Adjuvant Palbociclib May be Associated with Delayed Recurrence in Completely Resected Retroperitoneal Liposarcoma: Results of a Single-Institution Retrospective Cohort Study.

BACKGROUND: Retroperitoneal liposarcomas are locally aggressive and frequently recur following complete surgical resection. Palbociclib, a cyclin-dependent kinase (CDK) 4/CDK6 inhibitor, is effective in the treatment of metastatic or unresectable liposarcoma. OBJECTIVE: The purpose of this study was to describe our initial experience using adjuvant palbociclib to delay recurrence. METHODS: Patients with resected RPS were identified from a prospectively maintained institutional database. In 2017, we began offering adjuvant palbociclib to patients following complete gross resection. Treatment interval, defined as the time between surgical resection and re-resection or change in systemic therapy, was compared between patients selected for adjuvant palbociclib or observation. RESULTS: Between 2017 and 2020, 12 patients underwent a total of 14 operations (14 patient cases) and were selected for adjuvant palbociclib for recurrence prevention. These patients were compared with 14 patients who, since 2010, underwent a total of 20 operations (20 patient cases) and were selected for observation. Histology was primarily dedifferentiated liposarcoma for both groups (observation: 70% [14/20]; adjuvant palbociclib: 64% [9/14]). All patients underwent complete gross resection. Neither age, number of previous surgeries, histologic grade, or Eastern Cooperative Oncology Group (ECOG) performance status differed between groups (p > 0.05 for all). Patients selected for adjuvant palbociclib experienced a longer treatment interval than those selected for observation, although it did not reach statistical significance (20.5 months vs. 13.1 months, p = 0.08, log rank). CONCLUSION: Adjuvant palbociclib may be associated with a prolonged interval between liposarcoma resection and the need for re-resection or other systemic therapy. Palbociclib may be effective in delaying liposarcoma recurrence, and its use for this indication warrants prospective study.

Outcomes of chimney and fenestrated endografting using Viabahn VBX and atrium iCAST stents.

BACKGROUND: The Atrium iCAST balloon expandable stent is the traditional choice of stent for chimney and fenestrated endovascular aneurysm repair (ChEVAR and FEVAR respectively). Due to the iCAST's lack of flexibility, the Gore Viabahn balloon-expandable stent (VBX; W. L. Gore & Associates, Inc., Newark, DE, USA) has arisen as a flexible alternative for parallel or branch graft placement during complex EVAR. Our purpose was to analyze patients' outcomes after undergoing ChEVAR or FEVAR using VBX or iCAST stents with the major outcome of assessing stent graft patency. The secondary outcome was residual aneurysm sac behavior. METHODS: We retrospectively reviewed patients who were treated by ChEVAR or FEVAR with placement of iCAST or VBX stents from July 2012 to August 2018. Patients received follow-up CT scan and/or aortic duplex imaging. RESULTS: We examined 53 cases (70% ChEVAR and 30% FEVAR) with 15.6 months (0-76.5 months) mean follow-up period. Placement of stents included renal (65 iCAST and 38 VBX), superior mesenteric (12 iCAST and 13 VBX), celiac (4 iCAST and 5 VBX), and iliac arteries (1 iCAST and 5 VBX). A total of 143 stents (57% iCAST and 43% VBX) were successfully deployed with 100% initial patency. Follow-up patency was similar for both stent types (100% VBX vs 98.7% iCAST). VBX and iCAST had the same follow-up Type 1a endoleak occurrence (9%). Average aneurysm sac sizes for iCAST decreased more than VBX (9% iCAST and 4% VBX, P=0.21), however, the iCAST group had longer follow-up. CONCLUSIONS: Our experience demonstrates that the use of VBX stents for ChEVAR and FEVAR is a safe and effective alternative to iCAST stents with excellent mid-term patency without a negative impact on endoleak frequency.

Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic Strategy for Hemangioendothelioma.

AIMS: Hemangiomas are endothelial cell tumors and the most common soft tissue tumors in infants. They frequently cause deformity and can cause death. Current pharmacologic therapies have high-risk side-effect profiles, which limit the number of children who receive treatment. The objectives of this work were to identify the mechanisms through which standardized berry extracts can inhibit endothelial cell tumor growth and test these findings in vivo. RESULTS: EOMA cells are a validated model that generates endothelial cell tumors when injected subcutaneously into syngeneic (129P/3) mice. EOMA cells treated with a blend of powdered natural berry extracts (NBE) significantly inhibited activity of multidrug resistance protein-1 (MRP-1) compared to vehicle controls. This resulted in nuclear accumulation of oxidized glutathione (GSSG) and apoptotic EOMA cell death. When NBE-treated EOMA cells were injected into mice, they generated smaller tumors and had a higher incidence of apoptotic cell death compared to vehicle-treated EOMA cells as demonstrated by immunocytochemistry. Kaplan-Meier survival curves for tumor-bearing mice showed that NBE treatment significantly prolonged survival compared to vehicle-treated controls. INNOVATION: These are the first reported results to show that berry extracts can inhibit MRP-1 function that causes apoptotic tumor cell death by accumulation of GSSG in the nucleus of EOMA cells where NADPH oxidase is hyperactive and causes pathological angiogenesis. CONCLUSIONS: These findings indicate that berry extract inhibition of MRP-1 merits consideration and further investigation as a therapeutic intervention and may have application for other cancers with elevated MRP-1 activity. Antioxid. Redox Signal. 26, 1009-1019.