Invasion and Grading of Pulmonary Non-Mucinous Adenocarcinoma.

Lung adenocarcinoma staging and grading were recently updated to reflect the link between histologic growth patterns and outcomes. The lepidic growth pattern is regarded as "in-situ," whereas all other patterns are regarded as invasive, though with stratification. Solid, micropapillary, and complex glandular patterns are associated with worse prognosis than papillary and acinar patterns. These recent changes have improved prognostic stratification. However, multiple pitfalls exist in measuring invasive size and in classifying lung adenocarcinoma growth patterns. Awareness of these limitations and recommended practices will help the pathology community achieve consistent prognostic performance and potentially contribute to improved patient management.

A nomogram based on the quantitative and qualitative features of CT imaging for the prediction of the invasiveness of ground glass nodules in lung adenocarcinoma.

PURPOSE: Based on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients. MATERIALS AND METHODS: Altogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models. RESULTS: In the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06-10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011-1.043), maximum CT value (OR = 1.025, 95%CI: 1.004-1.047), mean CT value (OR = 1.035, 95%CI: 1.008-1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148-3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345-4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885-0.934) and 0.902 (95%CI: 0.859-0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer-Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability. CONCLUSION: Combined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.

Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway.

Glioma is the most common type of primary intracranial malignant tumor, and because of its high invasiveness and recurrence, its prognosis remains poor. The present study investigated the biological function of piggyBac transportable element derived 5 (PGBD5) in glioma. Glioma and para-cancerous tissues were obtained from five patients. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of PGBD5. Transwell assay and flow cytometry were used to evaluate cell migration, invasion, apoptosis and cell cycle distribution. In addition, a nude mouse tumor transplantation model was established to study the downstream pathways of PGBD5 and the molecular mechanism was analyzed using transcriptome sequencing. The mRNA and protein expression levels of PGBD5 were increased in glioma tissues and cells. Notably, knockdown of PGBD5 in vitro could inhibit the migration and invasion of glioma cells. In addition, the knockdown of PGBD5 expression promoted apoptosis and caused cell cycle arrest in the G2/M phase, thus inhibiting cell proliferation. Furthermore, in vivo experiments revealed that knockdown of PGBD5 expression could inhibit Ki67 expression and slow tumor growth. Changes in PGBD5 expression were also shown to be closely related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In conclusion, interference with PGBD5 could inhibit the malignant progression of glioma through the PPAR pathway, suggesting that PGBD5 may be a potential molecular target of glioma.

Identification of molecular characteristics of hepatocellular carcinoma with microvascular invasion based on deep targeted sequencing.

BACKGROUND: As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. METHODS: We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co-mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. RESULTS: Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI-positive and one was MVI-negative, and there was a co-occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease-free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p-values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8+ T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55). CONCLUSIONS: TERTp+/TP53+ was significantly enriched in MVI-positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI-positive patients and poor prognosis, laying a preliminary foundation for further exploration of co-mutation in HCC with MVI and clinical treatment.

New strategy for intraoperative phonosurgical management of recurrent laryngeal nerve infiltrated by thyroid carcinoma.

PURPOSE: Treating an infiltration of the recurrent laryngeal nerve (RLN) by thyroid carcinoma remains a subject of ongoing debate. Therefore, this study aims to provide a novel strategy for intraoperative phenosurgical management of RLN infiltrated by thyroid carcinoma. METHODS: Forty-two patients with thyroid carcinoma infiltrating the RLN were recruited for this study and divided into three groups. Group A comprised six individuals with medullary thyroid cancer who underwent RLN resection and arytenoid adduction. Group B consisted of 29 differentiated thyroid cancer (DTC)patients who underwent RLN resection and ansa cervicalis (ACN)-to-RLN anastomosis. Group C included seven patients whose RLN was preserved. RESULTS: The videostroboscopic analysis and voice assessment collectively indicated substantial improvements in voice quality for patients in Groups A and B one year post-surgery. Additionally, the shaving technique maintained a normal or near-normal voice in Group C one year post-surgery. CONCLUSION: The new intraoperative phonosurgical strategy is as follows: Resection of the affected RLN and arytenoid adduction is required in cases of medullary or anaplastic carcinoma, regardless of preoperative RLN function. Suppose RLN is found infiltrated by well-differentiated thyroid cancer (WDTC) during surgery, and the RLN is preoperatively paralyzed, we recommend performing resection the involved RLN and ACN-to-RLN anastomosis immediately during surgery. If vocal folds exhibit normal mobility preoperatively, the MACIS scoring system is used to assess patient risk stratification. When the MACIS score > 6.99, resection of the involved RLN and immediate ACN-to-RLN anastomosis were performed. RLN preservation was limited to patients with MACIS scores ≤ 6.99.

Challenges and technical aspects in the management of muscle invasive bladder cancer as retrograde radical cystectomy with ileal conduit.

Objective: To evaluate long-term outcomes in patients homogenously treated with radical cystectomy and ileal conduit for muscle invasive bladder cancer. METHODS: The retrospective study was conducted at the Urology Department of Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data from December 25, 2017, to January 16, 2023, related to patients who underwent radical cystectomy with ileal conduit with or without neo-adjuvant and adjuvant radiation, chemotherapy, or immunotherapy for papillary urothelial carcinom of the bladder. Clinical trajectory, histopathological characteristics and long-term clinical outcomes were noted. Data was analysed using SPSS 20. RESULTS: In our study of 40 patients with muscle invasive bladder cancer, males predominated (32, 80%), with a median age of 57.4 years (IQR: 29-80). Diagnosis was early in 5 (12.5%) patients with varying haematuria durations, while 34 (85%) patients had a smoking history. Comorbidities included hypertension in 17 (42.5%) patients, diabetes in 1 (2.5%) patient, both hypertension and diabetes in 9 (22.5%) patients and a combination of hypertension, diabetes, and ischaemic heart disease in 3 (7.5%) patients. Transurethral resection was performed once in 13 (32.5%) patients and multiple times in 27 (67.5%) patients. Additionally, 5 (12.5%) patients received immunotherapy, 11 (27.5%) patients underwent non-adjuvant radiation, and 14 (35%) patients received non-adjuvant chemotherapy. Papillary urothelial carcinoma was the predominant histological subtype among 37 (92.5%) patients. Patients receiving chemotherapy had significantly better overall survival (p=0.02). No significant differences were noted in recurrence or survival by therapy modality (p>0.05). These findings highlight the significance of early diagnosis, tailored treatments, and comorbidity management in muscle invasive bladder cancer patients. Age stratification revealed significant survival differences across groups (χ²=10.923, df=3, p= 0.012). Analysis by complications did not show age-related survival variations (χ² =3.978, df = 3, p=0.264). Conclusion: Achieving excellent long-term survival in MIBC patients requires a multidisciplinary approach, emphasizing early diagnosis, tailored treatment, and adherence to guidelines and protocols.

The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

BACKGROUND: Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. METHOD: This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. RESULTS: This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. CONCLUSIONS: The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

The mechanisms behind the dual role of long non-coding RNA (lncRNA) metastasis suppressor-1 in human tumors: Shedding light on the molecular mechanisms.

When the expression levels of metastasis suppressor-1 (MTSS1) were discovered to be downregulated in a metastatic cancer cell line in 2002, it was proposed that MTSS1 functioned as a suppressor of metastasis. The 755 amino acid long protein MTSS1 connects to actin and organizes the cytoskeleton. Its gene is located on human chromosome 8q24. The suppressor of metastasis in metastatic cancer was first found to be MTSS1. Subsequent reports revealed that MTSS1 is linked to the prevention of metastasis in a variety of cancer types, including hematopoietic cancers like diffuse large B cell lymphoma and esophageal, pancreatic, and stomach cancers. Remarkably, conflicting results have also been documented. For instance, it has been reported that MTSS1 expression levels are elevated in a subset of melanomas, hepatocellular carcinoma associated with hepatitis B, head and neck squamous cell carcinoma, and lung squamous cell carcinoma. This article provides an overview of the pathological effects of lncRNA MTSS1 dysregulation in cancer. In order to facilitate the development of MTSS1-based therapeutic targeting, we also shed light on the current understanding of MTS1.

Cancer cell invasion: Caveolae and invadosomes are partners in crime.

During cancer progression, tumor cells need to disseminate by remodeling the extracellular tumor matrix. A recent study sheds light on the intricate cooperation between caveolae and invadosomes that facilitates the spread of cancer cells.

Can MRI Accurately Diagnose and Stage Endometrial Adenocarcinoma?

Background and Objectives: Endometrial carcinoma is one of the most common gynecological cancers, and benign lesions such as endometrial hyperplasia, polyps, adenomyosis and leiomyomas should be included in the differential diagnosis. Magnetic resonance imaging has an important role in evaluating endometrial cancer and assessing the depth of myometrial invasion, and it closely correlates with the prognosis of the patient. The purpose of this study is to evaluate the MRI semiology of the endometrial carcinomas that mimic benign lesions, the main factors that may affect the correct diagnosis and the feasibility of magnetic resonance imaging to evaluate the depth of the myometrial invasion of endometrial cancer. Materials and Methods: This is a retrospective analysis of 45 patients that underwent MRI examinations and the lesions were pathologically diagnosed as endometrial carcinoma after surgical resection. This study evaluated the staging accuracy of T2-weighted imaging, diffusion-weighted imaging (DWI), ADC mapping and T1-weighted imaging with fat saturation before and after gadolinium injection. Results: In 36 of the 45 cases, the MRI of the lesion showed the characteristics of endometrial cancer and the diagnosis was certain. Nine lesions (20%) were described as unequivocal and had unspecific MR appearance. In eight of the nine cases (89%), the histopathologic report revealed the presence of leiomyomas and two of these cases (22%) were also associated with adenomyosis. The cause of underestimation in these patients was coexisting lesions exhibiting heterogenous intensity and contrast enhancement, which made it difficult to detect the margins of the lesions. The depth of the myometrial invasion was underestimated in nine cases and overestimated in three cases. The staging accuracy with MRI was 74%. There was a significant correlation between MR imaging and histopathologic finding in the assessment of myometrial invasion (p < 0.001). Cervical extension was noted in eight cases (18%), but was missed on MR imaging in two patients and overstaged in none. Six of them were associated with myometrial invasion in more than 50% of the thickness. There was a significant correlation between MR imaging and histopathologic finding in the assessment of cervical extension (p < 0.001). Conclusions: Our data confirm the high accuracy of MRI in the diagnosis and local staging of endometrial carcinoma. The information provided by MRI has an important role in planning the treatment and the prognosis of the patients.

Atlas of Tumor and Tumor Microenvironment Cells of Lymphovascular Space Invasion (LVSI) in High-Grade Serous Endometrial Adenocarcinoma: A Case Study.

Lymphovascular invasion (LVSI) is defined as the presence of tumor cells within a definite endothelial-lined space (lymphatics or blood vessels) in the organ surrounding invasive carcinoma. The presence of LVI is associated with an increased risk of lymph nodes and distant metastases. Lymphovascular invasion is described as cancer within blood or lymph vessels and is an independent risk factor for metastasis, recurrence, and mortality. This study aims to present the marker-based immunohistological characterization of cells around LVSI in a high-grade adenocarcinoma of the endometrium to build a cellular atlas of cells of LVSI. A cellular characterization of the cells around lymphovascular space invasion in a 67-year-old female patient with invasive high-grade serous endometrial adenocarcinomas is presented. Resected tumor tissue from a consented patient with invasive high-grade serous endometrial adenocarcinoma was obtained within an hour of surgery. The expressions of the epithelial markers (CK8, 18, and EpCAM), LCA (leukocyte common antigen) marker (CD45), proliferation marker (Ki67), apoptosis markers (cleaved PARP and cleaved caspase3), immune cell markers (CD3, CD4, CD8, CD56, CD68, CD163, FoxP3, PD-1, PD-L1), pro-inflammatory marker (IL-12-RB2), and fibroblast/mesenchyme markers (S100A7, SMA, and TE-7) of the resected tissue on the IHC stains were evaluated and scored by a pathologist. Acknowledging the deterministic role of LVSI in a high-grade adenocarcinoma of the endometrium, our study presents the first marker-based immunohistological atlas of the tumor and TME compartments in the context of epithelial cell markers, proliferation markers, apoptosis markers, macrophage markers, and fibroblast markers. Our study demonstrates that an aggressive disease like a high-grade adenocarcinoma of the endometrium inflicts the pro-metastatic event of LVSI by involving the immune landscape of both tumor and TME. This study demonstrates, for the first time, that the tumor cells within LVSI are positive for IL-12R-B2 and S100A4.

Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer.

PURPOSE: The aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). METHODS: A total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. RESULTS: Univariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558-7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327-5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919-8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344-6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1-1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056-16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933-12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003-17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. CONCLUSIONS: Cervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.

Office-based management of Non-Muscle Invasive Bladder Cancer (NMIBC): A position paper on current state of the art and future perspectives.

To the Editor, Bladder cancer is one of the most common cancers in humans, representing the 7th and 17th type of neoplasm in both genders. Its incidence and mortality are quite heterogeneous in different countries and are due to different risk factors, quality and prevalence of healthcare and the possibility of early diagnosis and treatment of the tumor and its potential recurrences [...].

Unraveling a hidden player in lymphovascular invasion in bladder cancer.

Tumor invasion into the lymphatic vasculature represents a critical step during malignant progression of epithelial cancers. In this issue of Cancer Cell, Zheng et al. unravel how cancer-associated fibroblasts interact with lymphatic endothelial cells and the extracellular matrix to promote lymphatic tumor invasion and suggest that these processes could be treatment targets.

Diagnostic Accuracy of JES Classification for Prediction of Invasion Depth in Superficial Esophageal Squamous Carcinoma: Meta-Analysis.

Prediction of the depth of invasion in superficial oesophageal squamous carcinoma (SESC) is an important factor for choosing the treatment. Recently, the Japan Esophageal Society (JES) designed a magnifying endoscopy classification based on the Inoue and Arima classifications. The aim of this study was to conduct a meta-analysis of the published literature on JES classification. Meta-Disc version 1.4, Review Manager 5.4 as well as stata 14.0 were used. The analysis combined sensitivity and specificity with the respective 95% CI, to draw a summary receiver operating characteristic curve (SROC), and estimated the area under curve (AUC) for overdiagnosis and underdiagnosis for each type B. Eight studies were included in the meta-analysis comprising 1279 patients. Type B1 has high sensitivity (0.86, 95%CI: 0.83-0.88) and specificity (0.84, 95%CI: 0.81-0.88) for the prediction of EP/LPM classifications. The AUC was calculated to be 0.92 with a high proportion of underdiagnosis (17%). The sensitivity and specificity of type B2 were 0.66 (95% CI, 0.6-0.72) and 0.84 (95% CI, 0.82-0.86) respectively. The overdiagnosis and underdiagnosis of type B2 were 14% and 39%. Type B3, sensitivity was low (0.49, 95% CI: 0.41-0.56), with high specificity and AUC (specificity: 0.99; AUC: 0.95). JES classification is a useful and reliable modality for predicting the depth of invasion of SESC, but other modalities should be considered for additional assessment when type B2 is detected. Key Words: JES classification, Superficial oesophageal squamous carcinoma, Depth of invasion, Magnifying endoscopy, Meta-analysis.

Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion.

Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding brain tissue. While lower-grade gliomas present more circumscribed borders, high-grade gliomas are aggressive tumors with widespread brain infiltration and dissemination. Glioblastoma (GBM) is known for its high invasiveness and association with poor prognosis. Its low survival rate is due to the certainty of its recurrence, caused by microscopic brain infiltration which makes surgical eradication unattainable. New insights into GBM biology at the single-cell level have enabled the identification of mechanisms exploited by glioma cells for brain invasion. In this review, we explore the current understanding of several molecular pathways and mechanisms used by tumor cells to invade normal brain tissue. We address the intrinsic biological drivers of tumor cell invasion, by tackling how tumor cells interact with each other and with the tumor microenvironment (TME). We focus on the recently discovered neuronal niche in the TME, including local as well as distant neurons, contributing to glioma growth and invasion. We then address the mechanisms of invasion promoted by astrocytes and immune cells. Finally, we review the current literature on the therapeutic targeting of the molecular mechanisms of invasion.

The value of varying diffusion curvature MRI for assessing the microvascular invasion of hepatocellular carcinoma.

PURPOSE: Varying diffusion curvature (VDC) MRI is an emerging diffusion-weighted imaging (DWI) technique that can capture non-Gaussian diffusion behavior and reflect tissue heterogeneity. However, its clinical utility has hardly been evaluated. We aimed to investigate the value of the VDC technique in noninvasively assessing microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: 74 patients with HCCs, including 39 MVI-positive and 35 MVI-negative HCCs were included into this prospective study. Quantitative metrics between subgroups, clinical risk factors, as well as diagnostic performance were evaluated. The power analysis was also carried out to determine the statistical power. RESULTS: MVI-positive HCCs exhibited significantly higher VDC-derived structural heterogeneity measure, D1 (0.680 ± 0.100 × 10-3 vs 0.572 ± 0.148 × 10-3 mm2/s, p = 0.001) and lower apparent diffusion coefficient (ADC) (1.350 ± 0.166 × 10-3 vs 1.471 ± 0.322 × 10-3 mm2/s, p = 0.0495) compared to MVI-negative HCCs. No statistical significance was observed for VDC-derived diffusion coefficient, D0 between the subgroups (p = 0.562). Tumor size (odds ratio (OR) = 1.242) and alpha-fetoprotein (AFP) (OR = 2.527) were identified as risk factors for MVI. A predictive nomogram was constructed based on D1, ADC, tumor size, and AFP, which exhibited the highest diagnostic accuracy (AUC = 0.817), followed by D1 (AUC = 0.753) and ADC (AUC = 0.647). The diagnostic performance of the nomogram-based model was also validated by the calibration curve and decision curve. CONCLUSION: VDC can aid in the noninvasive and preoperative diagnosis of HCC with MVI, which may result in the clinical benefit in terms of prognostic prediction and clinical decision-making.