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Purpose: This study compared survival and metastasis occurrence between colorectal neuroendocrine neoplasms (cNEN) and colorectal adenocarcinoma with neuroendocrine differentiation (cNED) and further explored their prognostic factors and treatment indicators. Methods: Patients diagnosed as cNEN and cNED in West China Hospital from January 2009 to December 2020 were enrolled. The diagnosis and metastasis rates were calculated. Univariate and multivariate Cox analyses were conducted for progression-free survival (PFS) in cNEN surgical patients, and generalized linear regression was used for metastatic disease. Result: The study enrolled 435 patients, including 257 neuroendocrine tumors (NET), 52 neuroendocrine carcinomas (NEC), 29 mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN), and 97 NED patients, of whom 202 received local resection, and 233 received radical resection. Metastasis rates were higher in MiNEN and NEC groups compared to other groups (NED: 28.9%, MiNEN: 58.6%, NEC: 65.4%, NET: 8.6%, p < 0.001). The liver is the main metastatic site in cNEN, whereas cNED metastasized to various sites. For NEC and MiNEN patients, colon location (p = 0.002) and T stage > 2 (p = 0.040) were associated with disease progression separately. Independent risk factors for metastatic NET included tumor grade G2/G3 (p < 0.001), colon location (p = 0.001), size ≥ 1 cm (p = 0.005), and CK20 partial positive (p < 0.001). Conclusion: cNEN show high metastatic capacity and are challenging to diagnose. More aggressive treatment and follow-up strategies are necessary for those patients. NET tumor grade higher than G2, size larger than 1 cm, or located in the colon should be managed with radical surgery. [ABSTRACT FROM AUTHOR]

The success of deep learning (DL) relies heavily on training data from which DL models encapsulate information. Consequently, the development and deployment of DL models expose data to potential privacy breaches, which are particularly critical in data-sensitive contexts like medicine. We propose a new technique named DiffGuard that generates realistic and diverse synthetic medical images with annotations, even indistinguishable for experts, to replace real data for DL model training, which cuts off their direct connection and enhances privacy safety. We demonstrate that DiffGuard enhances privacy safety with much less data leakage and better resistance against privacy attacks on data and model. It also improves the accuracy and generalizability of DL models for segmentation and classification of mediastinal neoplasms in multi-center evaluation. We expect that our solution would enlighten the road to privacy-preserving DL for precision medicine, promote data and model sharing, and inspire more innovation on artificial-intelligence-generated-content technologies for medicine. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the value of CT radiomics combined with radiological features in predicting pathological grade of stage I invasive pulmonary adenocarcinoma (IPA) based on the International Association for the Study of Lung Cancer (IASLC) new grading system. Methods: The preoperative CT images and clinical information of 294 patients with stage I IPA were retrospectively analyzed (159 training set; 69 validation set; 66 test set). Referring to the IASLC new grading system, patients were divided into a low/intermediate-grade group and a high-grade group. Radiomic features were selected by using the least absolute shrinkage and selection operator (LASSO), the logistic regression (LR) classifier was used to establish radiomics model (RM), clinicalradiological features model (CRM) and combined rad-score with radiological features model (CRRM), and visualized CRRM by nomogram. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the performance and fitness of models. Results: In the training set, RM, CRM, and CRRM achieved AUCs of 0.825 [95% CI (0.735-0.916)], 0.849 [95% CI (0.772-0.925)], and 0.888 [95% CI (0.819-0.957)], respectively. For the validation set, the AUCs were 0.879 [95% CI (0.734-1.000)], 0.888 [95% CI (0.794-0.982)], and 0.922 [95% CI (0.835-1.000)], and for the test set, the AUCs were 0.814 [95% CI (0.674-0.954)], 0.849 [95% CI (0.750-0.948)], and 0.860 [95% CI (0.755-0.964)] for RM, CRM, and CRRM, respectively. Conclusion: All three models performed well in predicting pathological grade, especially the combined model, showing CT radiomics combined with radiological features had the potential to distinguish the pathological grade of early-stage IPA. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer stands as one of the most prevalent malignancies globally, conventional endoscopic specimens have been the primary means of diagnosing preoperative gastric histopathology, however, their limitations in capturing intra-tumor heterogeneity compromise their efficacy in evaluating angiogenesis. Perfusion Computed Tomography (P-CT) emerges as a pivotal functional imaging modality, facilitating objective assessment of tissue perfusion, serving as a marker of angiogenesis. So, our research objective was to evaluate the efficacy of CT perfusion imaging in the prediction of histological grades of gastric tumors using quantitative perfusion parameters such as permeability surface (PS), blood flow (BF), mean transient time (MTT), and blood volume (BV), in addition to the qualitative scoring system then comparing the findings with the histopathological results. Results: PS and BF were statistically significant predictors of the grade of differentiation, their odds ratio (OR) was (1.05, 95% CI 1.02–1.09, for each of them) (P = 0.004, P = 0.009, respectively). MTT also emerged as a significant predictor of the grade of differentiation with an OR of 0.76 (95% CI 0.57–0.93, P = 0.025). Using multivariate logistic regression model, PS was the most potent individual P-CT predictor of differentiation of the grade and the diagnosis of poorly differentiated tumors at ≥ 39 mL/100 g/min cut off point, followed by BF at ≥ 82.2 mL/100 g/min, and MTT at < 8.4 s. Regarding the qualitative scoring system P-CT, poorly differentiated tumors generally received higher scores of PS (P < 0.001), BF (P < 0.001), and BV (P = 0.017), than well and moderately differentiated tumors, however, MTT showed that poorly differentiated tumors were more frequently scored as low compared to well and moderately differentiated tumors (P < 0.001). Conclusions: P-CT is an innovative, non-invasive biomarker for predicting gastric cancer grade by quantitative and qualitative assessment by P-CT parameters (PS, BF and MTT) with particular role of PS as the strongest individual P-CT predictor of differentiation grade followed by BF and MTT at specific cut off points. [ABSTRACT FROM AUTHOR]

Background: Enhancing the prognosis and treatment outcomes of oral cancer relies heavily on its early detection. This study aims to establish a connection between serum and salivary dipeptidyl peptidase-4 (DPP-4) levels and oral squamous cell carcinoma (OSCC), comparing them with oral potentially malignant lesions (OPMLs) and control subjects and validating salivary DPP-4 as a diagnostic marker for the early detection of oral cancer. Methodology: Forty-five systemically healthy individuals were categorized into three groups: Group I consisted of 15 patients diagnosed with OSCC, Group II comprised 15 patients with OPMLs (including leukoplakia and oral lichen planus), and Group III included 15 participants without any oral mucosal lesions. Serum and whole unstimulated salivary samples were collected from all participants to assess DPP-4 levels using an enzyme-linked immunosorbent assay (ELISA) kit. Receiver operating characteristic (ROC) analysis was conducted to determine the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy of DPP-4. Results: Both serum and salivary DPP-4 levels were highest in the healthy group, followed by OPMLs, and lowest in the OSCC group, with statistically significant differences observed. ROC analysis demonstrated excellent diagnostic accuracy of salivary DPP-4 in distinguishing OSCC from healthy individuals, OPMLs from healthy individuals, and OSCC from OPMLs, with accuracies of 100%, 100%, and 96.67%, respectively. Salivary DPP-4 levels also exhibited a statistically significant correlation with OSCC grades. Conclusions: DPP-4 appears to play a protective, anti-oncogenic role in maintaining oral tissue health. The remarkable diagnostic accuracy of both serum and salivary DPP-4 in discriminating between OSCC, OPMLs, and healthy controls suggests its potential utility as a well-established marker for early oral cancer diagnosis. Salivary DPP-4, being non-invasive, could serve as a convenient chair-side diagnostic tool for the early detection of OSCC. Clinical trial registration: The study was retrospectively registered on clinicaltrial.gov with NCT06087042, date of registration (first posted date): 17/10/2023 [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Materials and Methods Results Conclusions This study aimed to develop and internally validate a prognostic nomogram for predicting nodal recurrence‐free survival (NRFS) in patients with early‐stage oral squamous cell carcinoma (OSCC) with clinically negative neck lymph nodes.The management of early‐stage oral cancer patients with clinically negative neck lymph nodes (cN0) remains controversial, especially concerning the need for elective neck dissection. Data from a single institution spanning 2010 to 2020 were utilized to develop and evaluate the nomogram. The nomogram was constructed using multivariable Cox regression and LASSO regression analyses to identify independent risk factors for lymph node metastasis. Internal validation was performed using bootstrap resampling to assess the nomogram's predictive accuracy.A total of 930 cN0 patients with T1 and T2 stage OSCC were randomly divided into training and validation cohorts (8:2 ratio). Independent risk factors for lymph node metastasis included tumor pathological grade (well: reference, moderate/poor: OR 1.69), cT (cT1: reference, cT2: OR 2.01), history of drinking (never: reference, current/former: OR 1.72), and depth of invasion (0 mm < DOI ≤ 5 mm: reference, 5 mm < DOI ≤ 10 mm: OR 1.31). The nomogram, incorporating these variables, demonstrated good predictive accuracy with a C‐index of 0.67 (95% CI: 0.58–0.76) in the validation set. In both training and validation groups, the nomogram effectively stratified patients into low‐risk and high‐risk groups for occult cervical nodal metastases (p < 0.05).The nomogram enables risk stratification and improved identification of occult cervical nodal metastases in clinically node‐negative OSCC patients by incorporating tumor‐specific and patient‐specific risk factors. [ABSTRACT FROM AUTHOR]

The current research on geriatric patients with spinal chondrosarcoma is limited. This study aimed to investigate the demographics, patterns of care, and survival of geriatric patients with chondrosarcoma of the mobile spine. The National Cancer Database was queried from 2008 to 2018 for geriatric patients (60–89 years) with chondrosarcoma of the mobile spine. The primary outcome of this study was overall survival. The secondary outcome was treatment utilization patterns. Survival analyses were conducted using log-rank tests and Cox proportional hazards regressions. Logistic regression models were utilized to assess correlations between baseline variables and treatment utilization. The database retrieved 122 patients. While 43.7% of the patients presented with tumors exceeding 5 cm in size, the incidence of regional lymph node involvement or distant metastases was relatively low, affecting only 5% of the patients. Furthermore, 22.3% of the patients had tumors graded as 3–4. The 5-year overall survival rate was 52.9% (95% confidence interval: 42–66.6). The mortality risk was significantly associated with age, tumor grade and stage, and treatment plan. Most patients (79.5%) underwent surgery, while 35.9% and 4.2% were treated with radiotherapy and chemotherapy, respectively. Age, race, comorbidities, geographical region, tumor stage, and healthcare facility type significantly correlated with treatment utilization. Surgical resection significantly lowered the mortality risk in geriatric patients with spinal chondrosarcomas. Demographic and geographical factors significantly dictated treatment plans. Further studies are required to assess the role of radiotherapy and chemotherapy in treating these patients in the modern era. [ABSTRACT FROM AUTHOR]

The classification and management of neuroendocrine neoplasms (NENs) arising in the tubular gastrointestinal (GI) tract and pancreas have significantly evolved over the last decades. In the latest WHO classification published in 2022, NENs are separated regardless of their primary origin into two main groups: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The substantial changes in the grading system changed the definition of grade 3 to include high-grade well-differentiated NETs (G3-NETs), and poorly differentiated NECs (-NECs). Although these two subgroups are considered high grades with Ki-67 >20%, they have different genomic profiles, prognosis, and clinical behavior, which critically influence their treatment strategies. The available clinical trial data to guide therapy of these high-grade subgroups are extremely limited, which impacts their management. In this review, we will summarize the current advances in the multidisciplinary approach for the management of high-grade gastroenteropancreatic NENs (GEP-NENs) including G3-NETs and NECs. [ABSTRACT FROM AUTHOR]

Background: In response to the COVID-19 pandemic, the European Association of Urology (EAU) Guidelines defined priority groups to guide the prioritization of surgery for urological malignancies. The objective of this study was to evaluate the impact of the COVID-19 prioritization recommendations on tumor pathological characteristics in a real-world setting at our academic referral institution. Methods: We compared baseline and pathological tumor features of all patients with urological malignancies treated during the pandemic period (2020–2021) versus in the post-pandemic period (2022–2023). Our institution adhered to the international recommendations and prioritized those cases defined as "high-risk". Results: Data from 9196 patients treated for urological malignancies were reviewed and grouped according to period of surgery (4401 in the pandemic period vs. 4785 in the post-pandemic period). The overall number of surgical procedures was comparable for all diseases except for the number of radical prostatectomies (1117 vs. 1405; p = 0.03) and partial nephrectomies (609 vs. 759; p = 0.02), which were significantly lower in the pandemic period. Regarding tumor pathological features, none of the recorded variables were found to differ according to period of surgery, including disease stage, tumor grading, presence of necrosis, lymphovascular invasion, and histological variants. Conclusions: A correct policy of prioritization of oncological pathologies during emergency periods and a centralization of oncological cases in reference centers reduce the possible risk of worsening cancer disease features related to the reorganization of healthcare resources. [ABSTRACT FROM AUTHOR]

Background: Chondrosarcomas (CS) are a rare and heterogenic group of primary malignant bone tumors. In the literature, data on prognostic factors in chondrosarcomas are scarce, and most studies are limited by a short follow-up. The aim of this retrospective study was therefore to determine factors associated with the survival and local recurrence of chondrosarcomas and to compare the results with previous studies. Methods: We retrospectively evaluated 77 patients who were treated for chondrosarcoma of the extremities or pelvis at our tertiary sarcoma center between 1998 and 2007. Patient-related data (age, sex, etc.), tumor characteristics (localization, grading, presence of metastases, etc.), and treatment-related data (previous surgical treatment, type of local treatment, surgical margins, etc.) were evaluated and analyzed for possible correlation with patients' outcomes. A statistical analysis was performed, including multivariate analysis. Results: The mean survival in our patients was 207 months, which resulted in a five-year survival rate of 76%. Negative prognostic factors for survival were histopathological grading, a patient aged over 70 years, and metastatic disease. The quality of the resection (clear or contaminated margins) negatively influenced both the development of local recurrence and survival too, at least in the univariate analysis. In contrast, factors such as tumor localization (extremities vs. pelvis), pathological fractures, or an initial inadequate resection elsewhere had no significant effect on survival. Conclusions: In accordance with results in the literature, the survival of patients with chondrosarcomas is mainly influenced by factors such as tumor grading, age, and metastases. However, complete resection remains paramount for the outcome in patients with chondrosarcoma—a primary malignant bone tumor with limited alternative treatment options. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (HNSCC) are among the most common malignancies in men worldwide. Nevertheless, their clinical management is hampered by the limited availability of reliable predictive and prognostic biomarkers. Protein kinase D (PKD) isoforms contribute to major cellular processes. However, their potential role in HNSCC has not been studied systematically, which is the focus of this study. A total of 63 therapy-naive patients with squamous cell carcinoma were consecutively enrolled. Tissue microarray duplicate cores from each case were tested in situ for PKD1, PKD2, and PKD3 expression using immunohistochemistry, and the results were correlated with clinicopathological parameters. We found a high frequency of PKD1/PKD2 positive cases in oropharyngeal and PKD2 positive cases in laryngeal localizations. Only high PKD2 levels were statistically linked to elevated tumor grades, more advanced TNM (3–4) tumor stages, and p16INK4a expression, while elevated PKD3 levels were associated with favorable disease-specific survival. Both PKD2 and PKD3 have been proposed to promote tumor cell proliferation, migration/invasion, and angiogenesis. However, the role of PKD3 was elusive in some cancers. Our findings suggest that testing for PKD isotypes with immunohistochemistry may support the diagnostic estimation of tumor progression and prognosis in HNSCC with a potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied how different types of high-risk human papillomavirus (HR-HPV) are distributed in early and advanced precancerous cervical lesions to better understand cervical cancer risks. A total of 559 cases were analyzed with results from a diagnostic test for HR-HPV and a special immunostaining method (DS) that helps identify cervical precancer potential that could enhance the effectiveness of the secondary cervical cancer prevention The investigation included a corresponding histology result from a colposcopic biopsy. The study found significant differences in the presence of HPV 16 and positive staining results between advanced lesions and those that were either negative or less severe. However, no significant difference was found between negative and less severe lesions. This study highlights the importance of understanding HPV type distribution and the use of dual staining in detecting and assessing the risk of cervical precancers. Background: Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Methods: Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ2 test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. Results: A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. Conclusions: The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status. [ABSTRACT FROM AUTHOR]

Simple Summary: Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma have potential to serve as an alternative for non-invasive Gleason score characterization, for the prediction of biochemical recurrence and to differentiate benign from malignant increased tracer uptake. However, prior to their implementation in clinical practice, additional, clinically relevant studies performed according to recently published guidelines and checklists, offering full transparency, including large enough datasets as well as external validation, are mandatory. Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following 177Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Improved outcomes have been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative breast cancer, regardless of age. In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. A higher discontinuation rate for abemaciclib was reported in patients ≥65 years and it can be assumed that discontinuation rates may increase with more older patients. If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population. Background: Despite early diagnosis, approximately 20% of patients with ER-positive and HER2-negative breast cancer (BC) will experience disease recurrence. Improved survival has been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative BC, regardless of age. Older patients have higher rates of ER-positive/HER2-negative BC than younger patients. Methods: In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. Results: Eligibility rates in patients ≤40 years and >80 years who underwent mastectomy were 27.8% and 24.7% for abemaciclib, respectively, and 56.6% and 65.2% for ribociclib, respectively. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. Conclusions: If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is mainly found in Southeast Asia and North Africa. Most patients with NPC are diagnosed at an advanced stage, which increases the risk of recurrence and metastasis. A cohort of 41 NPC tumor samples from Morocco and North Africa were analyzed using shotgun proteomics. Within the cohort, three proteomically defined clusters were identified. We also examined sex and stage differences from a proteomic perspective. In total, 59 and 26 differentially abundant proteins were identified between male and female patients and patients with early and advanced stages within the cohort. Data were then compared to 21 healthy controls from a prior study. Across the two datasets, 6532 proteins were identified, of which 1507 proteins were differentially abundant between patients and controls. Differentially abundant proteins between tumor and healthy samples included PI3K, MAPK, BCL2, and PPIA proteins, which are involved in various biological pathways related to cell proliferation and growth. This study lays a foundation for both mechanistic and biomarker studies into NPC in Morocco and North African populations. Background: Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck that is highly prevalent in Southeast Asia and North Africa. Though an extensive analysis of environmental and genetic contributors has been performed, very little is known about the proteome of this disease. A proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissues can provide valuable information on protein expression and molecular patterns for both increasing our understanding of the disease and for biomarker discovery. To date, very few NPC proteomic studies have been performed, and none focused on patients from Morocco and North Africa. Methods: Label-free Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) was used to perform a proteomic analysis of FFPE tissue samples from a cohort of 41 NPC tumor samples of Morocco and North Africa origins. The LC-MS/MS data from this cohort were analyzed alongside 21 healthy controls using MaxQuant 2.4.2.0. A differential expression analysis was performed using the MSstats package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations were carried out using the DAVID bioinformatic tool. Results: 3341 proteins were identified across our NPC cases, revealing three main clusters and five DEPs with prognostic significance. The sex disparity of NPC was investigated from a proteomic perspective in which 59 DEPs were found between males and females, with significantly enriched terms associated with the immune response and gene expression. Furthermore, 26 DEPs were observed between patients with early and advanced stages of NPC with a significant cluster related to the immune response, implicating up-regulated DEPs such as IGHA, IGKC, and VAT1. Across both datasets, 6532 proteins were quantified between NPC patients and healthy controls. Among them, 1507 differentially expressed proteins (DEPs) were observed. GO and KEGG pathway analyses showed enriched terms of DEPs related to increased cellular activity, cell proliferation, and survival. PI3K and MAPK proteins as well as RAC1 BCL2 and PPIA were found to be overexpressed between cancer tissues and healthy controls. EBV infection was also one of the enriched pathways implicating its latent genes like LMP1 and LMP2 that activate several proteins and signaling pathways including NF-Kappa B, MAPK, and JAK-STAT pathways. Conclusion: Our findings unveil the proteomic landscape of NPC for the first time in the Moroccan population. These studies additionally may provide a foundation for identifying potential biomarkers. Further research is still needed to help develop tools for the early diagnosis and treatment of NPC in Moroccan and North African populations. [ABSTRACT FROM AUTHOR]

Objectives: To compare the clinicopathological, molecular, and immune features of conventional and high‐grade transformation (HGT) secretory carcinoma (SC) in salivary glands. Materials and Methods: The clinicopathological data of 88 cases including 74 conventional SCs and 14 SCs with HGT were reviewed. Targeted next‐generation sequencing was performed in 11 SCs with HGT and 7 conventional SCs. The level of PD‐L1 and CD8+ TILs was determined by immunohistochemistry. Results: Compared with the conventional group, the rates of nodal metastasis, local recurrence, distant metastasis and mortality were significantly higher in the HGT cohort. Mutations of ARID1A/B, KMT2A, HOXD13, NRG1 and ETV6 genes were identified in HGT SCs. A recurrent E307G mutation in GATA6 gene was also observed in two cases. Two deceased HGT patients with distant metastasis harboured NOTCH3 mutations. ETV6‐RET translocation was prone to occur in the HGT SCs. Additionally, PD‐L1 expression was low, and CD8+ TILs were sparse in most HGT cases. Conclusion: Our findings reveal novel gene alterations involved in the progression of HGT in SCs. Most HGT SCs patients cannot benefit from PD‐L1 blocking and may be approached with a distinct treatment strategy including the lymph node dissection and application of molecular target drugs in precision oncology. [ABSTRACT FROM AUTHOR]

Background: The association between surgical performance ratings and clinical outcomes in robotic surgery is poorly understood. Additionally, no studies have reported on the relationship between the surgeon's initial case-skill evaluation and the learning curve in robot-assisted surgery. We evaluated whether an objective surgical technique evaluation score for initial robot-assisted radical prostatectomy (RARP) was associated with clinical outcomes and surgeons' learning curves. Methods: Six surgeons who were trained in and started to perform RARP at our institution were included. Anonymized, unedited videos of each surgeon's 10th RARP case were evaluated by three reviewers, using modified Objective Structured Assessment of Technical Skill (OSATS) scores. We then divided the surgeons into two groups on the basis of these OSATS scores. We retrospectively compared the clinical outcomes and learning curves of the console time of the two groups for consecutive RARPs, performed from March 2018 to July 2023. Results: We analyzed 258 RARPs (43 cases/surgeon), including 129 cases performed by high-OSATS score surgeons (18.2–19.3 points) and 129 cases performed by low-OSATS score surgeons (11.9–16.0 points). Overall, the high-OSATS score group had significantly shorter operation and console times than the low-OSATS score group did (both P < 0.01) and their patients' rate of continence recovery by 3 months post-RARP was significantly higher (P = 0.03). However, complications, blood loss, and positive margins did not differ between the groups (P = 0.08, P = 0.51, and P = 0.90, respectively). The high-OSATS score group had a significantly shorter console time than the low-OSATS score group did after the 11–20 cases. Conclusions: The OSATS score in early RARP cases can predict subsequent surgical outcomes and surgeons' learning curves. [ABSTRACT FROM AUTHOR]

Endoscopic endonasal Trans-sphenoidal surgery for sellar-suprasellar tumors is considered the preferred route. The ideal instruments in skull base surgery should be able to manipulate adequately through the narrow corridors with effective tissue removal and bleeding control and reduce collateral damage to nearby vital structures. The present study sought to compare the nasal morbidity following transnasal sphenoidal surgery for pituitary macroadenoma using Coblation and Electrocautery. 160 undergoing Endoscopic TSS for non-functioning PAs were enrolled. The patients were randomly allocated into Coblation (n = 80) and electrocautery (n = 80) groups. All operations were performed by the same group of surgeons skilled in their surgical techniques. There were 59 and 53 patients with Knosp grade II tumors in the cautery and coblation group, respectively, while 21 and 27 patients had Knosp grade III tumors. The average duration of surgery using cautery was 96+/-4.5 min, while with coblation, the average time was 83+/-3.5 min, and the difference was statistically significant. Nasal crusting and granulation severity were observed more in the electrocautery group. The coblation group patients had clear surgical fields with few ooze points; the difference between the two groups was significant. Nasal synechiae and decreased nasal patency were common in the electrocautery group. There were no statistical differences in nasal bleeding, nasal deformity, or sense of smell parameters. Advanced medical tools like coblation are safe and effective for the dissection and ablation of the mucosa. They result in better intra-operative visualization and lesser postoperative nasal morbidity, which will help patients achieve a better quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Anaplastic meningiomas, categorized as WHO grade 3 tumors, are rare and highly aggressive, accounting for 1-2% of all meningioma cases. Despite aggressive treatment, including surgery and Radiation, they exhibit a high recurrence rate and poor survival outcomes. The aggressive histopathological features emphasize the urgent need for effective management strategies. Methods: A retrospective multi-institutional analysis was conducted on patients with recurrent anaplastic meningioma who underwent re-irradiation between 2017 and 2023. Clinical, dosimetric, and outcome data were collected and analyzed, focusing on local control, progression free survival and treatment-related adverse events. Results: Thirty-four cases were analyzed, with a median follow-up 11 months after re-irradiation. Progression-free survival at 12 months was 61.9%, with higher doses correlating with better outcomes. Concomitant Bevacizumab improves progression-free survival and reduces the risk of radiation necrosis. CDKN2A homozygote deletion correlated with a higher risk of local failure. Symptomatic radiation necrosis occurred in 20.5% of cases, but its incidence was lower with concomitant Bevacizumab treatment. Conclusion: Re-irradiation presents a viable option for recurrent anaplastic meningioma despite the associated risk of radiation necrosis. Higher doses with concomitant Bevacizumab improve clinical outcomes and reduce toxicity. Individualized treatment approaches are necessary, emphasizing the importance of further research to refine management strategies for this challenging disease. [ABSTRACT FROM AUTHOR]

Context.--The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. Objective.--To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. Design.--A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. Results.--Among 35 pathologists, the k statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathol-ogists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. Conclusions.--We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules. [ABSTRACT FROM AUTHOR]

Objective: We reviewed our institutional experience of radical prostatectomy with and without preoperative multiparametric magnetic resonance imaging (mpMRI) to assess the impact of preoperative prostate mpMRI on surgical outcomes of radical prostatectomy. Methods: We identified patients at our institution who underwent radical prostatectomy for prostate cancer (PCa) between January 2012 and December 2017 ( n = 1044). Using propensity scoring analysis, patients who underwent preoperative mpMRI (n = 285) were matched 1:1 to patients who did not receive preoperative mpMRI (n = 285). Multivariable regression analysis was performed to identify factors predictive of operative time, estimated blood loss (EBL), lymph node yield, rates of complications within 30 days, and positive surgical margin (PSM). Results: There were no significant differences in operative time, EBL, PSM, lymph node yield, or complication rates between the two cohorts. Multivariable analysis demonstrated that preoperative mpMRI was not predictive of the measured perioperative outcomes. Significant comorbidity (Charlson Comorbidity Index ≥3) was the sole predictor of perioperative complications ( P = 0.015). Increasing biopsy Gleason score predicted increased lymph node yield (P < 0.001). The probability of PSM was associated with increasing preoperative prostate-specific antigen (odds ratio 1.036, P = 0.009). Body mass index was a predictor of operative time (P = 0.016) and EBL (P = 0.001). Conclusions: Although preoperative mpMRI has an important role in the diagnosis and staging of PCa, it does not impact perioperative radical prostatectomy outcomes. Our findings do not support the routine use of preoperative mpMRI for surgical planning in patients already diagnosed with clinically localized PCa. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is one of the most common cancers in the world and is associated with high treatment costs and mortality. The role of different enzymes and molecules in this cancer has been the subject of extensive research in recent years. Among these, the role of metabolic enzymes such as FASN and LDH has been studied less than others. Therefore, the present study was designed to investigate the role of FASN and LDH in bladder cancer patients. Methods: One hundred cases diagnosed with bladder cancer and 50 sex-age-matched healthy individuals as control were examined. FASN and LDH serum levels in both patients and controls were determined by human-specific sandwich ELISA kits. Results: Serum levels of FASN and LDH elevated in bladder cancer patients in comparison to healthy individuals (P= 0.03, P= 0.01, respectively). We also found that than higher stages of bladder cancer (III-IV) had higher serum levels of LDH and FASN compared to early stages (I-II) (P= 0.007 and P= 0.006, respectively). Moreover, there was a statistically significant association between smoking history and serum FASN levels in bladder cancer patients (P=0.015). However, there were no remarkable associations between the serum levels of LDH and FASN with other clinicopathological features including sex, age, tumor grade, and tumor size. Conclusion: The data indicate that LDH and FASN may be good and useful biomarkers in the diagnosis and clinical management of bladder cancer. However, further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. Research design and methods: Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. Result: We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05). Conclusion: Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making. [ABSTRACT FROM AUTHOR]

Backgrounds. Glioma stands as one of the most formidable brain tumor types, with patient outcomes remaining bleak even in the face of advancements in treatment modalities. FBXW4, a constituent of the F‐box and WD repeat domain‐containing protein family, is recognized for its participation in diverse cellular activities, including those related to tumor dynamics. Yet, the therapeutic relevance and specific role of FBXW4 in the context of glioma are not well defined. This study aims to elucidate the functional dynamics and significance of FBXW4 in glioma cases. Methods. This research undertook a comprehensive analysis of FBXW4's expression patterns and clinical relevance in glioma by harnessing data from the TCGA and GTEx databases. Results. The investigation revealed a distinct downregulation of FBXW4 in glioma tissues compared to normal brain counterparts, with a pronounced correlation between FBXW4 levels and disease severity. Intriguingly, FBXW4 expression inversely related to WHO tumor grades, with the most advanced grade IV gliomas exhibiting the lowest FBXW4 levels, whereas grade II tumors demonstrated the highest. Cases presenting with IDH1/2 mutations or 1p/19q codeletions were also associated with elevated FBXW4 levels. Furthermore, diminished FBXW4 expression aligned with an increased risk of mortality. Conclusions. The findings suggest that FBXW4 holds promise as a prognostic marker and a potential therapeutic avenue in glioma management. Nonetheless, future research is imperative to decode the intricate signaling pathways involving FBXW4 and to understand its broader clinical ramifications in glioma treatment paradigms. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. Methods: A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. Results: Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19–53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13–72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6–12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). Conclusions: Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. Level of evidence: level IV Therapeutic. [ABSTRACT FROM AUTHOR]

Purpose Experimental design Results Conclusions Prior studies testing the association between insulin resistance (IR) and prostate cancer (PC) risk are inconsistent. We examined the association between Homeostatic Assessment of Insulin Resistance (HOMA‐IR; calculated from fasting baseline insulin and glucose) and PC in REDUCE, a 4‐year randomized trial of dutasteride vs. placebo for PC prevention.All patients had prestudy negative biopsies and underwent study mandated biopsies at 2 and 4 years regardless of prostate‐specific antigen. Multivariable logistic regression models were used to investigate the associations between log‐transformed or categorized HOMA‐IR scores and PC risk. Multinominal regression was used to assess associations between HOMA‐IR scores and tumor grade (low grade [grade group 1]; high‐grade [grade groups 2–5]).Among 5430 REDUCE participants (1212 with PC; 856 low‐ and 356 high‐grade), higher HOMA‐IR was associated with lower PC risk (log‐HOMA‐IR: OR, 0.89; 95% CI, 0.80–0.99; p = .03; categorized HOMA‐IR: p‐trend = .04). When stratified by grade, HOMA‐IR was significantly associated with reduced low‐grade PC risk (log‐HOMA‐IR: OR, 0.84; 95% CI , 0.74–0.94; p = .003; categorized HOMA‐IR: p‐trend = .002) but was unrelated to high‐grade PC (log‐HOMA‐IR: OR, 1.02; 95% CI, 0.86–1.21; p = .81; categorized HOMA‐IR: p‐trend = .26). Results were similar in placebo and treatment arms.In summary, higher HOMA‐IR was associated with a reduced risk of low‐grade PC but was not associated with high‐grade disease. The mechanisms to explain these findings are unclear. [ABSTRACT FROM AUTHOR]

Background: Traditional survival analysis is frequently used to assess the prognosis of ependymomas (EPNs); however, it may not provide additional survival insights for patients who have survived for several years. Thus, the conditional survival (CS) pattern of this disease is yet to be further investigated. This study aimed to evaluate the improvement of survival over time using CS analysis and develop a CS-based nomogram model for real-time dynamic survival estimation for EPN patients. Methods: Data on patients with EPN were collected from the Surveillance, Epidemiology, and End Results (SEER) database. In order to construct and validate the model effectively, the selected patients were randomly divided at 7:3 ratio. CS is defined as the probability of surviving for a specified time period (y years) after initial diagnosis, given that the patient has survived x years. The CS pattern of EPN patients were explored. Then, the least absolute shrinkage and selection operator (LASSO) regression method with tenfold cross-validation was employed to identify prognostic predictors. Multivariate Cox regression was employed to develop a CS-based nomogram model, and we used this model to quantify EPN patient risk. Finally, the performance of the prediction model was also evaluated and verified. Results: In total, 1829 patients diagnosed with EPN were included in the study, with 1280 and 549 patients in the training and validation cohorts, respectively. The CS analysis demonstrated that patients' OS saw gradual improvements over time. With each additional year of survival post-diagnosis, the 10-year survival rate of EPN patients saw an increase, updating from 74% initially to 79%, 82%, 85%, 87%, 89%, 91%, 93%, 96%, and 98% (after surviving for 1–9 years, respectively). The LASSO regression model, which implements tenfold cross-validation, identified 7 significant predictors (age, tumor grade, tumor site, tumor extension, tumor size, surgery and radiotherapy) to develop a CS-based nomogram model. And further risk stratification was conducted based on nomogram model for these patients. Furthermore, this survival prediction model was successfully validated. Conclusion: This study described the CS pattern of EPN patients and highlighted the gradual improvement of survival observed over time for long-term survivors. We also developed the first novel CS-nomogram model that enabled individualized and real-time prognosis prediction. But patients must be counselled that individual circumstances may not always accurately reflect the findings of the nomogram. [ABSTRACT FROM AUTHOR]

Objective: High-risk neuroblastoma patients often have poor outcomes despite multi-treatment options. The risk stratification of high-risk MYCN-not-amplified (HR-MYCN-NA) patients remains difficult. This study aims to identify a gene set signature that can help further stratify HR-MYCN-NA patients for a potential personalized therapeutic strategy. Methods: Three microarrays and one single-cell RNA sequence dataset were acquired and analyzed. Firstly, the prognostic-related genes (PRGs) in HR-MYCN-NA tumor cells were identified using TARGET-NB and GSE137804 datasets. Then, the prognostic model was established by LASSO-Cox regression, and verified in external cohort (GSE49710, GSE45547). Moreover, a time-dependent receiver operating characteristic curve (ROC) and area under the ROC (AUC) was used to assess survival prediction. A nomogram was established to predict the 1-, 3- and 5-year overall survival (OS) of HR-MYCN-NA patients. Results: In the training set, a five-PRGs signature, which include GAL, GFRA3, MARCKS, PSMD13, and ZNHIT3 genes, was identified and successfully stratified HR-MYCN-NA patients into ultra-high risk (UHR) and high-risk (HR) subtypes (HR = 4.29, P < 0.001). ROC curve analysis confirmed its predictive power (AUC = 0.74–0.82), suggesting a good predictive efficacy. Consistently, high-risk scores also predicted worse OS (HR = 2, P = 0.033) in the external validation dataset (AUC = 0.67–0.71). Moreover, the overall C-index of the nomogram was 0.75 (P < 0.001), which indicated good agreement between the observed and predicted survival rates. Further integrating the five PRGs signature with clinical factors, these 5 gene signature (HR = 4.45, P < 0.001) and tumor grade (HR = 4.15, P = 0.02) were found to be independent prognostic factors for HR-MYCN-NA patients. Conclusion: The novel five PRGs signature could well predict the survival of HR-MYCN-NA patients, which may provide constructive information for these subsets. [ABSTRACT FROM AUTHOR]

Background: Malignant tumors represent a significant pathology with a profound global impact on the medical system. The fight against cancer represents a significant challenge, with multidisciplinary teams identifying numerous areas requiring improvement to enhance the prognosis. Facilitating the patient's journey from diagnosis to treatment represents one such area of concern. One area of research interest is the use of various biomarkers to accurately predict the outcome of these patients. A substantial body of research has been conducted over the years examining the relationship between C-reactive protein (CRP) and malignant tumors. The existing literature suggests that combining imaging diagnostic modalities with biomarkers, such as CRP, may enhance diagnostic accuracy. Methods: A systematic review was conducted on the PubMed and Web of Science platforms with the objective of documenting the interrelationship between CRP value and tumor grading for malignant tumors. After the application of the exclusion and inclusion criteria, 17 studies were identified, published between 2002 and 2024, comprising a total of 9727 patients. Results: These studies indicate this interrelationship for soft tissue sarcomas and for renal, colorectal, esophageal, pancreatic, brain, bronchopulmonary, ovarian, and mesenchymal tumors. Conclusions: Elevated CRP levels are correlated with higher grading, thereby underscoring the potential utility of this biomarker in clinical prognostication. [ABSTRACT FROM AUTHOR]

Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with high-grade gliomas have a poor prognosis, with a median survival of only 11–18 months from the initial diagnosis after standard treatment. Surgery and chemoradiation are the first-line treatment strategies for malignant gliomas, but achieving durable local tumor control is a major challenge due to the pervasive infiltrative nature of gliomas, their growth rate, and their recurrence rate. Gadolinium-enhanced magnetic resonance imaging (MRI) is currently the primary imaging technique for high-grade gliomas; however, it has limitations, including difficulty in differentiating between tumor recurrence and treatment-induced changes, as well as challenges in accurately assessing total tumor volume due to the restricted sensitivity of gadolinium contrast. It is therefore worth looking for alternative imaging modalities that can overcome these limitations. Positron emission tomography (PET) is one of them. To this end, the identification of PET-based markers that can be used in the imaging of high-grade gliomas is of paramount importance. 11C-Methionine (MET) is a widely utilized amino acid tracer in positron emission tomography (PET) imaging of primary brain tumors. 11C-MET PET offers valuable insights for tumor classification, facilitates treatment planning, and aids in monitoring therapeutic response. Its tracer properties allow better delineation of the active tumor volume, even in regions that show no contrast enhancement on conventional magnetic resonance imaging (MRI). This review focuses on the role of MET-PET in brain glioma imaging. The introduction provides a brief clinical overview of the problems of high-grade and recurrent gliomas. It discusses glioma management, radiotherapy planning, and the difficulties of imaging after chemoradiotherapy (pseudoprogression or radionecrosis). The mechanism of MET-PET is described. Additionally, the review encompasses the application of MET-PET in the context of primary gliomas, addressing its diagnostic precision, utility in tumor classification, prognostic value, and role in guiding biopsy procedures and radiotherapy planning. [ABSTRACT FROM AUTHOR]

Simple Summary: In this contribution, we show that, at a natural abundance, the nitrogen, carbon, and sulfur isotopic compositions of uterus cancerous and healthy tissues are different due to various metabolic pathways. These differences indicate that the isotopic composition might be a potential diagnostic and prognostic biomarker. We have tried to correlate the isotopic composition of tissues with that of serum, which would give us access to noninvasive biomarkers. In this respect, the obtained bulk isotopic compositions do not show any systematic correlation between the cancerous tissue and serum. Their application as biomarkers would probably require a position-specific isotopic analysis. Objectives: The metabolic pathway of cancerous tissue differs from healthy tissue, leading to the unique isotopic composition of stable isotopes at their natural abundance. We have studied if these changes can be developed into diagnostic or prognostic tools in the case of endometrial cancer. Methods: Measurements of stable isotope ratios were performed using isotope ratio mass spectrometry for nitrogen, carbon, and sulfur isotopic assessment. Uterine tissue and serum samples were collected from patients and the control group. Results: At a natural abundance, the isotopic compositions of all three of the studied elements of uterus cancerous and healthy tissues are different. However, no correlation of the isotopic composition of the tissues with that of serum was found. Conclusions: Differences in the isotopic composition of the tissues might be a potential prognostic tool. However, the lack of a correlation between the differences in the isotopic composition of the tissues and serum seems to exclude their application as diagnostic biomarkers, which, however, might be possible if a position-specific isotopic analysis is performed. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aims to explore how specific imaging features on computed tomography (CT) scans, related to lipid metabolism, can be linked to a protein called adipose differentiation-related protein (ADFP) in clear cell renal cell carcinoma. This study suggests that tumors with higher lipid content, which can be seen as lower values on a CT scan, are associated with lower-grade, less aggressive cancers that express ADFP. This finding is significant because it could lead to non-invasive methods for evaluating tumor characteristics, potentially helping better understand the nature of the cancer and tailor treatment plans without needing invasive procedures. This study aimed to investigate the association between metabolic lipid computed tomography (CT) features and adipose differentiation-related protein (ADFP) expression in clear cell renal cell carcinoma (ccRCC), providing insights into non-invasive methods for assessing ADFP expression and tumor characteristics. This study utilized data from The Cancer Genome Atlas and the Cancer Imaging Archive to analyze genetic alterations and imaging characteristics in ccRCC patients. Tumoral Hounsfield units (HU) analysis and quantification of abdominal adipose tissue compartments were performed using CT images. Statistical analyses were conducted to compare tumoral HU values according to ADFP gene expression and World Health Organization/International Society of Urological Pathology (WHO/ISUP) tumor grade, as well as to explore correlations between tumoral HU values and adipose tissue quantification. Among the 174 identified patients, those with ADFP gene expression showed significantly lower minimum tumoral HU values in low-grade cancers compared to high-grade cancers. Similarly, patients with low-grade cancers expressing ADFP exhibited lower minimum tumoral HU values compared to those without ADFP expression. Negative correlations were observed between minimum tumoral HU values and visceral adipose tissue, subcutaneous adipose tissue, and total adipose tissue in both ccRCC patients with and without ADFP expression. This study reveals a significant association between metabolic lipid CT features and ADFP expression in ccRCC patients. Lower minimum tumoral HU values, suggestive of higher intracellular lipid accumulation, were observed in tumors with low WHO/ISUP grade and ADFP expression. [ABSTRACT FROM AUTHOR]

Background: The ASCAPE project aims to improve the health-related quality of life of cancer patients using artificial intelligence (AI)-driven solutions. The current study employs a comprehensive dataset to evaluate sleep and urinary incontinence, thus enabling the development of personalized interventions. Methods: This study focuses on prostate cancer patients eligible for curative treatment with surgery. Forty-two participants were enrolled following their diagnosis and were followed up at baseline and 3, 6, 9, and 12 months after surgical treatment. The data collection process involved a combination of standardized questionnaires and wearable devices, providing a holistic view of patients' QoL and health outcomes. The dataset is systematically organized and stored in a centralized database, with advanced statistical and AI techniques being employed to reveal correlations, patterns, and predictive markers that can ultimately lead to implementing personalized intervention strategies, ultimately enhancing patient QoL outcomes. Results: The correlation analysis between sleep quality and urinary symptoms post-surgery revealed a moderate positive correlation between baseline insomnia and baseline urinary symptoms (r = 0.407, p = 0.011), a positive correlation between baseline insomnia and urinary symptoms at 3 months (r = 0.321, p = 0.049), and significant correlations between insomnia at 12 months and urinary symptoms at 3 months (r = 0.396, p = 0.014) and at 6 months (r = 0.384, p = 0.017). Furthermore, modeling the relationship between baseline insomnia and baseline urinary symptoms showed that baseline insomnia is significantly associated with baseline urinary symptoms (coef = 0.222, p = 0.036). Conclusions: The investigation of sleep quality and urinary incontinence via data analysis through the ASCAPE project suggests that better sleep quality could improve urinary disorders. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the expression of HER2 in patients with upper tract urothelial carcinoma (UTUC) in Southwest China by using a relatively large cohort, and to determine the relationship between HER2 expression and clinicopathological characters. Materials and methods: We retrospectively enrolled the clinical data of 155 UTUC patients who have undergone radical nephroureterectomy (RNU) from March 2019 to September 2022. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest (Scores of 0 or 1 + were considered as negative and 2 + or 3 + as positive). Tumor molecular phenotype was classified by the panel of CK20, CK5/6, and CD44. Results: HER2 was overexpressed in 55 (35.5%) patients. It was associated with pathologic characteristics such as grade (p = 0.017), tumor molecular phenotype (p < 0.001) and Ki-67 expression (p = 0.017). On univariate and multivariable logistic regression analysis, HER2 overexpression remained associated with higher grade (HR, 10.6; 95% CI 1.0–112.6; p = 0.050) and luminal molecular phenotype (HR, 8.0; 95% CI 1,6–38.4; p = 0.010). During disease progression after nephroureterectomy, the phenotype of the tumor might change and a switch phenomenon in phenotype after recurrence in the bladder was reported. Conclusion: According to our study, in Southwest China, one-third of UTUC patients overexpressed HER2. Tumors with high grade or luminal phenotype tended to be HER2 positive. HER2 may represent a promising target for therapy in UTUC. [ABSTRACT FROM AUTHOR]

Background: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. Methods: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. Results: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. Conclusions: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks. [ABSTRACT FROM AUTHOR]

High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P < 0.001), background rich in eosinophils (P = 0.002), higher expression of the germinal centre marker LMO2 (P = 0.080), lower expression of MUM1 (P = 0.004), BCL2 (P = 0.007), and LEF1 (P = 0.080), and lower positivity for EBER in situ hybridisation (P = 0.027). Notably, one case in our series was EBV-positive, a finding not previously reported in the literature. Furthermore, comparing the prognosis between these two groups, AR-HGBL-11q showed a relatively favorable prognosis (P = 0.15), although the difference was not statistically significant. We analyzed this rare lymphoma entity in the HIV setting and highlighted the importance of integrating histomorphological and immunophenotypic features in its diagnosis and classification. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is well known as the commonest cancer in men and the second leading cause of cancer-related death. CT, MRI and bone scintigraphy are considered the commonly widely used imaging diagnostic tools for detection, staging and follow-up of prostate cancer. Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, that can be concentrated in prostate cancer cells up to 100 times higher than in normal cells. PSMA-targeted imaging modalities have now proven their efficacy in diagnosis, staging and follow-up of prostate cancer. The use of 68Ga PSMA PET-CT has efficiently improved the detection of loco-regional and metastatic disease. 68Ga PSMA PET-CT also has an effective role in the primary diagnosis, staging, and detecting biochemical recurrence after curative treatment and in metastasis-targeted therapy. This work aims to review the role of 68Ga PSMA PET-CT in anatomical staging of prostate cancer in correlation with histopathological staging. Results: Zonal correlation between 68Ga PSMA findings and biopsy results showed sensitivity ranging between 76.9 and 90.6% and specificity ranging from 85.7 to 100%. There was high significant correlation between the SUVmax uptake and the biopsy results, between the SUVmax uptake and the local staging as well as between the Gleason score and 68Ga PSMA PET/CT findings. Conclusions: 68Ga PSMA PET/CT is a highly promising imaging modality with an effective role in detection of prostate cancer showing high sensitivity and specificity in prediction of zonal histopathological results and loco-regional Gleason score staging with significant positive correlation between the SUV uptake results, Gleason score and the PSA levels. [ABSTRACT FROM AUTHOR]

Vessel density within tumor tissues strongly correlates with tumor proliferation and serves as a critical marker for tumor grading. Recognition of vessel density by pathologists is subject to a strong inter-rater bias, thus limiting its prognostic value. There are many challenges in the task of object detection in pathological images, including complex image backgrounds, dense distribution of small targets, and insignificant differences between the features of the target to be detected and the image background. To address these problems and thus help physicians quantify blood vessels in pathology images, we propose Pathological Images-YOLO (PI-YOLO), an enhanced detection network based on YOLOv7. PIYOLO incorporates the BiFormer attention mechanism, enhancing global feature extraction and accelerating processing for regions with subtle differences. Additionally, it introduces the CARAFE upsampling module, which optimizes feature utilization and information retention for small targets. Furthermore, the GSConv module improves the ELAN module, reducing model parameters and enhancing inference speed while preserving detection accuracy. Experimental results show that our proposed PI-YOLO network has higher detection accuracy compared to Faster-RCNN, SSD, RetinaNet, YOLOv5 network, and the latest YOLOv7 network, with a mAP value of 87.48%, which is 2.83% higher than the original model. We also validated the performance of this network on the ICPR 2012 mitotic dataset with an F1 value of 0.8678, outperforming other methods, demonstrating the advantages of our network in the task of target detection in complex pathology images. [ABSTRACT FROM AUTHOR]

Glioma is the most aggressive intracranial malignancy and is associated with poor survival rates and limited quality of life, impairing neuropsychological function and cognitive competence in survivors. The Proteasome Subunit Alpha Type-5 (PSMA5) is a multicatalytic proteinase complex that has been linked with tumor progression but is rarely reported in glioma. This study investigates the expression pattern, prognostic characteristics, and potential biological functions of PSMA5 in glioma. PSMA5 was significantly overexpressed in 28 types of cancer when compared to normal tissue. Furthermore, elevated levels of PSMA5 were observed in patients with wild-type isocitrate dehydrogenase 1 and exhibited a positive correlation with tumor grade. It was also found to be a standalone predictor of outcomes in glioma patients. Additionally, inhibiting PSMA5-induced cell cycle arrest may provide a therapeutic option for glioma. [ABSTRACT FROM AUTHOR]

Significance: Histopathological examination of surgical biopsies, such as in glioma and glioblastoma resection, is hindered in current clinical practice by the long time required for the laboratory analysis and pathological screening, typically taking several days or even weeks to be completed. Aim: We propose here a transportable, high-density, spectral scanning-based hyperspectral imaging (HSI) setup, named HyperProbe1, that can provide in situ, fast biochemical analysis, and mapping of fresh surgical tissue samples, right after excision, and without the need for fixing, staining nor compromising the integrity of the tissue properties. Approach: HyperProbe1 is based on spectral scanning via supercontinuum laser illumination filtered with acousto-optic tunable filters. Such methodology allows the user to select any number and type of wavelength bands in the visible and nearinfrared range between 510 and 900 nm (up to a maximum of 79) and to reconstruct 3D hypercubes composed of high-resolution (4 to 5 µm), widefield images (0.9 × 0.9 mm²) of the surgical samples, where each pixel is associated with a complete spectrum. Results: The HyperProbe1 setup is here presented and characterized. The system is applied to 11 fresh surgical biopsies of glioma from routine patients, including different grades of tumor classification. Quantitative analysis of the composition of the tissue is performed via fast spectral unmixing to reconstruct the mapping of major biomarkers, such as oxy-(HbO2) and deoxyhemoglobin (HHb), as well as cytochrome-c-oxidase (CCO). We also provided a preliminary attempt to infer tumor classification based on differences in composition in the samples, suggesting the possibility of using lipid content and differential CCO concentrations to distinguish between lower and higher-grade gliomas. Conclusions: A proof of concept of the performances of HyperProbe1 for quantitative, biochemical mapping of surgical biopsies is demonstrated, paving the way for improving current post-surgical, histopathological practice via non-destructive, in situ streamlined screening of fresh tissue samples in a matter of minutes after excision. [ABSTRACT FROM AUTHOR]

Background: In Egypt, bladder cancer (BC) is among the most common cancers. Piwi-interacting RNA associated with bladder cancer (piRABC) expression was downregulated in bladder cancer tissue. The piRABC increase TNFSF4 levels that leads to cancer cell death. This study aimed to assess the roles of piRABC and TNFSF4 in BC detection and to evaluate their roles in cancer grading and staging. Methods: Forty BC patients and 40 controls were enrolled. A quantitative real-time PCR was used to measure the expression of piRABC. ELISA kit was used for determining serum TNFSF4. Results: Compared to controls, BC patients had significantly lower PiRABC expression l and TNFSF4 levels (p<0.0001). With an area under the ROC curve of 0.938 for PiRABC and 0.874 for the TNFSF4, they were able to detect BC. On multivariate analysis, low PiRABC and TNFSF4 levels were significant independent predictive factors of BC (AOR = 133 and 12.4, respectively). With more advanced BC stages, PiRABC expression displayed a negative trend. For BC patients' overall survival, PiRABC and TNFSF4 may be significant independent prognostic factors (p = 0.038 and 0.026, respectively). Conclusions: Decreased levels of piRABC expression and TNFSF4 appear to be independent predictors of BC. The low expression of piRABC had accepted prediction criteria for BC better than TNFSF4. The piRABC showed a decreasing trend with tumor grading and staging, while TNFSF4 exhibited a declining tendency throughout BC stages, despite having a small impact in BC grading. Greater expression of TNFSF4 and piRABC was linked to prolonged patient survival rates. [ABSTRACT FROM AUTHOR]

Simple Summary: The mechanisms underlying the size progression of vestibular schwannomas remain poorly understood. Accordingly, this study was focused on investigating the potential role of messenger substances in regulating the growth of these tumors. These cytokines are produced by the tumor cells themselves or by other cells, such as immune cells. The influence of the cytokines on the size progression of tumors could facilitate the development and establishment of drug therapies for vestibular schwannoma patients, which are currently unavailable for sporadic vestibular schwannomas. Sporadic vestibular schwannomas (VSs) often exhibit slow or negligible growth. Nevertheless, some VSs increase significantly in volume within a few months or grow continuously. Recent evidence indicates a role of inflammation in promoting VS growth. Therefore, our study aimed to identify cytokines, which are associated with larger VSs. The expression of different cytokines in VS tumor samples and VS primary cultures was investigated. Additionally, the concentration of cytokines in cell culture supernatants of VS primary cultures and cerebrospinal fluid (CSF) of VS patients and healthy controls were determined. Correlation analysis of cytokine levels with tumor volume, growth rate, Koos grade, age, and hearing was examined with Spearman's-rank test. The mRNA expression of CC-chemokine ligand (CCL) 18, growth differentiation factor (GDF) 15, and interferon regulatory factor 4 correlated positively with tumor volume. Moreover, the amount of GDF15 in the cell culture supernatant of primary cells correlated positively with tumor volume. The concentrations of the cytokines CCL2, CCL5, and CCL18 and transforming growth factor beta (TGFB) 1 in the CSF of the patients were significantly different from those in the CSF controls. Inhibition of immune cell infiltration could be a putative approach to prevent and control VS growth. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases from systemic cancer are the most common tumors of the central nervous system. For prostate metastases to the brain, the clinical progression is poorly understood. This retrospective study aims to elucidate clinical risk factors associated with overall survival (OS; months post-diagnosis) in prostate metastases to the brain, and then develop a nomogram to aid in clinical decision making for this vulnerable population. We identified several factors associated with survival, including race, tumor size, and the presence of additional metastases. This study should serve as a clinical framework for prognostication in metastatic prostate cancer to the brain. Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study of 61 patients with diffuse gliomas, APT-weighted imaging in the solid tumor component provided quantitative metrics associated with WHO grade and survival. Mean APT values of the necrotic component showed high variability between subjects, warranting further investigation. These results highlight the importance of assessing the different tumor components with APT-weighted imaging, to provide useful diagnostic and prognostic information for the management of patients with gliomas. Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: The DNA damage response protein p53-binding protein 1 (53BP1) exhibits abnormal foci in the nucleus during carcinogenesis in various organs. However, the pathophysiological changes that occur during the carcinogenic process of hypopharyngeal squamous cell carcinoma remain unclear. This study revealed a stepwise increase in aberrant 53BP1 expression on the tumor surface during carcinogenesis. In addition, a significant difference in the co-expression of 53BP1 and Ki67 was observed on the tumor surface when the tumor thickness exceeded 1000 µm, which is considered the threshold at which the risk of lymph node metastasis and vascular invasion increases in hypopharyngeal cancer. These findings suggest that 53BP1 could be useful for the pathological diagnosis of hypopharyngeal cancer and for predicting the prognosis of patients with this disease. The DNA damage response protein p53-binding protein 1 (53BP1) accumulates and forms foci at double-strand DNA breaks, indicating the extent of DNA instability. However, the potential role of 53BP1 as a molecular biomarker for hypopharyngeal squamous cell carcinoma (HPSCC) diagnosis remains unknown. Here, we evaluated the potential of immunofluorescence-based analysis of 53BP1 expression to differentiate the histology of hypopharyngeal neoplasms. A total of 125 lesions from 39 surgically or endoscopically resected specimens from patients with HPSCC was histologically evaluated. 53BP1 expression in the nucleus was examined using immunofluorescence. The number of 53BP1 nuclear foci increased with the progression from non-tumorous to low-grade dysplasia, high-grade dysplasia, and squamous cell carcinoma. Unstable 53BP1 expression served as an independent factor for distinguishing lesions that required intervention. Colocalization of 53BP1 foci in proliferating cells, as assessed by Ki67, was increased in tumors ≥ 1000 µm in depth compared to those <1000 µm in depth at the tumor surface. Hence, the expression patterns of nuclear 53BP1 foci were associated with the progression of hypopharyngeal neoplasms. These findings suggest that 53BP1 could serve as an ancillary marker to support histological diagnosis and predict the factors that influence prognosis in patients with HPSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Very few studies have proven chemotherapy efficacy against canine mammary carcinomas. As a result, we still lack efficient standardized protocols, which do exist in human cases, to treat these carcinomas or to adapt treatment according to the aggressiveness of the tumor in dogs. In this case report, we describe a highly aggressive mammary carcinoma; we applied an intensive treatment combining radical surgery and intensive adjuvant chemotherapy, which included metronomic and maximal-tolerated-dose chemotherapy, nonsteroidal anti-inflammatory drugs and inhibitors of tyrosine kinase. We obtained the informed consent of the owner, who was aware of the poor prognosis without treatment and of the fact that this combinatorial treatment had not been published yet. The treatment enabled this one dog to live for 218 days with very good quality of life. A large-scale prospective study will be needed to confirm this result. Very few studies, often with very small cohorts, have proven chemotherapy efficacy against canine aggressive mammary carcinomas, either in terms of metastasis or median survival, in dogs after surgery and chemotherapy, with such outcomes not being confirmed by other studies. As a result, we lack efficient standardized protocols, which exist in human cases, according to the grade and stage of the tumor in dogs. In this case report, we describe a relapsing grade III solid mammary carcinoma evolving into prominent lymphatic intravascular invasion with multifocal nodal extension (stage IV); we applied an intensive treatment combining radical surgery and intensive adjuvant chemotherapy. The latter combined carboplatin maximal-tolerated-dose chemotherapy, with doses adjusted as necessary, and metronomic chemotherapy with firocoxib, toceranib and chloraminophene, progressively administered and carefully monitored. Adapting the doses prevented adverse events and resulted in 218 days of survival with good quality of life. To our knowledge, this is the first description of such a treatment combination. Our result should be confirmed with a large-scale prospective study. [ABSTRACT FROM AUTHOR]

Simple Summary: Squamous cell carcinoma of the anus or anal cancer is increasing in prevalence, and the standard treatment of mitomycin and 5-fluorouracil is too toxic for many patients. Unfortunately, there is currently no standard of care for what to do for this disease when someone is not a candidate for this aggressive treatment. Here, we demonstrate the promising preliminary toxicity profile and efficacy of the combination of weekly carboplatin and paclitaxel chemotherapy for patients with localized anal cancer. This regimen was able to complete 80% of the intended treatments with anticipated toxicities, and 89% achieved a complete clinical response. This combination is a promising regimen and is already being investigated further in a clinical trial. Background: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. Methods: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Results: Ten patients were included; eight were female, and the median age was 75.5 years (54–87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40–100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4–50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. Methods: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. Results: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H–B) grade, of which two patients deteriorated from H–B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H–B grade according to tumor size at the time of diagnosis or change in tumor size. Conclusion: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function. [ABSTRACT FROM AUTHOR]

Meningioma calcification is thought to predict reduced growth potential and aggression. However, historical studies have primarily focused on correlating calcification in small meningiomas (diameter less than 2.5 cm) rather than analyzing characteristics of calcified meningiomas across all sizes. In this study, we investigate the pathologic and clinical implications of meningioma calcification. We utilized a historical database of 342 consecutive newly diagnosed intracranial meningiomas with preoperative computed tomography and magnetic resonance imaging scans treated at a single institution from 2005 to 2019. We correlated the presence of calcification with patient demographics, grade, Mindbomb Homolog-1 index, location, volume, Simpson grade, and recurrence using both univariate and multivariate generalized linear models. On univariate analysis, no single variable correlated with tumor calcification. Notably, neither tumor 2021 World Health Organization grade (P = 0.91) nor Mindbomb Homolog-1 index (P = 0.62) predicted calcification. After accounting for demographic characteristics and tumor volume and location, there was no significant association between 2021 World Health Organization grade (P = 0.52) and Mindbomb Homolog-1 index (P = 0.54) and calcification. Calcification had no influence on resection grade (P = 0.59) or recurrence (P = 0.80). In this series, calcified meningiomas exhibited similar 2021 World Health Organization tumor grading distribution, proliferation indexes, and immediate surgical outcomes compared to their noncalcified counterparts. These findings question the historical role of using meningioma calcification as an independent guide to their management. [ABSTRACT FROM AUTHOR]