Tumor Biology and Immune Infiltration Define Primary Liver Cancer Subsets Linked to Overall Survival After Immunotherapy

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. Using supervised and unsupervised approaches, we identify stable molecular subtypes linked to overall survival and distinguished by two axes of aggressive tumor biology and microenvironmental features. Moreover, molecular responses to immune checkpoint inhibitor treatment differ between subtypes. Thus, patients with heterogeneous liver cancer may be stratified by molecular status indicative of treatment response to immune checkpoint inhibitors

Bridging the Gap Between Sorafinib Efficacy and Effectiveness in Advanced Hepatocellular Carcinoma

In this editorial, the generalizability of trial results to the geriatric population is discussed. Specifically, the results from a recent observational study are compared with results from the SHARP trial, and recommendations are made for bridging the gap between efficacy and effectiveness in clinical research, particularly with regard to older patients

Using Relations to Index Biological Document Repositories for Efficient Searching

In this paper we propose a rule-based mechanism using Natural Language Processing techniques for extracting biological relations from biomedical text documents. While the rules identify frequently occurring patterns that can be potential relations, significant relations are identified using statistical analysis. Evaluation of the technique has been done on MEDLINE abstracts obtained from the GENIA corpus. Results indicate that our technique has good potential for other text mining applications also. Preliminary analysis shows that indexing biomedical documents on these relations can facilitate high precision document retrieval. 1

New Horizons for Precision Medicine in Biliary Tract Cancers

AbstractBiliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review.Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943–62. ©2017 AACR.</jats:p

A clinical comparison of propofol and etomidate in patients with end-stage renal disease undergoing renal transplantation

Background: Induction of anesthesia is a critical part of anesthetizing patients with end-stage renal disease, as they are at risk of wide hemodynamic fluctuation due to their pathophysiological alterations in the cardiovascular system. It is desirable to use pharmacological agents that provide hemodynamic stability with fewer adverse effects. Aims and Objectives: This study aimed to evaluate the effects of propofol and etomidate by comparing hemodynamic variables such as a change in mean arterial pressure (MAP) and heart rate (HR) during induction, laryngoscopy, and up to 10 min after tracheal intubation as a primary outcome and any associated adverse effect as a secondary outcome. Methods: After getting institutional ethical committee approval, 60 American Society of Anesthesiologist Grade III patients aged 20–60 years, scheduled for renal transplantation, were randomized into two groups (Group P: propofol 1% and Group E: etomidate). The dose of induction agents was targeted to achieve a bispectral index value of 40. Hemodynamic variables were recorded at induction, laryngoscopy, and up to 10 min after tracheal intubation. Adverse effects related to the study drug were recorded. Results: The decrease in MAP in Group P was statistically significant (P < 0.05) as compared to Group E, at induction of anesthesia. We observed a significant increase in HR at induction of anesthesia in Group E (P < 0.05). The incidence of myoclonus was 0 versus 73.3% in Groups P and E, respectively, while pain on injection and hypotension were more in Group P (P < 0.05). Conclusions: In conclusion, etomidate provides better hemodynamic stability with fewer adverse effects in patients with end-stage renal disease