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Simple Summary: Liver metastases presenting as small hyperintense lesions on diffusion-weighted imaging pose a therapeutic challenge for conventional thermal ablation, as they are often occult on ultrasound and CT. This study aimed to assess the efficacy of the Hepatic Arteriography and C-Arm CT-Guided Ablation (HepACAGA) technique, a novel approach that integrates C-arm CT hepatic arteriography with C-arm CT-guided navigation, for treating small liver metastases (≤10 mm) detected on MRI. A total of 15 patients with 26 liver metastases were included. The metastases originated predominantly from colorectal cancer (73%), followed by neuro-endocrine tumors (15%), breast cancer (8%) and esophageal cancer (4%). The HepACAGA technique achieved a 100% technical success rate in detecting and ablating the small metastases. After a median follow-up of 9 months, one tumor recurred (4%) which was successfully treated with a subsequent re-ablation. No complications were observed. These findings demonstrate that the HepACAGA technique can effectively ablate subcentimeter liver metastases identified on MRI. Purpose: Liver metastases presenting as small hyperintense foci on diffusion-weighted imaging (DWI) pose a therapeutic challenge. Ablation is generally not possible since these lesions are often occult on ultrasound and CT. The purpose of this prospective study was to assess if small liver metastases (≤10 mm) detected on DWI can be successfully localized and ablated with the Hepatic Arteriography and C-Arm CT-Guided Ablation technique (HepACAGA). Materials and Methods: All consecutive patients with small liver metastases (≤10 mm), as measured on DWI, referred for ablation with HepACAGA between 1 January 2021, and 31 October 2023, were included. Re-ablations and ablations concomitant with another local treatment were excluded. The primary outcome was the technical success rate, defined as the intraprocedural detection and subsequent successful ablation of small liver metastases using HepACAGA. Secondary outcomes included the primary and secondary local tumor progression (LTP) rates and the complication rate. Results: A total of 15 patients (26 tumors) were included, with liver metastases from colorectal cancer (73%), neuro-endocrine tumors (15%), breast cancer (8%) and esophageal cancer (4%). All 26 tumors were successfully identified, punctured and ablated (a technical success rate of 100%). After a median follow-up of 9 months, primary and secondary LTP were 4% and 0%, respectively. No complications occurred. Conclusion: In this proof-of-concept study, the HepACAGA technique was successfully used to detect and ablate 100% of small liver metastases identified on DWI with a low recurrence rate and no complications. This technique enables the ablation of subcentimeter liver metastases detected on MRI. [ABSTRACT FROM AUTHOR]

Simple Summary: Catheter-assisted ablations have shown significant improvements in the outcomes of percutaneous thermal ablation for liver cancer. A novel approach within this category is the Hepatic Arteriography and C-Arm CT-Guided Ablation (HepACAGA) technique, which integrates C-arm CT hepatic arteriography with C-arm guided navigation. This cohort study aimed to assess the effectiveness and safety of the HepACAGA technique compared to conventional ultrasound/CT-guided thermal ablation in treating hepatocellular carcinoma and colorectal liver metastasis. A total of 68 patients with 120 tumors undergoing HepACAGA and 53 patients with 78 tumors undergoing conventional ablation were included. The HepACAGA technique demonstrated superior outcomes: lower rates of local tumor recurrence, longer local tumor recurrence-free survival, and fewer procedure-related complications. These findings suggest that HepACAGA is a safer and more effective ablation technique in liver cancer treatment compared to conventional ablation methods. Purpose: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic–arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. Materials and Methods: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. Results: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). Conclusions: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. Materials and Methods: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. Results: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09–21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00–1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00–1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). Conclusion: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. Trail registration: NCT01031784, registered December 2009. NCT01612325, registered June 2012. [ABSTRACT FROM AUTHOR]

Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC. Methods: We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry. Results: High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8+ T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8+ T cells in non-metastatic tumors. CD8+ T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort. Conclusion: We conclude that localization of phenotypically distinct CD8+ T cells within stroma may predict metastasis formation in MSI-H CRC. [ABSTRACT FROM AUTHOR]

Purpose: DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer. Methods: Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples. Correlations between the subcellular localization of DDX3 and CRM1 and the difference in overall survival between patients with and without nuclear DDX3 were studied. In addition, DDX3 mutants were created for in vitro evaluation of the mechanism behind nuclear retention of DDX3. Results: DDX3 was present in the nucleus of 35% of colorectal and 48% of breast cancer patient samples and was particularly strong in the nucleolus. Nuclear DDX3 correlated with worse overall survival in both colorectal (hazard ratio [HR] 2.34, P<0.001) and breast cancer (HR 2.39, P=0.004) patients. Colorectal cancers with nuclear DDX3 expression more often had cytoplasmic expression of the nuclear exporter CRM1 (relative risk 1.67, P=0.04). In vitro analysis of DDX3 deletion mutants demonstrated that CRM1-mediated export was most dependent on the N-terminal nuclear export signal. Conclusion: Overall, we conclude that nuclear DDX3 is partially CRM1-mediated and predicts worse survival in colorectal and breast cancer patients, putting it forward as a target for therapeutic intervention with DDX3 inhibitors under development in these cancer types. [ABSTRACT FROM AUTHOR]