Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes

Clinical value of diffusion-weighted MRI for differentiation between benign and malignant gallbladder disease:a systematic review and meta-analysis

BACKGROUND: Radiological differentiation between benign and malignant gallbladder disease is important but remains challenging. Furthermore, the clinical value of diffusion-weighted imaging (DWI) remains unclear. PURPOSE: To determine the value of DWI in discriminating benign from malignant gallbladder disease by conducting a systematic review and meta-analysis. MATERIAL AND METHODS: The literature was systematically searched. Studies analyzing diagnostic value of DWI in gallbladder disease with histopathology or follow-up as reference standard were included. Study selection and data extraction were done by two reviewers independently. Methodological quality was assessed using the QUADAS-2 tool. Sensitivity and specificity were calculated and displayed in a forest plot. A sensitivity analysis was performed in case of outliers. Pooled sensitivity and specificity of DWI were plotted on a hierarchical summary receiver operating characteristic curve. If available, the added value of DWI to conventional magnetic resonance imaging (MRI) sequences was analyzed. RESULTS: Out of 2456 articles, eight studies fulfilled the inclusion criteria; 592 patients with 221 malignant lesions were included. Pooled sensitivity and specificity rates were 0.87 and 0.84, respectively. In two studies, diagnostic accuracy rates improved after adding DWI to conventional MRI (64% and 75% for conventional MRI vs. 89% and 94% after combining conventional MRI with DWI). In another study, the area under the curve increased from 0.92 to 0.95. CONCLUSION: DWI appears to be an accurate imaging technique in discriminating benign from malignant gallbladder disease. To achieve optimal patient care, it should be part of multiparametric MRI and should be combined with other imaging modalities

Oncogenic KRAS Desensitizes Colorectal Tumor Cells to Epidermal Growth Factor Receptor Inhibition and Activation12

Epidermal growth factor receptor (EGFR)-targeting therapeutics have shown efficacy in the treatment of colorectal cancer patients. Clinical studies have revealed that activating mutations in the KRAS protooncogene predict resistance to EGFR-targeted therapy. However, the causality between mutant KRAS and resistance to EGFR inhibition has so far not been demonstrated. Here, we show that deletion of the oncogenic KRAS allele from colorectal tumor cells resensitizes those cells to EGFR inhibitors. Resensitization was accompanied by an acquired dependency on the EGFR for maintaining basal extracellular signal-regulated kinase (ERK) activity. Deletion of oncogenic KRAS not only resensitized tumor cells to EGFR inhibition but also promoted EGF-induced NRAS activation, ERK and AKT phosphorylation, and c-FOS transcription. The poor responsiveness of mutant KRAS tumor cells to EGFR inhibition and activation was accompanied by a reduced capacity of these cells to bind and internalize EGF and by a failure to retain EGFR at the plasma membrane. Of 16 human colorectal tumors with activating mutations in KRAS, 15 displayed loss of basolateral EGFR localization. Plasma membrane localization of the EGFR could be restored in vitro by suppressing receptor endocytosis through Rho kinase inhibition. This caused an EGFR-dependent increase in basal and EGF-stimulated ERK phosphorylation but failed to restore tumor cell sensitivity to EGFR inhibition. Our results demonstrate a causal role for oncogenic KRAS in desensitizing tumor cells not only to EGFR inhibitors but also to EGF itself

Predicting futility of upfront surgery in perihilar cholangiocarcinoma:Machine learning analytics model to optimize treatment allocation

BACKGROUND: Whilst resection remains the only curative option for perihilar cholangiocarcinoma (PHC), it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in PHC surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided in a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analysed: among them, 309 were classified within the "futile group" (13.6%). ASA score = 3 (OR 1.60; p = 0.005), bilirubin at diagnosis = 50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 = 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter = 3 cm (OR 1.76; p < 0.001) and left sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (i.e., low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSION: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. non-surgical treatments) according to preoperative features