Cigarette smoking-related OLC1 overexpression associated with poor prognosis in bladder urothelial carcinoma.

AIMS: To explore the clinical significance of OLC1 and cigarette smoking in bladder urothelial carcinoma (UBC). MATERIALS AND METHODS: OLC1 mRNA expression was detected in 106 UBC samples by mRNA array or reverse real-time PCR. OLC1 protein expression in 114 UBC samples was detected by immunohistochemical staining. Wild-type C57BL/6J mice were injected with cigarette smoke condensate (n = 12) or exposed to cigarette smoke (n = 6) to investigate the correlations between cigarette smoking and OLC1 expression using mRNA array. KEY FINDINGS: The mRNA and protein expression of OLC1 were higher in tumor samples (p < 0.01) and significantly correlated with tumor stage (p < 0.05). OLC1 protein expression and smoking history were correlated with disease-free survival (p < 0.05). OLC1 expression was significantly elevated in smoking patients with higher smoking intensity on both mRNA and protein levels (p < 0.05). Cigarette smoke exposure experiments revealed that OLC1 mRNA overexpressed in bladder uroepithelium of mice. SIGNIFICANCE: OLC1 could serve as a potential prognosis biomarker of UBC, especially for smoking patients.

Serum IgA as a Prognostic Beacon: Anticipating Systemic Therapy Efficacy in Metastatic Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Immunotherapy-tyrosine kinase inhibitor (IO-TKI) therapy has revolutionized the treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC); however, the absence of effective biomarkers poses a challenge in predicting the efficacy of these regimens. This study aims to explore the predictive and prognostic value of serum immunoglobulin A (IgA) in mccRCC patients undergoing IO-TKI therapy. METHODS: Ninety-six mccRCC patients treated with IO-TKI therapy from 2019 to 2023 were enrolled and serum IgA levels were assessed at the pretreatment baseline and after 3 months of treatment. RESULTS: Notably, baseline levels of IgA showed no correlation with the objective response rate. However, patients achieving complete or partial responses exhibited a remarkable decrease in IgA levels, while those with stable or progressive disease displayed an increase in IgA levels after 3 months of treatment. Furthermore, the dynamic alteration in IgA levels after 3 months of treatment demonstrated predictive value for both progression-free survival (PFS) and overall survival (OS). The time-dependent receiver operating characteristic curves exhibited outstanding performance in predicting PFS (AUC 0.793) and OS (AUC 0.738). CONCLUSION: Taken together, this study demonstrates that dynamic alteration of serum IgA after 3 months of treatment was significantly correlated with prognosis and therapeutic efficacy in mccRCC patients.

MRI evaluation of vesical imaging reporting and data system for bladder cancer after neoadjuvant chemotherapy.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. METHODS: In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. RESULTS: The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39-70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893-0.977) for experienced readers, and 0.910 (95% CI: 0.831-0.959) for inexperienced readers, and 0.932 (95% CI: 0.892-0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0-80.9%) and 94.1% (range: 88.6-97.7%) for experienced readers, and 63.9% (range: 59.6-68.1%) and 86.4% (range: 84.1-88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79-0.92). CONCLUSIONS: VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Downstaging guided neoadjuvant strategy shift and bladder preservation in locally advanced bladder cancer: A case report.

Background: The study of bladder preservation for muscle-invasive bladder cancer (MIBC) mainly focuses on the T2 stage, which remains difficult in the T3 and T4 stage. Pembrolizumab has been applied as neoadjuvant therapy followed by radical cystectomy for MIBC, gaining encouraging results in the phase II study. Disitamab vedotin, an antibody-drug conjugate (ADC), also achieved promising efficacy for refractory bladder cancer. However, the neoadjuvant therapy strategy of these drugs for bladder sparing remains further exploration. Case presentation: A patient with locally advanced MIBC at our institute underwent a neoadjuvant therapeutic regimen followed by transurethral resection of bladder tumor (TURBT) and concurrent chemoradiotherapy. In light of limited initial efficacy, we enacted an adaptive shift in the neoadjuvant treatment strategy, transitioning from a combination of gemcitabine, cis-platinum, and pembrolizumab to disitamab vedotin with pembrolizumab. This approach ultimately achieved bladder preservation, complete response, and a remarkable 1-year disease-free survival (DFS). Conclusion: Proactive evaluation in the early stages of tumor downstaging can serve as a guiding principle for neoadjuvant strategies. This is the first successful case of neoadjuvant pembrolizumab combined with disitamab vedotin and chemotherapy in MIBC patients achieving complete response and bladder preservation.

Comprehensive analysis of m6 A methylome and transcriptome by Nanopore sequencing in clear cell renal carcinoma.

N6 -methyladenosine (m6 A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m6 A modification patterns in tumor progression. However, the relationship between m6 A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m6 A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m6 A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m6 A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ2 test demonstrated a significant association between the levels of m6 A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m6 A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.

MSNSegNet: attention-based multi-shape nuclei instance segmentation in histopathology images.

In clinical research, the segmentation of irregularly shaped nuclei, particularly in mesenchymal areas like fibroblasts, is crucial yet often neglected. These irregular nuclei are significant for assessing tissue repair in immunotherapy, a process involving neovascularization and fibroblast proliferation. Proper segmentation of these nuclei is vital for evaluating immunotherapy's efficacy, as it provides insights into pathological features. However, the challenge lies in the pronounced curvature variations of these non-convex nuclei, making their segmentation more difficult than that of regular nuclei. In this work, we introduce an undefined task to segment nuclei with both regular and irregular morphology, namely multi-shape nuclei segmentation. We propose a proposal-based method to perform multi-shape nuclei segmentation. By leveraging the two-stage structure of the proposal-based method, a powerful refinement module with high computational costs can be selectively deployed only in local regions, improving segmentation accuracy without compromising computational efficiency. We introduce a novel self-attention module to refine features in proposals for the sake of effectiveness and efficiency in the second stage. The self-attention module improves segmentation performance by capturing long-range dependencies to assist in distinguishing the foreground from the background. In this process, similar features get high attention weights while dissimilar ones get low attention weights. In the first stage, we introduce a residual attention module and a semantic-aware module to accurately predict candidate proposals. The two modules capture more interpretable features and introduce additional supervision through semantic-aware loss. In addition, we construct a dataset with a proportion of non-convex nuclei compared with existing nuclei datasets, namely the multi-shape nuclei (MsN) dataset. Our MSNSegNet method demonstrates notable improvements across various metrics compared to the second-highest-scoring methods. For all nuclei, the D i c e score improved by approximately 1.66 % , A J I by about 2.15 % , and D i c e obj by roughly 0.65 % . For non-convex nuclei, which are crucial in clinical applications, our method's A J I improved significantly by approximately 3.86 % and D i c e obj by around 2.54 % . These enhancements underscore the effectiveness of our approach on multi-shape nuclei segmentation, particularly in challenging scenarios involving irregularly shaped nuclei.

Nucleus-Aware Self-Supervised Pretraining Using Unpaired Image-to-Image Translation for Histopathology Images.

Self-supervised pretraining attempts to enhance model performance by obtaining effective features from unlabeled data, and has demonstrated its effectiveness in the field of histopathology images. Despite its success, few works concentrate on the extraction of nucleus-level information, which is essential for pathologic analysis. In this work, we propose a novel nucleus-aware self-supervised pretraining framework for histopathology images. The framework aims to capture the nuclear morphology and distribution information through unpaired image-to-image translation between histopathology images and pseudo mask images. The generation process is modulated by both conditional and stochastic style representations, ensuring the reality and diversity of the generated histopathology images for pretraining. Further, an instance segmentation guided strategy is employed to capture instance-level information. The experiments on 7 datasets show that the proposed pretraining method outperforms supervised ones on Kather classification, multiple instance learning, and 5 dense-prediction tasks with the transfer learning protocol, and yields superior results than other self-supervised approaches on 8 semi-supervised tasks. Our project is publicly available at https://github.com/zhiyuns/UNITPathSSL.

Prognosis and Clinicopathological Characters of Adult TFEB-Altered Renal Cell Carcinoma: A Single Center Experience of 18 Cases.

INTRODUCTION: TFEB-altered renal cell carcinoma (RCC) is a rare entity characterized by the rearrangement of the TFEB gene or TFEB amplified. The therapeutic implications and long-term survival of TFEB-altered RCC remain unclear, especially for metastatic cases. MATERIALS AND METHODS: The current study initially enrolled 7604 consecutive RCC patients at our center and a total of 248 patients were selected for FISH and immunohistochemistry (IHC) analysis. Eventually, eighteen TFEB-altered RCC patients were identified. We then reported the clinical, morphological, IHC, and radiological features of these cases. RESULTS: The median age at initial diagnosis was 45 years, ranging from 18 years to 66 years. The majority of the TFEB-altered RCC patients were male (61.1%), with localized disease (T1-2N0M0, 77.8%). The median split TFEB fluorescent signal was 24%, ranging from 15%-80%. The morphological characteristics of TFEB-altered RCC were variable, with acinar, papillary, solid, or nest patterns. IHC and magnetic resonance imaging features of TFEB-altered RCC were nonspecific. Nine patients with localized disease received partial nephrectomy and five patients with localized disease received radical nephrectomy. During the median follow-up of 67 months, no signs of recurrence or metastasis were found in these patients. Two patients had distant metastasis and received axitinib plus PD-1 immunotherapy. One of them died at 40-month follow-up and another still alive at 88-month follow-up. CONCLUSION: TFEB-altered RCC is an extremely rare variant, exhibited mixed morphological characteristics. The radiological feature lack specificity, resembling clear cell RCC or papillary RCC. Genetic analyses including FISH analysis is crucial in the diagnosis of TFEB-altered RCC. For localized TFEB-altered RCC, both radical nephrectomy and partial nephrectomy conferred satisfactory prognosis. For metastatic TFEB-altered RCC, immunotherapy-based drug combinations could be a promising treatment strategy.

Neutrophil extracellular traps in relationship to efficacy of systemic therapy for metastatic renal cell carcinoma.

BACKGROUND: The efficacy of systemic therapy regimens, such as immune checkpoint inhibitors and tyrosine kinase inhibitors (IO-TKI) and targeted therapy, for metastatic clear cell renal cell carcinoma (ccRCC) remains unpredictable due to the lack of effective biomarkers. Neutrophil extracellular trap (NET) plays an important role in promoting ccRCC. This study explores the NET predictive value of the efficacy in metastatic ccRCC. METHODS: In this retrospective study, patients with metastatic ccRCC who received targeted drugs and IO-TKI were included. Immunofluorescence staining was utilized to quantify the levels of tissue NETs through cell counts of H3Cit(+) and MPO(+) cells. RESULTS: A total of 183 patients with metastatic ccRCC were enrolled, including 150 patients who received TKIs and 33 patients who received IO-TKI. The levels of NETs in tumor tissue were significantly higher than in para-tumor tissue (p < 0.001). In terms of predicting drug efficacy, a correlation between NET levels and progression-free survival (PFS) was observed in the TKI with metachronous metastasis group (HR 1.73 [95% CI 1.02-2.91], log-rank p = 0.037), while no correlation was observed in the TKI with synchronous metastasis group and IO-TKI group. Regarding overall survival (OS), activated NET levels were associated with poor OS in both TKI (HR 1.60 [95% CI 1.05-2.43], log-rank p = 0.017) and IO-TKI group (HR 4.35 [95% CI 1.06-17.82], log-rank p =0.047). IMDC score (HR 1.462 [95% CI 1.030-2.075], p = 0.033) and tumor tissue NET levels (HR 1.733 [95% CI 1.165-2.579], p = 0.007) were independent prognostic risk factors for OS in patients with metastatic ccRCC.NET level was associated with poor OS in both TKI (HR 1.60 [95% CI 1.05-2.43], log-rank p = 0.017). CONCLUSIONS: The active NET levels in tumor tissue can predict drug efficacy in patients with metastatic ccRCC who received systemic therapy. Elevated levels of NETs in tumor tissue were also associated with poor efficacy in OS.

Exploration of the immunogenetic landscape of hyperprogressive disease after combined immunotherapy in cancer patients.

The immune-genetic changes that occur in cancer patients experiencing hyperprogressive disease (HPD) during combined immunotherapy are unclear. In this study, HPD patients with pre- and post-HPD samples and non-HPD patients with solid tumors were molecularly characterized by genetic and tumor immune microenvironment (TiME) analyses of paired samples by whole-exome sequencing, RNA sequencing, and multiplex immunofluorescence. The genetic analysis of paired samples showed that almost all the tumor driver gene mutations were preserved between pre- and post-HPD tumors. HPD patients had higher frequencies of mutations in TP53 and CNN2, and a significantly higher mutant-allele tumor heterogeneity than non-HPD patients. Tumor IL-6 mRNA was upregulated in post-HPD samples vs. pre-HPD, accompanied by a potential immune suppressive TiME with an elevated M2/M1 ratio. Salvage treatment with irinotecan plus bevacizumab was effective in one HPD patient, who experienced prolonged survival. These genetic features and TiME characteristics might help identify the features of HPD after immunotherapy.

Cyclic Learning: Bridging Image-Level Labels and Nuclei Instance Segmentation.

Nuclei instance segmentation on histopathology images is of great clinical value for disease analysis. Generally, fully-supervised algorithms for this task require pixel-wise manual annotations, which is especially time-consuming and laborious for the high nuclei density. To alleviate the annotation burden, we seek to solve the problem through image-level weakly supervised learning, which is underexplored for nuclei instance segmentation. Compared with most existing methods using other weak annotations (scribble, point, etc.) for nuclei instance segmentation, our method is more labor-saving. The obstacle to using image-level annotations in nuclei instance segmentation is the lack of adequate location information, leading to severe nuclei omission or overlaps. In this paper, we propose a novel image-level weakly supervised method, called cyclic learning, to solve this problem. Cyclic learning comprises a front-end classification task and a back-end semi-supervised instance segmentation task to benefit from multi-task learning (MTL). We utilize a deep learning classifier with interpretability as the front-end to convert image-level labels to sets of high-confidence pseudo masks and establish a semi-supervised architecture as the back-end to conduct nuclei instance segmentation under the supervision of these pseudo masks. Most importantly, cyclic learning is designed to circularly share knowledge between the front-end classifier and the back-end semi-supervised part, which allows the whole system to fully extract the underlying information from image-level labels and converge to a better optimum. Experiments on three datasets demonstrate the good generality of our method, which outperforms other image-level weakly supervised methods for nuclei instance segmentation, and achieves comparable performance to fully-supervised methods.

Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target.

In addition to the anti-infection response, neutrophils are linked to tumor progression through the secretion of inflammation components and neutrophil extracellular traps (NETs) formation. NET is a web-like structure constituted by a chromatin scaffold coated with specific nuclear and cytoplasmic proteins, such as histone and granule peptides. Increasing evidence has demonstrated that NETs are favorable factors to promote tumor growth, invasion, migration, and immunosuppression. However, the cell-cell interaction between NETs and other cells (tumor cells and immune cells) is complicated and poorly studied. This work is the first review to focus on the intercellular communication mediated by NETs in cancer. We summarized the complex cell-cell interaction between NETs and other cells in the tumor microenvironment. We also address the significance of NETs as both prognostic/predictive biomarkers and molecular targets for cancer therapy. Moreover, we presented a comprehensive landscape of cancer immunity, improving the therapeutic efficacy for advanced cancer in the future.

UCseek: ultrasensitive early detection and recurrence monitoring of urothelial carcinoma by shallow-depth genome-wide bisulfite sequencing of urinary sediment DNA.

BACKGROUND: Current methods for the detection and surveillance of urothelial carcinomas (UCs) are often invasive, costly, and not effective for low-grade, early-stage, and minimal residual disease (MRD) tumors. We aimed to develop and validate a model from urine sediments to predict different grade and stage UCs with low cost and high accuracy. METHODS: We collected 167 samples, including 90 tumors and 77 individuals without tumors, as a discovery cohort. We assessed copy number variations and methylation values for them and constructed a diagnostic classifier to detect UC, UCseek, by using an individual read-based method and support vector machine. The performance of UCseek was validated in an independent cohort derived from three hospitals (n = 206) and a relapse cohort (n = 42) for monitoring recurrence. FINDINGS: We constructed UCseek, which could predict UCs with high sensitivity (92.7%), high specificity (90.7%), and high accuracy (91.7%) in the independent validation set. The accuracy of UCseek in low-grade and early-stage patients reached 91.8% and 94.3%, respectively. Notably, UCseek retained great performance at ultralow sequencing depths (0.3X-0.5X). It also demonstrated a powerful ability to monitor recurrence in a surveillance cohort compared with cystoscopy (90.91% vs. 59.09%). INTERPRETATION: We optimized an improved approach named UCseek for the noninvasive diagnosis and monitoring of UCs in both low- and high-grade tumors and in early- and advanced-stage tumors, even at ultralow sequencing depths, which may reduce the burden of cystoscopy and blind second surgery. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgments section.

Optimizing targeted drug selection in combination therapy for patients with advanced or metastatic renal cell carcinoma: A systematic review and network meta-analysis of safety.

OBJECTIVE: For patients with advanced or metastatic renal cell carcinoma (RCC), the dose of targeted agents was recommended in combination with immune checkpoint inhibitors. We performed a network meta-analysis to describe a categorized safety ranking profile and assess the adaptability of the combination options of targeted agents. METHODS: The targeted agents refer to vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Randomized controlled trials comparing these drugs were enrolled in a Bayesian model network meta-analysis. RESULTS: Nineteen clinical trials with 11 treatments and 10,615 patients were included. For grade ≥ 3 adverse events (AEs), compared with placebo, lenvatinib plus everolimus showed worse safety than all other treatments except for lenvatinib (placebo vs. OR 0.23, 95% CI 0.07-0.78). Everolimus was generally the safest agent (OR 1.23, 95% CI 0.50-3.14). Sorafenib arose the least renal AEs (placebo vs. OR 0.85, 95% CI 0.06-11.64), whereas lenvatinib plus everolimus had the highest risk of renal toxicity (placebo vs. 0.17 95% CI 0.01-1.02). For gastrointestinal symptoms, everolimus was related to much lower toxicity than other agents. In the respiratory safety analysis, tivozanib (placebo vs. OR 0.15, 95% CI 0.07-0.31) and axitinib (OR 5.43, 95% CI 3.26-9.22) were the riskiest agents. In terms of hepatobiliary (placebo vs. OR 0.44, 95% CI 0.09-2.10) and hemotoxicity (placebo vs. OR 1.03, 95% CI 0.14-7.68) related AEs, lenvatinib was found to be the safest treatment compared to placebo. CONCLUSIONS: Everolimus, with the best safety of grade ≥ 3, gastrointestinal, and respiratory AEs, was more likely to be considered for combination therapies. Lenvatinib appears to be the safest for blood/lymphatic and hepatobiliary AEs. For patients with renal disorders, sorafenib arises the least renal toxicity AEs. This study will guide treatment options and optimize the trial design for advanced or metastatic RCC.

Dynamic alteration and prognostic significance of tumor-associated CD68+ and CD68+ PD-L1- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC). METHODS: Multiplex immunofluorescence staining was performed to examine CD68+ TAM, CD4+ T cell, CD8+ T cell, FOXP3+ Treg cell, and PD-L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR). RESULTS: There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68+ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68+ PD-L1- (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68+ PD-L1+ and TILs. The infiltration of CD68+ (p = 0.033), CD68+ PD-L1- (p = 0.033), and CD68+ PD-L1+ (p < 0.001) TAMs in stroma area were significantly associated with poorer disease-free survival rate (DFS) of MIBC patients. CONCLUSION: CD68+ and CD68+ PD-L1- TAMs infiltration levels decreased significantly after NAC and pre-treatment TAM infiltration levels were independent prognostic factors for MIBC patients. While there was no sufficient evidence demonstrating that pre-treatment TILs or TAMs could predict response to NAC in MIBC patients.

A novel nomogram can predict pathological T3a upstaged from clinical T1a in localized renal cell carcinoma

ABSTRACT Hypothesis: Nomogram can be built to predict the pathological T3a upstaging from clinical T1a in patients with localized renal cell carcinoma before surgery. Purpose: Renal cell carcinoma (RCC) patients with clinical T1a (cT1a) disease who are upstaged to pathological T3a (pT3a) have reduced survivals after partial nephrectomy. We aimed to develop a nomogram-based model predicting pT3a upstaging in RCC patients with preoperative cT1a based on multiple preoperative blood indexes and oncological characteristics. Materials and Methods: Between 2010 and 2019, 510 patients with cT1a RCC were individually matched according to pT3a upstaging and pathological T1a (pT1a) at a 1:4 ratio using clinicopathologic features. Least absolute shrinkage and selection operator regression analysis was used to identify the most important risk factor from 40 peripheral blood indicators, and a predictive model was established. Multivariate logistic regression analysis was performed with the screened blood parameters and clinical data to identify significant variables. Harrell's concordance index (C-index) was applied to evaluate the accuracy of the model for predicting pT3a upstaging in patients with cT1a RCC. Results: Out of 40 blood indexes, the top ranked predictor was fibrinogen (FIB). Age, the ratio of the tumor maximum and minimum diameter (ROD), FIB, and tumor size were all independent risk factors for pT3a upstaging in multivariate analysis. A predictive ARFS model (Age, ROD, FIB, tumor Size) was established, and the C-index was 0.756 (95% CI, 0.681-0.831) and 0.712 (95% CI, 0.638-0.785) in the training and validation cohorts, respectively. Conclusions: Older age, higher ROD, increased FIB level, and larger tumor size were independent risk factors for upstaging. The ARFS model has a high prediction efficiency for pT3a upstaging in patients with cT1a RCC.

Efficacy and safety of surgery in renal carcinoma patients 75 years and older: a retrospective analysis.

OBJECTIVE: To investigate the efficacy and complications of surgical treatment in patients with renal cell carcinoma aged ≥ 75 years. METHODS: From January 2009 to May 2019, we assessed 166 patients aged 75 years and older, who either had radical nephrectomy (RN) or partial nephrectomy (PN) as treatments for diagnosed renal cell carcinoma. Patients were divided into one group of patients aged 75-79 years and the second group of patients ≥ 80 years. The complications and survival were compared between the two groups. RESULTS: All 166 patients were successfully operated on. Differences between the two groups were statistically significant in intraoperative and postoperative complications and Clavien-Dindo score of ≥ 1 (P = 0.02, P < 0.001, P = 0.001). Univariate analysis revealed no significant correlation between a Clavien-Dindo score ≥ 1 versus gender, body mass index (BMI), lack of symptoms, KPS, baseline GFR, postoperative GFR, tumor size, tumor location, surgical method, and transfusion or no transfusion (ALL P > 0.05). Multifactor analysis showed that age ≥ 80 years, partial nephrectomy, and operation time were independent predictors of a Clavien-Dindo score ≥ 1. No significant difference was found in OS between the two groups, (P < 0.0001), and no significant difference in CSS (P = 0.056). There was no significant difference in OS and CSS between the RN and PN groups (P = 0.143, P = 0.281, respectively). CONCLUSIONS: According to our findings, the overall safety of surgical therapy for elderly patients with renal cell carcinoma is adequate. PN should be carefully examined, especially over the age of 80. To select suitable patients based on an assessment of the tumor's complexity and patients' physical condition, such as age, underlying diseases and other conditions, technical feasibility, balance of benefits and a case-by-case.

Telomerase positive CTCs with PSMA high expression associated with prostate cancer metastasis.

Background: Whether circulating tumor cells (CTCs) with prostate-specific membrane antigen (PSMA) high expression was related to the metastatic progress in prostate cancer (PCa) remains explored. This study aimed to provide evidence to elucidate this relationship via the telomerase reverse transcriptase (TERT)-based CTC detection method. Methods: A total of 71 patients were enrolled and divided into the local PCa group (n=44) and metastatic PCa group (n=27). TERT-based CTC detection (TBCD) was used to detect CTCs. CTCs single-cell sequencing data were analyzed using gene ontology (GO) functional classification and enrichment. Results: The mean 'TERT+ CTCs' number was 6.11±9.63 in the metastatic group and 4.09±3.41 in the local group. GO enrichment analysis for 77 prostate CTCs single-cell sequencing confirmed that proliferation-related terms were enriched in the PSMA-high expression group, and 27 metastasis-related gene panels also had high expression in this group. Then, PSMA antibody was applied to mark the 'TERT+ CTCs'. The proportion of patients with 'TERT+ PSMA+ CTCs' was positively associated with the Gleason score. Furthermore, the proportion of 'TERT+ PSMA+ CTCs' patients was 48.15% in the metastatic group, significantly higher than 22.72% in the local group. Conclusions: This study suggested that TERT positive CTCs with high PSMA expression were associated with the PCa metastatic progress.