Chronic hypercortisolism disrupts the principal functional gradient in Cushing's disease: A multi-scale connectomics and transcriptomics study.

Cushing's disease (CD) represents a state of cortisol excess, serving as a model to investigate the effects of prolonged hypercortisolism on functional brain. Potential alterations in the functional connectome of the brain may explain frequently reported cognitive deficits and affective disorders in CD patients. This study aims to elucidate the effects of chronic hypercortisolism on the principal functional gradient, which represents a hierarchical architecture with gradual transitions across cognitive processes, by integrating connectomics and transcriptomics approaches. Utilizing resting-state functional magnetic resonance imaging data from 140 participants (86 CD patients, 54 healthy controls) recruited at a single center, we explored the alterations in the principal gradient in CD patients. Further, we thoroughly explored the underlying associative mechanisms of the observed characteristic alterations with cognitive function domains, biological attributes, and neuropsychiatric representations, as well as gene expression profiles. Compared to healthy controls, CD patients demonstrated changes in connectome patterns in both primary and higher-order networks, exhibiting an overall converged trend along the principal gradient axis. The gradient values in CD patients' right prefrontal cortex and bilateral sensorimotor cortices exhibited a significant correlation with cortisol levels. Moreover, the cortical regions showing gradient alterations were principally associated with sensory information processing and higher-cognitive functions, as well as correlated with the gene expression patterns which involved synaptic components and function. The findings suggest that converged alterations in the principal gradient in CD patients may mediate the relationship between hypercortisolism and cognitive impairments, potentially involving genes regulating synaptic components and function.

A three-dimensional renal tumor anatomy and intrarenal relationship nephrometry (ADDD) for robot-assisted partial nephrectomy : 3D-CT based nephrometry for RAPN.

OBJECTIVE: To develop a 3D scoring system of tumor anatomy and intrarenal relationship for assessing surgical complexity and outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We prospectively enrolled patients with a renal tumor who had a 3D model and underwent RAPN between Mar 2019 and Mar 2022. The ADDD nephrometry consisted of the contact surface area between tumor and parenchyma (A), the depth of tumor invasion into the renal parenchyma (D1), the distance from tumor to the main intrarenal artery (D2), and to the collecting system (D3). The primary outcomes included perioperative complication rate and trifecta outcome (WIT ≤ 25 min, negative surgical margins, and no major complications). RESULTS: We enrolled a total of 301 patients. The mean tumor size was 2.93 ± 1.44 cm. There were 104 (34.6%) patients, 119 (39.5%) patients, and 78 (25.9%) patients in the low-, intermediate-, and high-risk groups, respectively. Each point increase in the ADDD score increased the risk of complications [hazard ratio (HR) 1.501]. A lower grade indicated a lower risk of failed trifecta (HR low group 15.103, intermediate group 9.258) and renal function damage (HR low risk 8.320, intermediate risk 3.165) compared to the high-risk group. The AUC of ADDD score and grade were 0.738 and 0.645 for predicting major complications, 0.766 and 0.714 for predicting trifecta outcome, and 0.746 and 0.730 for predicting postoperative renal function reservation. CONCLUSION: The 3D-ADDD scoring system shows the tumor anatomy and its intraparenchymal relationships and has better efficacy in predicting surgical outcomes of RAPN.

Posteriorly Augmented Anastomotic Ureteroplasty with Lingual Mucosal Onlay Grafts for Long Proximal Ureteral Strictures: 10 Cases of Experience.

Objective: To share the technique of posteriorly augmented anastomotic ureteroplasty with lingual mucosal onlay grafts for long proximal ureteral strictures as well as our initial experience with the technique. Methods: From October 2018 to September 2019, 10 cases of robotic and laparoscopic posteriorly augmented anastomotic ureteroplasty with lingual mucosal onlay grafts for long proximal ureteral strictures were recruited from our database of Reconstruction of Urinary Tract: Technology, Epidemiology and Result (RECUTTER). The perioperative and follow-up data were recorded. Complete success was defined as the absence of clinical symptoms, relieved stenosis on imaging, and a stable estimated glomerular filtration rate without serious complications. Results: All surgeries were completed without serious complications. There were eight laparoscopic surgeries and two robotic surgeries. The median length of defect after posteriorly augmented anastomosis was 3 cm (range, 3-5 cm). The median length of the lingual mucosa graft was 4 cm (range, 3-5 cm). The median operative time was 237 minutes (range, 189-310 minutes). The median estimated blood loss was 40 mL (range, 10-100 mL). The median postoperative length of stay was 7.5 days (range, 5-22 days). The Double-J stent was removed median 3.5 months (range, 2-7 months) after the surgery. At the median follow-up of 11 months (range, 7-20 months), all patients achieved the successful criteria of treatment. Conclusion: The posteriorly augmented anastomotic ureteroplasty with lingual mucosal onlay grafts for long proximal ureteral strictures is a feasible and safe technique, which may be an option especially for strictures marginally longer than those that can be safely repaired via end-to-end anastomosis.

Prognostic significance of the combination of preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in patients with renal cell carcinoma after nephrectomy.

BACKGROUND: To evaluate the prognostic significance of the novel index combining preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in renal cell carcinoma (RCC) patients. METHODS: We enrolled 1360 patients who underwent nephrectomy in our institution from 2001 to 2010. The cutoff values for HALP, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were defined by using X-tile software. Survival was analyzed by the Kaplan-Meier method, with differences analyzed by the log-rank test. Multivariate Cox proportional-hazards model was used to evaluate the prognostic significance of HALP for RCC. RESULTS: Low HALP was significantly associated with worse clinicopathologic features. Kaplan-Meier and log-rank tests revealed that HALP was strongly correlated with cancer specific survival (P < 0.001) and Cox multivariate analysis demonstrated that preoperative HALP was independent prognostic factor for cancer specific survival (HR = 1.838, 95%CI:1.260-2.681, P = 0.002). On predicting prognosis by nomogram, the risk model including TNM stage, Fuhrman grade and HALP score was more accurate than only use of TNM staging. CONCLUSIONS: HALP was closely associated with clinicopathologic features and was an independent prognostic factor of cancer-specific survival for RCC patients undergoing nephrectomy. A nomogram based on HALP could accurately predict prognosis of RCC.

Partial nephrectomy for T3aN0M0 renal cell carcinoma: shall we step forward?

ABSTRACT Objectives: To evaluate the prognosis of non-metastatic T3a renal cell carcinoma (RCC) with partial nephrectomy (PN). Patients and Methods: We retrospectively evaluated 125 patients with non-metastatic T3a RCC. Patients undergoing PN and radical nephrectomy (RN) were strictly matched by clinic-pathologic characteristics. Log-rank test and Cox regression model were used for univariate and multivariate analysis. Results: 18 pair patients were matched and the median follow-up was 35.5 (10-86) months. PN patients had a higher postoperative eGFR than RN patients (P=0.034). Cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ between two groups (P=0.305 and P=0.524). On multivariate analysis, CSS decreased with positive surgical margin and anemia (both P <0.01) and RFS decreased with Furhman grade, positive surgical margin, and anemia (all P<0.01). Conclusions: For patients with non-metastatic pT3a RCC, PN may be a possible option for similar oncology outcomes and better renal function.

Partial nephrectomy for T3aN0M0 renal cell carcinoma: shall we step forward?

OBJECTIVES: To evaluate the prognosis of non-metastatic T3a renal cell carcinoma (RCC) with partial nephrectomy (PN). PATIENTS AND METHODS: We retrospectively evaluated 125 patients with non-metastatic T3a RCC. Patients undergoing PN and radical nephrectomy (RN) were strictly matched by clinic-pathologic characteristics. Log-rank test and Cox regression model were used for univariate and multivariate analysis. RESULTS: 18 pair patients were matched and the median follow-up was 35.5 (10-86) months. PN patients had a higher postoperative eGFR than RN patients (P=0.034). Cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ between two groups (P=0.305 and P=0.524). On multivariate analysis, CSS decreased with positive surgical margin and anemia (both P<0.01) and RFS decreased with Furhman grade, positive surgical margin, and anemia (all P<0.01). CONCLUSIONS: For patients with non-metastatic pT3a RCC, PN may be a possible option for similar oncology outcomes and better renal function.

Prognostic Value of Inflammatory and Nutritional Scores in Renal Cell Carcinoma After Nephrectomy.

INTRODUCTION: We compared the prognostic significance of inflammatory and nutritional scores, including the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in patients with renal cell carcinoma (RCC) undergoing nephrectomy. PATIENTS AND METHODS: We retrospectively analyzed the data from 1360 patients with RCC undergoing nephrectomy from 2001 to 2010. The PNI was calculated as the serum albumin level (g/L) + 5 × lymphocyte count (109/L). The receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values. The areas under the ROC curve (AUCs) were calculated to compare the predictive ability of the indexes. Univariate and multivariate analyses were used to identify the prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: The median follow-up period after surgery was 67 months (range, 2-108 months). The PNI had the largest AUC for both OS and PFS. On univariate analysis, each index was associated with OS and PFS. On multivariate analysis, PNI, rather than other inflammatory and nutritional scores, remained as a risk factor for OS (hazard ratio [HR], 1.645; 95% confidence interval [CI], 1.153-2.348; 2P = .006) and PFS (HR, 1.705; 95% CI, 1.266-2.296; 2P < .001). CONCLUSION: The preoperative PNI might be a good prognostic factor for both OS and PFS in RCC patients undergoing nephrectomy.

A Novel Predictor of Survival with Renal Cell Carcinoma After Nephrectomy.

PURPOSE: To validate plasma fibrinogen and serum cholesterol levels as prognostic factors for patients with renal cell carcinoma (RCC) and to explore the prognostic value of their combination. PATIENTS AND METHODS: Medical data for 1360 RCC patients after nephrectomy were collected. X-tile software was used to determine the cutoff values. The association between clinicopathological factors and fibrinogen and cholesterol levels was determined, and factors predicting survival were examined by multivariate analysis. RESULTS: The median follow-up was 67 months (interquartile range 36-74 months). On univariate and multivariate analysis, both preoperative plasma fibrinogen and serum cholesterol were independent prognostic factors of cancer-specific survival (CSS) and progression-free survival (PFS). By combining the two factors, we developed a novel index, fibrinogen-cholesterol (FC) score and found it to have better prognostic accuracy than the two factors alone. FC was an independent prognostic factor for both CSS (FC score = 1: hazard ratio [HR] = 3.207, 95% confidence interval [CI] = 1.775-5.793; FC score = 2: HR = 5.516, 95% CI = 2.891-10.527) and PFS (FC score = 1: HR = 2.178, 95% CI = 1.545-3.071; FC score = 2: HR = 3.709, 95% CI = 2.355-5.840). CONCLUSION: Both preoperative plasma fibrinogen and serum cholesterol levels are independent prognostic factors for CSS and PFS in RCC patients after nephrectomy. A novel indicator, FC score, could be considered a novel preoperative prognostic index in RCC.

Could Magnetic Resonance Imaging Help to Identify the Presence of Prostate Cancer Before Initial Biopsy? The Development of Nomogram Predicting the Outcomes of Prostate Biopsy in the Chinese Population.

PURPOSE: This study was designed to investigate the effectiveness of magnetic resonance imaging (MRI) in diagnosing prostate cancer (PCa) and high-grade prostate cancer (HGPCa) before transrectal ultrasound (TRUS)-guided biopsy. METHODS: The clinical data of 894 patients who received TRUS-guided biopsy and prior MRI test from a large Chinese center was reviewed. Based on Prostate Imaging Reporting and Data System (PI-RADS) scoring, all MRIs were re-reviewed and assigned as Grade 0-2 (PI-RADS 1-2; PI-RADS 3; PI-RADS 4-5). We constructed two models both in predicting PCa and HGPCa (Gleason score ≥ 4 + 3): Model 1 with MRI and Model 2 without MRI. Other clinical factors include age, digital rectal examination, PSA, free-PSA, volume, and TRUS. RESULTS: PCa and HGPCa were present in 434 (48.5 %) and 218 (24.4 %) patients. An MRI Grade 0, 1, and 2 were assigned in 324 (36.2 %), 193 (21.6 %) and 377 (42.2 %) patients, which was associated with the presence of PCa (p < 0.001) and HGPCa (p < 0.001). Particularly in patients aged ≤55 years, the assignment of MRI Grade 0 was correlated with extremely low rate of PCa (1/27) and no HGPCa. The c-statistic of Model 1 and Model 2 for predicting PCa was 0.875 and 0.841 (Z = 4.2302, p < 0.001), whereas for predicting HGPCa was 0.872 and 0.850 (Z = 3.265, p = 0.001). Model 1 exhibited higher sensitivity and specificity at same cutoffs, and decision-curve analysis also suggested the favorable clinical utility of Model 1. CONCLUSIONS: Prostate MRI before biopsy could predict the presence of PCa and HGPCa, especially in younger patients. The incorporation of MRI in nomograms could increase predictive accuracy.

The Significance of Metastasectomy in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy.

OBJECTIVE: To investigate the efficacy of surgery in the treatment of metastatic renal cell carcinoma (mRCC) and to identify prognostic factors. METHODS: A single center retrospective study of 96 patients with mRCC from December 2004 to August 2013. RESULTS: The median follow-up time was 45 months. Thirty-one (32.3%) of the patients received complete resection of metastatic sites, 11 (11.5%) of the patients underwent incomplete resection of metastatic sites, and 54 (56.3%) of the patients received no surgery. In the univariate Kaplan-Meier analysis, the median overall survival times of the three groups were 52 months, 16 months, and 22 months, respectively (p < 0.001). The difference in the overall survival time was statistically significant between complete resection and no surgery groups (HR = 0.43, p = 0.009), while there was no significant difference between the incomplete metastasectomy and no surgery groups (HR = 1.80, p = 0.102). According to the multivariate Cox regression analysis, complete metastasectomy (HR = 0.49, p = 0.033), T stage > 3 (HR = 1.88, p = 0.015), disease free interval <12 months (HR = 2.34, p = 0.003), and multiorgan involvement (HR = 2.00, p = 0.011) were significant prognostic factors. CONCLUSION: In the era of targeted therapy, complete metastasectomy can improve overall survival. Complete metastasectomy, T stage > 3, disease free interval <12 months, and multiorgan involvement are independent prognostic factors.

Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to Overall Survival.

Sorafenib has been recommended as first- or second-line treatment for metastatic renal cell carcinoma (mRCC) by several guidelines. The objective of this study is to evaluate the efficacy of sorafenib monotherapy in Chinese patients with mRCC and determine the prognostic clinicopathologic factors associated with survival in these patients.This is a single-arm retrospective study conducted in 2 tertiary medical centers; 140 mRCC patients were enrolled between January 2007 and June 2014. Sorafenib was administered at a dose of 400 mg twice daily, and continued until disease progression, at which point the dose was increased to 600 or 800 mg twice daily, or the onset of an intolerable adverse drug event (ADE) that required dose reduction or temporary suspension of treatment.The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.The median follow-up time was 32 months. The median OS and PFS were 24 months (range, 3-88 months) and 16 months (range, 0-88 months), respectively. Patients with clear cell carcinoma had a greater OS (P=0.001) whereas sarcomatoid differentiation (P=0.045) and disease progression (P=0.010) negatively impacted OS; time from kidney surgery or biopsy to initiation of sorafenib treatment was associated with PFS (P=0.027). Efficacy analysis revealed that 3 (2.1%) patients achieved complete responses, 28 (20.0%) patients experienced partial responses, 88 (62.9%) patients had stable disease, and 21 (15.0%) patients developed progressive disease. Moreover, the ORR was 22.1%, and the DCR was 85.0%. Most ADEs were classified as grades 1 or 2 with only 14 (10.0%) patients experiencing a severe ADE (grade 3).Sorafenib monotherapy can achieve promising OS and PFS for Chinese patients with mRCC, especially in those with clear cell carcinoma, with manageable adverse events.