The Application of CT Radiomics in the Diagnosis of Vein Wall Invasion in Patients With Renal Cell Carcinoma Combined With Tumor Thrombus.

OBJECTIVE: The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy. MATERIALS AND METHODS: We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set. RESULTS: Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000). CONCLUSION: Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).

Factors predicting indistinct plane of surgical capsule in patients underwent HoLEP procedures.

PURPOSE: To evaluate factors that effectively predict indistinct plane (IP) in patients who underwent holmium laser enucleation of the prostate (HoLEP). METHODS: Data of 208 consecutive patients from our HoLEP database were reviewed and analyzed. IP was defined in 107 cases, as the plane could be identified only depending on endoscopic beak dissection rather than laser dissection in the initial stage of HoLEP, whereas the control group consisted of 101 cases. Variables including age, body mass index, prostatic volume (PV), intravesical prostatic protrusion, prostate-specific antigen, prostate-specific antigen density, bladder stones, urinary tract infection, microscopic hematuria, prior biopsy (PB), diabetes, hypertension, history of acute urinary retention, 5-alpha reductase inhibitor treatment, catheter dependency, residual urine, region, smoking, and alcohol consumption were compared between the two groups. The risk factors for predicting the presence of IP were determined using a multivariable binary logistic regression model using a forward selection approach with a focus on improvement in the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of IP was 51.4% (107/208). PV (OR = 0.977, p < 0.001) and PB (OR = 0.297, p = 0.028) were identified as the independent predictors of capsule plane status. PV with a cutoff of 54 ml had the best predictive effectiveness for IP based on AUC (0.727; 95% CI 0.659-0.795). The specificity and sensitivity of this cutoff were 82.2% and 53.3%, respectively. CONCLUSION: PV is the most reliable factor to predict IP during HoLEP procedures. There is a high possibility of IP in patients with a PV less than 54 ml.

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

OBJECTIVES: Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). METHODS: This study included young adult patients aged 18-40 years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. RESULTS: A total of 300 RCC patients aged 18-40 years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4 ± 6.1 years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p < 0.001). There was no statistically significant difference observed in overall survival (OS) (p = 0.069). Pathological stage was a significant independent predictor for OS (p = 0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p = 0.020; p = 0.005). CONCLUSIONS: The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Neoadjuvant stereotactic ablative body radiotherapy combined with surgical treatment for renal cell carcinoma and inferior vena cava tumor thrombus: a prospective pilot study.

BACKGROUND: Surgical treatment for renal cell carcinoma (RCC) and inferior vena cava (IVC) tumor thrombus (TT) is difficult, and the postoperative complication rate is high. This study aimed to explore the safety and oncologic outcomes of neoadjuvant stereotactic ablative body radiotherapy (SABR) combined with surgical treatment for RCC and IVC-TT. METHODS: Patients with RCC and IVC-TTs were enrolled in this study. All patients received neoadjuvant SABR focused on the IVC at a dose of 30 Gy in 5 fractions, followed by 2 ~ 4 weeks of rest. Then, radical nephrectomy and IVC tumor thrombectomy were performed for each patient. Adverse effects, perioperative outcomes, and long-term prognoses were recorded. RESULTS: From June 2018 to January 2019, 8 patients were enrolled-4 with Mayo grade II TT and 4 with Mayo grade III TT. Four (50%) patients had complicated IVC wall invasion according to CT/MRI. All patients received neoadjuvant SABR as planned. Short-term local control was observed in all 8 patients. Only Grade 1-2 adverse events were reported. In total, 3 (37.5%) laparoscopic surgeries and 5 (62.5%) open surgeries were performed. The median operation time was 359 (IQR: 279-446) min, with a median intraoperative bleeding volume of 750 (IQR: 275-2175) ml. The median postoperative hospital stay was 7 (5-10) days. With a 26-month (range: 5-41) follow-up period, the estimated mean overall survival was 30.67 ± 5.38 months. CONCLUSIONS: This is the first preoperative radiotherapy study in Asia that focused on patients with TT. This study revealed the considerable safety of neoadjuvant SABR for RCC with IVC-TT. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trials Registry on 2018-03-08 (ChiCTR1800015118). For more information, please see the direct link ( https://www.chictr.org.cn/showproj.html?proj=25747 ).

[Discussion on the surgical timing of rupture and hemorrhage of renal angiomyolipoma].

OBJECTIVE: To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma (RAML) with rupture and hemorrhage. METHODS: The demographic data and perioperative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected. The surgery within 7 days after hemorrhage was defined as a short-term surgery group, the surgery between 7 days and 6 months after hemorrhage was defined as a medium-term surgery group, and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group. The perioperative related indicators among the three groups were compared. RESULTS: This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage, of whom 13 were males and 18 were females, with an average age of (46.2±11.3) years. The short-term surgery group included 7 patients, the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients. In terms of tumor diameter, the patients in the long-term surgery group were significantly lower than those in the recent surgery group [(6.6±2.4) cm vs. (10.0±3.0) cm, P=0.039]. In terms of operation time, the long-term surgery group was significantly shorter than the mid-term surgery group [(157.5±56.8) min vs. (254.8±80.1) min, P=0.006], and there was no significant difference between other groups. In terms of estimated blood loss during surgery, the long-term surgery group was significantly lower than the mid-term surgery group [35 (10, 100) mL vs. 650 (300, 1 200) mL, P < 0.001], and there was no significant difference between other groups. In terms of intraoperative blood transfusion, the long-term surgery group was significantly lower than the mid-term surgery group [0 (0, 0) mL vs. 200 (0, 700) mL, P=0.014], and there was no significant difference between other groups. In terms of postoperative hospitalization days, the long-term surgery group was significantly lower than the mid-term surgery group [5 (4, 7) d vs. 7 (6, 10) d, P=0.011], and there was no significant difference between other groups. CONCLUSION: We believe that for patients with RAML rupture and hemorrhage, reoperation for more than 6 months is a relatively safe time range, with minimal intraoperative bleeding. Therefore, it is more recommended to undergo surgical treatment after the hematoma is systematized through conservative treatment.

The tumour-associated stroma correlates with poor clinical outcomes and immunoevasive contexture in patients with upper tract urothelial carcinoma: results from a multicenter real-world study (TSU-01 Study).

BACKGROUND: In this real-world study, we aimed to elucidate the predictive value of tumour-associated stroma for clinical prognostic and therapeutic response in upper tract urothelial carcinoma (UTUC) by reviewing the clinicopathologic characteristics of 1015 UTUC patients through a nationwide multicenter analysis. METHODS: The tumour-stroma ratio (TSR) was assessed based on tissue sections stained for hematoxylin and eosin (H&E), and patients were further stratified into stroma-high (>50% stroma) and stroma-low group (≤50% stroma). Kaplan-Meier curve and Cox regression hazard analysis were conducted to assess the survival outcomes of UTUC patients. Bioinformatics analysis and immunostaining analysis were applied to portray the tumour microenvironment (TME). RESULTS: Stroma-high UTUC was significantly associated with poorer survival outcomes and inferior chemotherapeutic responsiveness. Our established nomogram achieved a high prognostic accuracy in predicting overall survival and cancer-specific survival in both of the discovery cohort (area under the curve [AUC] 0.663 and 0.712) and the validation cohort (AUC 0.741 and 0.747). Moreover, stroma-high UTUC was correlated with immunoevasive TME accompanied by increased cancer-associated fibroblasts, tumour-associated macrophages and, conspicuously a cluster of highly exhausted CD8+ T cells. CONCLUSION: Our results showed stroma-high UTUC was associated with an inferior prognosis and an immunoevasive TME with exhausted CD8+ T cells in UTUC patients. Our TSR-based nomogram could be used to refine prognosis and inform treatment decisions of patients with UTUC.

Prolonged anesthesia induces neuroinflammation and complement-mediated microglial synaptic elimination involved in neurocognitive dysfunction and anxiety-like behaviors.

BACKGROUND: Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive. METHODS: Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats' cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization. RESULTS: This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the "Eat Me" complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted. CONCLUSIONS: These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients.

Preoperative predictive model of early urinary continence recovery after laparoscopic radical prostatectomy.

PURPOSE: To develop and validate a predictive model include magnetic resonance imaging (MRI) parameters preoperatively which can assess the risk of incontinence after laparoscopic radical prostatectomy (LRP) accurately. METHODS: We retrospectively reviewed and included 170 patients with prostate cancer who underwent LRP between July 2015 and June 2018 in our institution. All 170 patients were randomly resampled and divided into training set (n = 124) and verification set (n = 46) according to the ratio of 7:3. The Nomogram prediction model of the risk of incontinence after LRP was established through the training set and verified by the verification set. Baseline patient characteristics were obtained, including age, body mass index, and prostate volume. Perioperative characteristics such as pre-biopsy prostate specific antigen, biopsy Gleason score, clinical staging, and NVB sparing status were also collected. MRI parameters preoperatively including membranous urethral length (MUL), prostate apex depth ratio (PADR), and intravesical prostatic protrusion length (IPPL) were obtained. The C index and visual inspection of calibration curve were used to evaluate the discrimination and calibration of the model. RESULTS: According to the urinary incontinence (UI) at 3 months postoperatively, the patients were divided into 104 cases (61.2%) in the group with no incontinence and 66 patients (38.8%) in the group with incontinence. Multivariate logistic regression analysis of training set showed that cT3a (OR = 0.427, 95% CI 0.142-1.281, P = 0.1288), MUL (OR = 0.237, 95% CI 0.102-0.551, P < 0.01), PADR (OR = 0.276, 95% CI 0.116-0.655, P < 0.01), and IPPL (OR = 0.073, 95% CI 0.030-0.179, P < 0.01) were independent predictors of urinary incontinence at 3 months postoperatively. The model showed good discrimination with an area under the receiver operating characteristic (ROC) curve of 0.880, with the sensitivity and specificity 0.800 and 0.816, respectively, and good calibration (Hosmer-Lemeshow test result of 5.57, P = 0.695). Decision curve analysis demonstrated that the model was clinically useful. CONCLUSION: This study developed and validated a preoperative model in the form of a nomogram to predict the risk of UI after LRP at 3 months. MUL, PADR, and IPPL were significant independent predictive factors of the postoperative early urinary continence.

Comparison of minimally invasive versus open pelvic organ-preserving radical cystectomy in female patients with bladder cancer: a multicenter propensity score matching analysis.

PURPOSE: To compare the perioperative and oncologic outcomes between minimally invasive pelvic organ-preserving radical cystectomy (MIPOPRC) and open pelvic organ-preserving radical cystectomy (open POPRC) among female patients with bladder cancer (BCa). METHODS: We identified female patients who underwent POPRC for BCa at three centers between January 2006 and April 2018. Female patients who underwent open POPRC were matched with those who underwent MIPOPRC using 1:1 propensity score (PS) matching. The patient demographics and perioperative and oncologic outcomes were evaluated for the comparison between MIPOPRC and open POPRC. RESULTS: Among the 158 patients enrolled, 83 patients underwent MIPOPRC, and 75 underwent open POPRC. A total of 60 MIPOPRC and 60 open POPRC patients were matched successfully. The cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ significantly in the propensity score-weighted cohort (p = 0.297 and p = 0.600, respectively). Subgroup analysis by age and pathologic stage in the matched cohort revealed that CSS and RFS were with no differences among all subgroups. Moreover, multivariable Cox regression analyses showed that the surgical approach (MIPOPRC vs open POPRC) was not a predictor of CSS (p = 0.250). CONCLUSION: MIPOPRC was non-inferior to open POPRC in terms of oncologic outcomes among female patients. MIPOPRC could be technically feasible in selected female patients with BCa.

STING-IFN-I pathway relieves incision induced acute postoperative pain via inhibiting the neuroinflammation in dorsal root ganglion of rats.

BACKGROUND: The purpose of this study was to study the effect of STING-IFN-I pathway on incision induced postoperative pain in rats and its possible mechanisms. METHODS: The pain thresholds were evaluated by measuring the mechanical withdrawal threshold and the thermal withdrawal latency. The satellite glial cell and macrophage of DRG were analyzed. The expression of STING, IFN-a, P-P65, iNOS, TNF-α, IL-1ß and IL-6 in DRG was evaluated. RESULTS: The activation of STING-IFN-I pathway can reduce the mechanical hyperalgesia, thermal hyperalgesia, down-regulate the expression of P-P65, iNOS, TNF-α, IL-1ß and IL-6, and inhibit the activation of satellite glial cell and macrophage in DRG. CONCLUSIONS: The activation of STING-IFN-I pathway can alleviate incision induced acute postoperative pain by inhibiting the activation of satellite glial cell and macrophage, which reducing the corresponding neuroinflammation in DRG.

Adrenocortical carcinoma with venous tumor invasion: is there a role for mini-invasive surgery?

OBJECTIVE: This study aims to investigate early oncologic outcomes in patients with adrenocortical carcinoma (ACC) with venous invasion (VI) treated using both open and mini-invasive approaches. PATIENTS AND MATERIALS: We conducted a retrospective analysis of 4 international referral center databases, including all the patients undergoing adrenalectomy for ACC with VI from January 2007 to March 2020. According to CT scan or MRI, the tumor thrombus was classified into four levels: (1) adrenal vein invasion; (2) renal vein invasion; (3) infra-hepatic Inferior vena cava (IVC); and (4) retro-hepatic IVC. In addition, we divided our patients into patients who had undergone open surgery and mini-invasive surgery. RESULTS: We identified 20 patients with a median follow-up of 12 months. The median tumor size was 110mm. ENSAT stage was II in 4 patients, III in 13 patients, and IV in 3 patients. Tumor thrombus extended in the adrenal vein (n=5), renal vein (n=1), infra-hepatic IVC (n=9), or into the retro-hepatic IVC (n=5). Ten patients were treated with a mini-invasive approach. The patient treated with an open approach reported a more aggressive disease. The two groups did not differ in surgical margins, surgical time, blood losses, complications, and length of stay. The prognosis resulted worse in the patient undergoing open. Kaplan-Meier analysis indicated a difference in OS for the patients stratified by ENSAT stage (Log-rank p=0.011); we also reported a difference in DFS for patients stratified for thrombus extension (p=0.004) and ENSAT stage (p<0.001). CONCLUSION: The DFS of patients with VI from ACC is influenced by the staging and the extension of the venous invasion; the staging influences the OS. The mini-invasive approach seems feasible in selected patients; however, further studies investigating the oncological outcomes are needed. A mini-invasive approach for adrenal tumors with venous invasion is an explorable option in very selected patients.

The value of enhanced multiparameteric MRI diagnostic model for preoperatively predicting surgical methods of inferior vena cava in patients with renal tumors and inferior vena cava tumor thrombus.

BACKGROUND: Inferior vena cava tumor thrombus (IVCTT) invading the IVC wall majorly affects the surgical method choice and prognosis in renal tumors. Enhanced multiparameteric MRI plays an important role in preoperative evaluation. In this work, an MRI-based diagnostic model for IVCTT was established so as to guide the preoperative decisions. METHODS: Preoperative MR images of 165 cases of renal tumors with IVCTT were retrospectively analyzed, and imaging indicators were analyzed, including IVCTT morphology and Mayo grade, IVCTT diameter measurements, bland thrombosis, primary MRI-based diagnosis of renal tumor, and involvement of contralateral renal vein. The indicators were analyzed based on intraoperative performance and resection scope of the IVC wall. Multivariate logistic regression analysis was used to establish the diagnostic model. RESULTS: The morphological classification of the IVCTT, primary MRI-based diagnosis of renal tumors, maximum transverse diameter of IVCTT, and length of the bland thrombus were the main indexes predicting IVC wall invasion. The MRI-based diagnostic model established according to these indexes had good diagnostic efficiency. The prediction probability of 0.61 was set as the cutoff value. The area under the curve of the test set was 0.88, sensitivity was 0.79, specificity was 0.85, and prediction accuracy was 0.79 under the optimal cutoff value. CONCLUSION: The preoperative MRI-based diagnostic model could reliably predict IVC wall invasion, which is helpful for better prediction of IVC-associated surgical operations.

Comparative analysis of surgical and oncologic outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy: a propensity-matched cohort study.

OBJECTIVE: To provide insight into the surgical and oncological outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy (RALRN-VT, LRN-VT, ORN-VT) in patients with renal tumor and venous thrombus. MATERIALS AND METHODS: A propensity-matched retrospective cohort study containing 324 patients with renal tumor and venous thrombus from January 2014 to August 2021 was analyzed. We compared surgical outcomes and we used the Kalan-Meier method to assess the overall survival (OS), tumor-specific survival (TSS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). The Pearson chi-square test and Fisher exact test, Wilcoxon rank sum test, Cox proportional hazards regression model and log-rank test were used. RESULTS: After matching, baseline characteristics were comparable in the RALRN-VT, LRN-VT and ORN-VT group. The RALRN-VT group had the least operative time (median 134 min vs 289 min vs 330 min, P < 0.001), the least blood loss (median 250 ml vs 500 ml vs 1000 ml, P < 0.001) and the fewest packed red blood cells transfusion (median 400 ml vs 800 ml vs 1200 ml, P < 0.001). The ORN-VT group had the highest complication rate (18.2 vs 22.7 vs 43.2%, P = 0.005), the highest Clavien grade (P = 0.001) and the longest postoperative hospital stay (median 7d vs 8d vs 10d, P < 0.001). No significant difference in OS, TSS and MFS between the minimally invasive procedures (MIP, including RALRN-VT and LRN-VT) group and ORN-VT group was found. The hazard ratio of LRFS for the MIP group was 0.20 (95% CI 0.06-0.70, P = 0.01) compared with ORN-VT group. CONCLUSIONS: RALRN-VT can result in the best surgical outcomes compared with LRN-VT and ORN-VT. The MIP group had a better LRFS compared with ORN-VT group.

Long-term outcomes after cytoreductive nephrectomy and thrombectomy of patients with metastatic renal cell carcinoma with venous tumor thrombus: a retrospective study from a large Chinese center.

BACKGROUND: Targeted therapy combined with immunotherapy is the current first-line treatment for metastatic renal cell carcinoma (mRCC), but patients with tumor thrombus (TT) may suffer from lower limb edema or even sudden cardiac death, so the purpose of this study is to investigate the efficacy and safety of surgical treatment in patients with mRCC and TT and explore worse factors to affect the prognosis in this series of patients. PATIENTS AND METHODS: A total of 85 mRCC patients with TT who received cytoreductive nephrectomy and thrombectomy at our medical center from 2014 to 2023 are included. All patients received postoperative systemic therapy. Overall survival (OS) is defined as the time from surgery to death due to any reason or the last follow-up. Kaplan-Meier analysis was performed to evaluate OS and differences among groups were tested by log-rank. Multivariable Cox proportional hazards analysis was performed to ascertain independent relationships between clinicopathological factors and OS. RESULTS: The median age of patients was 58 years old. Eleven patients (12.9%) had no symptoms, 39 patients (45.9%) had local symptoms, 15 patients (17.6%) had systemic symptoms, and 20 patients (23.5%) had both. Mayo grade of TT was 0, 1, 2, 3, and 4 for 12, 27, 31, 7, and 8 patients respectively. Fifty-five patients had lung metastasis, 23 had bone metastasis, 16 had liver metastasis, 13 had adrenal metastasis, and 9 had lymph node metastasis. Of all patients, 17 patients had multiple metastases. The median operation time is 289 min and the median intraoperative hemorrhage is 800 ml. Twenty-eight patients experienced postoperative complications, 8 of which were serious complications of modified Clavien grade III or higher. The median OS of all patients was 33 months and median follow up time was 26 months. In multivariate analysis, systemic symptom (p = 0.00753), pathological type (p = 0.0166), sarcomatous degeneration (p = 0.0334), and perirenal fat infiltration (p = 0.0202) are independent predictors of OS. CONCLUSION: Cytoreductive nephrectomy and thrombectomy is relatively safe and effective for patients with mRCC accompanied by TT. In this series of patients, the worse prognosis is associated with systemic symptoms, non-clear cell carcinoma, sarcomatous degeneration and perirenal fat infiltration.

Outcome comparison of radical prostatectomy versus seed brachytherapy for clinically localized prostate cancer using two biochemical recurrence definitions.

OBJECTIVE: We compared the outcome of radical prostatectomy (RP) with seed brachytherapy (BT) in clinically localized prostate cancer (LPCa) using two different biochemical recurrence (BCR) definitions. METHODS: Clinical data of 1117 patients with non-metastatic prostate cancer (PCa) treated with either RP or BT as the basis of the multimodal therapy from a single tertiary hospital between 2007 and 2021 were retrospectively analyzed. 843 LPCa patients (RP = 737, BT = 106) with at least one prostate-specific antigen (PSA) test after treatment were finally included. The BCR survival was evaluated by direct comparison and one-to-one propensity score matching (PSM) analysis using surgical definition (PSA ≥ 0.2ng/ml) for RP and surgical/Phoenix definition (PSA nadir + 2ng/ml ) for BT. The propensity score (PS) was calculated by multivariable logistic regression based on the clinicopathological parameters. RESULTS: Median follow-up was 43 months for RP patients and 45 months for BT patients. Kaplan-Meier analysis did not show any statistically significant differences in terms of BCR-free survival (BFS) between the two groups when using Phoenix definition for BT (P > 0.05). Similar results were obtained in all D'Amico risk groups when stratified analyses were conducted. However, RP achieved improved BFS compared to BT in the whole cohort and all risk groups with the surgical definition for BT(P < 0.05). After adjusting PS, 192 patients were divided into RP and BT groups (96 each). RP presented a better BFS than BT when using the surgical definition (P < 0.001), but no significant difference was found when using the Phoenix definition (P = 0.609). CONCLUSION: Inconsistent BCR-free survival outcomes were acquired using two different BCR definitions for BT patients. RP provided comparable BFS with BT using the Phoenix definition but better BFS using the surgical definition, regardless of whether the PSM was performed. Our findings indicated that an exact BCR definition was critical for prognostic assessment. The corresponding results will assist physicians in pretreatment consultation and treatment selection.

Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial.

BACKGROUND: Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer. METHODS: CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478. FINDINGS: Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group. INTERPRETATION: In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile. FUNDING: Jiangsu Hengrui Pharmaceuticals.

Activation of locus coeruleus-spinal cord noradrenergic neurons alleviates neuropathic pain in mice via reducing neuroinflammation from astrocytes and microglia in spinal dorsal horn.

BACKGROUND: The noradrenergic neurons of locus coeruleus (LC) project to the spinal dorsal horn (SDH), and release norepinephrine (NE) to inhibit pain transmission. However, its effect on pathological pain and the cellular mechanism in the SDH remains unclear. This study aimed to explore the analgesic effects and the anti-neuroinflammation mechanism of LC-spinal cord noradrenergic pathway (LC:SC) in neuropathic pain (NP) mice with sciatic chronic constriction injury. METHODS: The Designer Receptors Exclusively Activated by Designer Drugs (DREADD) was used to selectively activate LC:SC. Noradrenergic neuron-specific retro-adeno-associated virus was injected to the spinal cord. Pain threshold, LC and wide dynamic range (WDR) neuron firing, neuroinflammation (microglia and astrocyte activation, cytokine expression), and α2AR expression in SDH were evaluated. RESULTS: Activation of LC:SC with DREADD increased the mechanical and thermal nociceptive thresholds and reduced the WDR neuron firing. LC:SC activation (daily, 7 days) downregulated TNF-α and IL-1ß expression, upregulated IL-4 and IL-10 expression in SDH, and inhibited microglia and astrocytes activation in NP mice. Immunofluorescence double staining confirmed that LC:SC activation decreased the expression of cytokines in microglia of the SDH. In addition, the effects of LC:SC activation could be reversed by intrathecal injection of yohimbine. Immunofluorescence of SDH showed that NE receptor α2B-AR was highly expressed in microglia in CCI mice. CONCLUSION: These findings indicate that selective activation of LC:SC alleviates NP in mice by increasing the release of NE and reducing neuroinflammation of astrocytes and microglia in SDH.

Procedural analgesic interventions in China: a national survey of 2198 hospitals.

BACKGROUND: Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies. METHODS: Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology. RESULTS: Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3-11.4] cases per day, with 7.3 [3.2-13.6] performed in Grade III hospitals and 3.4 [1.8-6.8] performed in Grade II hospitals (z = -7.065, p < 0.001). CONCLUSIONS: Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions.

Diagnosis and treatment strategies for intraoperative pulmonary embolism caused by renal tumor thrombus shedding.

AIM: To provide an overview of techniques for prevention, immediate diagnosis, and treatment strategies of intraoperative pulmonary embolism caused by renal tumor thrombus shedding. METHODS: A total of 290 patients admitted into our medical center from March 2015 to May 2021 were retrospectively analyzed. All patients underwent radical nephrectomy with tumor thrombectomy. Six patients were diagnosed as pulmonary embolism during the perioperative period, of which two patients had tumor thrombus shedding. One patient underwent thoracotomy and thrombectomy, one patient underwent interventional thrombectomy, and four patients underwent conservative treatment. All patients have gone through our diagnosis and strategy flow chart. Demographic data, tumor characteristics, tumor thrombus characteristics, and follow-up data were collected. RESULTS: In the preoperative risk factor assessment, of the 253 patients who entered the follow-up, 163 were women, 48 were older than 60 years old, and 83 had a duration of more than 2 months. In addition, 27 patients had tumor thrombus with bland thrombus, and 43 patients had floating tumor thrombus. 78 patients underwent postoperative anticoagulation after evaluation. The average follow-up time was 23.3 ± $\pm $ 8.6 months (range, 7-31 months). All patients were alive during the follow-up period. CONCLUSION: For acute pulmonary embolism during nephrectomy and tumor thrombectomy, management strategies can be used to deal with intraoperative emergencies and provide reference.

Nomogram for predicting survival of renal cell carcinoma with tumor thrombus based on perioperative clinicopathological factors from a Chinese high-volume center.

OBJECTIVES: To investigate perioperative clinicopathological predictors and establish a predictive nomogram for survival in patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy. METHODS: Patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy were included in the study between January 2014 and June 2020. Cox regression analysis was used for univariate and multivariate survival analyses. A predictive nomogram for survival was established and internally validated using bootstrap resampling method. RESULTS: A total of 228 patients were enrolled in this study. The median age was 60 years (interquartile range 53-66 years), consisting of 174 (76.3%) males and 54 (23.7%) females. The median follow-up time was 17.5 months (range 1-74 months), 26.8% (61 of 228) patients died of all causes. In multivariable analysis, hemoglobin less than the lower limit of normal (hazard ratio 1.73; 95% confidence interval 1.01-2.96; P = 0.045), sarcomatoid feature (hazard ratio 3.67; 95% confidence interval 1.97-6.82; P < 0.001), perirenal fat invasion (hazard ratio 1.80; 95% confidence interval 1.05-3.09; P = 0.033), histological subtype (hazard ratio 2.74; 95% confidence interval 1.39-5.41; P = 0.004), and metastasis at surgery (hazard ratio 1.71; 95% confidence interval 1.01-2.90; P = 0.047) were independently associated with overall survival. The result of internal validation presented that the predictive performance of the nomogram for survival measured by C-index was 0.77. CONCLUSIONS: We developed a predictive nomogram with well-internal validation for survival in patients with renal cell carcinoma and venous tumor thrombus, which can greatly promote risk stratification and treatment planning.