Comparative Analysis of Transradial and Transfemoral Approaches in Transarterial Radioembolization for Liver Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: Transarterial radioembolization (TARE) is a minimally invasive therapy combining embolization and radiation for cancer treatment. This meta-analysis compares radiation exposure, quality of life, and safety of the transradial (TRA) versus transfemoral (TFA) approaches in TARE for liver tumors. MATERIALS AND METHODS: We searched PubMed, SCOPUS, Cochrane, EMBASE, and Web of Science for studies comparing TRA versus TFA in TARE for liver tumors. Our primary outcomes focused on various measures of patient radiation exposure, including procedure time, fluoroscopy time, air kerma, and dose-area product (DAP). For secondary outcomes, we evaluated safety parameters, such as overall pain experienced during the procedure, pain in the recovery room post-procedure, the incidence of adverse events, and the impact on quality of life. Study quality was assessed using Cochrane's ROB 2 tool for RCTs and the Newcastle-Ottawa scale for observational studies. Data analysis was conducted with REVMAN 5.4.1 software. RESULTS: Six studies, comprising one RCT and five cohort studies with 1,209 patients, underwent comprehensive analysis. The aggregated findings revealed a significant reduction in procedure duration associated with TRA (MD =- 6.30, 95% CI [- 9.88, - 2.73], P = 0.005). However, no statistically significant differences were found between TRA and TFA groups concerning fluoroscopy time, recovery time, air kerma, DAP, pain in the recovery room, overall pain during the procedure, quality of life measuring mental health and physical function or adverse events. CONCLUSION: TRA and TFA showed comparable results in TARE for liver tumors, but TRA offered a shorter procedure time. Further RCTs with larger samples are needed to confirm these findings. Future studies should assess long-term efficacy for a more complete evaluation.

Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors.

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.

Reappraisal of liver resection as an alternative to transplantation in locally advanced hepatoblastoma: A systematic review and analysis of pooled individual patient data.

BACKGROUND: There is ongoing debate regarding liver transplantation (LT) versus liver resection (LR) for locally advanced hepatoblastoma. However, comparative studies are lacking. Consequently, a significant evidence gap persists, hindering the establishment of consensus guidelines. This study aimed to compare LT and LR for locally advanced hepatoblastoma, using predefined inclusion criteria to ensure comparable intervention groups. METHODS: According to current Children's Oncology Group (COG) and SIOPEL (European Childhood Liver Tumour Study Group) recommendations, hepatoblastoma that requires LT evaluation was defined as either PRETEXT (PRE-Treatment EXTent of tumor) IV F+, POST-TEXT (POST-Treatment EXTent of tumor) IV, POST-TEXT P+, and/or POST-TEXT V+. A systematic literature search (Medline/Web-of-Science/Embase) was performed. Only patients who met the aforementioned criteria were included. Patient data were extracted individually and pooled. RESULTS: A total of 189 patients with locally advanced hepatoblastoma from 55 studies met the specified criteria, with 111 undergoing LT and 78 LR. There were no significant differences between the two groups in age, alpha-fetoprotein (AFP), and PRETEXT stages. Local recurrence was more common after LR (14% vs. 3% in LT, p = .008), while distant recurrence was more often observed after LT (16% vs. 5% in LR, p = .035). Overall survival (OS) and event-free survival (EFS) did not differ significantly between LT and LR (5-year OS: LT = 75.3% [95% confidence interval: 66.5-85.2], LR = 87.6% [80.4-95.6], p = .140; 5-year EFS: LT = 68.5% [59.3-79.1], LR = 71.1% [60.7-83.3], p = .700). CONCLUSION: Real-life data revealed that a considerable number of patients with locally advanced hepatoblastoma underwent LR. This analysis suggests that outcomes are similar and favorable for both approaches. LR can therefore be considered an effective alternative to LT in selected cases even in locally advanced hepatoblastoma.

Laparoscopic ablation for liver malignancies: initial experience at a Scandinavian high volume HPB center.

BACKGROUND: Ablation is an effective, parenchymal-sparing treatment for primary liver cancer and liver metastases. The purpose of this study was to report our initial experience with laparoscopic microwave ablation regarding postoperative complications, rate of conversions to open procedure, and technical efficacy. METHODS: This was a quality improvement project carried out at a tertiary care center in Denmark. Patients ≥ 18 years old with liver malignancies, not available for percutaneous ablation, and treated with ultrasound-guided laparoscopic ablation were included. RESULTS: From March 2023 to December 2023, 39 patients were referred for laparoscopic ablation after a multidisciplinary team conference. Of these, two procedures were converted to open procedures due to adhesion and tumor progression. Three patients rejected the sharing of medical information, two procedures were canceled and in one case the strategy was changed perioperatively. Therefore, 32 procedures in 31 patients were available for analysis. Complete ablation was evaluated after 1 month and was achieved in 100% of the procedures. None of the patients died, and no complications were reported in 21 cases (65.6%). Most patients with complications had a grade 1 complication based on the Clavien-Dindo classification, which among others included abdominal and shoulder pain, atrial fibrillation, and subcutaneous hematoma. Two patients had a complication grade 2 (wound infection and decompensated cirrhosis) and one had a grade 4b (sepsis due to pneumonia and urinary tract infection). The median Comprehensive Complication Index was 12.2 (interquartile range 8.7-24.2). Furthermore, univariable logistic regression showed that ≥ 2 tumors treated were associated with a higher risk of complications (odds ratio 6.37, 95% confidence interval [1.20;33.85], p-value = 0.0297). CONCLUSION: Ultrasound-guided laparoscopic microwave ablation of liver malignancies is feasible and safe with little risk for complications, a high technical efficacy, and a low rate of conversions to open procedures.

Hepatic resections for pediatric hepatoblastoma: analysis of 30-day outcomes using the National Surgical Quality Improvement Program-Pediatric database.

BACKGROUND: Surgical resection remains the cornerstone of treatment for hepatoblastoma in children and offers the best chance of disease-free survival. We aimed to analyze the 30 day outcomes of hepatic resection for hepatoblastoma stratified by extent using the National Surgical Quality Improvement Program-Pediatric (NSQIP-P). METHODS: We queried NSQIP-P for children undergoing resection of Hepatoblastoma from 2012 to 2021. Relevant clinical characteristics and outcomes were extracted for multivariate logistic regression to identify predictors of common adverse outcomes. RESULTS: We included 458 children with a median age of 1.90 years. Overall complications were rare, and perioperative blood transfusion (64.2%) and postoperative ventilation > 48 h (10.0%) were the only adverse events prevalent in more than 5% of patients. Median transfusion volume was 15.7 ml/kg. On multivariate regression, only patients undergoing Trisectionectomy (aOR = 3.387, 95% C.I. = 1.348-8.510) had higher odds of receiving > 75th percentile blood transfusion. Furthermore, only perioperative transfusion and postoperative ventilation > 48 h were statistically more common in patients undergoing extended versus standard resections. CONCLUSIONS: Outcomes following resection of hepatoblastoma are excellent, with low rates of postoperative adverse events. Although children undergoing trisectionectomy likely require greater transfusion volume, extended hepatic resections do not appear to have worse 30 day outcomes despite greater operative complexity and duration.

When the Belly Looks Okay but Is Actually Not: A Case of Hepatoblastoma in a Well-Appearing Child.

Hepatoblastoma is one of the pediatric tumors with genetic and intrauterine risk factors. It is typically asymptomatic at diagnosis, at which time most patients have metastasis to the lungs and are in an advanced stage of liver disease. We report an interesting case of a 13-month-old child who presented with a one-month history of abdominal distention. A review of the systems was unremarkable but a physical examination revealed a well-appearing child with abdominal distention, normal vital signs, and an abdominal mass. Abdominal imaging revealed a well-defined heterogeneously-enhancing mass arising from the right hepatic lobe and laboratory results were consistent with a diagnosis of hepatoblastoma. The mass was resected and the patient underwent chemotherapy with continued follow-up management. We shed light on pediatric hepatoblastoma and its clinical presentation, pathology, and laboratory and imaging findings, to aid clinicians in diagnosing the condition correctly.

Minimally invasive and robotic-assisted approaches applied to pediatric surgical oncology.

The management of pediatric tumors is complex, with surgery, chemotherapy, and radiotherapy being cornerstones in their treatment. Tumor removal is increasingly performed by a minimally invasive approach, which allows for quicker postoperative recovery and less postoperative pain. The goal of this report is to give an overview of minimally invasive surgical approaches for common pediatric tumors, with a focus on technical considerations and postoperative outcomes.

[Prophylactic surgery for hepatic and biliary tumors]. / Chirurgie prophylactique des tumeurs du foie et des voies biliaires.

Benign tumors of the liver and biliary tract are rare entities, and some of them require surgical management to prevent their malignant transformation. Tumors from the biliary tract with malignant potential are treated either by hepatic resection, for mucinous cystic neoplasm and ciliated hepatic foregut cysts, or by biliary resections, for biliary papillary neoplasm and type I and IV choledochal cysts. The pathologies requiring prophylactic cholecystectomy are polyps larger than 10 mm, porcelain gallbladder and pancreaticobiliary maljunction. Finally, hepatocellular adenoma over 5cm, occurring in male patients, or exon 3 mutated beta-catenin, should lead to prophylactic resection by hepatic segmentectomy. This article describes these different pathologies and their management.

Comparison of CT and MRI in the Diagnosis of Liver Tumors: A Retrospective Case-Control Analysis.

OBJECTIVE: To compare the diagnostic value of multi-slice computed tomography (CT) and magnetic resonance imaging (MRI) in liver tumors. METHODS: Retrospective selection of CT and MRI imaging data from 109 cases of liver tumors treated in our hospital from January 2020 to March 2023. The selection was determined through pathological examination. RESULTS: According to the pathological examination results, 61 cases were benign tumors, and 48 cases were malignant tumors. The hepatic portal flow (HPF), hepatic artery perfusion index (HPI) and hepatic artery perfusion (HAF) of malignant tumors were significantly lower than in benign tumors (P<0.05). The signal enhancement ratio of malignant tumors was significantly higher than in benign tumors, and the peak time was significantly lower than in benign tumors (P<0.05). The sensitivity (97.92%) and accuracy (97.25%) of the combined examination were significantly higher than those of MRI (83.33%, 90.83%) or CT alone (81.25%, 88.99%) (P<0.05). CONCLUSION: CT and MRI have high application value in the diagnosis and evaluation of liver tumors, and the combination of these two methods can further improve diagnostic sensitivity and accuracy, providing an objective reference for early diagnosis and treatment of liver cancer.

Adjusted Tumor Enhancement on Dual-Phase Cone-Beam CT: Predictor of Response and Overall Survival in Patients with Liver Malignancies Treated with Hepatic Artery Embolization.

The aim of this study was to examine the value of tumor enhancement parameters on dual-phase cone-beam CT (CBCT) in predicting initial response, local progression-free survival (L-PFS) and overall survival (OS) following hepatic artery embolization (HAE). Between Feb 2016 and Feb 2023, 13 patients with 29 hepatic tumors treated with HAE were analyzed. Pre- and post-embolization, subtracted CBCTs were performed, and tumor enhancement parameters were measured, resulting in three parameters: pre-embolization Adjusted Tumor Enhancement (pre-ATE), post-embolization ATE and the difference between pre- and post-ATE (∆ATE). Treatment response was evaluated using the mRECIST criteria at 1 month. Tumors were grouped into complete response (CR) and non-complete response (non-CR) groups. To account for the effect of multiple lesions per patient, a cluster data analytic method was employed. The Kaplan-Meier method was utilized for survival analysis using the lesion with the lowest ∆ATE value in each patient. Seventeen (59%) tumors showed CR and twelve (41%) showed non-CR. Pre-ATE was 38.5 ± 10.6% in the CR group and 30.4 ± 11.0% in the non-CR group (p = 0.023). ∆ATE in the CR group was 39 ± 12 percentage points following embolization, compared with 29 ± 11 in the non-CR group (p = 0.009). Patients with ∆ATE > 33 had a median L-PFS of 13.1 months compared to 5.7 in patients with ∆ATE ≤ 33 (95% CI = 0.038-0.21) (HR, 95% CI = 0.45, 0.20-0.9, p = 0.04). Patients with ∆ATE ≤ 33 had a median OS of 19.7 months (95% CI = 3.77-19.8), while in the ∆ATE > 33 group, median OS was not reached (95% CI = 20.3-NA) (HR, 95% CI = 0.15, 0.018-1.38, p = 0.04). CBCT-derived ATE parameters can predict treatment response, L-PFS and OS following HAE.

Leveraging radiomics and AI for precision diagnosis and prognostication of liver malignancies.

Liver tumors, whether primary or metastatic, have emerged as a growing concern with substantial global health implications. Timely identification and characterization of liver tumors are pivotal factors in order to provide optimum treatment. Imaging is a crucial part of the detection of liver tumors; however, conventional imaging has shortcomings in the proper characterization of these tumors which leads to the need for tissue biopsy. Artificial intelligence (AI) and radiomics have recently emerged as investigational opportunities with the potential to enhance the detection and characterization of liver lesions. These advancements offer opportunities for better diagnostic accuracy, prognostication, and thereby improving patient care. In particular, these techniques have the potential to predict the histopathology, genotype, and immunophenotype of tumors based on imaging data, hence providing guidance for personalized treatment of such tumors. In this review, we outline the progression and potential of AI in the field of liver oncology imaging, specifically emphasizing manual radiomic techniques and deep learning-based representations. We discuss how these tools can aid in clinical decision-making challenges. These challenges encompass a broad range of tasks, from prognosticating patient outcomes, differentiating benign treatment-related factors and actual disease progression, recognizing uncommon response patterns, and even predicting the genetic and molecular characteristics of the tumors. Lastly, we discuss the pitfalls, technical limitations and future direction of these AI-based techniques.

Endoscopic ultrasound-guided tissue acquisition for the diagnosis of focal liver lesion.

In patients with liver tumors, the histopathology examination can assist in diagnosis, staging, prognosis, and therapeutic management strategy. Endoscopic ultrasound (EUS)-guided tissue acquisition using fine needle aspiration (FNA) or more newly fine needle biopsy (FNB) is a well-developed technique in order to evaluate and differentiate the liver masses. The goal of the EUS-FNA or EUS-FNB is to provide an accurate sample for a histopathology examination. Therefore, malignant tumors such as hepatocarcinoma, cholangiocarcinoma and liver metastasis or benign tumors such as liver adenoma, focal hyperplastic nodular tumors and cystic lesions can be accurately diagnosed using EUS-guided tissue acquisition. EUS-FNB using 19 or 22 Ga needle provide longer samples and a higher diagnostic accuracy in patients with liver masses when compared with EUS-FNA. Few data are available on the diagnostic accuracy of EUS-FNB when compared with percutaneously, ultrasound, computer tomography or transjugulary-guided liver biopsies. This review will discuss the EUS-guided tissue acquisition options in patients with liver tumors and its efficacy and safety in providing accurate samples. The results of the last studies comparing EUS-guided liver biopsy with other conventional techniques are presented. The EUS-guided tissue acquisition using FNB can be a suitable technique in suspected liver lesions in order to provide an accurate histopathology diagnosis, especially for those who require endoscopy.

SADSNet: A robust 3D synchronous segmentation network for liver and liver tumors based on spatial attention mechanism and deep supervision.

Highlights: • Introduce a data augmentation strategy to expand the required different morphological data during the training and learning phase, and improve the algorithm's feature learning ability for complex and diverse tumor morphology CT images.• Design attention mechanisms for encoding and decoding paths to extract fine pixel level features, improve feature extraction capabilities, and achieve efficient spatial channel feature fusion.• The deep supervision layer is used to correct and decode the final image data to provide high accuracy of results.• The effectiveness of this method has been affirmed through validation on the LITS, 3DIRCADb, and SLIVER datasets. BACKGROUND: Accurately extracting liver and liver tumors from medical images is an important step in lesion localization and diagnosis, surgical planning, and postoperative monitoring. However, the limited number of radiation therapists and a great number of images make this work time-consuming. OBJECTIVE: This study designs a spatial attention deep supervised network (SADSNet) for simultaneous automatic segmentation of liver and tumors. METHOD: Firstly, self-designed spatial attention modules are introduced at each layer of the encoder and decoder to extract image features at different scales and resolutions, helping the model better capture liver tumors and fine structures. The designed spatial attention module is implemented through two gate signals related to liver and tumors, as well as changing the size of convolutional kernels; Secondly, deep supervision is added behind the three layers of the decoder to assist the backbone network in feature learning and improve gradient propagation, enhancing robustness. RESULTS: The method was testing on LITS, 3DIRCADb, and SLIVER datasets. For the liver, it obtained dice similarity coefficients of 97.03%, 96.11%, and 97.40%, surface dice of 81.98%, 82.53%, and 86.29%, 95% hausdorff distances of 8.96 mm, 8.26 mm, and 3.79 mm, and average surface distances of 1.54 mm, 1.19 mm, and 0.81 mm. Additionally, it also achieved precise tumor segmentation, which with dice scores of 87.81% and 87.50%, surface dice of 89.63% and 84.26%, 95% hausdorff distance of 12.96 mm and 16.55 mm, and average surface distances of 1.11 mm and 3.04 mm on LITS and 3DIRCADb, respectively. CONCLUSION: The experimental results show that the proposed method is effective and superior to some other methods. Therefore, this method can provide technical support for liver and liver tumor segmentation in clinical practice.

A comparison of three different microwave systems for laparoscopic liver tumor ablation.

BACKGROUND: Our aim was to perform a comparison of three current microwave ablation (MWA) systems widely used for laparoscopic liver ablations in terms of ablation kinetics and geometry of ablation zones. METHODS: This was a retrospective, institutional review board-approved study comparing Emprint, Emprint HP, and NeuWave systems for laparoscopic liver ablation. Analyses were performed via Mann-Whitney U and χ2 tests. Continuous data are presented as median (interquartile range). RESULTS: For Emprint, Emprint HP, and NeuWave groups, tumor size was 1.16 (0.8), 1.21 (0.7), and 1.27 (0.9) cm (p = 0.54). Ablation time per lesion was 7 (6), 4 (2.8), and 4 (3.3) min (p < 0.0001), yielding similar ablation zone volumes and margins. The time to first ablation bubble was 1 (0.13), 1.5 (0.85), and 0.75 (0.5) min, and total ablation times were 7 (4.4), 4 (2), and 3.5 (2.8) min (p < 0.0001). The roundness index A, B, and transverse were 0.94, 0.98, and 0.79; 0.95, 0.95, and 0.78; and 1.02, 0.95, and 0.96. CONCLUSIONS: Although a saline-cooling system with Emprint system allowed for larger diameter spherical ablation zones to be created, it led to decreased efficiency compared to the CO2-cooled NeuWave system, which exposes the active antenna directly to tissue. Increased power delivered by Emprint HP improved the efficiency of saline-cooled design, as demonstrated by faster ablation times.

Hepatic Diffuse Large B-cell Lymphoma: A Case Report and Review of Literature of Primary Liver Tumors.

Liver tumors rank as the fourth most common cause of cancer. This case report highlights a 45-year-old female patient who presented persistent abdominal pain and no other symptoms. Initially, she was approached with a probable hepatitis of unknown origin, but her condition worsened rapidly. An endoscopic ultrasound was used to characterize the lesion, and a fine needle biopsy of the lesion was performed which revealed a diffuse large B-cell lymphoma that is CD20+ and Ki67+. Hepatic diffuse large B-cell lymphoma, as diagnosed in the patient, is a rare type of lymphoma that arises in the liver. The treatment usually involves chemotherapy, immunotherapy, and radiation therapy. However, the prognosis depends on the stage of the disease and the patient's overall health. This case reinforces the importance of considering hepatic diffuse large B-cell lymphoma in differential diagnosis for primary liver neoplasia.

Assessment of the mode of action of perchloroethylene-induced mouse liver tumors.

Perchloroethylene (PCE) is used as a solvent and chemical intermediate. Following chronic inhalation exposure, PCE selectively induced liver tumors in mice. Understanding the mode of action (MOA) for PCE carcinogenesis in mice is important in defining its possible human cancer risk. The proposed MOA is based on the extensive examination of the peer-reviewed studies that have assessed the mouse liver effects of PCE and its major oxidative metabolite trichloroacetic acid (TCA). Similar to PCE, TCA has also been demonstrated to liver tumors selectively in mice following chronic exposure. The Key Events (KE) of the proposed PCE MOA involve oxidative metabolism of PCE to TCA [KE 1]; activation of the peroxisome proliferator-activated receptor alpha (PPARα) [KE 2]; alteration in hepatic gene expression including cell growth pathways [KE 3]; increase in cell proliferation [KE 4]; selective clonal expansion of hepatic preneoplastic foci [KE 5]; and formation of hepatic neoplasms [KE 6]. The scientific evidence supporting the PPARα MOA for PCE is strong and satisfies the requirements for a MOA analysis. The PPARα liver tumor MOA in rodents has been demonstrated not to occur in humans; thus, human liver cancer risk to PCE is not likely.

Arterial embolization of focal nodular hyperplasia of the liver: A case report.

INTRODUCTION AND IMPORTANCE: Focal nodular hyperplasia (FNH) is a benign liver lesion that can pose diagnostic and management dilemmas, especially when distinguishing it from other hypervascular hepatic lesions. The benign nature of FNH often makes conservative management a priority; however, intervention may be necessary in symptomatic cases or when diagnostic uncertainty exists. CASE PRESENTATION: A 19-year-old male presenting with abdominal pain, found to have a large 25 cm FNH lesion in the right lobe of the liver. Initial diagnosis was achieved through ultrasonography and contrast-enhanced computed tomography (CECT), with histopathological confirmation via core needle biopsy. Given the lesion's size and the patient's symptomatic presentation, we opted for arterial embolization, a less invasive surgical approach, over traditional resection methods. This technique not only led to symptom resolution but also resulted in a significant reduction in lesion size. CLINICAL DISCUSSION: Our approach to managing this FNH case involved a multidisciplinary team. The decision to employ arterial embolization over more invasive surgical options was based on the lesion's characteristics, the patient's age, and the potential for significant morbidity associated with traditional surgery. Arterial embolization of the FNH lesion resulted in complete resolution of symptoms and a significant reduction in lesion size, from 25 cm to 12 cm, demonstrating the effectiveness of this technique in managing large FNH lesions. CONCLUSION: Our findings contribute to the scientific literature by showcasing the potential of less invasive surgical techniques in the management of FNH, offering valuable insights for clinicians faced with similar diagnostic and therapeutic challenges.

Chromatin and DNA Dynamics in Mouse Models of Liver Cancers.

In recent years, important efforts have been made to understand how the expression of a specific gene repertoire correlates with chromatin accessibility, histone mark deposition, as well as with chromatin looping establishing connectivity with regulatory regions. The emergence of new techniques for genome-wide analyses and their progressive optimization to work on low amounts of material allows the scientific community to obtain an integrated view of transcriptional landscapes in physiology and disease. Here, we describe our own experience aiming at correlating the TCF-4/ß-catenin cistrome during liver tumorigenesis with chromatin remodeling, histone mark modifications, and long-distance DNA looping.

Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors.

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.

Improved identification of tumors in 18F-FDG-PET examination by normalizing the standard uptake in the liver based on blood test data.

PURPOSE: Standardized uptake values (SUVs) derived from 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography are a crucial parameter for identifying tumors or abnormalities in an organ. Moreover, exploring ways to improve the identification of tumors or abnormalities using a statistical measurement tool is important in clinical research. Therefore, we developed a fully automatic method to create a personally normalized Z-score map of the liver SUV. METHODS: The normalized Z-score map for each patient was created using the SUV mean and standard deviation estimated from blood-test-derived variables, such as alanine aminotransferase and aspartate aminotransferase, as well as other demographic information. This was performed using the least absolute shrinkage and selection operator (LASSO)-based estimation formula. We also used receiver operating characteristic (ROC) to analyze the results of people with and without hepatic tumors and compared them to the ROC curve of normal SUV. RESULTS: A total of 7757 people were selected for this study. Of these, 7744 were healthy, while 13 had abnormalities. The area under the ROC curve results indicated that the anomaly detection approach (0.91) outperformed only the maximum SUV (0.89). To build the LASSO regression, sets of covariates, including sex, weight, body mass index, blood glucose level, triglyceride, total cholesterol, γ-glutamyl transpeptidase, total protein, creatinine, insulin, albumin, and cholinesterase, were used to determine the SUV mean, whereas weight was used to determine the SUV standard deviation. CONCLUSION: The Z-score normalizes the mean and standard deviation. It is effective in ROC curve analysis and increases the clarity of the abnormality. This normalization is a key technique for effective measurement of maximum glucose consumption by tumors in the liver.