Impact of Aspirin Use on Outcomes in Patients With Hepatocellular Cancer: A Nationwide Analysis.

Background: Despite the use of new immunotherapies, hepatocellular carcinoma (HCC) has a poor survival rate. Through multiple molecular mechanisms, aspirin (ASA) has demonstrated a reduced incidence of HCC, however, the impact of long-term ASA use on in-hospital outcomes has not been studied. Methods: We queried the National Inpatient Sample (NIS) database from 2016 to 2020 to identify patients with HCC. Patients were stratified into two groups, based on long-term ASA use. Information was collected regarding patient demographics, Elixhauser comorbidities, interventions, etiology, and decompensations of liver disease. Outcomes studied included sepsis, shock, acute kidney injury (AKI), intensive care unit (ICU) admission, and in-hospital mortality. The association between long-term ASA use and outcomes was studied using multivariate analysis. Results: A total of 224,735 patients were included in the study. Of them, 18,835 (8.4%) patients were on long-term ASA. The majority of the patients with ASA use were White (61.3%), men (78.2%), and aged > 65 years old (68.8%). Patients in the ASA group had a higher incidence of non-alcoholic steatohepatitis (NASH) and decreased rates of hepatic decompensation than those not on ASA. Patients with ASA use had lower incidence of sepsis (2.76% vs. 3.54%), shock (4.86% vs. 8.23%), AKI (30.9% vs. 33.4%), ICU admission (3.88% vs. 7.4%) and in-hospital mortality (5.18% vs. 9.87%). After adjusting for confounding factors, ASA use was associated with a 30% lower risk of in-hospital mortality (adjusted odds ratio (aOR): 0.70, 95% confidence interval (CI): 0.60 - 0.82, P < 0.001). ASA users also had 21% lower odds of developing shock (aOR: 0.79, 95% CI: 0.67 - 0.94, P = 0.007) and 31% lower odds of requiring ICU admission (aOR: 0.69, 95% CI: 0.54 - 0.78, P < 0.001). Conclusions: Our study noted that patients on long-term ASA use had better in-hospital outcomes such as mortality, shock, and ICU admissions compared to non-ASA users. These findings are of interest, and further randomized clinical trials confirming the benefits of ASA in improving outcomes in HCC patients need to be conducted.

Transitioning ifosfamide chemotherapy regimens to the ambulatory setting: reviewing cost savings and safety profile.

PURPOSE: To characterize and compare both the outcome and cost of treatment of outpatient (OP) and inpatient (IP) ifosfamide therapy. METHODS: A single-center retrospective chart review of patients 18 years and older receiving ifosfamide therapy. The primary endpoint compares and evaluates the side effect profiles of ifosfamide-treated patients in the OP/IP settings. The adverse event grading system was characterized using the CTCAE Version 5.0. The highest grade was documented per cycle. The secondary endpoint of this study compares the costs of OP/IP therapy. It was assumed that the cost of medication was equivalent for IP/OP treatments. The cost saved with OP administration was determined by the average cost of hospital stay for IP admission. RESULTS: Ifosfamide therapy of 86 patients (57 OP, 29 IP) was reviewed. The predominant OP regimens were doxorobucin-ifosfamide-mesna (AIM) with 43.9% and ifosfamide-etoposide (IE) with 29.8%. Grade 4 anemia, thrombocytopenia, and neutropenia were most frequent in IP vs OP therapies (22.9% IP vs 4.3% OP, 21.6% IP vs 9.2% OP, and 22.8% IP vs 19.6% OP respectively). Neutropenic fever (NF) occurred in 20 OP patients which were predominantly treated with AIM or IE and led to average hospital stay of 6 days. Neurotoxicity, treated with methylene blue (MB) occurred in 4 OP patients. OP therapy saved a total of 783 hospital days, leading to a cost savings of $2,103,921. CONCLUSIONS: Transitioning ifosfamide to the OP setting is feasible for academic and community infusion centers with the OP administration being safe, well-tolerated, and associated with decreased total cost of care. The current processes allow for safe transition of chemotherapy of chemotherapy under times of COVID.

Targeting the Bone Microenvironment in Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is universally incurable and represents an area of substantial unmet medical need. Novel targets and therapeutic strategies have emerged based on an improved understanding of the crosstalk between prostate cancer cells and the bone microenvironment. A wide variety of signaling systems including the RANKL/RANK/OPG, IGF-I, FGF and Wnt:DKK-1 pathways can be targeted to suppress tumor growth and treatment resistance. Antisurvival factor therapy can increase the efficacy of standard antineoplastic regimens by targeting biologic molecules acting as "survival factors" within the bone microenvironment. Novel agents can also be used to mobilize the host immune system to attack prostate cancer cells. Clinical testing of these therapeutic approaches has produced encouraging objective clinical responses in subsets of patients with mCRPC. The present review summarizes data regarding the emerging strategies used to target the bone microenvironment in mCRPC.

RSPO2 Enhances Canonical Wnt Signaling to Confer Stemness-Associated Traits to Susceptible Pancreatic Cancer Cells.

Cancer stem cells (CSC) present a formidable clinical challenge by escaping therapeutic intervention and seeding tumors through processes that remain incompletely understood. Here, we describe small subpopulations of pancreatic cancer cells with high intrinsic Wnt activity (Wnt(high)) that possess properties indicative of CSCs, including drug resistance and tumor-initiating capacity, whereas cell populations with negligible Wnt activity (Wnt(low)) preferentially express markers of differentiation. Spontaneous response to extrinsic Wnt signals induces signaling networks comprising ERK1/2 and epithelial-mesenchymal transition that subsequently confer cancer stemness traits to susceptible cells. Wnt enhancer R-Spondin 2 (RSPO2) seems to play a prominent upstream role in regulating this interplay. In this context, Wnt(high) cells were more likely to give rise to Wnt(high) progeny, tended to be more metastatic, and revealed higher levels of RSPO2 expression. Our studies reveal adaptive aspects of pancreatic cancer stemness arising from driver populations of CSCs that misappropriate functional and responsive elements of archetypical self-renewal pathways. Blocking such stemness-promoting pathways in conjunction with established chemotherapy could provide means to disrupt dynamic CSC process and present novel therapeutic targets and strategies.