Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma.

This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.

GINS1 promotes ZEB1-mediated epithelial-mesenchymal transition and tumor metastasis via ß-catenin signaling in hepatocellular carcinoma.

GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through ß-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via ß-catenin signaling in HCC.

Case Report and Literature Review of Multi-drugs Synergy and Targeted Comprehensive Treatment in Advanced Hepatocellular Carcinoma.

BACKGROUND: A 43-year-old female patient was found to have an abnormal liver function, abnormally elevated alpha-fetoprotein and space-occupying lesions in the liver on routine screening. The patient came to our hospital for further diagnosis and treatment. CASE PRESENTATION: Investigations: Laboratory investigations, digital subtraction angiography (DSA) of the hepatic artery, abdominal ultrasound examination, and magnetic resonance imaging (MRI) scan were conducted using pathological staining and immunohistochemistry. DIAGNOSIS: Clinical diagnosis: cT3NxM0. Barcelona clinic liver cancer (BCLC) staging: BCLC stage C. China liver cancer (CNLC) staging: CNLC IIIa. DISCUSSION: The patient was hospitalized for the first time for transcatheter arterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Then, the second and third hospital admissions were given HAIC based on FOLFOX. Camrelizumab and oncolytic virus were also injected into the liver cancer through the microcatheter in the first three treatments. On the fourth admission, the patient's indicators were improved, and the tumor shrank. Furthermore, as the patient suffered adverse reactions the first few times, we suspended the treatment of FOLFOX and the oncolytic virus. Before surgical treatment, lenvatinib was used throughout the treatment. On the fifth admission, the patient underwent liver cancer resection. CONCLUSION: It proves the value of multiple combination therapy, which can provide guidance for patients with advanced hepatocellular carcinoma that cannot be surgically removed.

circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer.

Objectives: To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients. Methods: circRNA RNA-seq technology was used to screen differentially expressed circRNAs in CRC. Sanger sequencing was used to identify circRNA back-splice junction sites. The relative expression levels of hsa_circ_0003761 (circMSH3) in CRC tissues and cell lines were detected by quantitative real-time fluorescence PCR technology. An RNA-protein pull-down assay was used to detect protein binding to circRNAs. Dual-luciferase reporter gene vectors were constructed to verify that circRNAs bind to microRNAs. Results: Four hundred twenty circRNAs were found to be upregulated, and 616 circRNAs were downregulated. circMSH3 was derived from the MutS homolog 3 (MSH3) gene and was formed by a loop of exons 9, 10, 11, and 12. In 110 pairs of CRC and adjacent tissues, circMSH3 expression was 4.487-fold higher in CRC tissues. circMSH3 was also highly expressed in the HT-29 and LOVO CRC cell lines. The expression level of circMSH3 was associated with distant metastasis in CRC patients (P = 0.043); the area under the curve (AUC) of circMSH3 for CRC diagnosis was 0.75, with a sensitivity and specificity of 70.9% and 66.4%, respectively. circMSH3 could bind to a variety of proteins, mainly those involved in RNA transcription, splicing, cell cycle, and cell junctions. Furthermore, circMSH3 could bind to miR-1276, miR-942-5p, and miR-409-3p. Conclusion: circMSH3 is a potential biomarker for the diagnosis of CRC and affects the distant metastasis of CRC. Multiple RNA-binding protein binds to circMSH3, and circMSH3 binds to miR-1276, miR-942-5p, and miR-409-3p, thereby affecting the expression of circMSH3.

A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma.

Background: Liver cancer remains one of the tricky malignancies nowadays. GINS complex subunit 3 (GINS3), part of the GINS tetrameric complex, is significantly upregulated in many cancers, including liver hepatocellular carcinoma (LIHC). With the development of liver cancer treatment, immune and molecular targeted therapy gradually becomes a promising treatment. However, the key target for liver cancer is still indistinct. Herein, the underneath mechanism of GINS3 was investigated to verify its role as a biomarker in LIHC. Methods: Genomic expression, genetic alteration, and methylation analyses were obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The University of Alabama at Birmingham CANcer (UALCN), and Human Protein Atlas (HPA), cBioPortal, and MethSurv databases. Subsequently, the diagnostic and prognostic role of GINS3 in LIHC were analyzed based on data from receiver operating characteristic (ROC), Kaplan-Meier plotter (KM-plotter), and univariate and multivariate cox regression analyses. The functional analyses were conducted with GeneMANIA and STRING databases, gene-gene, and protein-protein interaction (PPI) networks, Gene Ontology (GO) term, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction Database (TISIDB), and Gene Expression Profiling Interactive Analysis (GEPIA) were utilized to explore the internal connection with the immune escape. Results: Through the analyses of genomic expression, GINS3 was significantly upregulated in LIHC and positively correlated with higher T classification. ROC analysis indicated GINS3 as a potential biomarker in the diagnosis of LIHC. KM-plotter, univariate and multivariate cox regression analyses both associated GINS3 with poor prognosis in LIHC patients. GINS3 genetic alteration, gene-gene interaction, PPI networks, and enrichment analysis further revealed that GINS3 played a pivotal role in the progression of LIHC. Furthermore, hypermethylation of GINS3 at different cytosine-guanine (CpG) sites was correlated with better or worse overall survival (OS) in LIHC and GINS3 was also closely correlated with m6A modification. Moreover, results supported that GINS3 could influence the tumor microenvironment and relate to the immune checkpoints. Conclusions: Taken together, comprehensive analyses from this study supported GINS3 as a novel targeted biomarker in LIHC.

Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase.

Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo. Closer mechanistic examination revealed that PD suppressed the activity of acid sphingomyelinase (SMPD1), a lysosomal phosphodieserase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine, by directly occupying its surface groove, with Trp148 in SMPD1 acting as a major binding residue; this suppression of SMPD1 activity irreversibly triggers lysosomal injury and initiates lysosome-dependent cell death. Furthermore, PD-enhanced lysosomal membrane permeabilization to release sorafenib, augmenting the anticancer effect of sorafenib both in vivo and in vitro. Overall, our study suggests that PD can potentially be further developed as a novel autophagy inhibitor, and a combination of PD with classical chemotherapeutic anticancer drugs could represent a novel therapeutic strategy for HCC intervention.

Laparoscopic Common Bile Duct Exploration in Patients with a Previous History of Biliary Tract Surgery.

For recurrent choledocholithiasis, abdominal adhesions in previous surgeries lead to changes in anatomical structures, and a secondary injury occurs easily when performing another operation for laparoscopic common bile duct exploration (LCBDE), which was once considered a relative contraindication. In view of the limitations of the current surgical technique, this study summarized the surgical approaches and crucial anatomical landmarks for reoperation for LCBDE. Four general surgical approaches were proposed to expose the common bile duct, including the ligamentum teres hepatis approach, the anterior hepatic duodenal ligament approach, the right hepatic duodenal ligament approach, and the hybrid approach. Additionally, this study highlighted seven crucial anatomical landmarks: the parietal peritoneum, the gastrointestinal serosa, the ligamentum teres hepatis, the inferior margin of the liver, the gastric antrum, the duodenum, and the hepatic flexure of the colon, which were helpful to safely separate abdominal adhesions and expose the common bile duct. Moreover, to shorten the time of choledocholithotomy, a sequential method was innovatively applied for the removal of the stones in common bile duct. Mastering the above surgical approaches, including identifying crucial anatomical landmarks and adopting the sequential method will improve the safety of reoperation for LCBDE, shorten the operation time, promote the fast recovery of patients, reduce postoperative complications, and contribute to the popularization and application of this technique.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Lung metastases after liver cancer resection cured by immunotherapy: case report and literature review.

The lung is the most common metastatic organ of primary liver cancer, accounting for 39.5-53.8% of extrahepatic metastasis, which seriously affects the prognosis of patients. In clinical treatment, it is difficult for one therapeutic schedule to achieve the desired effect sometimes, requiring two or even several combined methods for liver cancer lung metastasis. In this study, we report a liver cancer patient with lung metastases who received various combined therapies. However, the comprehensive treatment did not improve the patient's pulmonary metastasis symptoms until after the application of immunotherapy, and the lung metastases were gradually cured.

Laparoscopic Posterior Radical Antegrade Modular Pancreatosplenectomy for Distal Pancreatic Carcinoma.

Distal pancreatic carcinoma is a highly malignant tumor with strong invasiveness, often growing to the edge of the pancreas and penetrating the pancreatic capsule to infiltrate surrounding tissues. In conventional distal pancreatosplenectomy (DPS), tumor cells are prone to spread along the direction of blood and lymphatic reflux due to surgical compression. Additionally, inflammation makes it challenging to achieve R0 resection, leading to a lower patient survival rate. To address these limitations, radical antegrade modular pancreatosplenectomy (RAMPS) was developed, emphasizing deeper excision, including the left anterior renal fascia, the left anterior renal adipose sac, and even the left adrenal gland, to improve the R0 resection rate. With the advancement of minimally invasive surgical techniques, laparoscopic RAMPS (L-RAMPS) is being considered technically safe and feasible in oncology. However, due to technical difficulties and a lack of supporting evidence for clinical application, only a few institutions are currently conducting L-RAMPS. In this context, this article presents detailed techniques for laparoscopic posterior radical antegrade modular pancreatosplenectomy (L-pRAMPS), offering promise for future clinical applications.

Periplaneta americana extract alleviates steatohepatitis in a mouse model by modulating HMGB1-mediated inflammatory response.

Alcoholic abuse and obesity are the most common lifestyle implications of chronic liver injury, and always act synergistically to increase the risk of mortality. Periplaneta americana has a long history of being applied in medicine, including wound healing, antitumor, antibacterial, antiviral, antifibrotic, and cardiomyocyte-protecting. Ganlong capsule (GLC), a natural prescription drug extracted from Periplaneta americana, has been widely used in HBV-related symptoms. However, the anti-steatohepatitis efficacy and mechanisms of GLC have not yet been characterized. Here, we found the protective effect of GLC on the development of hepatic steatosis, oxidative stress, and inflammation in vivo under alcohol exposure combined with a high-fat and high-cholesterol diet (HFHC). Consistently, GLC exhibited a hepatoprotective property by preventing hepatocytes from oxidative stress injury and lipid accumulation in vitro. In addition, it exerted an anti-inflammation characteristic by reducing macrophage recruitment and decreasing the expression of pro-inflammatory genes in vivo and in vitro. Mechanically, GLC serum, isolated from GLC-treated mice, reduced extracellular high-mobility group box 1 (HMGB1) of dying hepatocytes; and suppressed subsequent M1 polarization of macrophages in the co-culture system. Furthermore, GLC serum inhibited inflammatory response via suppressing the HMGB1 release and blocking the downstream TLR4/NF-kB pathway. Collectively, GLC alleviates steatohepatitis induced by alcohol consumption and obesity through inhibition of the HMGB1-mediated inflammatory cascade. GLC might be a therapeutic candidate for the treatment of steatohepatitis developed by alcohol abuse and metabolic disorders.

Norcantharidin triggers apoptotic cell death in non-small cell lung cancer via a mitophagy-mediated autophagy pathway.

BACKGROUND: Norcantharidin (NCTD) is known to impact on cell progression in many cancers; however, its activity in non-small cell lung cancer (NSCLC) has not yet been characterized. In the present study, we set out to determine the cytotoxic effects of NCTD on the proliferation and apoptosis on A549 cells and their underlying mechanisms. METHODS: NSCLC cell line A549 cells were cultured. A549 cells were treated with different concentrations of NCTD. Cell proliferation was detected by MTT and cell clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. After A549 cells were treated with NCTD for 24 hours, the mitochondrial membrane potential was measured. The protein expression of Bcl-2, Bax, light chain 3 (LC3), et al. was tested by western blot. The expression of LC3 and Tom20 protein was detected by immunofluorescence. RESULTS: NCTD suppressed the proliferation of NSCLC cells while decreasing mitochondrial membrane potential and inducing G2/M phase arrest. NCTD induced apoptosis, as demonstrated by increased B-cell lymphoma 2/Bcl-2-associated X protein and Bcl-2-associated X protein/myeloid cell leukemia 1 ratios. Aside from autophagy, NCTD induced mitophagy, with an increase in LC3 expression and a decrease in sequestosome 1 (p62) expression in the cytoplasm, accompanied by increased levels of Phospho-adenosine 5'-monophosphate -activated protein kinase (p-AMPK), Phospho-c-Jun NH2-Terminal Kinase (p-JNK), and Phospho-c-jun (p-c-jun) and a decreased level of Phospho-protein kinase B (p-AKT). CONCLUSIONS: This study has elucidated that NCTD restrains NSCLC cell progression via regulation of AMPK/mammalian target of rapamycin (mTOR)/uncoordinated 51-like kinase 1 (ULK1)/JNK pathways. This evidence provides insight into a novel treatment for NSCLC.

A Novel Post-Operative ALRI Model Accurately Predicts Clinical Outcomes of Resected Hepatocellular Carcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading malignant tumors worldwide. Prognosis and long-term survival of HCC remain unsatisfactory, even after radical resection, and many non-invasive predictors have been explored for post-operative patients. Most prognostic prediction models were based on preoperative clinical characteristics and pathological findings. This study aimed to investigate the prognostic value of a newly constructed nomogram, which incorporated post-operative aspartate aminotransferase to lymphocyte ratio index (ALRI). METHODS: A total of 771 HCC patients underwent radical resection from three medical centers were enrolled and grouped into the training cohort (n = 416) and validation cohort (n = 355). Prognostic prediction potential of ALRI was assessed by receiver operating curve (ROC) analysis. The Cox regression model was used to identify independent prognostic factors. Nomograms for overall survival (OS) and disease-free survival (DFS) were constructed and further validated externally. RESULTS: The ROC analysis ranked ALRI as the most effective prediction marker for resected HCC patients, with the cut-off value determined at 22.6. Higher ALRI level positively correlated with larger tumor size, higher tumor node metastasis (TNM) stage, and inversely with lower albumin level and shorter OS and DFS. Nomograms for OS and DFS were capable of discriminating HCC patients into different risk-groups. CONCLUSIONS: Post-operative ALRI was of prediction value for HCC prognosis. This novel nomogram may categorize HCC patients into different risk groups, and offer individualized surveillance reference for post-operative patients.

mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer.

Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the production of deoxyribonucleotides (dNTPs) for DNA replication and it is also essential for cancer cell proliferation. As the RNR inhibitor, Gemcitabine is widely used in cancer therapies, however, resistance limits its therapeutic efficacy and curative potential. Here, we identified that mTORC2 is a main driver of gemcitabine resistance in non-small cell lung cancers (NSCLC). Pharmacological or genetic inhibition of mTORC2 greatly enhanced gemcitabine induced cytotoxicity and DNA damage. Mechanistically, mTORC2 directly interacted and phosphorylated RNR large subunit RRM1 at Ser 631. Ser631 phosphorylation of RRM1 enhanced its interaction with small subunit RRM2 to maintain sufficient RNR enzymatic activity for efficient DNA replication. Targeting mTORC2 retarded DNA replication fork progression and improved therapeutic efficacy of gemcitabine in NSCLC xenograft model in vivo. Thus, these results identified a mechanism through mTORC2 regulating RNR activity and DNA replication, conferring gemcitabine resistance to cancer cells.

Biomarkers (mRNAs and Non-Coding RNAs) for the Diagnosis and Prognosis of Colorectal Cancer - From the Body Fluid to Tissue Level.

In recent years, the diagnosis and treatment of colorectal cancer (CRC) have been continuously improved, but the mortality rate continues to be high, especially in advanced patients. CRC patients usually have no obvious symptoms in the early stage and are already in the advanced stage when they are diagnosed. The 5-year survival rate is only 10%. The blood markers currently used to screen for CRC, such as carcinoembryonic antigen and carbohydrate antigen 19-9, have low sensitivity and specificity, whereas other methods are invasive or too expensive. As a result, recent research has shifted to the development of minimally invasive or noninvasive biomarkers in the form of body fluid biopsies. Non-coding RNA molecules are composed of microRNAs, long non-coding RNAs, small nucleolar RNAs, and circular RNAs, which have important roles in the occurrence and development of diseases and can be utilized for the early diagnosis and prognosis of tumors. In this review, we focus on the latest findings of mRNA-ncRNA as biomarkers for the diagnosis and prognosis of CRC, from fluid to tissue level.

TANK-Binding Kinase 1 (TBK1) Serves as a Potential Target for Hepatocellular Carcinoma by Enhancing Tumor Immune Infiltration.

Background: Numerous cancer types present the aberrant TANK-binding kinase 1 (TBK1) expression, which plays an important role in driving inflammation and innate immunity. However, the prognostic role of TBK1 and its relationship with immune cell infiltration in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression and prognostic value of TBK1 was analyzed by Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and further confirmed in the present cohort of patients with HCC. The association between TBK1 and HCC immune infiltrates, and its potential mechanism were investigated via analyses of the Tumor Immune Estimation Resource, tumor-immune system interactions database (TISIDB), CIBERSORT, STRING, and Metascape. The effect of TBK1 on immune infiltrates and the therapeutic value of targeting TBK1 were further investigated in a HCC mouse model by treatment with a TBK1 antagonist. Results: The level of TBK1 expression in HCC was higher than that measured in normal tissues, and associated with poorer overall survival (GEPIA: hazard ratio [HR]=1.80, P=0.038; Kaplan-Meier plotter: HR=1.87, P<0.001; CPTAC: HR=2.23, P=0.007; Our cohort: HR=2.92, P=0.002). In addition, high TBK1 expression was found in HCC with advanced TNM stage and identified as an independent poor prognostic factor for overall survival among patients with HCC. In terms of immune infiltration, tumor tissues from HCC patients with high TBK1 expression had a low proportion of CD8+ T cells, and TBK1 expression did not show prognostic value in HCC patients with enriched CD8+ T cells. Furthermore, TBK1 expression was positively correlated with the markers of T cell exhaustion and immunosuppressive cells in the HCC microenvironment. Mechanistically, the promotion of HCC immunosuppression by TBK1 was involved in the regulation of inflammatory cytokines. In vivo experiments revealed that treatment with a TBK1 antagonist delayed HCC growth by increasing the number of tumor-infiltrating CD8+ T cells. Conclusions: The up-regulated expression of TBK1 may be useful in predicting poor prognosis of patients with HCC. In addition, TBK1, which promotes the HCC immunosuppressive microenvironment, may be a potential immunotherapeutic target for patients with HCC.

Myofibroblast-Specific Msi2 Knockout Inhibits HCC Progression in a Mouse Model.

BACKGROUND AND AIMS: Myofibroblasts play a pivotal role in the development and progression of HCC. Here, we aimed to explore the role and mechanism of myofibroblast Musashi RNA binding protein 2 (MSI2) in HCC progression. APPROACH AND RESULTS: Myofibroblast infiltration and collagen deposition were detected and assessed in the tissues from 117 patients with HCC. Transgenic mice (Msi2ΔCol1a1 ) with floxed Msi2 allele and collagen type I alpha 1 chain (Col1a1)-ligand inducible Cre recombinases (CreER) were constructed to generate a myofibroblast-specific Msi2 knockout model. Mouse HCC cells were orthotopically transplanted into the Msi2ΔCol1a1 or the control mice (Msi2F/F ). We found that the deposition of collagen fibers, the main product of myofibroblasts, predicted a poor prognosis for HCC; meanwhile, we detected high MSI2 expression in the peritumoral infiltrated myofibroblasts. Conditional deletion of Msi2 in myofibroblasts significantly inhibited the growth of orthotopically implanted HCC, reduced both intrahepatic and lung metastasis, and prolonged the overall survival of tumor-bearing mice (P = 0.002). In vitro analysis demonstrated that myofibroblasts promoted cell proliferation, invasion, and epithelial-mesenchymal transformation of HCC cells, whereas Msi2 deletion in myofibroblasts reversed these effects. Mechanically, Msi2 knockout decreased myofibroblast-derived IL-6 and IL-11 secretion by inhibiting the extracellular signal-regulated kinase 1/2 pathway, and thus attenuated the cancer stem cell-promoting effect of myofibroblasts. Interestingly, we found that the simultaneous knockout of Msi2 in myofibroblasts and knockdown of Msi2 in HCC cells could not further attenuate the implanted HCC progression. CONCLUSIONS: Myofibroblast-specific Msi2 knockout abrogated the tumor-promoting function of myofibroblasts and inhibited HCC progression in mouse models. Targeting myofibroblast MSI2 expression may therefore prove to be a therapeutic strategy for HCC treatment in the future.

Laparoscopic partial splenectomy of benign tumors assisted by microwave ablation.

OBJECTIVE: The aim of this study is to investigate the application and the feasibility of microwave ablation in laparoscopic partial splenectomy. MATERIALS AND METHODS: From January 2018 to June 2019, four patients with benign spleen lesions in our hospital underwent laparoscopic partial splenectomy assisted by microwave ablation. The reviewed parameters included the operation time, intraoperative blood loss, ablation time, frequency of ablation, postoperative drainage time, postoperative hospitalization time, and postoperative complications. RESULTS: All four patients underwent laparoscopic partial splenectomy assisted by microwave ablation successfully, and there were no cases of conversion to laparotomy. The operation time was 100-200 min (mean, 152.5 min) and ablation time was 16-35 min (mean, 22.8 min). The frequency of ablation was 4-7 times (mean, 5.3 times), and the intraoperative blood loss was 5-300 ml (mean, 138.8 ml). The postoperative drainage time was 3-5 d (mean, 3.3 d), and postoperative hospital stay was 3-9 d (mean, 7.8 d). There were no complications such as peripheral tissue injury, massive bleeding, infestation of spleen fossa, and pancreatic leakage. CONCLUSION: Microwave ablation is worthy of clinical application in laparoscopic partial spleen resection as it is safe and effective with low rates of bleeding and fast recovery.

Clinical Applied Anatomy in Trans-Areolar Endoscopic Thyroidectomy: Crucial Anatomical Landmarks.

Introduction: Endoscopic thyroidectomy (ET) has been successfully established as an excellent surgical approach. This study summarizes and describes the crucial anatomical landmarks for clinical applied anatomy in trans-areolar ET, which may help further improve the quality and safety of trans-areolar ET. Materials and Methods: Five hundred forty patients who underwent trans-areolar ET from January 2015 to June 2018 at our institution were evaluated. Several crucial anatomical landmarks were described during the surgical procedures. The surgical outcomes, including the operative time, conversion, intraoperative blood loss, postoperative complications, and postoperative stay, were collected. Results: All patients successfully underwent trans-areolar ET without conversion. The mean operative time was 142.18 ± 49.91 minutes (150.84 ± 50.32 minutes for total thyroidectomy and 110.20 ± 32.4 for lobectomy with isthmusectomy). The mean intraoperative blood loss was 20.45 ± 10.89 mL. The postoperative stay was 5.42 ± 1.49 days. The postoperative complication rate was 7.78%, including transient hypocalcemia in 30 patients, transient recurrent laryngeal nerve palsy in 3 patients, and skin ecchymosis in 9 patients. Conclusions: An understanding of crucial anatomical landmarks for clinical applied anatomy may improve the quality and safety of trans-areolar ET and subsequently help promote the development of ET.

Giant Mesenteric Mixed Hemangioma Misdiagnosed as Ovarian Cyst: A Case Report and a Literature Review.

Hemangiomas are congenital vascular disorders that occur primarily in the face and neck, extremely rare in the mesentery. Here, we report a rare small mesenteric mixed hemangioma. A 34-year-old woman was admitted to the gynecology department for an extended menstrual cycle. A cystic multi-atrial mass at the right anterior of uterus was observed by ultrasound examination, which was about 12.5 × 9.5 × 14.9 cm in size. The gynecologist mostly considered the possibility of the ovarian cyst. However, there was a huge multi-atrial cyst in the small intestine mesentery without the right ovarian cyst in the surgical exploration. The grape-like cystic mass about 15 cm in diameter adhered to the mesenteric root of the small intestine. The cyst was diagnosed as the mesenteric mixed hemangioma in the final histopathology.