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Atezolizumab plus Bevacizumab represents the current standard of care for first-line treatment of advanced HCC. However, direct comparison with other combination treatments including immune-checkpoint inhibitors (ICI) plus tyrosine-kinase inhibitors (TKIs) or anti-CTLA4 are lacking. The aim of this network meta-analysis (NMA) is to indirectly compare the efficacy and the safety of first-line systemic treatments. Literature search of MEDLINE, EMBASE and SCOPUS databases was conducted up to October, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including Sorafenib and Lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time (RMST). A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio (ISER) as measure of net health benefit was calculated as the difference in probability of SAEs divided by difference in survival between the 2 most effective treatments. Nine RCTs enrolling 6600 patients were included. Atezolizumab+bevacizumab showed the highest probability (88%) of being the best in 30-month OS. Pembrolizumab+lenvatinib showed the highest probability (94%) of being the best in terms of PFS. ICI monotherapies were the most safe combination. At a willingness-to-risk threshold of 10% of SAEs for month-year gained, atezolizumab+bevacizumab was favored in 76% of cases, while at a threshold of 30% of SAEs for month-year gained, pembrolizumab+lenvatinib was favored in 72% of cases. Atezolizumab plus Bevacizumab is the preferred option in unfit patients with high tumor burden, while Pembrolizumab plus Lenvatinib could be preferred for fit patients with less advanced vascular tumor spread [ABSTRACT FROM AUTHOR]

Abstract: Background: The accuracy and effectiveness of targeted oesophageal biopsies in Barrett's oesophagus to detect dysplasia using new magnification techniques are unknown. Aim of this study was to investigate whether the combined use of acetic acid, magnification and electronic filters allows the same accuracy as the four-quadrant random biopsies pattern; pathologist interobserver agreement both in low grade and high grade dysplasia was also assessed. Methods: Fifty-four consecutive patients newly diagnosed with Barrett's oesophagus were enrolled in a prospective study from a single endoscopy unit. Biopsies were evaluated by the local pathologist and by an expert pathologist from another pathology unit. Main outcome measurement: Dysplasia detection rate and interobserver agreement for the histologic diagnosis of dysplasia. Results: The use of acetic acid, magnification and electronic filters showed an unacceptably low dysplasia detection rate by the two pathologists (9.2% and 5.5% for targeted biopsies, respectively). The interobserver agreement for low grade dysplasia between pathologists was low (Cohen's K weighted=0.45). Conclusions: In an average setting, the standard four-quadrant method should still be preferred, along with the implementation of a routine second evaluation by an expert pathologist. [Copyright &y& Elsevier]

Abstract: Background: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting. Aims: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls. Methods: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers. Results: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores. Conclusions: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients. [Copyright &y& Elsevier]