Superior bowel preparation quality for colonoscopy with 1L-PEG compared to 2L-PEG and picosulphate: Data from a large real-world retrospective outpatient cohort.

BACKGROUND: Several randomized clinical trials comparing different bowel preparations (BP) have shown similar efficacy; however, there is a lack of real-world studies on this topic. AIMS: This study aims to identify the most effective BP regimen in a real-world setting and any predictors of inadequate BP. METHODS: A retrospective single-center study was conducted over 14 months at an academic hospital including outpatient colonoscopies in which adult patients did not teach on how to perform BP before colonoscopy. Colonoscopies with 1L-PEG, 2L-PEG and picosulphate mixtures were considered. A multivariable analysis for factors associated to poor BP was fitted. RESULTS: Overall, 1779 patients (51 %F, 60±14) years were included. The 1L-PEG regimen provided a higher rate of BP adequacy at multivariate analysis (adjusted OR 2.30, 95 %CI 1.67-3.16,p < 0.001) and was associated with higher median Boston Bowel Preparation Scale score (p < 0.001), higher rate of right-colon cleansing (p < 0.001) and exam completion (p = 0.04). Furthermore, we identified male sex, history of constipation, active smoking, previous pelvic surgery, concomitant psychiatric/neurological or chronic kidney diseases as predictors of inadequate BP. CONCLUSIONS: This is the largest real-world study comparing 1L-PEG to other BP regimens. Our results suggest 1L-PEG provides better BP in a non-controlled setting, improving clinical practice quality and minimizing the need for repeated colonoscopies and saving healthcare resources.

Prognostic Role of Basal Serum Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma Suitable for Curative Treatment.

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child-Pugh class B-C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.

A Comprehensive Review on Bariatric Endoscopy: Where We Are Now and Where We Are Going.

Background: Obesity is a chronic disease that impairs quality of life and leads to several comorbidities. When conservative therapies fail, bariatric surgical options such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies to induce persistent weight loss. Over the last two decades, bariatric endoscopy has become a valid alternative to surgery in specific settings. Primary bariatric endoscopic therapies: Restrictive gastric procedures, such as intragastric balloons (IGBs) and endoscopic gastroplasty, have been shown to be effective in inducing weight loss compared to diet modifications alone. Endoscopic gastroplasty is usually superior to IGBs in maintaining weight loss in the long-term period, whereas IGBs have an established role as a bridge-to-surgery approach in severely obese patients. IGBs in a minority of patients could be poorly tolerated and require early removal. More recently, novel endoscopic systems have been developed with the combined purpose of inducing weight loss and improving metabolic conditions. Duodenal mucosal resurfacing demonstrated efficacy in this field in its early trials: significant reduction from baseline of HbA1c values and a modest reduction of body weight were observed. Other endoscopic malabsorptive have been developed but need more evidence. For example, a pivotal trial on duodenojejunal bypasses was stopped due to the high rate of severe adverse events (hepatic abscesses). Optimization of these more recent malabsorptive endoscopic procedures could expand the plethora of bariatric patients that could be treated with the intention of improving their metabolic conditions. Revisional bariatric therapies: Weight regain may occur in up to one third of patients after bariatric surgery. Different endoscopic procedures are currently performed after both RYGB and SG in order to modulate post-surgical anatomy. The application of argon plasma coagulation associated with endoscopic full-thickness suturing systems (APC-TORe) and Re-EndoSleeve have shown to be the most effective endoscopic treatments after RYGB and SG, respectively. Both procedures are usually well tolerated and have a very low risk of stricture. However, APC-TORe may sometimes require more than one session to obtain adequate final results. The aim of this review is to explore all the currently available primary and revisional endoscopic bariatric therapies focusing on their efficacy and safety and their potential application in clinical practice.

Human Cytomegalovirus and Epstein-Barr virus specific immunity in patients with ulcerative colitis.

Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are endowed with the ability of establishing lifelong latency in human hosts and reactivating in immunocompromised subjects, including patients suffering from ulcerative colitis (UC). We, therefore, aimed to investigate virus-specific immunity in UC patients. A cohort of 24 UC patients (14 responders and 10 refractory to therapy) and 26 control subjects was prospectively enrolled to undergo virus-specific serology (by ELISA assay) and assessment of both CD4+ and CD8+ virus-specific T-cell response (by interferon-γ enzyme-linked immunospotanalysis). In parallel, mucosal viral load was determined by quantitative real-time PCR and the values were correlated with both clinical and endoscopic indexes of activity. For statistics, the t-test, Mann-Withney test, Fisher's exact test and Spearman rank correlation test were applied; p < 0.05 was considered significant. EBV-specific CD4+ and CD8+ T-cell responses were significantly lower in UC patients compared to controls (p < 0.0001 and p = 0.0006, respectively), whereas no difference was found for HCMV-specific T-cell response. When dividing the UC group according to response to therapy, both responders and refractory UC patients showed a deficient EBV-specific CD4+ T-cell response with respect to controls (p < 0.04 and p = 0.0003, respectively). Moreover, both EBV and HCMV mucosal loads were significantly higher in refractory UC than in responders and controls (p = 0.007 and 0.003; and p = 0.02 and 0.001, respectively), and correlated with activity indexes. Steroid therapy seemed the main risk factor for triggering EBV colitis. Finally, no cases of IgM positivity were found in the study population. An impaired EBV-specific immunity was clearly evident in UC patients, mostly in those refractory to therapy. The ELISPOT assay may serve as new tool for quantifying and monitoring virus-specific T-cell immunity in UC.

Incidence and risk factors for preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 referred for colonoscopy.

BACKGROUND: Colorectal cancer (CRC) diagnosed before the age of 50, known as early-onset CRC (eoCRC), is considered uncommon. We aimed at analysing the incidence of preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 years old and to identify possible predictors Methods: We retrospectively collected data from 1778 patients under 50 years old (mean age 39.9±7.8) referred for colonoscopy between 2015-2018. Cumulative incidence of adenomas and eoCRC was assessed. Multivariable regression models were fitted Results: The cumulative incidence for adenomas was 11.0% (95% CI 9-12), while it was 1.5% (95% CI 1-2) for eoCRC (metastatic disease in 13/27 patients). Age as a continuous variable was associated with the presence of adenomas (incidence rate ratio 1.06; 95% CI 1.03-1.09; p<0.001). EoCRC arose in most cases in the rectum (13/27, 48.1%). Age ≥40 was the main risk factor (OR 2.25; 95% CI 1.35-3.73; p=0.002) for both adenomas (160/196 patients, 81.6%) and eoCRC (20/27 patients, 74.1%), while smoking seemed to have no role (p=0.772). The presence of alarm symptoms was statistically significant at bivariable analysis for eoCRC only (OR 3.70; 95% CI 1.49-9.22; p=0.005), as well as having multiple gastrointestinal symptoms (OR 19.85; 95% CI 2.64-149.42; p=0.004). Only 3/27 (11.1%) patients with eoCRC had a family history for CRC Conclusions: A high cumulative incidence rate of both adenomas and eoCRC was found, this latter occurring more common in patients aged 40-49, without apparent risk factors. The presence of alarm symptoms or multiple gastrointestinal symptoms led to a late diagnosis.

Upper gastrointestinal bleeding in COVID-19 inpatients: Incidence and management in a multicenter experience from Northern Italy.

BACKGROUND: COVID-19 patients have an increased susceptibility to develop thrombotic complications, thus thromboprophylaxis is warranted which may increase risk of upper gastrointestinal bleeding (UGIB). Our aim was to evaluate incidence of UGIB and use of upper GI endoscopy in COVID-19 inpatients. METHODS: The medical and endoscopic management of UGIB in non-ICU COVID-19 patients has been retrospectively evaluated. Glasgow Blatchford score was calculated at onset of signs of GI bleeding. Timing between onset of signs of GI bleeding and execution, if performed, of upper GI endoscopy was evaluated. Endoscopic characteristics and outcome of patients were evaluated overall or according to the execution or not of an upper GI endoscopy before and after 24h. RESULTS: Out of 4871 COVID-19 positive patients, 23 presented signs of UGIB and were included in the study (incidence 0.47%). The majority (78%) were on anticoagulant therapy or thromboprophylaxis. In 11 patients (48%) upper GI endoscopy was performed within 24h, whereas it was not performed in 5. Peptic ulcer was the most common finding (8/18). Mortality rate was 21.7% for worsening of COVID-19 infection. Mortality and rebleeding were not different between patients having upper GI endoscopy before or after 24h/not performed. Glasgow Blatchford score was similar between the two groups (13;12-16 vs 12;9-15). CONCLUSION: Upper GI bleeding complicated hospital stay in almost 0.5% of COVID-19 patients and peptic ulcer disease is the most common finding. Conservative management could be an option in patients that are at high risk of respiratory complications.

Safety and durability of PEG-J: a single-centre experience.

INTRODUCTION: Although percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is currently indicated in a variety of conditions, limited data are available regarding its safety and the best timing for its replacement. We herein describe a single-centre cohort of patients who underwent PEG-J placement or replacement to assess the short- and long-term safety of the procedure. METHODS: Demographic and procedure-related data regarding all patients undergoing a PEG-J procedure between March 2010 and 2020, either first placement or any replacement, at the Endoscopy Unit of a University Hospital in Northern Italy (IRCCS Policlinico San Matteo, Pavia, Italy), were retrospectively collected. Data were collected until last available follow-up. RESULTS: We included 73 patients (mean age 70 ± 9.7, 60.3% female) who underwent a PEG-J procedure. Data on a total of 215 procedures were gathered with a median follow up time of 21 months (IQR 9.3-39.5). No immediate adverse events (AEs) were reported. Short-term (within 30 days) AEs, including jejunal extension dislocations, accidental removal, obstruction and kinking occurred in 12 patients (5.6% of the total procedures), whilst long-term AEs (obstruction, tube malfunctions, inner tube dislocation, pyloric ulcer, hypergranulation tissue, wear, buried bumper syndrome and accidental removal) were reported in 40 patients. The risk of developing an AE was not reduced if tube replacement was performed electively. The median duration of the PEG-J before replacement was 12 months (IQR 6-16 months). CONCLUSION: PEG-J placement and replacement are safe procedures. Although PEG-J durability is variable an elective procedure might be indicated to reduce urgent replacements.

Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease.

The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.

Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

AIM: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). METHODS: A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. RESULTS: All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. CONCLUSION: Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.