Glycolysis regulation in tumor-associated macrophages: Its role in tumor development and cancer treatment.

Tumor-associated macrophages constitute the main cell population in the tumor microenvironment and play a crucial role in regulating the microenvironment composition. Emerging evidence has revealed that the metabolic profile determines the tumor-associated macrophage phenotype. Tumor-associated macrophage function is highly dependent on glucose metabolism, with glycolysis being the major metabolic pathway. Recent reports have demonstrated diversity in glucose flux of tumor-associated macrophages and complex substance communication with cancer cells. However, how the glucose flux in tumor-associated macrophages connects with glycolysis to influence tumor progression and the tumor microenvironment is still obscure. Moreover, while the development of single-cell sequencing technology allows a clearer and more accurate classification of tumor-associated macrophages, the metabolic profiles of tumor-associated macrophages from the perspective of single-cell omics has not been well summarized. Here, we review the current state of knowledge on glucose metabolism in tumor-associated macrophages and summarize the metabolic profiles of different tumor-associated macrophage subtypes from the perspective of single-cell omics. Additionally, we describe the current strategies targeting glycolysis in tumor-associated macrophages for cancer therapy.

Bispecific Nanobody-Aptamer Conjugates for Enhanced Cancer Therapy in Solid Tumors.

Bispecific antibodies possess exceptional potential as therapeutic agents due to their capacity to bind to two different antigens simultaneously. However, challenges pertain to unsatisfactory stability, manufacturing complexity, and limited tumor penetration hinder their broad applicability. In this study, a versatile technology is presented for the rapid generation of bispecific nanobody-aptamer conjugates with efficient tumor penetration. The approach utilizes microbial transglutaminase (MTGase) and click chemistry to achieve site-specific conjugation of nanobodies and aptamers, which are termed nanotamers. The nanotamers recognize and bind to two types of molecular targets expressed on cancer cells. As a prototype, a bispecific nanotamer is developed that binds both clusters of differentiation 47 (CD47) and mesenchymal epithelial transition receptor (Met) expressed on the tumor cell membrane. This CD47-Met nanotamer demonstrates high affinity and specificity toward tumor cells expressing both targets, exhibits improved receptor functional inhibition through a strong steric hindrance effect. Moreover, its capacity for deep tumor penetration greatly enhances the impact of conventional chemotherapy on antitumor efficacy. The as-developed nanotamer synthesis approach shows promise to customize bispecific molecular probes targeting different cancer types and different therapeutic goals.

Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis.

While the expression of either NKG2D ligands or PD-1 ligands has been reported in various types of cancers, the co-expression of the two sets of ligands in the same tumour tissues is still un-investigated. After examining 68 primary ovarian cancer samples, we observed around 80% of the co-expression in low grade serous and endometrioid ovarian cancer samples. We then constructed a dual CAR system that splits the conventional single-input of a 2nd generation CAR into two independent chimeric receptors, one composed of the NKG2D extracellular domain linked with DAP12 for T cell activation and another using the PD-1 extracellular domain linked with 4-1BB for costimulatory signal 2 input. Given the limitation of the low-affinity PD-1 receptor in recognizing cancer cells with low levels of PD-1 ligands, we also used a high-affinity scFv specific to PD-L1 in our combinatorial approach to expand the range of target cancer cells with different expression levels of PD-L1. The two types of dual CAR-T cells were generated through electroporation of non-viral piggyBac transposon plasmids and were effective in eliminating the target cancer cells. Especially, the dual CAR-T cells with anti-PD-L1 scFv were capable of eradicating established tumors in mouse models of peritoneal metastasis of colorectal cancer and ovarian cancer. Since both NKG2D ligands and PD-1 ligands have been marked as favourable cancer therapeutic targets, the new dual CAR-T cells developed in this study hold attractive application potential in treating metastatic peritoneal carcinoma.

A Single-Center, Randomized, Double-Blind Study of 94 Patients Undergoing Surgery for Cerebral Glioma to Compare Postoperative Thromboprophylaxis with and without Rivaroxaban.

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Minimally invasive pancreaticoduodenectomy for periampullary disease: a comprehensive review of literature and meta-analysis of outcomes compared with open surgery.

BACKGROUND: Minimally invasive pancreatoduodenectomy (MIPD) has been gradually attempted. However, whether MIPD is superior, equal or inferior to its conventional open pancreatoduodenectomy (OPD) is not clear. METHODS: Studies published up to May 2017 were searched in PubMed, Embase, Cochrane Library, and Web of Science. Main outcomes were comprehensively reviewed and measured including conversion to open approach, operation time (OP), estimated blood loss (EBL), transfusion, length of hospital stay (LOS), overall complications, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post-pancreatectomy hemorrhage (PPH), readmission, reoperation and reasons of preoperative death, number of retrieved lymph nodes (RLN), surgical margins, recurrence, and survival. The software of Review Manage version 5.1 was used for meta-analysis. RESULTS: One hundred studies were included for systematic review and 26 out of them (totally 3402 cases, 1064 for MIPD, 2338 for OPD) were included for meta-analysis. In the early years, most articles were case reports or non-control case series studies, while in the last 6 years high-volume and comparative researches were increasing gradually. Systematic review revealed conversion rates of MIPD to OPD ranged from 0% to 40%. The mean or median OP of MIPD ranged from 276 to 657 min. The total POPF rates vary between 3.8% and 50% observed in all systematic reviewed studies. Meta-analysis demonstrated MIPD had longer OP (WMD = 99.4 min; 95%CI: 46.0 ~ 152.8, P < 0.01), lower blood loss (WMD = -0.54 ml; 95% CI, -0.88 ~ -0.20 ml; P < 0.01), lower transfusion rate (RR = 0.73, 95%CI: 0.57 ~ 0.94, P = 0.02), shorter LOS (WMD = -3.49 days; 95%CI: -4.83 ~ -2.15, P < 0.01). There was no significant difference in time to oral intake, postoperative complications, POPF, reoperation, readmission, perioperative mortality and number of retrieved lymph nodes. CONCLUSION: Our study demonstrates MIPD is technically feasible and safety on the basis of historical studies. MIPD is associated with less blood loss, faster postoperative recovery, shorter length of hospitalization and longer operation time. These findings are waiting for being confirmed with robust prospective comparative studies and randomized clinical trials.

T cells with split CARs specific for NKG2D ligands and PD-L1 exhibit improved selectivity towards monocyte-derived cells while effective in eliminating acute myeloid leukaemia in vivo.

PURPOSE: The expression of NKG2D ligands and PD-L1 has been detected on acute myeloid leukaemia (AML) cells, as well as normal cells of the myeloid lineage. To target leukemic cells while minimizing collateral damage to normal cells, we constructed a split dual CAR system based on the AND-gate logic. METHODS: The NKG2D extracellular domain linked with DAP12 without a co-stimulatory signal was used for the basal activation of T cells, and used together with the PD-L1-specific chimeric costimulatory receptor containing the 4-1BB activating domain for co-stimulatory signal 2 input. This dual CAR displayed cell-type specificity and activity similar as a 2nd generation NKG2D ligand-specific CAR. RESULTS: When compared to CD64 and PD-L1-specific 2nd generation CARs, we observed that the split dual CAR offered an improved myeloid cell type selectivity. For example, PD-L1-specific CAR-T cells lysed all tested myeloid cell types that expressed PD-L1, including M0 macrophages (Mø0), LPS-polarized Mø1, IFN-γ polarized Mø1, IL-4 polarized Mø2, monocytes, immature dendritic cells (imDCs), mature DCs, as well as KG-1 AML cells, while the dual CAR-T cells displaying killing activity only towards LPS polarized Mø1, mature DCs and KG-1 cells that expressed both NKG2D ligands and PD-L1. In a mouse liquid tumor model, the dual CAR-T cells were effective in eradicating established KG-1 AML xenografts. CONCLUSION: The improved cell type specificity offered by our split dual CAR-T cell system targeting paired antigens would favour the reduction of the on-target off-tumor toxicity towards normal myeloid cells during the treatment of myeloid leukaemia.

Evolution of Immunotherapy for Ovarian Cancer from a Bird's-Eye Perspective: A Text-Mining Analysis of Publication Trends and Topics.

Objectives: Ovarian tumors are among the most prominent gynecological malignancies and have a poor prognosis. Immunotherapy has undergone incredible progress in the past two decades. Our study aimed to use a bibliometric approach to identify research trends in ovarian cancer immunotherapy. Methods: Literature on this topic published from 2000-2020 was retrieved from the Web of Science Core Citation database and analyzed using the bibliometric analysis software VOSviewer and CiteSpace. Results: A total of 1729 articles on ovarian cancer immunotherapy published from January 2000 to December 2020 were identified. The number of published articles increased each year, from 40 in 2000 to 209 in 2020. These publications were from 61 countries, and the USA showed a dominant position in publication output, total citations, and average number of citations per paper. Co-citation networks revealed 14 subtopics. 'PD-L1 expression,' 'tumor reactive til,' and 'parp inhibitor' are the current potential subtopics. Furthermore, we determined research trends according to the timeline analysis. Conclusion: Our study exhaustively describes the development and summarizes the research trends of ovarian cancer immunotherapy over the past 20 years.

Steering surface reconstruction of copper with electrolyte additives for CO2 electroreduction.

Electrocatalytic CO2 reduction to value-added hydrocarbon products using metallic copper (Cu) catalysts is a potentially sustainable approach to facilitate carbon neutrality. However, Cu metal suffers from unavoidable and uncontrollable surface reconstruction during electrocatalysis, which can have either adverse or beneficial effects on its electrocatalytic performance. In a break from the current catalyst design path, we propose a strategy guiding the reconstruction process in a favorable direction to improve the performance. Typically, the controlled surface reconstruction is facilely realized using an electrolyte additive, ethylenediamine tetramethylenephosphonic acid, to substantially promote CO2 electroreduction to CH4 for commercial polycrystalline Cu. As a result, a stable CH4 Faradaic efficiency of 64% with a partial current density of 192 mA cm-2, thus enabling an impressive CO2-to-CH4 conversion rate of 0.25 µmol cm-2 s-1, is achieved in an alkaline flow cell. We believe our study will promote the exploration of electrochemical reconstruction and provide a promising route for the discovery of high-performance electrocatalysts.

A tumor-suppressive circular RNA mediates uncanonical integrin degradation by the proteasome in liver cancer.

Circular RNAs (circRNAs) have emerged as important regulators of various cellular processes and have been implicated in cancer. Previously, we reported the discovery of several dysregulated circRNAs including circPABPC1 (polyadenylate-binding protein 1) in human hepatocellular carcinoma (HCC), although their roles in HCC development remained unclear. Here, we show that circPABPC1 is preferentially lost in tumor cells from clinical samples and inhibits both intrahepatic and distant metastases in a mouse xenograft model. This tumor-suppressive function of circPABPC1 can be attributed to its inhibition of cell adhesion and migration through down-regulating a key member of the integrin family, ITGB1 (ß1 integrin). Mass spectrometry and biochemical evidence demonstrate that circPABPC1 directly links ITGB1 to the 26S proteasome for degradation in a ubiquitination-independent manner. Our data have revealed an uncanonical route for integrin turnover and a previously unidentified mode of action for circRNAs in HCC that can be harnessed for anticancer treatment.

Simultaneous multiple primary cancers with concomitant inflammatory myofibroblastic tumor: a case report.

Multiple primary cancers are of rare occurrence. Most multiple primary cancers are metachronous multiple primary cancers, while simultaneous multiple primary cancers are rare. Inflammatory myofibroblastic tumors are rare. Inflammatory myofibroblastic tumor occurs most frequently in children and young adults. Herein, we report a rare case of simultaneous multiple primary cancers and inflammatory myofibroblastic tumor. A 44-year-old woman was admitted for a breast mass evaluation. The patient was positive for antinuclear, anti-mitochondrial, and anti-RO52 antibodies. Breast magnetic resonance imaging revealed a right breast mass. After neoadjuvant chemotherapy, modified radical mastectomy was performed. Postoperative histopathology revealed an invasive ductal carcinoma. Two months later, computed tomography revealed a nodule in the right upper lobe and ground-glass opacity in the lower lobe of the lungs. Lobectomy and lobe biopsy were performed. Postoperative histopathology revealed that the mass in the right upper lobe was an inflammatory myofibroblastic tumor and the right lower lobe lesion was an invasive adenocarcinoma. Immunohistochemistry of the inflammatory myofibroblastic tumor revealed negativity for anaplastic lymphoma kinase. At the 4-month follow-up, the patient showed good recovery. The etiology of multiple primary cancers and inflammatory myofibroblastic tumors is still unknown; in this case, we believe that autoimmune factors are the main cause of multiple primary cancers with concomitant inflammatory myofibroblastic tumor. Tissue biopsy is needed to ensure correct diagnosis of multiple primary cancers and inflammatory myofibroblastic tumor. Surgery-based comprehensive therapy is recommended. The prognosis is favorable and regular follow-up is necessary.

Association of circulating 25-Hydroxyvitamin D and its related genetic variations with hepatocellular carcinoma incidence and survival.

BACKGROUND: Vitamin D plays a key role of anti-cancer process, however, the association of vitamin D level and its related genetic variants with hepatocellular carcinoma (HCC) risk and prognosis is not fully understood. METHODS: We enrolled 100 HCC patients and 8,242 health controls from Sir Run Run Shaw Hospital. Logistic regression model was used to calculate the odds ratio (OR) and 95% CI for HCC risk according to serum 25(OH)D concentration. Mendelian randomization (MR) approach was also conducted to validate the potential causal association of 25(OH)D with HCC risk. Hazard ratio (HR) for the association of SNPs with overall survival and disease-free survival was assessed by multivariate Cox hazard proportional regression model. RESULTS: Plasma 25(OH)D level greater than 20 ng/mL increased HCC risk (OR =7.56, 95% CI: 4.58-12.50). MR analysis also showed a slightly increased risk of HCC by 25(OH)D increasing, yet did not reach statistical significance (OR =1.03, 95% CI: 0.31-3.47). With regard to HCC survival, compared to patients with rs8018720 GG genotype, patients with rs8018720 CC/CG genotype had a longer disease-free survival time (HR =0.39, 95% CI: 0.18-0.81). There was an interaction between rs12785878 and 25(OH)D level in continuous scale for HCC mortality. An interaction between rs12785878 and dichotomized 25(OH)D concentration for disease-free survival of HCC patients was also confirmed. CONCLUSIONS: There is hazard of circulating 25(OH)D concentration for HCC occurrence, but protective effect of the interaction between circulating 25(OH)D concentration and its related genetic variation for HCC prognosis. Further study is needed to confirm or refute these findings in a larger population.

Androgen receptor affects the response to immune checkpoint therapy by suppressing PD-L1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with gender-related differences in onset and course. Androgen receptor (AR), a male hormone receptor, is critical in the initiation and progression of HCC. The role of AR in HCC has been mechanistically characterized and anti-AR therapies have been developed, showing limited efficacy. Immunotherapy targeting immune checkpoint proteins may substantially improve the clinical management of HCC. The mechanism by which AR influences HCC immune state remains unclear. In this study, we demonstrated that AR negatively regulated PD-L1, by acting as a transcriptional repressor of PD-L1. Notably, AR over-expression in HCC cells enhanced CD8+T function in vitro. We then verified the AR/PD-L1 correlation in patients. In animal experiment we found that lower AR expressed tumor achieved better response to PD-L1 inhibitor. Thus, AR suppressed PD-L1 expression, possibly contributing to gender disparity in HCC. Better understanding of the roles of AR during HCC initiation and progression will provide a novel angle to develop potential HCC immunotherapies.

Wnt signaling in liver disease: emerging trends from a bibliometric perspective.

BACKGROUND: The Wnt signaling pathway, an evolutionarily conserved molecular transduction cascade, has been identified as playing a pivotal role in various physiological and pathological processes of the liver, including homeostasis, regeneration, cirrhosis, and hepatocellular carcinoma (HCC). In this study, we aimed to use a bibliometric method to evaluate the emerging trends on Wnt signaling in liver diseases. METHODS: Articles were retrieved from the Web of Science Core Collection. We used a bibliometric software, CiteSpace V 5.3.R4, to analyze the active countries or institutions in the research field, the landmark manuscripts, important subtopics, and evolution of scientific ideas. RESULTS: In total, 1,768 manuscripts were published, and each was cited 33.12 times on average. The U.S. published most of the articles, and the most active center was the University of Pittsburgh. The top 5 landmark papers were identified by four bibliometric indexes including citation, burstness, centrality, and usage 2013. The clustering process divided the whole area into nine research subtopics, and the two major important subtopics were "liver zonation" and "HCC." Using the "Part-of-Speech" technique, 1,743 terms representing scientific ideas were identified. After 2008, the bursting phrases were "liver development," "progenitor cells," "hepatic stellate cells," "liver regeneration," "liver fibrosis," "epithelial-mesenchymal transition," and etc. CONCLUSION: Using bibliometric methods, we quantitatively summarized the advancements and emerging trends in Wnt signaling in liver diseases. These bibliometric findings may pioneer the future direction of this field in the next few years, and further studies are needed.

High expression of ERCC5 predicts a poor prognosis in hepatocellular carcinoma.

Human cells exposed to environmental or endogenous carcinogens can develop DNA damage. This DNA damage may contribute to a susceptibility to cancer; therefore, it is important to repair these defects. The nucleotide excision repair pathway (NER) is a versatile DNA repair pathway that eliminates a wide variety of helix-distorting base lesions induced by environmental or endogenous carcinogenic sources. The excision repair cross-complementation group 5 (ERCC5) gene is a central component of NER. Ectopic expression of ERCC5 has been linked to different types of cancers, including hepatocellular carcinoma (HCC). However, previous reports, mainly based on mRNA level and the role of ERCC5 in cancer, remain conflicting and unclear. In this study, we examined 104 cases of HCC for immunohistochemistry to explore the role of ERCC5 protein in HCC. We found the expression of ERCC5 protein was significantly increased in tumor tissues compared to paracancerous ones (P<0.01). The percentage of positive staining of ERCC5 in tumor tissues was 28.8% (30/104), while only 4.8% (5/104) in paracancerous tissues. Patients with low ERCC5 expression levels had a better overall survival rate and remained disease-free longer (both P<0.01). In addition, univariate and multivariate analysis showed a high expression of ERCC5 protein and large tumor size predict a poor prognosis for patients with HCC (P<0.05).

Jejunojejunal intussusception after Roux-en-Y gastric bypass in a situs inversus totalis patient: A case report.

INTRODUCTION: Situs inversus totalis (SIT) is an uncommon clinical manifestation. Patients with SIT typically have malformation in the thorax and abdomen. The incidence of SIT ranges from 1/10,000 to 1/20,000 (Al-Jumaily and Hoche. J Laparoendosc Adv Surg Tech A 2001;11:229). Jejunojejunal intussusception is a rare complication after Roux-en-Y gastric bypass. Intussusception in adult cases accounts for 5% of adult intestinal obstruction cases, while in children, the occurrence is high and the majority of them are idiopathic cases. CASE REPORT: Here, we present an uncommon case of jejunojejunal intussusception after Roux-en-Y gastric bypass in an SIT patient. We performed reduction at the beginning and resection was done finally. DISCUSSION: We explore the potential causes and discuss the diagnosis and therapy. CONCLUSION: Intussusception in an SIT patient is an uncommon case. The symptoms are vague, and it is difficult to diagnose. Clinicians should be vigilant postoperatively, especially when abdominal pain after gastrointestinal surgery occurs. It is a rare case worth learning.

Covered Stents versus Uncovered Stents for Unresectable Malignant Biliary Strictures: A Meta-Analysis.

AIM: To summarize the covered or uncovered SEMS for treatment of unresectable malignant distal biliary obstruction, comparing the stent patency, patient survival, and incidence of adverse events between the two SEMSs. METHODS: The meta-analysis search was performed independently by two of the authors, using MEDLINE, EMBASE, OVID, and Cochrane databases on all studies between 2010 and 2015. Pooled effect was calculated using either the fixed or the random effects model. RESULTS: Statistics shows that there is no difference between SEMSs in the hazard ratio for patient survival (HR 1.04; 95% CI, 0.92-1.17; P = 0.55) and stent patency (HR 0.87, 95% CI: 0.58 to 1.30, P = 0.5). However, incidence of adverse events (OR: 0.74, 95% CI: 0.57 to 0.97, P = 0.03) showed significant different results in the covered SEMS, with dysfunctions events (OR: 0.75, 95% CI: 0.56 to 1.00, P = 0.05) playing a more important role than complications (OR: 0.87, 95% CI: 0.58 to 1.30, P = 0.50). CONCLUSIONS: Covered SEMS group had lower incidence of adverse events. There is no significant difference in dysfunctions, but covered SEMS trends to be better, with no difference in stent patency, patient survival, and complications.

IGF-1 induces hypoxia-inducible factor 1α-mediated GLUT3 expression through PI3K/Akt/mTOR dependent pathways in PC12 cells.

Glucose metabolism is essential for most mammalian neurons, and the passage of glucose across cell membranes is mainly facilitated by glucose transporter 3 (GLUT3). In ischemia/reperfusion injured brains, increase of IGF-1 secretion and GLUT3 up-regulation, are regarded as protective processes. Recent works have shown that various growth factors and cytokines including IGF-1 can stimulate HIF-1α expression, thereby triggering transcription of numerous hypoxia-inducible genes by oxygen-independent mechanisms. So, we hypothesized that HIF-1α might play important role in the process of IGF-1 induced GLUT3. Using echinomycin, a HIF-1 inhibitor, and HIF-1α siRNA, we demonstrated IGF-1 induced GLUT3 expression through HIF-1α in neuronal PC12 cells. Moreover, IGF-1 stimulated HIF-1α and GLUT3 protein expression through phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR dependent pathways. Analysis of GLUT3 promoter deletion sequences indicated that a putative hypoxia-response element (HRE) was critical in GLUT3 promoter activity when PC12 cells were treatment with CoCl(2) and IGF-1. In conclusion, we showed that the expression of GLUT3 in response to IGF-1 was dependent on PI-3-kinase and mTOR activity, and required the transcription factor HIF-1α.

Therapy and prognosis of intracranial invasive olfactory neuroblastoma.

OBJECTIVE: There is currently no consensus on a standardized treatment strategy for olfactory neuroblastoma (ONB), especially for intracranial invasion. This purpose of this study is to explore the appropriate treatment modality and prognostic factors of intracranial invasive ONB. STUDY DESIGN: Case series with chart review. SETTING: The study was conducted at the Sun Yat-sen Memorial Hospital and the Cancer Center of Sun Yat-sen University, China. SUBJECTS AND METHODS: Twenty-five cases of intracranial invasive ONB were collected and investigated using a retrospective review analysis from patients diagnosed between 1980 and 2005. RESULTS: The 1-, 3-, and 5-year overall survival rates for the group were 55%, 46%, and 31%, respectively. The subgroups who did not receive surgical treatment had worse survival rates than those who did receive treatment. In particular, patients who did not receive any therapy did not live past 1 year. In contrast, the group of patients treated by intranasal resection in combination with radiotherapy and/or chemotherapy showed a slightly better survival rate. It is important to note that the group of patients treated by craniofacial surgery combined with radiotherapy and/or chemotherapy had a markedly favorable prognosis, with 1-, 3-, and 5-year overall survival rates of up to 100%, 88%, and 66%, respectively. CONCLUSIONS: Craniofacial surgery in combination with radiotherapy and/or chemotherapy was an effective treatment for intracranial invasive ONB. In addition, it was found that age may not be an important prognostic factor for intracranial invasive ONB; however, the rate of intracalvarial invasion was found to be a potent marker for predicting the prognosis of patients.