Multi-Phase Cross-modal Learning for Noninvasive Gene Mutation Prediction in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most common cause of cancer-related death worldwide. Understanding the underlying gene mutations in HCC provides great prognostic value for treatment planning and targeted therapy. Radiogenomics has revealed an association between non-invasive imaging features and molecular genomics. However, imaging feature identification is laborious and error-prone. In this paper, we propose an end-to-end deep learning framework for mutation prediction in APOB, COL11A1 and ATRX genes using multiphasic CT scans. Considering intra-tumour heterogeneity (ITH) in HCC, multi-region sampling technology is implemented to generate the dataset for experiments. Experimental results demonstrate the effectiveness of the proposed model.Comment: Accepted version to be published in the 42nd IEEE Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2020, Montreal, Canad

Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources’ Allocation

Background. Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases. Methods. SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources' allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed. Results. There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate- multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to "urgent"cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19- related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question. Conclusions. In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed

Global management of a common, underrated surgical task during the COVID-19 pandemic: Gallstone disease - An international survery

Background: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. Methods: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. Results: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50–75%, 10(27.8%) by 25–50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months. In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. Conclusion

A proteomic based approach for the identification of biliary markers of Cholangiocarcinoma

Cholangiocarcinoma is a cancer of the biliary epithelia with a rising incidence and a dismal prognosis. The lack of clinically useful biomarkers of the disease has led to the use of bile as a more proximal fluid in proteomic based biomarker discovery experiments. Early results have shown inherent difficulties in the acquisition, processing and reproducibility of this approach. By first establishing sample banking and developing a robust, streamlined method for processing bile for down stream proteomic investigations, we were able to perform two separate proteomic based analyses. Firstly, with the initial aim of cataloguing proteins in .bile from a patient with cholangiocarcinoma, we used a shotgun GeLC-MS/MS approach. By this method, .895 proteins were identified of which 621 had two or more significant peptides. A number of these proteins were of interest based on their known involvement in other cancers. Downstream studies on two of these molecules, Matrix Metalloproteinase-9 and Lipocalin-2, revealed up-regulation in CCA when compared to normal, benign and predisposed disease categories, suggesting they represent potential biomarkers. Secondly, we employed Difference Gel Electrophoresis (DIGE) in a comparative analysis to identify biliary markers of CCA. DIGE has greatly advanced the sensitivity and reproducibility of 2D PAGE based experiments and has, as yet, not been described in bile. Using a protocol developed in-house, we carried out a comparative analysis of bile from patients with cholangiocarcinoma and compared this between normal, benign and predisposed disease categories. By this method, 6 spots on 2D DIGE gels showed significant expression differences between disease categories with 5 showing down regulation and 1 showing upregulation in cholangiocarcinoma. This spot was identified iii as Glutathione-S-Transferase pi by MS/MS analysis and differential expression was subsequently confirmed in validation studies. The work carried out here has developed a reproducible method of processing bile for proteomic analysis and using this technique carried out two parallel proteomic based approach which has resulted in three biliary proteins that have shown promising early results. Further validation studies and newer techniques in this area are currently being undertaken.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Multilobar Insular-Involving Gliomas: Results with Hyperaggressive Resection.

Objective Hyperaggressive resection refers to a philosophy that maximal resection should be pursued in gliomas, wherever possible. In this study, we provide a detailed report of the outcomes with hyperaggressive surgery for multilobar insular-involving gliomas (MIGs).  Methods We report outcomes in patients with MIGs undergoing surgery aiming at gross total resection in all cases. Risk factors for neurologic deficits and survival were modeled using logistic and Cox regression. Results There were 72 consecutive patients, of whom 53 (74%) had undergone previous surgery. A greater than 90% resection was obtained in 67 patients (93%). Nineteen of 23 patients (83%) with Grade 2 tumors survived to the end of the follow-up period. Patients with Grade 3 tumors experienced 75% two-year survival rates and 48% four-year survival rates. Patients with Grade 4 tumors experienced 55% one-year survival rates and 33% two-year survival rates; eight of 33 patients (24%) lived longer than three years and three of 33 patients were alive at five years. Fifty-eight of 68 patients (85%) surviving to the three-month follow-up had a Karnofsky performance status (KPS) of 70 or greater, and 31 of 72 patients (43%) experienced improvement in KPS postoperatively. Permanent weakness occurred in 12 patients (17%), and permanent speech problems in three patients (13% of left-sided tumors). Conclusion Hyperaggressive surgical resection of MIGs yields rates of neurologic deficits within acceptable ranges and are lower than expected. In many cases, patients exceed the long-term survival expectations of conventional treatment