CREPT/RPRD1B promotes tumorigenesis through STAT3-driven gene transcription in a p300-dependent manner.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) has been shown to upregulate gene transcription during tumorigenesis. However, how STAT3 initiates transcription remains to be exploited. This study is to reveal the role of CREPT (cell cycle-related and elevated-expression protein in tumours, or RPRD1B) in promoting STAT3 transcriptional activity. METHODS: BALB/c nude mice, CREPT overexpression or deletion cells were employed for the assay of tumour formation, chromatin immunoprecipitation, assay for transposase-accessible chromatin using sequencing. RESULTS: We demonstrate that CREPT, a recently identified oncoprotein, enhances STAT3 transcriptional activity to promote tumorigenesis. CREPT expression is positively correlated with activation of STAT3 signalling in tumours. Deletion of CREPT led to a decrease, but overexpression of CREPT resulted in an increase, in STAT3-initiated tumour cell proliferation, colony formation and tumour growth. Mechanistically, CREPT interacts with phosphorylated STAT3 (p-STAT3) and facilitates p-STAT3 to recruit p300 to occupy at the promoters of STAT3-targeted genes. Therefore, CREPT and STAT3 coordinately facilitate p300-mediated acetylation of histone 3 (H3K18ac and H3K27ac), further augmenting RNA polymerase II recruitment. Accordingly, depletion of p300 abolished CREPT-enhanced STAT3 transcriptional activity. CONCLUSIONS: We propose that CREPT is a co-activator of STAT3 for recruiting p300. Our study provides an alternative strategy for the therapy of cancers related to STAT3.

Crossing vessels with suspension versus transposition in laparoscopic pyeloplasty of patients with ureteropelvic junction obstruction: a retrospective study.

PURPOSE: To compare the effects of two different methods of laparoscopic pyeloplasty for the treatment of crossing vessels. METHODS: From January 2016 to August 2019, 33 patients with ureteropelvic junction obstruction (UPJO) underwent laparoscopic pyeloplasty at our center, including 21 men and 12 women, ranging from 14 to 66 years of age. There were 20 and 13 cases on the left and right sides, respectively. Patients underwent laparoscopic pyeloplasty (Anderson-Hynes operation). During the operation, either a Hem-o-lok clip suspension or transposition was used to treat the crossing vessels. The double-J stent was removed 8 weeks after the operation. The clinical data of patients were collected and follow-ups were regularly performed after the operation. RESULTS: All the crossing vessels were successfully preserved, and none of them were severed during the operation. The average operation time was 210.6 ± 58.9 min in this group and the average time to manage the crossing vessel was 8.0 ± 3.5 min, 5.9 ± 1.4 min in the suspension group, and 11.7 ± 3.0 min in the transposition group. The dilation of the affected side was 4.8 ± 1.5 cm before operation and 1.2 ± 1.3 cm 3 months after operation. The difference was statistically significant (P < 0.05). Follow-up to February 2020 showed no significant changes in the kidney size in all patients and hydronephrosis was relieved. CONCLUSION: For UPJO patients with crossing vessel compression, the method of Hem-o-lok suspension or vascular transposition can be used to relieve crossing vascular compression and improve the success of pyeloplasty.

Challenges and management of laparoscopic treatment of pyonephrosis caused by calculi.

BACKGROUND: Calculous pyonephrosis is a disease characterized by infectious hydronephrosis associated with pyogenic destruction of the renal parenchyma, with complete or almost complete loss of renal function. METHODS: The clinical data of laparoscopic nephrolithotomy performed at Peking University People's Hospital from May 2017 to June 2020 were analyzed retrospectively. Eight patients (2 men; 6 women) aged 27 to 65 years (average age, 45.8 years) were included. Among them, 7 patients were treated with retroperitoneal approach and 1 patient by transperitoneal approach. All patients had received more than one endoscopic lithotripsy before nephrectomy. Renal dynamic imaging and computed tomography revealed the absence of function in pyonephrosis before nephrectomy. General clinical data and perioperative data were recorded. All nephrectomies were performed by the same physician. RESULTS: Laparoscopic surgery was successfully performed in 7 patients; however, 1 patient underwent open surgery because of bleeding. The operation time, average operation time, and blood loss were 1.5-4.5 h, 3.4 h, and 100-1000 ml (average, 300 ml), respectively. The postoperative pathology showed inflammatory renal disease in 6 patients, xanthogranulomatous pyelonephritis in 1 patient, and high-grade urothelial cancer in 1 patient. The average postoperative hospital stay was 5.3 days. One patient had a Clavien-Dindo Grade IIIb complication (severe hematuria), which required laparotomy, and was found that there was bleeding of ureteral stump. None of the patients experienced poor healing of endoscopic wounds. CONCLUSION: For patients with complicated calculous pyonephrosis, renal inflammation could not be effectively controlled, and renal function was seriously damaged. Thus, kidneys should be immediately resected. With laparoscopy, patients may recover quickly, but surgeons require enough experience when performing laparoscopy to achieve safety.

High Novel Oncogene with Kinase-Domain (NOK) Gene Expression is Associated with the Progression of Renal Cell Carcinoma.

BACKGROUND: To study the expression levels of the NOK (novel oncogene with kinase-domain) gene in renal cell carcinoma and its association with the progression of this cancer. METHODS: In this study, immunohistochemistry (IHC) and Western blot analyses were applied to investigate the NOK expression level in RCC and adjacent normal renal tissue samples. MTT, colony formation, and migration assays were also utilized to evaluate the role of NOK in RCC cell lines. RESULTS: Knocked-down expression of NOK in an RCC cell line (786-0) suppressed cellular proliferation and migration by restraining the activation of AKT and ERK. We found that the expression level of NOK was significantly higher in RCC tissues than in their adjacent tissues, and more importantly, overexpression of NOK was evidently correlated with the tumor TNM stage and Fuhrman grade (p < 0.001). A high level of NOK was also associated with poor overall survival (p < 0.05) and disease-free survival (p < 0.05) by Kaplan-Meier analysis. CONCLUSIONS: NOK expression increased in RCC and was significantly correlated with TNM stage, Fuhrman grade, poor overall survival, poor disease-free survival, metastasis, and proliferation in RCC cells by regulating the activation of AKT and ERK, suggesting that NOK may play important roles as a positive regulator to RCC.

[Comparison of tubeless-percutaneous nephrolithotomy and ureteroscopic lithotripsy in treatment of upper-ureteral calculi sized ≥ 1.5 cm].

OBJECTIVE: To compare the efficacy and safety of tubeless percutaneous nephrolithotomy (tubeless-PCNL) and ureteroscopic lithotripsy (URL) in treatment of impacted upper-ureteral calculi ≥ 1.5 cm in size. METHODS: Patients with ureteral stones sized ≥ 1.5 cm and lodged above the fourth lumbar vertebra who were treated between September 2009 and July 2013 in Peking University People's Hospital were retrospectively analyzed. In the study, 182 patients underwent tubeless-PCNL or URL treatment respectively, and the operation success rates were compared. The duration of operation, intraoperative blood loss(average hemoglobin decrease), complications, mean hospital stay and residual stone rates were also compared. RESULTS: Fifty-four patients underwent tubeless-PCNL treatment,the average stone size was (1.9 ± 0.4) cm,nephrostomy tubes were placed in two patients,and the operation success rate was 96.3%(52/54). In the rest of the 52 patients,and the mean operation time was (30.1 ± 14.8) minutes with an average postoperative hemoglobin decrease of (10.2 ± 6.1) g/L, and the mean hospital stay was (3.0 ± 1.4) days. Only one of the patients had residual fragments (2%). The main complications included minor perirenal hematoma in 1 patient, fever in 2 patients,elevated blood WBC in 11 patients,and analgesics requirement in 3 patients. In the study, 128 patients were treated with URL,the average stone size was (1.7 ± 0.3) cm. 19 procedures failed,and 10 patients were converted to PCNL,extracorporeal shock wave lithotripsy was executed subsequently after double-J stent placement in 5 patients,and migration of calculi or stone fragments happened in 4 patients. The mean operative time was (51.3 ± 25.5) minutes for the remaining 109 patients with a hemoglobin reduction of (5.2 ± 7.2) g/L. The mean hospital stay was (2.9 ± 1.3) days, and residual stones were found in 13 of the 109 patients (11.9%). The main complications included fever in 3 patients, elevated blood WBC in 42 patients, analgesics requirement in 13 patients because of pain in the urethra or flank. The size of the stones between the two group didn't show significant difference,but the success rate of the tubeless-PCNL procedure was significantly higher. Except that hemoglobin decrease was slightly higher in the tubeless-PCNL group,the mean operative time, the rate of residual stones and rate of complications of the tubeless-PCNL group were lower significantly. CONCLUSION: Treating stones above 4th lumbar vertebra larger than 1.5 cm were challenging. It is difficult to treat these stones with URL because of a high probability to fail, but on the contrary, tubeless-PCNL was more likely to be performed successfully. For surgeons experienced with the PCNL technology, treating stones ≥ 1.5 cm with tubeless-PCNL procedure may turn out to be more efficient and with a higher operation success rate, and the risk of complications was lower without lengthening the postoperative hospital stay.

m6A Methylation-Mediated Stabilization of LINC01106 Suppresses Bladder Cancer Progression by Regulating the miR-3148/DAB1 Axis.

BACKGROUND: The pivotal roles of long noncoding RNAs (lncRNAs) in the realm of cancer biology, inclusive of bladder cancer (BCa), have been substantiated through various studies. Remarkably, RNA methylation, especially m6A modification, has demonstrated its influence on both coding and noncoding RNAs. Nonetheless, the explicit impact of RNA methylation on lncRNAs and its subsequent contribution to the progression of BCa remains to be elucidated. METHODS: In the present investigation, we scrutinized the expression and m6A methylation status of LINC01106, employing quantitative real-time PCR (qRT-PCR) and methylated RNA immunoprecipitation (MeRIP)-qPCR. To decipher the regulatory mechanism underpinning LINC01106, we utilized RNA immunoprecipitation (RIP)-qPCR, methylated RNA immunoprecipitation (MeRIP) assays, and bioinformatic analysis. Furthermore, the CRISPR/dCas13b-METTL3-METTL14 system was implemented to probe the function of LINC01106. RESULTS: The findings of our study indicated that LINC01106 is under expressed and exhibits diminished m6A methylation levels in BCa tissues when compared those of normal controls. A diminished expression of LINC01106 was associated with a less favorable prognosis in BCa patients. Intriguingly, CRISPR-mediated hypermethylation of LINC01106, facilitated by dCas13b-M3-M14, abolished the malignant phenotype of the BCa cells, an effect that could be inverted by Disabled-1 (DAB1) knockdown. From a mechanistic standpoint, we identified an m6A modification site on LINC01106 and highlighted YTHDC1 as a potential reader protein implicated in this process. Additionally, a positive correlation between DAB1 and LINC01106 expression was observed, with miR-3148 potentially acting as a mediator in this relationship. CONCLUSIONS: In summary, our research unveils a suppressive regulatory role of the LINC01106/miR-3148/DAB1 axis in the progression of BCa and underscores the YTHDC1-mediated m6A modification mechanism in regards to LINC01106. These revelations propose a new therapeutic target for the management of BCa.

[Tubeless 24 F tract percutaneous nephrolithotomy in treatment of renal and proximal ureteral calculi].

OBJECTIVE: To evaluate the feasibility and efficacy of tubeless 24 F (1 F=0.33 mm)tract percutaneous nephrolithotomy (PCNL) in the treatment of renal and proximal ureteral stones in Chinese patients. METHODS: In the study, 108 patients treated with tubless 24 F tract PCNLs during September 2009 and April 2013 in our department were retrospectively analyzed, of whom, 42 were with renal calculi (the max diameter of calculi 2-4 cm, including 4 with simple staghorn stones), 41 with upper ureteral stones (the max diameter of calculi more than 1.5 cm or failure treated with extracorporeal shock wave lithotripsy), and 25 with upper ureteral stones combined with simple renal stones. Tubeless 24 F tract PCNL was performed when serious renal infection, obstraction in the distal of stone, the thickness of cortex less than 5 mm, operation time more than 90 min, residual stones needing second PCNL, severe bleeding during operation, pelvic perforation and obvious urinous infiltration were excluded. RESULTS: All the 108 patients were treated successfully with tubeless 24 F tract PCNL. Residual stone(about 5 mm in diameter)was found only 1 patient's lower calyces. The stone clearance rate was 99.1%, the average operation time was (40.5±9.1) min, the mean VAS on the first day postoperation was 3.0±1.6, the preoperative and postoperative hemoglobin decrease was (4.8±2.7) g/L, no blood transfusion and angiography and embolization needed, no pleural and other adjacent organ injury occurred. One patient got fever postoperatively (>38.5 °C). No perirenal hematoma and urine leakage were found. The average postoperative hospital stay was (2.4±0.6) days. All the patients were followed up for 1 month, and no other complication occurred. CONCLUSION: Tubeless 24 F tract PCNL can be a feasible way for renal stones and upper ureteral stones treatment, based on the severity candidate, perfect operative procedures and precise judgment at the end of the operation.

Development of Prognostic Biomarkers by TMB-Guided WSI Analysis: A Two-Step Approach.

The rapid development of computational pathology has brought new opportunities for prognosis prediction using histopathological images. However, the existing deep learning frameworks lack exploration of the relationship between images and other prognostic information, resulting in poor interpretability. Tumor mutation burden (TMB) is a promising biomarker for predicting the survival outcomes of cancer patients, but its measurement is costly. Its heterogeneity may be reflected in histopathological images. Here, we report a two-step framework for prognostic prediction using whole-slide images (WSIs). First, the framework adopts a deep residual network to encode the phenotype of WSIs and classifies patient-level TMB by the deep features after aggregation and dimensionality reduction. Then, the patients' prognosis is stratified by the TMB-related information obtained during the classification model development. Deep learning feature extraction and TMB classification model construction are performed on an in-house dataset of 295 Haematoxylin & Eosin stained WSIs of clear cell renal cell carcinoma (ccRCC). The development and evaluation of prognostic biomarkers are performed on The Cancer Genome Atlas-Kidney ccRCC (TCGA-KIRC) project with 304 WSIs. Our framework achieves good performance for TMB classification with an area under the receiver operating characteristic curve (AUC) of 0.813 on the validation set. Through survival analysis, our proposed prognostic biomarkers can achieve significant stratification of patients' overall survival (P 0.05) and outperform the original TMB signature in risk stratification of patients with advanced disease. The results indicate the feasibility of mining TMB-related information from WSI to achieve stepwise prognosis prediction.

Comparative analysis of salvage partial nephrectomy versus radical nephrectomy after the failure of initial partial nephrectomy.

OBJECTIVES: To compare the oncologic outcomes and renal function discrepancy of salvage partial nephrectomy (sPN) and salvage radical nephrectomy (sRN) after an initial failed PN. MATERIALS AND METHODS: Retrospective data from multiple centers between 2008 and 2022 were analyzed in this study. Patients who received sPN or sRN after an initial failed PN were identified. Comparative analysis and propensity score matching (PSM) was performed and the RENAL score, tumor size, and pathological T stage at salvage surgery were used to match the 2 groups. Local recurrence-free survival (LRFS) and recurrence-free survival (RFS) were assessed using the Cox proportional hazards model and log-rank tests. Renal function after salvage surgery was assessed using the Wilcoxon rank sum test. RESULTS: A total of 140 patients who underwent salvage surgery were evaluated, of whom 60 were considered for PSM analysis after matching. At a median follow-up of 27.0 months, LRFS and RFS showed no significant difference between sPN and sRN, either before (LRFS, HR = 0.673 [95% CI: 0.171-2.644], P = 0.610; RFS, HR = 0.744 [95% CI: 0.271-1.344], P = 0.595) or after matching (LRFS, HR = 1.080 [95% CI: 0.067-17.30], P = 0.957; RFS, HR = 1.199 [95% CI: 0.241-5.983], P = 0.822). During long-term follow-up, sPN preserved renal function (after matching, eGFR, 71.4 vs. 54.0, P < 0.001) and prevented eGFR loss (after matching: 6.6% vs. 25.6%, P < 0.001). CONCLUSION: Salvage partial nephrectomy offers a better alternative than sRN for recurrence after initial PN, as sPN preserves renal function better while maintaining parallel tumor control and acceptable complication rates.

[Application of a novel intracorporeal combined pneumatic and ultrasonic lithotriptor (CQS-01) in percutaneous nephrolithotomy].

OBJECTIVE: To evaluate the safety and efficacy of a new intracorporeal pneumatic and ultrasonic lithotriptor (CQS-01) in percutaneous nephrolithotomy (PNL). METHODS: In the study, 408 patients with renal or upper ureteral stones suitable for PNL treatment were treated with CQS-01 ultrasonic and pneumatic lithotripter. Their stone position: Single side 368 patients and bilaterial 40 patients. Simple kidney stones: 312 patients, combined ureteral and kidney 42 patients, and simple ureteral stones 54 patients. Stone burden: staghorn stone: 95 patients. All the patients were followed up for 1 week post-operation. The data were collected and analyzed with regard to stone burden, postoperative stone clearance rate, operation time, occurrence rate of adverse events. RESULTS: The postoperative stone-free rate was 91.2% and the residual stone rate 8.8%; The mean operation time was (90.5±68.0) min; There were 6 patients (1.5%) who received selective renal artery embolism because of bleeding after operation. One patient had severe urinary infection and no other severe complications happened. CONCLUSION: CQS-01 ultrasonic and pneumatic lithotriptor is safe and effective in PNL, and suitable for clinical application.

Concomitant Treatment of Ureteropelvic Junction Obstruction Complicated by Renal Calculi with Laparoscopic Pyeloplasty and Pyelolithotomy via 19.5F Rigid Nephroscope: A Report of 12 Cases.

Objective: To introduce our experience of concomitant laparoscopic pyeloplasty (LP) and pyelolithotomy via 19.5 F rigid nephroscope to treat ureteropelvic junction obstruction (UPJO) complicated with renal calculi.Methods: The data of 42 patients with UPJO who underwent LP from June 2016 to August 2019 were retrospectively reviewed. Twelve patients with ipsilateral renal calculi underwent LP and concomitant pyelolithotomy via 19.5 F rigid nephroscope. Perioperative data of this group were compared with other 12 matched patients without calculi who underwent LP only.Results: Of 12 patients with renal calculi, only 4 patients had simple stone and the other 8 patients suffered complex stones. Anatomical solitary kidney was found in 2 patients. The mean diameter of the largest stone was 1.1 cm (ranged from 0.6 to 1.7). The mean operative time was 171 min, the mean time of nephroscopic management was 17.2 min, 7 patients received pyelolithotomy by forceps, 3 patients received pyelolithotomy and ultrasonic lithotripsy, 1 patient received ultrasonic lithotripsy, the mean number of stones retrieved was 8.9 (ranged from 0-53), in one case the calculus was inaccessible because it was located in a narrow neck caliceal diverticulum. Overall stone-free rate was 91.7% (11/12). No difference in operative time, postoperative hemoglobin drop, postoperative hospital stay and incidence of complications was observed between the 2 groups. At the mean follow-up of 17.9 months, no patients had obstruction or recurrent stones.Conclusion: LP and concomitant pyelolithotomy via 19.5 F rigid nephroscope is a safe and feasible option to treat UPJO with renal calculi, with acceptable success rate and stone-free rate.

[Clinical safety and efficacy of a novel intracorporeal combined pneumatic and ultrasonic lithotriptor (CQS-01) compared with Swiss LithoClast Master (EMS-III)].

OBJECTIVE: To evaluate the safety and efficacy of a new intracorporeal pneumatic and ultrasonic lithotriptor (CQS-01). METHODS: Eighty-six patients with renal or upper ureteral stones suitable for percutaneous nephrolithotomy (PNL) treatment were randomly divided into trial group (treated with CQS-01 device) and control group (treated with EMS-III device), with 43 patients in either group respectively. All the patients were followed up for 7 ± 3 days post-operation. The data were collected and analyzed with regard to stone burden, postoperative stone clearance rate, operation time, stone fragmentation and extraction time, volume of extracted stones, changes of red blood cells (RBC) and hemoglobin (Hb), occurrence rate of transfusion, changes of blood urea nitrogen (BUN) and creatinine (Cr), serum electrolytes, white blood cells (WBC), as well as body temperature and adverse events rate at 24 hours and 7 ± 3 days post PNL operation. RESULTS: No significant differences were found between the trial group and the control group (P>0.05), in terms of patients demography, renal characteristics and stone characteristics. In the trial group and the control group, respectively: the postoperative stone-free rate was 76.74% and 79.07% (P=0.796) and the partial stone clearance rate was 23.26% and 20.93% (P=0.796), the operation time was (92.49 ± 76.59) min and (87.28 ± 50.01) min (P=0.485), the stone fragmentation and extraction time was (50.16 ± 57.11) min and (40.59 ± 31.01) min (P=0.976), the volume of extracted stones was (10.85 ± 20.08) mL and (5.05 ± 6.00) mL (P=0.041). There were also no significant differences in postoperative RBC and Hb drops, occurrence rate of transfusion, post-operative BUN and Cr, body temperature changes, postoperative systemic inflammatory response and adverse events rate at 24 hours and 7 ± 3 days post-operation between the trial and control groups (P>0.05). CONCLUSION: There is no significant difference in clinical safety, efficacy, and the stone clearance capability between CQS-01 device and EMS-III device.

CRDet: Improving Signet Ring Cell Detection by Reinforcing the Classification Branch.

Detecting signet ring cells on histopathologic images is a critical computer-aided diagnostic task that is highly relevant to cancer grading and patients' survival rates. However, the cells are densely distributed and exhibit diverse and complex visual patterns in the image, together with the commonly observed incomplete annotation issue, posing a significant barrier to accurate detection. In this article, we propose to mitigate the detection difficulty from a model reinforcement point of view. Specifically, we devise a Classification Reinforcement Detection Network (CRDet). It is featured by adding a dedicated Classification Reinforcement Branch (CRB) on top of the architecture of Cascade RCNN. The proposed CRB consists of a context pooling module to perform a more robust feature representation by fully making use of context information, and a feature enhancement classifier to generate a superior feature by leveraging the deconvolution and attention mechanism. With the enhanced feature, the small-sized cell can be better characterized and CRDet enjoys a more accurate signet ring cell identification. We validate our proposal on a large-scale real clinical signet ring cell data set. It is shown that CRDet outperforms several popular convolutional neural network-based object detection models on this particular task.

m6A-mRNA Methylation Regulates Gene Expression and Programmable m6A Modification of Cellular RNAs With CRISPR-Cas13b in Renal Cell Carcinoma.

Background: N6-methyladenosine (m6A) is the most extensive messenger RNA modification. Despite recent advances in the biological roles of m6A, its role in the development and progression of renal cell carcinoma (RCC) remains unclear. Methods: In this study, we gained the transcriptome-wide m6A profile and gene expression pattern in RCC and paired adjacent peritumoral tissues by meRIP-seq and RNA-seq. m6A modifications of mRNAs were validated by meRIP-qPCR in tissues, and targeted methylation or demethylation was validated by using a CRISPR-Cas13b-based tool in RCC cell lines. Results: Our findings showed that there were 13,805 m6A peaks among 5,568 coding gene transcripts (mRNAs) in adjacent tissues and 24,730 m6A peaks among 6,866 mRNAs in tumor tissues. Furthermore, m6A modification sites were usually located in the coding sequences (CDS), and some near the start and stop codons. Gene Ontology analysis revealed that coding genes had differential N6-methyladenosine sites and were enriched in kidney development and cancer-related signaling pathways. We also found that different levels of m6A modifications could regulate gene expression. Conclusion: In summary, our results provided evidence for studying the potential function of RNA m6A modification and m6A-mediated gene expression regulation in human RCC.

CREPT is required for murine stem cell maintenance during intestinal regeneration.

Intestinal stem cells (ISCs) residing in the crypts are critical for the continual self-renewal and rapid recovery of the intestinal epithelium. The regulatory mechanism of ISCs is not fully understood. Here we report that CREPT, a recently identified tumor-promoting protein, is required for the maintenance of murine ISCs. CREPT is preferably expressed in the crypts but not in the villi. Deletion of CREPT in the intestinal epithelium of mice (Vil-CREPTKO) results in lower body weight and slow migration of epithelial cells in the intestine. Vil-CREPTKO intestine fails to regenerate after X-ray irradiation and dextran sulfate sodium (DSS) treatment. Accordingly, the deletion of CREPT decreases the expression of genes related to the proliferation and differentiation of ISCs and reduces Lgr5+ cell numbers at homeostasis. We identify that CREPT deficiency downregulates Wnt signaling by impairing ß-catenin accumulation in the nucleus of the crypt cells during regeneration. Our study provides a previously undefined regulator of ISCs.

The Clinicopathological Features and Prognosis in Patients With Papillary Renal Cell Carcinoma: A Multicenter Retrospective Study in Chinese Population.

OBJECTIVE: The purpose of this study was to compare the clinicopathological characteristics of type 1 and type 2 papillary renal cell carcinoma (PRCC) and to explore the prognostic factors of PRCC in the Chinese population. METHODS: A total of 242 patients with PRCC from five Chinese medical centers were retrospectively included. From them, 82 were type 1 PRCC and 160 were type 2 PRCC. Clinicopathological features and oncologic outcomes were reviewed. The Kaplan-Meier analysis and log-rank test were performed to describe the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic factors of PRCC. RESULTS: Of the 242 patients, the average age at surgery was 55.3 ± 13.1 years. The mean tumor size was 5.1 ± 3.1 cm. Compared with type 1 PRCC patients, type 2 PRCC patients had a larger tumor size and were more likely to undergo radical nephrectomy. Besides, type 2 PRCC patients had higher tumor stage (p < 0.001) and WHO International Society of Urological Pathology (WHO/ISUP) grading (p < 0.001). Furthermore, tumor necrosis was more common in type 2 PRCC than type 1 PRCC (p = 0.030). The Kaplan-Meier survival analysis showed that the PFS and OS of type 1 PRCC patients were significantly better than those of type 2 PRCC patients (p = 0.0032 and p = 0.0385, respectively). Univariate analysis showed that tumor size, surgical procedures, pT stage, WHO/ISUP grading, and microvascular invasion were significant predictors of PFS and OS for type 2 PRCC patients. In the multivariate analysis, only pT stage (p = 0.004) and WHO/ISUP grading (p = 0.010) were the independent risk factors. Among type 2 PRCC patients with pT1 stage, no significant difference was found in PFS and OS between the partial nephrectomy and radical nephrectomy groups (p = 0.159 and p = 0.239, respectively). CONCLUSION: This multi-institutional study reveals the significant differences in clinicopathological variables and oncologic outcomes between type 1 and 2 PRCC. For type 2 PRCC in pT1 stage, the prognosis of partial nephrectomy is not inferior to that of radical nephrectomy, and nephron-sparing surgery can be considered.

Patient-Level Prediction of Multi-Classification Task at Prostate MRI Based on End-to-End Framework Learning From Diagnostic Logic of Radiologists.

The grade groups (GGs) of Gleason scores (Gs) is the most critical indicator in the clinical diagnosis and treatment system of prostate cancer. End-to-end method for stratifying the patient-level pathological appearance of prostate cancer (PCa) in magnetic resonance (MRI) are of high demand for clinical decision. Existing methods typically employ a statistical method for integrating slice-level results to a patient-level result, which ignores the asymmetric use of ground truth (GT) and overall optimization. Therefore, more domain knowledge (e.g., diagnostic logic of radiologists) needs to be incorporated into the design of the framework. The patient-level GT is necessary to be logically assigned to each slice of a MRI to achieve joint optimization between slice-level analysis and patient-level decision-making. In this paper, we propose a framework (PCa-GGNet-v2) that learns from radiologists to capture signs in a separate two-dimensional (2-D) space of MRI and further associate them for the overall decision, where all steps are optimized jointly in an end-to-end trainable way. In the training phase, patient-level prediction is transferred from weak supervision to supervision with GT. An association route records the attentional slice for reweighting loss of MRI slices and interpretability. We evaluate our method in an in-house multi-center dataset (N = 570) and PROSTATEx (N = 204), which yields five-classification accuracy over 80% and AUC of 0.804 at patient-level respectively. Our method reveals the state-of-the-art performance for patient-level multi-classification task to personalized medicine.

Deep Learning with Quantitative Features of Magnetic Resonance Images to Predict Biochemical Recurrence of Radical Prostatectomy: A Multi-Center Study.

Biochemical recurrence (BCR) occurs in up to 27% of patients after radical prostatectomy (RP) and often compromises oncologic survival. To determine whether imaging signatures on clinical prostate magnetic resonance imaging (MRI) could noninvasively characterize biochemical recurrence and optimize treatment. We retrospectively enrolled 485 patients underwent RP from 2010 to 2017 in three institutions. Quantitative and interpretable features were extracted from T2 delineated tumors. Deep learning-based survival analysis was then applied to develop the deep-radiomic signature (DRS-BCR). The model's performance was further evaluated, in comparison with conventional clinical models. The model achieved C-index of 0.802 in both primary and validating cohorts, outweighed the CAPRA-S score (0.677), NCCN model (0.586) and Gleason grade group systems (0.583). With application analysis, DRS-BCR model can significantly reduce false-positive predictions, so that nearly one-third of patients could benefit from the model by avoiding overtreatments. The deep learning-based survival analysis assisted quantitative image features from MRI performed well in prediction for BCR and has significant potential in optimizing systemic neoadjuvant or adjuvant therapies for prostate cancer patients.

[Characteristics of renal hemorrhage after percutaneous nephrolithotomy and the timing of selective embolization: a report of 13 cases].

OBJECTIVE: To investigate the characteristics of severe renal hemorrhage after percutaneous nephrolithotomy (PNL) and timing of selective transarterial embolization(TAE) . METHODS: Between May 2005 and March 2010, superselective renal angiography was used to control severe bleeding in 15 of 1418 cases (1520 PNL procedures, 1.06%). In the 15 cases, superselective renal angioembolization was used to control severe bleeding in 13 (0.92%) . The medical records of all the patients who underwent renal angiography and angioembolization were reviewed. RESULTS: Severe bleeding cases after PNL were divided into 3 types according to the clinical characteristics: type I (urgency type), type II (intermittence type) and type III (persistent slow type). There were 3 patients in type I, 6 in type II and 6 in type III. All the patients had a normal coagulation profile before surgery. A total of 11 patients (84.6%) underwent the first-time successful embolization and 2 (15.4%) the second-time successful embolization. The longer time between angioembolization and bleeding was, the more blood loss and transfusion volume were, except for 1 patient in type II . Temporality serum creatinine abnormality was found in 2 patients, one with a solitary kidney patient and the other with angioembolization for both renal bleeding. CONCLUSION: TAE is a minimally invasive, safe, simple, and highly effective modality for the management of post PNL renal bleeding. This option should be considered early in the management of these cases,especially for Urgency type bleeding.

[Infrared spectrophotometry for crystalline composition of staghorn calculi].

OBJECTIVE: To provide theoretic rationales for treatment and prevention of staghorn calculi by analyzing stone composition and studying the relationship between stone and urinary tract infections. METHODS: The clinical data of 51 staghorn calculi patients were analyzed retrospectively. The stone compositions were studied by infrared spectrophotometry. RESULTS: Six types of stone compositions were obtained. There were calcium oxalate monohydrate, calcium oxalate dehydrate, carbonate apatite, magnesium ammonium phosphate hexahydrate, uric acid and L-cystine. The majority of stones were of mixed compositions, pure stones were found in 15 cases (29.4%). Among all stones, calcium oxalate stones were found in 41 cases (80.4%) and uric stones in 10 cases (19.6%). Infectious stones were found in 26 cases (51.0%). Urinary tract infections were found in 40 (78.4%) patients and positive urine/stone culture was detected in 33 (64.7%) patients. CONCLUSION: With multiple crystalline compositions and etiological factors, the staghorn calculi are closely correlated with urinary tract infections.