranspeptidase (γGT), platelets counts, liver fibrosis, the occurrence of type 2 diabetes, baseline viremia, and IL28B genotype., Results: At multivariate analysis, baseline characteristics differentiating patients with HCV-1a versus HCV-1b were young age, male gender, no F4 fibrosis, and no diabetes. SVR was achieved by 37% of patients with subtype 1b and 45% of those with subtype 1a, a nonsignificant difference of 8% (p = 0.069). In patients with subtype 1a, predictors of SVR were IL28B CC (OR 5.78, CI 1.98-16.83), RVR (OR 4.18, CI 1.66-10.55), female gender (OR 2.83, CI 1.83-6.78), and HCVRNA (OR 0.55, CI 0.32-0.96). In patients with subtype 1b, the ranking of predictors was levels RVR (OR 6.49, CI 4.32-9.73), IL28B CC (OR 3.32, CI 2.15-4.58), γGT (OR 1.59, CI 0.14-2.22), HCVRNA (OR 0.61, CI 0.47-0.79), and age (OR 0.01, CI 0.02-0.42)., Conclusion: In Italy HCV-1 subtype 1a prevails in young male patients with less advanced liver damage, findings that imply a more recent spreading of the infection with this viral strain. The two HCV-1 subtypes appear equally responsive to Peg-IFN/RIBA, with IL28B genotyping and monitoring of RVR mostly influencing the therapeutic response.

Background & Aims: In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR., Results: In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, and rs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860CC&#95;ss469415590TT/TT&#95;rs8099917TT or the diplotype rs12979860CC&#95;ss469415590TT/TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917TT SNP was associated with improved response prediction., Conclusion: In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Aim was to select naïve patients with genotype 1 chronic hepatitis C having a high probability of response to Peg-interferon+ribavirin therapy., Methods: In 1073 patients (derivation cohort), predictors of rapid and sustained virological response were identified by logistic analysis; regression coefficients were used to generate prediction models for sustained virological response. Probabilities at baseline and treatment week 4 were utilized to develop a decision rule to select patients with high likelihood of response. The model was then validated in 423 patients (validation cohort)., Results: In the derivation cohort, 257 achieved rapid virological response and 818 did not, with sustained virological response rates of 80.2% and 25.4%, respectively; interleukin-28B polymorphisms, fibrosis staging, gamma-glutamyl transferase, and viral load predicted sustained virological response. Assuming a <30% sustained virological response probability for not recommending Peg-interferon+ribavirin, 100 patients (25.6%) in the validation cohort were predicted a priori to fail this regimen. Assuming a ≥80% sustained virological response probability as a threshold to continue with Peg-interferon+ribavirin, 61 patients were predicted to obtain sustained virological response, and 55 of them (90.2%) eventually did., Conclusions: This model uses easily determined variables for a personalized estimate of the probability of sustained virological response with Peg-interferon+ribavirin, allowing to identify patients who may benefit from conventional therapy., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: To investigate the feasibility of pegylated interferon plus ribavirin treatment in cirrhotic patients who presented with, or developed while on-treatment, platelet counts ≤ 80,000/μL and/or neutrophil counts ≤ 1,500/μL., Methods: A retrospective analysis of prospectively gathered data on 123 cirrhotic patients treated with pegylated interferon and ribavirin. Adverse effects and haematological changes were monitored: bleeding and infectious events were registered and related to platelet and absolute neutrophil counts., Results: Among the 58 patients (47.2%) with nadir platelets ≤ 50,000/μL during therapy, 6 (10.3%) experienced a bleeding episode; of the remaining 65 patients with platelets constantly >50,000/μL, 3 (4.6%) bled. Of the 11 bleedings, 3 manifested during an infection, while patients had platelets >50,000/μL. Nadir neutrophils ≤ 750/μL occurred in 45 patients (38.2%) during treatment, and 14 of them (29.8%) had an infectious event. Infections were also documented in 18 of the 76 patients (23.7%) with neutrophils constantly >750/μL., Conclusions: The study reveals the feasibility of treating cirrhotic patients with cytopenia with pegylated interferon and ribavirin, as bleeding or infectious events under therapy were unrelated to platelet and neutrophil counts. Withdrawal of therapy or variations in the pre-assigned dosages of either pegylated interferon or ribavirin owing to abnormally low haematological parameters seems to no longer be tenable., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: MicroRNAs (miRNAs) regulate diverse biological processes by inhibiting translation or inducing degradation of target mRNAs. miR-145 is a candidate tumor suppressor in colorectal carcinoma (CRC). Colorectal carcinogenesis involves deregulation of cellular processes controlled by a number of intertwined chief transcription factors, such as PPARγ and SOX9. Since PPAR family members are able to modulate complex miRNAs networks, we hypothesized a role of miRNA-145 in the interaction between PPARγ and SOX9 in colorectal carcinogenesis. To address this issue, we evaluated gene expression in tissue specimens of CRC patients and we took advantage of invitro models represented by CRC derived cell lines (CaCo2, SW480, HCT116, and HT-29), employing PPARγ activation and/or miRNA-145 ectopic overexpression to analyze how their interplay impact the expression of SOX9 and the development of a malignant phenotype., Results: PPARγ regulates the expression of miR-145 by directly binding to a PPAR response element (PPRE) in its promoter at -1207/-1194bp from the transcription start site. The binding is essential for miR-145 upregulation by PPARγ upon rosiglitazone treatment. Ectopic expression of miR-145, in turn, regulates SOX9 expression through the binding to specific seed motifs. The PPARγ-miR-145-SOX9 axis overarches cell cycle progression, invasiveness and differentiation of CRC derived cell lines. Together, these results suggest that miR-145 is a novel target of PPARγ, acts as a tumor suppressor in CRC cell lines and is a key regulator of intestinal cell differentiation by directly targeting SOX9, a marker of undifferentiated progenitors in the colonic crypts., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: Controversy prevails on the impact of preoperative biliary drainage (PBD) on postoperative complications and clinical outcome of pancreatic cancer. We determined whether PBD is associated with increased morbidity and mortality rates after pancreaticoduodenectomy., Methods: A total of 131 consecutive patients who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were included in this study. Overall, 57 % of jaundiced patients underwent PBD, while 43 % were not drained. The impact of PBD on postoperative morbidity and mortality was evaluated by means of logistic regression analysis. The Kaplan-Meier method was applied to determine the effect of PBD on survival of patients with malignant lesions., Results: Mortality and morbidity rate was 3 % and 54.6 %, respectively. PBD was demonstrated to be the unique predictor of complications (odds ration [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The jaundiced patients who were drained exhibited high frequencies of wound infection (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p < 0.001). In addition, an increased frequency of pancreatic fistula emerged among drained patients compared to those who were not drained (p = 0.036). PBD did not affect survival of patient with malignant lesions., Conclusions: With the exception of the classical indications, PBD should be carefully evaluated in patients with resectable pancreatic cancer.

Aim: To investigate the association of single nucleotide polymorphisms (SNPs) of genes involved in the regulation of immune responses, IL33, IL1RL1, IL23R, and IL10, with idiopathic achalasia in an Italian cohort of patients., Materials and Methods: A panel of eleven polymorphisms were genotyped in 116 unrelated idiopathic achalasic patients and 371 healthy subjects, by using TaqMan genotyping assays., Results: Significant differences of allele (P=0.0065, OR=1.59, CI=1.14-2.22) and genotype (P=0.0097, OR=1.74, CI=1.14-2.65) frequencies of the IL33 rs3939286 variant were found between achalasic patients and controls. No association of the other investigated SNPs was detected. No differences in genotype and allele distribution were found with respect to clinical characteristics of patients., Conclusion: We provide for the first time an association between the risk of developing idiopathic achalasia and IL-33 variant, underling the role of cytokines and inflammatory mediators on the pathogenesis of the disease., (Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)