Origin Of The Far Off-Axis GRB171205A

We show that observed properties of the low luminosity GRB171205A and its afterglow, like those of most other low-luminosity (LL) gamma ray bursts (GRBs) associate with a supernova (SN), indicate that it is an ordinary SN-GRB, which was produced by inverse Compton scattering of glory light by a highly relativistic narrowly collimated jet ejected in a supernova explosion and viewed from a far off-axis angle. As such, VLA/VLBI follow-up radio observations of a superluminal displacement of its bright radio afterglow from its parent supernova, will be able to test clearly whether it is an ordinary SN-GRB viewed from far off-axis or it belongs to a distinct class of GRBs, which are different from ordinary GRBs, and cannot be explained by standard fireball models of GRBs as ordinary GRBsComment: 5 pages, 6 figures, updated data in Fig. 3, Corrected GRB angular distance used in Fig.

Hepatic Arteriography and C-Arm CT-Guided Ablation (HepACAGA) to Improve Tumor Visualization, Navigation and Margin Confirmation in Percutaneous Liver Tumor Ablation

Purpose: We present a technique that combines Hepatic Arteriography with C-arm CT-Guided Ablation (HepACAGA) to improve tumor visualization, navigation and margin confirmation for percutaneous ablation of liver tumors. Materials and Methods: All consecutive patients scheduled for HepACAGA between April 20th, 2021, and November 2nd, 2021, were included in this retrospective, cohort study. HepACAGA was performed in an angiography-suite under general anesthesia. The hepatic artery was catheterized for selective contrast injection. C-arm CT and guidance software were then used to visualize the tumor and the microwave antenna was inserted during apnea. Pre- and post-ablation C-arm CTs were performed and ablation margins assessed. Technical success, antenna placement deviation, number of repositions, tumor recurrence, and safety were evaluated. Technical success was defined as a tumor that was ablated according to the HepACAGA technique. Results: A total of 21 patients (28 tumors) were included. The main tumor type was colorectal cancer liver metastases (11/21, 52%), followed by hepatocellular carcinoma (7/21, 33%), neuroendocrine tumor metastases (1/21, 5%), and other tumor types (2/21, 10%). The technical success rate was 93% (26/28 tumors) with two small hypovascular lesions unable to be identified. A single microwave antenna was used in all patients. The median antenna placement deviation was 1 mm (range 0–6 mm). At a median follow-up time of 16 months (range 5–22 months), there was no tumor recurrence in any patient. Safety analysis showed a complication rate of 5% grade 2 and 5% grade 3. Conclusion: HepACAGA was demonstrated to be a safe and effective percutaneous ablation technique, without any local tumor recurrence in this study. Graphic Abstract: [Figure not available: see fulltext.

90Y-/166Ho- ‘Radiation lobectomy’ for liver tumors induces abnormal morphology and impaired drainage of peritumor lymphatics

Background & Aims: High-dose unilobar radioembolization, or ‘radiation lobectomy’ (RL), is an induction therapy that achieves contralateral future liver remnant hypertrophy while simultaneously irradiating the tumor. As such, it may prevent further growth, but it is unknown whether RL affects intrahepatic lymphatics, a major route via which liver tumors disseminate. Methods: This was a case-control study conducted at University Medical Center Utrecht. The study compared lymph vessels in livers that had undergone RL (cases) with those in livers that had not undergone RL (controls). Histological samples were acquired from patients diagnosed with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) between 2017 and 2022. Lymph vessel morphology was analyzed by two researchers using podoplanin, a protein that is expressed in lymphatic endothelium. In vivo liver lymph drainage of radioembolized livers was assessed using intraoperative liver lymphangiography (ILL): during liver surgery, patent blue dye was injected into the liver parenchyma, followed by inspection for staining of perihepatic lymph structures. ILL results were compared to a previously published cohort. Results: Immunohistochemical analysis on post-RL tumor tissues from ten patients with CRLM and nine patients with HCC revealed aberrant morphology of irradiated liver lymphatics when compared to controls (n = 3 per group). Irradiated lymphatics were tortuous (p <0.05), thickened (p <0.05) and discontinuous (p <0.05). Moreover, post-RL lymphatics had larger lumens (1.5–1.7x, p <0.0001), indicating lymph stasis. ILL revealed diminished lymphatic drainage to perihepatic lymph nodes and vessels in irradiated livers when compared to non-radioembolized controls (p = 1.0x10-4). Conclusions: Radioembolization impairs peritumoral lymph vessel function. Further research is needed to evaluate if radioembolization impairs tumor dissemination via this route. Impact and implications: Unilobar radioembolization can serve as an alternative to portal venous embolization for patients who are considered unresectable due to an insufficient future liver remnant. This research suggests that radioembolization impairs the function of peritumoral liver lymph vessels, potentially hindering dissemination via this route. These findings provide support for considering unilobar radioembolization over standard portal venous embolization

Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe

Background &amp; Aims: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. Methods: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. Results: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p &lt;0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p &lt;0.001). Conclusions: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. Impact and implications: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.</p

Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe

Background &amp; Aims: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. Methods: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. Results: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p &lt;0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p &lt;0.001). Conclusions: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. Impact and implications: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.</p

Systematic review with meta-analysis: branched-chain amino acid supplementation in liver disease

BACKGROUND: Dietary supplementation with branched-chain amino acids (BCAA) is often used in cirrhotic patients to improve nutritional status. We wanted to explore the evidence for BCAA supplementation in chronic liver disease. METHODS: We searched MEDLINE and EMBASE for studies with BCAA supplementation with the presence of a disease-control group (placebo or no intervention) using search terms 'liver cirrhosis', 'hepatocellular carcinoma', 'branched chain amino acids' and relevant synonyms. Risk of bias was assessed using ROBINS-I and RoB 2.0 tools. Meta-analyses were performed with a random-effects model. Results were reported following EQUATOR guidelines. RESULTS: Of 3378 studies screened by title and abstract, 54 were included (34 randomized controlled trials, 5 prospective case-control studies, 13 retrospective case-control studies: in total 2308 patients BCAA supplementation, 2876 disease-controls). Risk of bias was high/serious for almost all studies. According to meta-analyses, long-term (at least 6 months) BCAA supplementation in cirrhotic patients significantly improved event-free survival (p = .008; RR .61 95% CI .42-.88) and tended to improve overall survival (p = .05; RR .58 95% CI .34-1.00). Two retrospective studies suggested the beneficial effects during sorafenib for hepatocellular carcinoma. Available studies reported no beneficial effects or contradictory results of BCAA after other specific therapeutic interventions (resection or radiological interventions for hepatocellular carcinoma, liver transplantation, paracentesis or variceal ligation). No convincing beneficial effects of BCAA supplementation on liver function, nutritional status or quality of life were found. No study reported serious side effects of BCAA. CONCLUSIONS: Prophylactic BCAA supplementation appears safe and might improve survival in cirrhotic patients

Conventional versus Hepatic Arteriography and C-Arm CT-Guided Ablation of Liver Tumors (HepACAGA): A Comparative Analysis

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

Nutritional status in patients with hepatocellular carcinoma: Potential relevance for clinical outcome

BACKGROUND: Impaired nutritional status is a risk factor for unfavorable outcome in cirrhosis. METHODS: In this prospective cohort study in hepatocellular carcinoma patients referred for tumor-specific therapy, nutritional status was assessed before and 3 months post-treatment using 4 complementary tools: hand-grip strength (HGS), Liver Frailty Index (LFI), Patient-Generated Subjective Global Assessment (PG-SGA) and skeletal muscle index (L3-SMI). Uni- and multivariable analyses were performed using Kaplan Meier curves and Cox's regression analyses with correction for Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein and age. RESULTS: 56 patients were evaluated at baseline and 38 patients 3 months post-treatment. Baseline BCLC stage was 0 in 14%, A in 27%, B in 36%, C in 21%, and D in 2%. HGS, LFI, PG-SGA and L3-SMI were impaired in 13%, 95%, 21% and 71% respectively. Of all patients, 52% died after (median, range) 373 (32-962) days. Of the nutritional assessment tools, only HGS was independently associated with complication-free survival (HR 0.304, 95%CI 0.10-0.88: p = 0.028) and, approaching significance, with overall survival (HR 0.323, 95%CI 0.103-1.008: p = 0.052). Tumor-specific therapy was administered in 50 patients (20% radiofrequency / microwave ablation, 4% resection, 74% transarterial radio- or chemoembolization, 2% sorafenib). Three months post-treatment, complete response occurred in 44%, partial response in 20%, stable disease in 20% and progressive disease in 16%. Child-Pugh scores deteriorated and such deterioration was independently associated with reduced overall and complication-free survival. CONCLUSIONS: reduced baseline HGS and deteriorated post-treatment Child-Pugh score are associated with reduced overall and complication-free survival in HCC

Prophylactic Medication during Radioembolization in Metastatic Liver Disease: Is It Really Necessary? A Retrospective Cohort Study and Systematic Review of the Literature

PURPOSE: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. METHODS: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (D h). Logistic regression models were used to investigate if variables (among which are P/UDCA and D h) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. RESULTS: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. D h was associated with biochemical toxicity ( p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. CONCLUSION: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization

Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe

Background & Aims: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. Methods: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. Results: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p <0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p <0.001). Conclusions: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. Impact and implications: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population