Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

PURPOSE: Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. MATERIALS AND METHODS: Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. RESULTS: 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. CONCLUSION: TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

Measurement of the Tumor-to-Normal Ratio for Radioembolization of Hepatocellular Carcinoma: A Prospective Study Comparing 2-Dimensional Perfusion Angiography, Technetium-99m Macroaggregated Albumin, and Yttrium-90 SPECT/CT.

PURPOSE: To calculate the preradioembolic tumor-to-normal (T:N) ratio in hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography and compare it with that calculated using technetium-99m macroaggregated albumin (99mTc MAA) single-photon emission computed tomography (SPECT)/computed tomography (CT). MATERIALS AND METHODS: This prospective single-arm study enrolled 15 participants with HCC who underwent 2D perfusion angiography immediately before the enrollment and with the microcatheter located at the same location as 99mTc MAA injection, after which SPECT/CT was performed. Quantitative digital subtraction angiography was used to calculate the area under the curve for the tumor and normal hepatic parenchyma and subsequently calculate the T:N ratio. The T:N ratio was calculated from the 99mTc MAA SPECT/CT and post-yttrium-90 bremsstrahlung SPECT/CT using dosimetry software. RESULTS: The mean participant age was 64.1 years ± 9.8, and the study included 14 (93%) men and 1 (7%) woman. The mean tumor size was 4.1 cm (SD ± 2.4), and all participants received segmental treatments with glass microspheres. The mean T:N ratio calculated by 99mTc MAA SPECT/CT was 2.28 (SD ± 0.89) vs 2.25 (SD ± 0.99) calculated by 2D perfusion angiography (P = .45). For the 13 participants who underwent selective internal radiation therapy (transarterial radioembolization), there was no significant difference between the T:N ratios calculated by 2D perfusion angiography and post-90Y SPECT/CT (2.25 [SD ± 1.05] vs 1.91 [SD ± 0.39]; P = .12). CONCLUSIONS: The T:N ratio calculated by 2D perfusion angiography correlated well with that calculated by 99mTc MAA SPECT/CT.

Prior ablation and progression of disease correlate with higher tumor-to-normal liver 99mTc-MAA uptake ratio in hepatocellular carcinoma.

PURPOSE: Factors affecting tumor-to-normal tissue ratio (T:N) have implications for patient selection, dosimetry, and outcomes when considering radioembolization for HCC. This study sought to evaluate patient, disease specific, and technical parameters that predict T:N as measured on planning pre-90Y radioembolization 99mTc-MAA scintigraphy for hepatocellular carcinoma (HCC). METHODS: 99mTc-MAA hepatic angiography procedures with SPECT/CT over a 4-year period were reviewed. Data recorded included patient demographics, details of underlying liver disease, tumor size, history of prior treatments for HCC and technical parameters from angiography. Anatomic-based segmentation was performed in 93 cases for measurement of tumor and perfused liver volumes and SPECT counts. T:N were calculated and correlated with collected variables. RESULTS: Mean calculated T:N was 2.52. History of prior ablation was significantly correlated with higher T:N (mean 3.39 vs 2.24, p = 0.003). Cases in which mapping was being performed for treatment of disease progression was significantly correlated with higher T:N (mean 3.35 vs 2.14, p = 0.001). Larger tumor size trended toward lower T:N (p = 0.052). CONCLUSION: Patients with history of ablation and those undergoing treatment for disease progression have higher T:N and, therefore, could be considered for radioembolization preferentially over alternative treatments.

Percutaneous Radiofrequency Ablation to Occlude the Thoracic Duct: Preclinical Studies in Swine for a Potential Alternative to Embolization.

PURPOSE: To investigate the feasibility of percutaneous radiofrequency (RF) ablation to occlude the thoracic duct (TD) in a swine model with imaging and histologic correlation. MATERIALS AND METHODS: Six swine underwent TD RF ablation. Two terminal (4 hours, 1 open and 1 percutaneous) and 4 survival (30 days, all percutaneous) studies were performed. Two 20-gauge needles were placed adjacent to the TD under direct visualization after right thoracotomy or under fluoroscopic guidance using a percutaneous transabdominal approach after intranodal lymphangiography. RF electrodes were advanced through the needles, and ablation was performed at 90°C for 90 seconds. Lymphangiography was performed, and the TD and adjacent structures were resected and examined microscopically at the end of each study period. RESULTS: Four of 6 subjects survived the planned study period and underwent follow-up lymphangiography. Two subjects in the survival group were euthanized early-1 after developing an acute chylothorax and 1 because of gastric volvulus 14 days after ablation. Occlusion of the targeted TD segment was noted on lymphangiography in 3 of the 4 remaining subjects (2 acute and 1 survival). Histology 4 hours after RF ablation demonstrated necrosis of the TD wall and hemorrhage within the lumen. Histology at 14 and 30 days revealed fibrosis with hemosiderin-laden macrophages replacing the ablated TD. Collagen degeneration within the aortic wall involving a maximum of 60% thickness was noted in 5 of the 6 subjects. CONCLUSIONS: Percutaneous RF ablation can achieve short-segment TD occlusion. Further study is needed to improve safety and demonstrate clinical efficacy in treating TD leaks.

Quantitative Assessment of the Hemodynamic Effects of Intra-Arterial Nitroglycerin on Hepatocellular Carcinoma using Two-Dimensional Perfusion Angiography.

PURPOSE: To determine the hemodynamic effects of intra-arterial nitroglycerin on hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography. MATERIALS AND METHODS: Two-dimensional perfusion angiograms obtained prior to radioembolization from September 2019 to February 2020 were retrospectively reviewed. The inclusion criteria were the presence of Liver Imaging Reporting and Data System-5 tumors and angiographically distinguishable tumor and background liver. The exclusion criteria were previously treated tumors and motion-degraded studies. Thirteen patients with 2D perfusion angiograms obtained before and 2 minutes ± 1 after the administration of intra-arterial nitroglycerin were analyzed. The mean patient age was 72 years ± 9 and 11 of 13 (85%) had cirrhosis. The mean maximum tumor dimension was 4.6 cm ± 2.1. Eight tumors were in the right lobe and 5 were in the left lobe. The tumor and background liver 2D perfusion data were processed and the areas under the time-density curves were calculated. The relative perfusion of HCC to background liver was compared before and after nitroglycerin administration using a 2-tailed paired t-test. RESULTS: The mean rate of contrast administration was 1.4 mL/s ± 0.7 and the mean volume administered was 7.1 mL ± 3.3. The mean nitroglycerin dose was 281 µg ± 69. Ten of 13 patients (77%) demonstrated a relative increase in tumor perfusion. The mean HCC to background liver area under the curve ratio was 1.94 ± 0.76 before and 2.40 ± 0.89 after nitroglycerin administration (P < .05). CONCLUSIONS: Intra-arterial nitroglycerin increases previously untreated HCC perfusion relative to background liver as measured by 2D perfusion angiography, but this effect is variable among patients and should be validated with 3-dimensional imaging techniques.

mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert).

A unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state. Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function. The extent to which stem cells can regulate quiescence is unknown. Here we show that the stem cell quiescent state is composed of two distinct functional phases, G0 and an 'alert' phase we term G(Alert). Stem cells actively and reversibly transition between these phases in response to injury-induced systemic signals. Using genetic mouse models specific to muscle stem cells (or satellite cells), we show that mTORC1 activity is necessary and sufficient for the transition of satellite cells from G0 into G(Alert) and that signalling through the HGF receptor cMet is also necessary. We also identify G0-to-G(Alert) transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into G(Alert) possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into G(Alert) functions as an 'alerting' mechanism, an adaptive response that positions stem cells to respond rapidly under conditions of injury and stress, priming them for cell cycle entry.

Engineering an in situ crosslinkable hydrogel for enhanced remyelination.

Remyelination has to occur to fully regenerate injured spinal cords or brain tissues. A growing body of evidence has suggested that exogenous cell transplantation is one promising strategy to promote remyelination. However, direct injection of neural stem cells or oligodendrocyte progenitor cells (OPCs) to the lesion site may not be an optimal therapeutic strategy due to poor viability and functionality of transplanted cells resulted from the local hostile tissue environment. The overall objective of this study was to engineer an injectable biocompatible hydrogel system as a supportive niche to provide a regeneration permissive microenvironment for transplanted OPCs to survive, functionally differentiate, and remyelinate central nervous system (CNS) lesions. A highly biocompatible hydrogel, based on thiol-functionalized hyaluronic acid and thiol-functionalized gelatin, which can be crosslinked by poly-(ethylene glycol) diacrylate (PEGDA), was used. These hydrogels were optimized first regarding cell adhesive properties and mechanical properties to best support the growth properties of OPCs in culture. Transplanted OPCs with the hydrogels optimized in vitro exhibited enhanced survival and oligodendrogenic differentiation and were able to remyelinate demyelinated axons inside ethidium bromide (EB) demyelination lesion in adult spinal cord. This study provides a new possible therapeutic approach to treat CNS injuries in which cell therapies may be essential.

Review of the first year of an overseas military gambling treatment program.

This study provides descriptive information and preliminary first-year outcome data on the only overseas military gambling treatment option currently available. Implemented in January 2003 within the Substance Abuse Rehabilitation Program, U.S. Naval Hospital, Okinawa, Japan, gambling treatment was developed as a specific track within the overall substance abuse program. The present study explores the various considerations and requirements for setting up such a program, as well as a description of individuals seeking gambling treatment and preliminary outcome data. Participants consisted of all gambling referrals (N = 35, 26 males; mean age, 33.2 years; SD = 8.93) obtained over the first year that gambling services were offered. A significant degree of depression, suicidality, and substance abuse problems were observed in the sample. Results revealed that the gambling program was easily implemented within an established substance abuse program. The program was effective in preventing suicides in both military members and eligible beneficiaries and was effective in facilitating the retention of military members with gambling problems.