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Background The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. Methods Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell–cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. Results Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. Conclusions This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

Malignant liver tumors include primary malignant liver tumors and liver metastases. They are among the most common malignancies worldwide. The disease has a poor prognosis and poor overall survival, especially with liver metastases. Therefore, early detection and differentiation between malignant liver tumors are critical for patient treatment selection. The detection of cancer and the prediction of its origin is possible with a DNA methylation profile of the tumor DNA compared to that of normal cells, which reflects tissue differentiation and malignant transformation. New technologies enable the characterization of the tumor methylome in circulating tumor DNA (ctDNA), providing a variety of new ctDNA methylation biomarkers, which can provide additional information to clinical decision-making. Our review of the literature provides insight into methylation changes in ctDNA from patients with common malignant liver tumors and can serve as a starting point for further research.

Background Malignant liver tumor is one of the main causes of human death. In order to help physician better diagnose and make personalized treatment schemes, in clinical practice, it is often necessary to segment and visualize the liver tumor from abdominal computed tomography images. Due to the large number of slices in computed tomography sequence, developing an automatic and reliable segmentation method is very favored by physicians. However, because of the noise existed in the scan sequence and the similar pixel intensity of liver tumors with their surrounding tissues, besides, the size, position and shape of tumors also vary from one patient to another, automatic liver tumor segmentation is still a difficult task. Results We perform the proposed algorithm to the Liver Tumor Segmentation Challenge dataset and evaluate the segmentation results. Experimental results reveal that the proposed method achieved an average Dice score of 68.4% for tumor segmentation by using the designed network, and ASD, MSD, VOE and RVD improved from 27.8 to 21, 147 to 124, 0.52 to 0.46 and 0.69 to 0.73, respectively after performing adversarial training strategy, which proved the effectiveness of the proposed method. Conclusions The testing results show that the proposed method achieves improved performance, which corroborated the adversarial training based strategy can achieve more accurate and robustness results on liver tumor segmentation task.

Liver cancer remains a leading cause of mortality worldwide, and precise diagnostic tools are essential for effective treatment planning. Liver Tumors (LTs) vary significantly in size, shape, and location, and can present with tissues of similar intensities, making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging. This review examines recent advancements in Liver Segmentation (LS) and Tumor Segmentation (TS) algorithms, highlighting their strengths and limitations regarding precision, automation, and resilience. Performance metrics are utilized to assess key detection algorithms and analytical methods, emphasizing their effectiveness and relevance in clinical contexts. The review also addresses ongoing challenges in liver tumor segmentation and identification, such as managing high variability in patient data and ensuring robustness across different imaging conditions. It suggests directions for future research, with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods. This paper contributes to a comprehensive understanding of current liver tumor detection techniques, provides a roadmap for future innovations, and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.

BackgroundUltrasonography (US) is widely used for the diagnosis of liver tumors. However, the accuracy of the diagnosis largely depends on the visual perception of humans. Hence, we aimed to construct artificial intelligence (AI) models for the diagnosis of liver tumors in US.MethodsWe constructed three AI models based on still B-mode images: model-1 using 24,675 images, model-2 using 57,145 images, and model-3 using 70,950 images. A convolutional neural network was used to train the US images. The four-class liver tumor discrimination by AI, namely, cysts, hemangiomas, hepatocellular carcinoma, and metastatic tumors, was examined. The accuracy of the AI diagnosis was evaluated using tenfold cross-validation. The diagnostic performances of the AI models and human experts were also compared using an independent test cohort of video images.ResultsThe diagnostic accuracies of model-1, model-2, and model-3 in the four tumor types are 86.8%, 91.0%, and 91.1%, whereas those for malignant tumor are 91.3%, 94.3%, and 94.3%, respectively. In the independent comparison of the AIs and physicians, the percentages of correct diagnoses (accuracies) by the AIs are 80.0%, 81.8%, and 89.1% in model-1, model-2, and model-3, respectively. Meanwhile, the median percentages of correct diagnoses are 67.3% (range 63.6%–69.1%) and 47.3% (45.5%–47.3%) by human experts and non-experts, respectively.Conclusion The performance of the AI models surpassed that of human experts in the four-class discrimination and benign and malignant discrimination of liver tumors. Thus, the AI models can help prevent human errors in US diagnosis.

Malignant liver tumors, including primary malignant liver tumors and liver metastases, are among the most frequent malignancies worldwide. The disease carries a poor prognosis and poor overall survival, particularly in cases involving liver metastases. Consequently, the early detection and precise differentiation of malignant liver tumors are of paramount importance for making informed decisions regarding patient treatment. Significant research efforts are currently directed towards the development of diagnostic tools for different types of cancer using minimally invasive techniques. A prominent area of focus within this research is the evaluation of circulating microRNA, for which dysregulated expression is well documented in different cancers. Combining microRNAs in panels using serum or plasma samples derived from blood holds great promise for better sensitivity and specificity for detection of certain types of cancer.

Objective: Respiratory movements are a significant factor that may hinder the use of image navigation systems during minimally invasive procedures used to destroy focal lesions in the liver. This article aims to present a method of estimating the displacement of the target point due to respiratory movements during the procedure, working in real time. Method: The real-time method using skin markers and non-rigid registration algorithms has been implemented and tested for various classes of transformation. The method was validated using clinical data from 21 patients diagnosed with liver tumors. For each patient, each marker was treated as a target and the remaining markers as target position predictors, resulting in 162 configurations and 1095 respiratory cycles analyzed. In addition, the possibility of estimating the respiratory phase signal directly from intraoperative US images and the possibility of synchronization with the 4D CT respiratory sequence are also presented, based on ten patients. Results: The median value of the target registration error (TRE) was 3.47 for the non-rigid registration method using the combination of rigid transformation and elastic body spline curves, and an adaptation of the assessing quality using image registration circuits (AQUIRC) method. The average maximum distance was 3.4 (minimum: 1.6, maximum 6.8) mm. Conclusions: The proposed method obtained promising real-time TRE values. It also allowed for the estimation of the TRE at a given geometric margin level to determine the estimated target position. Directions for further quantitative research and the practical possibility of combining both methods are also presented.

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

The most recent comparisons between liver resection (LR) and percutaneous thermal ablation (PTA) reported similar efficacy and survival outcomes for primary and secondary liver tumors ≤ 3 cm in size. Nevertheless, LR still remains the most popular treatment strategy worldwide, and percutaneous ablation is usually reserved to patients who are not surgical candidates. However, in our opinion, the debate should no longer be what is the most effective treatment for patients with resectable small liver cancer who are not candidates for liver transplantation, but rather when LR or PTA are best suited to the individual patient. Subcapsular tumors or tumors closely adjacent to critical structures or vulnerable organs should undergo LR because ablation can often not achieve an adequate safety margin. Conversely, PTA should be considered the first choice to treat central tumors because it has lower complication rates, lower costs, and shorter hospital stay. Furthermore, recent technical improvements in tumor targeting and accurate assessment of the extent of the safety margin, such as stereotactic navigation, fusion imaging and software powered by Artificial Intelligence enabling the immediate comparison between the pre-procedure planned margins and the ablation area, are also changing the approach to tumors larger than 3 cm. The next trials should be aimed at investigating up to what tumor size PTA supported by these advanced technologies can achieve outcomes comparable to LR.

Minimally invasive hepatectomy for benign and malignant liver lesions has gained popularity in the past decade due to improved perioperative outcomes when compared to conventional ‘open’ technique. We aim to investigate our initial experience of robotic hepatectomy undertaken in our hepatobiliary program. All patients undergoing robotic hepatectomy between 2013 and 2018 were prospectively followed. Data are presented as median (mean ± SD). A total of 80 patients underwent robotic hepatectomy within the study period. 60% of the patients were women, age of 63 (62.4 ± 14.1), body mass index of 28 (29.6 ± 9.4), ASA class of 2.5 (2.5 ± 0.6), and MELD score of 7 (8.2 ± 2.8). Size of resected lesion was 3.9 (4.6 ± 3) cm. Indications for resection were metastatic lesions (30%), hepatocellular carcinoma (28%), cholangiocarcinoma (7%), gallbladder cancer (5%), neuroendocrine tumors (4%), and benign lesions (26%). Formal hepatectomy (right or left) was performed in 30% of the patients. Operative time was 233 (267.2 ± 109.6) minutes, and estimated blood loss was 150 (265.7 ± 319.9) ml. Length of hospital stay was 3 (5.0 ± 4.6) days. One patient was converted to ‘open’ approach. 10 patients experienced postoperative complications. Readmissions within 30 days of hospital discharge were seen in eight patients. Our data support that robotic hepatectomy is safe and feasible, with favorable short-term outcomes and low conversion rate. Robotic technology extends the application of minimally invasive techniques in the field of hepatobiliary surgery.