CT radiomics models are unable to predict new liver metastasis after successful thermal ablation of colorectal liver metastases

Background Patients with colorectal liver metastases (CRLM) who undergo thermal ablation are at risk of developing new CRLM after ablation. Identification of these patients might enable individualized treatment. Purpose To investigate whether an existing machine-learning model with radiomics features based on pre-ablation computed tomography (CT) images of patients with colorectal cancer can predict development of new CRLM. Material and Methods In total, 94 patients with CRLM who were treated with thermal ablation were analyzed. Radiomics features were extracted from the healthy liver parenchyma of CT images in the portal venous phase, before thermal ablation. First, a previously developed radiomics model (Original model) was applied to the entire cohort to predict new CRLM after 6 and 24 months of follow-up. Next, new machine-learning models were developed (Radiomics, Clinical, and Combined), based on radiomics features, clinical features, or a combination of both. Results The external validation of the Original model reached an area under the curve (AUC) of 0.57 (95% confidence interval [CI]=0.56–0.58) and 0.52 (95% CI=0.51–0.53) for 6 and 24 months of follow-up. The new predictive radiomics models yielded a higher performance at 6 months compared to 24 months. For the prediction of CRLM at 6 months, the Combined model had slightly better performance (AUC=0.60; 95% CI=0.59–0.61) compared to the Radiomics and Clinical models (AUC=0.55–0.57), while all three models had a low performance for the prediction at 24 months (AUC=0.52–0.53). Conclusion Both the Original and newly developed radiomics models were unable to predict new CLRM based on healthy liver parenchyma in patients who will undergo ablation for CRLM.

Pre- and post-treatment image-based dosimetry in 90Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit

Objective: To evaluate the pre-treatment and post-treatment imaging-based dosimetry of patients treated with 90Y-microspheres, including accurate estimations of dose to tumor, healthy liver and lung. To do so, the Monte Carlo (MC) TOPAS platform is in this work extended towards its utilization in radionuclide therapy. Approach: Five patients treated at the Massachusetts General Hospital were selected for this study. All patients had data for both pre-treatment SPECT-CT imaging using 99mTc-MAA as a surrogate of the 90Y-microspheres treatment and SPECT-CT imaging immediately after the 90Y activity administration. Pre- and post-treatment doses were computed with TOPAS using the SPECT images to localize the source positions and the CT images to account for tissue inhomoegeneities. We compared our results with analytical calculations following the voxel-based MIRD scheme. Main results: TOPAS results largely agreed with the MIRD-based calculations in soft tissue regions: the average difference in mean dose to the liver was 0.14 Gy/GBq (2.6%). However, dose distributions in the lung differed considerably: absolute differences in mean doses to the lung ranged from 1.2 Gy/GBq to 6.3 Gy/GBq and relative differences from 153% to 231%. We also found large differences in the intra-hepatic dose distributions between pre- and post-treatment imaging, but only limited differences in the pulmonary dose. Significance: Doses to lung were found to be higher using TOPAS with respect to analytical calculations which may significantly underestimate dose to the lung, suggesting the use of MC methods for 90Y dosimetry. According to our results, pre-treatment imaging may still be representative of dose to lung in these treatments.

Label-free functional and structural imaging of liver microvascular complex in mice by Jones matrix optical coherence tomography

We demonstrate label-free imaging of the functional and structural properties of microvascular complex in mice liver. The imaging was performed by a custom-built Jones-matrix based polarization sensitive optical coherence tomography (JM-OCT), which is capable of measuring tissue’s attenuation coefficient, birefringence, and tiny tissue dynamics. Two longitudinal studies comprising a healthy liver and an early fibrotic liver model were performed. In the healthy liver, we observed distinctive high dynamics beneath the vessel at the initial time point (0 h) and reappearance of high dynamics at 32-h time point. In the early fibrotic liver model, we observed high dynamics signal that reveals a clear network vascular structure by volume rendering. Longitudinal time-course imaging showed that these high dynamics signals faded and decreased over time.

Gene Expression Characteristics of Liver Tissue Reveal the Underlying Pathogenesis of Hepatocellular Carcinoma

Background. Hepatocellular carcinoma (HCC) is high-mortality primary liver cancer and the most common malignant tumor in the world. This study is based on a hepatocellular carcinoma-related dysfunction module designed to explore the dysregulation of genes in liver cancer tissue. Methods. By downloading the relevant data on the GEO database, we performed a differential analysis of healthy liver tissue and liver cancer tissues as well as healthy liver tissue and hepatocellular carcinoma tissue and then obtained two sets of differential genes and combined them. We performed a cointerpretation analysis of these differential genes and constructed related functional disorder modules. A hypergeometric test was performed to calculate the potential regulatory effects of multiple factors on the module, and a series of ncRNA and TF regulators were identified. We obtained a total of 4479 differentially expressed genes in hepatocellular carcinoma, and these genes were clustered into ten hepatocellular carcinoma-related functional interpretation disorder modules. Results. Enrichment analysis revealed that these modular genes are mainly involved in signal transduction including cell cycle, TGF-beta signal transduction, and p53 signal transduction. Depending on the predictive analysis of multidimensional regulators, 323 ncRNAs and 52 TF-mediated hepatocellular carcinoma-related dysregulation modules were found to regulate disease progression. Conclusions. Based on a series of investigations, it was found that miR-30b-5p may participate in the peroxisome signal transduction by downregulating ABCD3-mediated module 1, thereby promoting the development and progression of hepatocellular carcinoma. Our research results not only provide a theoretical basis for biologists to study hepatocellular carcinoma further but also offer new methods and new ideas for the personalized care and treatment of hepatocellular carcinoma.

Assessment of safety and efficacy of a dietary supplement KaraLiv™ in supporting liver health: a double-blind, parallel, placebo-controlled randomized clinical trial

Background: The liver is responsible for many critical functions within the body. If the liver becomes diseased or injured, loss of those critical functions can cause significant damage to the body. KaraLivTM is a novel herbal formulation which contains a blend of different herbal extract ingredients. The current study tested the safety and efficacy of KaraLivTM versus a placebo control in supporting liver function.Methods: The study is a randomized, double-blind, parallel, and placebo-controlled study. A total of 60 patients were divided into 2 groups of 30 each. One group was given KaraLivTM and the other group was given a placebo for a period of 56 days. Treatment results were assessed by evaluating the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and alkaline phosphatase (ALP) in both groups.Results: The herbal supplement KaraLivTM significantly supported healthy liver function compared to the placebo following the 56 days of treatment. The treatment (KaraLivTM) group showed a statistically significant improvement in assessed liver enzyme levels compared to the placebo group.Conclusions: The all-natural herbal supplement KaraLivTM is a safe and effective product that can significantly help support healthy liver function.

Anti-Hepatotoxic Effect of Vananimbuka (Glycosmis pentaphylla Retz.)

Liver, one of the largest of organs and a chief site for intense metabolism and excretion. It has a surprising role in the maintenance, performance and regulating homeostasis of the body. The major functions of liver are carbohydrate, protein, and fat metabolism, detoxification, secretion of bile and storage of vitamin. Maintaining a healthy liver is a crucial factor for overall health and well-being. But it is continuously and frequently exposed to environmental toxins, abused by poor food habits and alcohol. Prescribed and over-the-counter drugs can eventually lead to various liver ailments like hepatitis and liver cirrhosis. Thus liver diseases are some of the fatal health issues in the world today. According to Ayurveda, Yakrut is considered as one of the 15 koshtangas. It is also considered as sthana of ranjaka pitta and plays an important role in maintenance of agni. Hepatic disorders can be compared to yakrut vikaras and yakrutpleeha vikaras. In ayurveda Vananimbuka discribtion is available for yakrut vikara.

The Role of Immunotherapy in a Tolerogenic Environment: Current and Future Perspectives for Hepatocellular Carcinoma

In contrast to several tumors whose prognoses are radically affected by novel immunotherapeutic approaches and/or targeted therapies, the outcomes of advanced hepatocellular carcinoma (HCC) remain poor. The underlying cirrhosis that is frequently associated with it complicates medical treatment and often determines survival. The landscape of HCC treatment had included sorafenib as the only drug available for ten years, until 2018, when lenvatinib was approved for treatment. The second-line systemic treatments available for hepatocellular carcinoma include regorafenib, cabozantinib, ramucirumab, and, more recently, immune checkpoint inhibitors. However, the median survival remains below 15 months. The results obtained in clinics should be interpreted whilst considering the peculiar role of the liver as an immune organ. A healthy liver microenvironment ordinarily experiences stimulation by gut-derived antigens. This setup elucidates the response to chronic inflammation and the altered balance between tolerance and immune response in HCC development. This paper provides an overview of the mechanisms involved in HCC pathogenesis, with a special focus on the immune implications, along with current and future clinical perspectives.