Using Voxel-based Dosimetry to evaluate sphere concentration and tumor dose in Hepatocellular Carcinoma treated with Y-90 Radiation Segmentectomy with glass microspheres.

PURPOSE: To utilize voxel-based dosimetry following radiation segmentectomy to understand microsphere distribution and validate current literature regarding radiologic and pathologic outcomes. METHODS: A retrospective, single-center analysis of solitary HCC patients (n=56) treated with Y90 radiation segmentectomy with glass microspheres (TheraSphere; Boston Scientific, Marlborough, MA, USA) from 2020 to 2022 was performed. Post-treatment voxel-based dosimetry was evaluated using Mirada DBx Build 1.2.0 Simplicit90Y software and utilized to calculate sphere concentration to tumor, as well as D70 (minimum dose to 70% total tumor volume), D90, and D99. Time to progression (TTP), treatment response, and adverse events were studied. RESULTS: Fifty-six solitary tumors were analyzed with a median tumor diameter of 3.4cm (range 1.2-6.8cm) and median tumor absorbed dose of 732Gy (range, 252-1776Gy). Median sphere activity (SA) at time of delivery was 1446Bq (range, 417-2621Bq). Median tumor sphere concentration was 12,868 spheres/mL (range, 2,655-37,183 spheres/mL). Sphere concentration into tumor and normal tissue inversely correlated with perfused treatment volume (R2=0.21 and 0.39, respectively). Of the 51 tumors with post-treatment imaging, objective response was noted in 49 patients (96%) and complete response in 42 patients (82%). The median TTP was not reached with a 2-year progression rate of 11%. 15 patients underwent liver transplant. Median tumor necrosis was 99% (range, 80-100%). Lower tumor volumes and higher D99 were associated with CPN (p<0.001 and p=0.022, respectively). CONCLUSION: Voxel-based dosimetry following Y90 radioembolization can be utilized to account for sphere deposition and distribution into tumor. Ablative RS with high SA yields durable radiologic and pathologic outcomes.

Spatial and temporal expression of PORCN is highly dynamic in the developing mouse cochlea.

The mammalian organ of Corti is a highly specialized sensory organ of the cochlea with a fine-grained pattern that is essential for auditory function. The sensory epithelium, the organ of Corti consists of a single row of inner hair cells and three rows of outer hair cells that are intercalated by support cells in a mosaic pattern. Previous studies show that the Wnt pathway regulates proliferation, promotes medial compartment formation in the cochlea, differentiation of the mechanosensory hair cells and axon guidance of Type II afferent neurons. WNT ligand expressions are highly dynamic throughout development but are insufficient to explain the roles of the Wnt pathway. We address a potential way for how WNTs specify the medial compartment by characterizing the expression of Porcupine (PORCN), an O-acyltransferase that is required for WNT secretion. We show PORCN expression across embryonic ages (E)12.5 - E14.5, E16.5, and postnatal day (P)1. Our results showed enriched PORCN in the medial domains during early stages of development, indicating that WNTs have a stronger influence on patterning of the medial compartment. PORCN was rapidly downregulated after E14.5, following the onset of sensory cell differentiation; residual expression remained in some hair cells and supporting cells. On E14.5 and E16.5, we also examined the spatial expression of Gsk3ß, an inhibitor of canonical Wnt signaling to determine its potential role in radial patterning of the cochlea. Gsk3ß was broadly expressed across the radial axis of the epithelium; therefore, unlikely to control WNT-mediated medial specification. In conclusion, the spatial expression of PORCN enriches WNT secretion from the medial domains of the cochlea to influence the specification of cell fates in the medial sensory domain.

Hemophagocytic lymphohistiocytosis in an HIV-positive patient with concomitant disseminated histoplasmosis.

A 46-year-old Dominican man, known to have HIV, presented with constitutional symptoms of two week's duration. The patient was found to have cytopenias, significantly elevated ferritin level and lymphadenopathy. Biopsies and laboratory studies met the criteria for hemophagocytic lymphohistiocytosis (HLH). A concomitant diagnosis of histoplasmosis was confirmed as the trigger for HLH and treatment resulted in clinical improvement and resolution of symptoms.