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BackgroundCirculating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging.MethodsWe searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages.ResultsIn this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17–4.39; HRPFS/DFS, 2.06; 95% CI, 1.72–2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85–3.19; HRPFS/DFS, 1.82; 95% CI, 1.66–1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85–3.19).ConclusionOur study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.

BackgroundBrain metastases (BM) include brain parenchymal (BPM) and leptomeningeal metastases (LM), which are associated with a poor prognosis and high mortality rate. Early and accurate diagnosis and timely, effective treatment are crucial for improving the overall survival of LM patients. Cerebrospinal fluid (CSF) biopsy technology has attracted widespread attention for its diagnostic value in diverse cancers, including LM. We summarized studies to compare the potential diagnostic value of CSF liquid biopsy techniques in BM patients with meta-analysis.MethodsThe study protocol was prospectively registered in PROSPERO, registration number CRD42022373263. We obtained the literature on liquid biopsy for BM from 7 databases (PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang Data knowledge service platform). Then, a systematic review of those studies was performed according to PRISMA criteria.ResultsNine publications have been obtained, and we found CSF liquid biopsy techniques to be more suitable for diagnosing LM. We analyzed the sensitivity, specificity, and area under the curve (AUC) of CSF liquid biopsy. The overall sensitivity, specificity, and AUC of CSF liquid biopsy in the diagnosis of LM were 0.65 (95% CI: 0.48 - 0.79), 0.70 (95% CI: 0.50 - 0.86), and 0.69, respectively. Then, we compared the diagnostic advantages of CSF liquid biopsy techniques and CSF cytology in LM. The results show that CSF liquid biopsy is superior to CSF cytology in LM diagnosis.ConclusionsOur meta-analysis suggested that CSF liquid biopsy is more suitable for LM diagnosis and has higher accuracy than CSF cytology.

IntroductionGrowing evidence suggests that the tumor microenvironment (TME) represented by cellular and acellular components plays a key role in the multistep process of metastases and response to therapies. However, imaging and molecular characterization of the TME in prostate cancer (PCa) and its role in predicting aggressive tumor behavior and disease progression is largely unexplored. The study explores the PCa TME through the characterization of cancer-associated fibroblasts (CAFs) using both immunohistochemistry (IHC) and genomics approaches. This is then correlated with transrectal ultrasound shear wave elastography (USWE)-measured tissue stiffness.Patients and MethodsThirty patients with clinically localized PCa undergoing radical prostatectomy for different risk categories of tumor (low, intermediate, and high) defined by Gleason score (GS) were prospectively recruited into this study. Prostatic tissue stiffness was measured using USWE prior to surgery. The CAFs within the TME were identified by IHC using a panel of six antibodies (FAP, SMAα, FSP1, CD36, PDGFRα, and PDGFRβ) as well as gene expression profiling using TempO-sequence analysis. Whether the pattern and degree of immunohistochemical positivity (measured by Quick score method) and expression of genes characterizing CAFs were correlated with USWE- and GS-measured tissue stiffnesses were tested using Spearman’s rank correlation and Pearson correlation.ResultsThere was a statistically significant correlation between GS of cancers, the pattern of staining for CAFs by immunohistochemical staining, and tissue stiffness measured in kPa using USWE (p < 0.001). Significant differences were also observed in immunohistochemical staining patterns between normal prostate and prostatic cancerous tissue. PDGFRβ and SMAα immunostaining scores increased linearly with increasing the USWE stiffness and the GS of PCa. There was a significant positive correlation between increasing tissue stiffness in tumor stroma and SMAα and PDGFRβ gene expression in the fibromuscular stroma (p < 0.001).ConclusionUSWE-measured tissue stiffness correlates with increased SMAα and PDGFRβ expressing CAFs and PCa GSs. This mechanistic correlation could be used for predicting the upgrading of GS from biopsies to radical surgery and response to novel treatments.

ObjectivesTo investigate the impact of ultrasound shear wave elastography (USWE) and multiparametric magnetic resonance imaging (mpMRI) in predicting a change in biopsy-assigned Gleason Score (GS) after radical surgery for localised prostate cancer (PCa).MethodA total of 212 men opting for laparoscopic radical prostatectomy (LRP) between September 2013 and June 2017 were recruited into this study. All the participants had 12-core transrectal ultrasound (TRUS) biopsies and imaging using USWE and mpMRI before radical surgery. The predictive accuracy for imaging modalities was assessed in relation to upgrading and downgrading of PCa GS between the biopsies and radical prostatectomy using Student’s t-test and multivariable logistic regression analyses. A decision analysis curve was constructed assessing the impact of nomogram on clinical situations using different thresholds of upgrading probabilities.ResultsMost GS 6 diseases on biopsies were upgraded on radical surgery (37/42, 88.1%). Major downgrading was seen in GS 8 category of disease (14/35; 37.1%), whereas no alteration was observed in GS 7 on biopsies in most men (55/75; 73.3%). In univariate analysis, higher preoperative prostate-specific antigen (PSA) (p = 0.001), higher prostate-specific antigen density (PSAD) (p = 0.002), stiffer USWE lesions (p = 0.009), and higher prostate imaging–reporting and data system (PIRADS) (p = 0.002) on mpMRI were significant predictors of upgrading. In multivariate logistic regression analyses, only PSA (p = 0.016) and USWE-measured tissue stiffness (p = 0.029) showed statistical significance in predicting upgrading.ConclusionsMeasurement of tissue stiffness using USWE in clinically localised PCa can predict upgrading of GS and has the potential to improve patient management options.

IntroductionOwing to the close vicinity of the optic chiasma, visual dysfunction is known as one of the most common surgical indications and postoperative complications in adult patients with craniopharyngiomas, probably leading to poor quality of life. Historically, very few consistent predictive factors associated with the visual outcome are identified, which may not be helpful for patient counseling and preoperative decision making. Recently, optical coherence tomography (OCT) serving as a novel high-resolution imaging technique can assess the retinal morphology by measuring the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex thickness. However, few studies have examined the prognostic utility of OCT parameters for visual outcome after surgery for craniopharyngiomas. This study aims to use the largest series to evaluate the association between OCT parameters and visual outcome after extended endoscopic endonasal surgery (EEES) for primary craniopharyngiomas in adults.Material and MethodsFrom October 2018 to October 2020, one hundred and seventy eyes in 88 adult patients with newly confirmed craniopharyngiomas were retrospectively reviewed and pertinent prognostic factors were analyzed.ResultsGross total resection was performed in 82 (93.2%) patients. The median postoperative follow-up time was 10.9 months. Multiple logistic regression analysis showed that increased temporal cpRNFL thickness was associated with higher odds of visual acuity (VA) improvement and maintenance (OR = 1.070; 95% CI, 1.005–1.140; p = 0.035), and greater inferior cpRNFL thickness was significantly associated with visual field (VF) improvement and maintenance (OR = 1.034; 95% CI, 1.001–1.068; p = 0.046). Furthermore, tight adhesion between optic nerves and craniopharyngiomas was demonstrated as an independent adverse factor for either postoperative VA or VF (p = 0.048, p = 0.030, respectively). The ROC results further verified the robustness of the prediction model either in VA (AUC = 0.843; 95% CI, 0.734–0.952; p < 0.001) or VF (AUC = 0.849; 95% CI, 0.741–0.958; p < 0.001).ConclusionPreoperative OCT can effectively predict visual outcome after EEES for adult craniopharyngiomas. It can also serve as a reliable alternative to evaluate preoperative visual field defects, especially for patients with lower compliance. Tight adhesion was confirmed as an independent risk factor for postoperative visual outcome. The OCT-based multivariable prediction models developed in the present study may contribute to patient counseling on visual prognosis.

BackgroundIt is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear.Methods and ResultsUsing the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein–protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages.ConclusionThe expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.

PurposeProstate cancer (PCa) has a high incidence among older men. Until now, there are no immunological markers available to predict PCa patients’ survival. Therefore, it is necessary to explore the immunological characteristics of PCa.MethodsFirst, we retrieved RNA-seq and clinical data of 499 PCa and 52 normal prostate tissue samples from the Cancer Genome Atlas (TCGA). We identified 193 differentially expressed immune-related genes (IRGs) between PCa and normal prostate tissues. Functional enrichment analyses showed that the immune system can participate in PCa initiation. Then, we constructed a correlation network between transcription factors (TFs) and IRGs. We performed univariate and multivariate Cox regression analyses and identified five key prognostic IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1). Finally, a predictive nomogram was established and verified by the C-index.ResultsWe successfully constructed and validated an immune-related PCa prediction model. The signature could independently predict PCa patients’ survival. Results showed that high-immune-risk patients were correlated with advanced stage. We also validated the S100A2 expression in vitro using PCa and normal prostate tissues. We found that higher S100A2 expressions were related to lower biochemical recurrences. Additionally, higher AMH expressions were related to higher Gleason score, lymph node metastasis and positive rate, and tumor stages, and higher ATGR1 expressions were related to lower PSA value.ConclusionOverall, we detected five IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1) that can be used as independent PCa prognostic factors.

BackgroundSkull base chordomas (SBCs) are rare malignant bone tumors with dismal long-term local control. Endoscopic endonasal surgeries (EESs) are increasingly adopted to resect SBCs recently. Gross total resection (GTR) favors good outcomes. However, the SBCs often invade the skull base extensively and hide behind vital neurovascular structures; the tumors were challenging to remove entirely. To improve the GTR, we established a surgical strategy for EES according to the tumor growth directions.MethodsA total of 112 patients with SBCs from 2018 to 2019 were classified into the derivation group. We retrospectively analyzed their radiologic images and operation videos to find the accurate tumor locations. By doing so, we confirmed the tumor growth directions and established a surgical strategy. Fifty-five patients who were operated on in 2020 were regarded as the validation group, and we performed their operations following the surgical strategy to verify its value.ResultsIn the derivation group, 78.6% of SBCs invade the dorsum sellae and posterior clinoid process region. 62.5% and 69.6% of tumors extend to the left and right posterior spaces of cavernous ICA, respectively. 59.8% and 61.6% of tumors extend to the left and right posterior spaces of paraclival and lacerum ICA (pc-la ICA), respectively. 30.4% and 28.6% of tumors extended along the left and right petroclival fissures that extend toward the jugular foramen, respectively. 30.4% of tumors involved the foramen magnum and craniocervical junction region. The GTR was achieved in 60.8% of patients with primary SBCs in the derivation group. Based on the tumors’ growth pattern, pituitary transposition and posterior clinoidectomy techniques were adopted to resect tumors that hid behind cavernous ICA. Paraclival ICA transposition was used when the tumor invaded the posterior spaces of pc-la ICA. Lacerum fibrocartilage resection and eustachian tube transposition may be warranted to resect the tumors that extended to the jugular foramen. GTR was achieved in 75.0% of patients with primary SBCs in the validation group.ConclusionBesides the midline clival region, the SBCs frequently grow into the eight spaces mentioned above. The surgical strategy based on the growth pattern contributes to increasing the GTR rate.

BackgroundThe growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1.Methods29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging.ResultsCompared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR < 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR < 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR < 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE < 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE < 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly.ConclusionsOur findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.

Background: Prostate cancer is a frequently diagnosed malignant solid tumor in men. The accuracy of diagnosis is becoming increasingly important. This meta-analysis evaluated the accuracy of micro-ultrasound in the diagnosis of clinically significant prostate cancer.Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases to recruit studies in English. The quality assessment of diagnostic accuracy studies-2 protocol was used to evaluate the literature quality. Publication bias was analyzed using Deeks' funnel plot asymmetry test. We calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95% confidence interval (95% CI) for studies of micro-ultrasound imaging for prostate cancer. The results were assessed by the summary receiver-operating characteristic curve (SROC). Ultimately, a univariable meta-regression and subgroup analysis, Fagan plot, and a likelihood matrix were conducted.Results: A total of seven studies containing 769 patients were included in this meta-analysis. Micro-ultrasound had a pooled sensitivity, specificity, DOR, and an area under the SROC of 0.91, 0.49, 10, and 0.82, respectively. Based on these findings, micro-ultrasound has superior ability to diagnose clinically significant prostate cancer.Conclusion: Micro-ultrasound is a more convenient and cost-effective method in real-time imaging during the biopsy procedure in detecting clinically significant prostate cancer. Although micro-ultrasound has shown promising results, more clinical data and comprehensive analysis are still needed.

Advances in the understanding of growth hormone-producing adenomas (GHomas) are ongoing, but current therapy is limited by moderate and variable efficacy and in need of life-long treatment. In this study, the molecular signaling pathway related to GHoma was investigated by proteomics and transcriptomics. The differentially expressed proteins and genes were significantly enriched in Extracellular Matrix-Receptor Interactions, Notch Signaling, Basal Cell Carcinoma Signaling, JAK-STAT3, Wnt Signaling, and Glioblastoma Multiforme Signaling by Ingenuity Pathway Analysis. Furthermore, the Notch2/Delta-like canonical Notch ligand (DLL) signaling pathway was identified to be associated with tumorigenesis and invasiveness of GHoma. In 76 patients, Notch2 and DLL3 were upregulated in invasive compared to those in non-invasive GHoma (p < 0.05). Disease-free survival was significantly longer in patients with low, compared with high, DLL3 expression (p = 0.027). Notch 2 knockdown inhibited cell migration in both GH3 cells and primary GHoma cells, along with downregulation of the mRNA expression of related genes. DAPT, a γ-secretase inhibitor, inhibited tumor growth and invasion in vivo and in vitro and suppressed the release of growth hormone in primary GHoma cells. The involvement of Notch2/DLL3 signaling in GHoma progression warrants additional study of Notch inhibitor, DAPT, as a potential GHoma treatment.Importance of the StudyCurrent treatments of GH adenomas (GHomas) are limited by their moderate and variable efficacy and in need of life-long treatment. We found that the Notch2/Delta-like Notch ligand 3 (DLL3) signaling pathway was active in GHoma tumorigenesis, progression, and invasion.The γ-secretase inhibitor DAPT is of potential use in GHoma treatment targeting Notch signaling.