Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Diagnostic value of computed tomography (CT) histogram analysis in thyroid benign solitary coarse calcification nodules.

This study was to investigate the diagnostic value of the computed tomography (CT) histogram in thyroid benign solitary coarse calcification nodules (BSCNs). A total of 89 thyroid solitary coarse calcification nodules (coarse calcification ≥5 mm, no definite soft tissue around calcification) confirmed either by surgery or histopathological examination in 86 cases enrolled from January 2009 to December 2015 were evaluated. These included 56 BSCNs and 33 malignant solitary coarse calcification nodules (MSCNs). Overall, 27 cut-off values were calculated by N (4≤N≤30) times of 50 Hounsfield units (HU) in the range of 200 to 1500 HU, and each cut-off value and the differences in the corresponding area percentages in the CT histogram were recorded for BSCN and MSCN. The optimal cut-off value and the corresponding area percentage were established by receiver operating characteristic (ROC) curve analysis. In the 19 groups with an ROC area under curve (AUC) of more than 0.7, at a cut-off value of 800 HU and at an area percentage of no more than 93.8%, the ROC AUC reached the maximum of 0.79, and the accuracy, sensitivity, and specificity were 75.3%, 80.4%, and 66.7%, respectively. At a cut-off value of 1050 HU and at an area percentage of no more than 93.6%, the accuracy, sensitivity, and specificity were 71.9%, 60.7%, and 90.9%, respectively. At a cut-off of 1150 HU and area of no more than 98.4%, the accuracy, sensitivity, and specificity were 70.8%, 57.1%, and 93.9%, respectively. At a cut-off of 600 HU and area of no more than 12.1%, the accuracy, sensitivity, and specificity were 61.8%, 39.3%, and 100.0%, respectively. Compared with the cut-off value of 800 HU and an area percentage of no more than 93.8%, the sensitivity of cut-off values and minimum areas of 1050 HU and 93.6%, of 1150 HU and 98.4%, and of 600 HU and 12.1%, was gradually decreasing; however, their specificity was gradually increasing. This can provide an important basis for reducing the misdiagnosis and unnecessary surgical trauma.

In vivo evaluation of bronchial injury of irreversible electroporation in a porcine lung ablation model by using laboratory, pathological, and CT findings.

Irreversible electroporation (IRE) creates permanent pores in the cell membrane, leading to irreversible cell death. In this study, the impact of IRE on bronchial injury was comprehensively examined in a timed series study. Altogether, 8 Bama miniature pigs were included in this study and were randomly assigned to experimental and control groups. The experimental group underwent IRE that was guided and monitored by spiral computed tomography (CT). The monopole probe of the IRE was positioned at the right pulmonary hilum. Specimens were collected at 0 h, 2 h, 2 d, 7 d, and 14 d after the IRE procedure for a pathological examination. A small amount of needle-tract bleeding occurred in two animals, and mild pneumothorax occurred in another. IRE can elicit acute bronchial inflammation, bleeding, and mucosal injury, but severe complications were not found. Pathological examinations and transmission electron microscopy (TEM) showed dead vascular epithelium cells in the region of the ablation, while the bronchioli and the vascular extracellular matrix were preserved. At 2 hours post-IRE, there were marked increases in bronchoalveolar macrophages (P<0.001), but the inflammation could recover after 14 days and showed no statistical significance when compared with the control group at the same time. In conclusion, CT-guided IRE ablation can elicit acute but recoverable bronchial inflammation, bleeding, and mucosal injury in porcine lung tissues. However, longer follow-up is still required to establish an evaluation of the long-term safety.

Age and composite end-point events in medium follow-up of patients with carotid artery total occlusion using drug therapy.

BACKGROUND AND AIMS: The outcome of carotid artery total occlusion (CATO) is unclear. The aim of this study is to report the medium incidence of composite end-point events and risk factors (especially age), in patients with CATO, treated medically. METHODS: This was a single center retrospective study. Composite end-point events included death, ischemic stroke, transient ischemic attack, hemorrhagic stroke, myocardial infarction, or angina. Logistic regression analysis was used to analyze risk factors of composite end-point events. RESULTS: A total of 94 patients with CATO were included in the study. The mean follow-up duration was 30 ± 16 months. There were 16 cases who experienced composite end-point events (17.0%); among them, there were 15 cases of death (16.0%), 8 cases of ischemic stroke (7 cases of fatal stroke and 1 case of non-fatal stroke) (8.5%), and 1 case of angina pectoris (1%) (the patient later developed ischemic stroke). With increased age, the incidence of composite end-point events was significantly increased (p = 0.002). Multivariate logistic regression analysis showed that only age was a risk factor (OR = 3.051 (1.351-6.890), p = 0.007). CONCLUSIONS: The incidence of composite end-point events in patients with CATO was as high as 17.0% at approximately 3 years after drug therapy alone. For every 10 years of age increase, the risk increase of composite end-point events doubles.

Evaluation of different small bowel contrast agents by multi - detector row CT.

OBJECTIVE: This study aims to evaluate the effects of different oral small bowel contrast agents towards the intestinal dilatation and intestinal wall structure exhibition by the abdominal multi - detector row CT (MDCT) examination. METHODS: 80 patients were performed the whole abdominal CT examination, then randomly divided into four groups, with 20 patients in each group. 45 minutes before the CT examination, the patients were served with a total of 1800 ml pure water, pure milk, dilute lactulose solution and isotonic mannitol solution, respectively. RESULTS: The images were blinded read by two experienced abdominal radiologists in the workstation, the cross-sectional diameters of duodenum, jejunum, proximal and terminal ends of ileum of each patient were measured, then the analysis of variance was performed to analyze the differences in the intestinal dilatation among the experimental groups. The scoring method was used to score the intestinal dilatation and intestinal structure exhibition. The diluted lactulose solution and 2.5% mannitol exhibited the best intestinal dilation degrees. Similarly, the diluted lactulose solution and 2.5% mannitol exhibited the highest scores in the entire small bowel dilatation degree and intestinal structure exhibition. CONCLUSIONS: 2.5% osmotic mannitol and the diluted lactulose solution enabled the full dilatation of small bowel, and could clearly exhibit the wall structure.

[Influence of As2O3-lipiodol emulsion via transarterial embolization on a VX2 liver tumor model in rabbits].

OBJECTIVE: To investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model. METHODS: VX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis. RESULTS: The growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05]. CONCLUSION: As2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.

A large congenital and solitary intrahepatic arterioportal fistula in an old woman.

Arterioportal fistula (APF) is a rare cause of portal hypertension and may lead to death. APF can be congenital, post-traumatic, iatrogenic (transhepatic intervention or biopsy) or related to ruptured hepatic artery aneurysms. Congenital APF is a rare condition even in children. In this case report, we describe a 73-year-old woman diagnosed as APF by ultrasonography, computed tomography, and hepatic artery selective arteriography. The fistula was embolized twice but failed, and she still suffered from alimentary tract hemorrhage. Then, selective arteriography of the hepatic artery was performed again and venae coronaria ventriculi and short gastric vein were embolized. During the 2-year follow-up, the patient remained asymptomatic. We therefore argue that embolization of venae coronaria ventriculi and short gastric vein may be an effective treatment modality for intrahepatic APF with severe upper gastrointestinal bleeding.

Evaluation of selective hepatic angiography and embolization in patients with massive hemobilia.

BACKGROUND: Massive hemobilia is a rare but potentially life-threatening cause of upper gastrointestinal hemorrhage. Transarterial embolization is considered the first line of intervention to stop the bleeding for most causes of hemobilia. This study was conducted to evaluate selective hepatic angiography and embolization in the diagnosis and treatment of patients with massive hemobilia. METHODS: The clinical data of 16 patients with massive hemobilia were analyzed retrospectively. These patients underwent emergency celiac and selective right or left hepatic artery angiography and treated by embolization using Gelfoam particles and/or coils. RESULTS: Hepatic artery angiography revealed hepatic artery pseudoaneurysms in 6 patients, cystic artery pseudoaneurysms in 2, diffuse hemorrhage of hepatic artery branches in 5, and right hepatic artery-bile duct fistulae in 3. The patients were diagnosed rapidly by angiography and treated successfully by embolization of the hepatic artery branch proximal to the bleeding point, and hemorrhage was stopped immediately. Two patients were embolized the second time for rebleeding. Neither recurrence of bleeding nor serious complication was found during the follow-up for 3 months to 2 years. The other 2 patients whose hemorrhage failed to be controlled died several days later. CONCLUSION: Being safe, reliable and minimally invasive, selective hepatic artery angiography and embolization are effective in the diagnosis and treatment of massive hemobilia.