TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

Background@#Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. @*Methods@#In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. @*Results@#Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. @*Conclusions@#We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme.@*METHODS@#The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests.@*RESULTS@#Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001).@*CONCLUSION@#For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.

Application of dynamic contrast enhanced status in multiparametric magnetic resonance imaging for prostatic cancer with PI-RADS 4 lesion / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the diagnostic value of dynamic contrast enhanced (DCE) of multiparametric magnetic resonance imaging (mpMRI) for prostate imaging reporting and data system (PI-RADS) 4 lesion in prostate peripheral zone.@*METHODS@#The clinical data of patients with PI-RADS 4 lesion in prostate peripheral zone who underwent prostate biopsy from January 2018 to September 2021 in Peking University First Hospital were retrospectively included. According to DCE status, the patients were divided into the conventional group (4 points for diffusion-weighted imaging) and the comprehensive group (3 points for diffusion-weighted imaging + 1 point for DCE positive). Pearson's chi-square test or Fisher's exact test for comparison was conducted between prostate cancer and non-cancer patients. Univariate and multivariate Logistic regression were performed to analyze the correlation of positive biopsy with age, total prostate specific antigen (PSA), free PSA/total PSA (f/tPSA), prostate volume (PV), PSA density (PSAD) and DCE status.@*RESULTS@#Among the 267 prostate biopsy patients, 217 cases were diagnosed as prostatic cancer (81.27%) and 50 cases were non-cancer (18.73%). Statistical analysis between the prostatic cancer group and the non-cancer group showed that there were significant differences in age, tPSA, PV and PSAD (all P < 0.05), but no significant differences in f/tPSA between the two groups. About different PI-RADS 4 lesion groups, the conventional group and the comprehensive group showed significant difference in biopsy results (P=0.001), and the conventional group had a higher positive rate. The PV of comprehensive group was larger than that of the conventional group. Among the prostate cancer patients diagnosed by biopsy, statistical analysis between the conventional group and comprehensive group showed that there were not significant differences in International Society of Urological Pathology (ISUP) grade and distinguishing clinically significant prostate cancer (all P > 0.05). Logistic univariate analysis showed that the diagnosis of prostate cancer was related to age, tPSA, f/tPSA, PV and DCE group status (all P < 0.05). Multivariate analysis showed that age, tPSA, PV and DCE group status (all P < 0.05) were independent risk factors for the diagnosis of prostatic cancer.@*CONCLUSION@#tPSA, f/tPSA, PV and PSAD are the indicators to improve the diagnosis of prostatic cancer with PI-RADS 4 lesion in peripheral zone lesions. DCE status is worth considering, so that we can select patients for biopsy more accurately, reduce the rate of missed diagnosis of prostate cancer as well as avoid unnecessary prostate puncture.

Comparative Study between ZOOMit and Conventional Intravoxel Incoherent Motion MRI for Assessing Parotid Gland Abnormalities in Patients with Early- or Mid-Stage Sjögren’s Syndrome

Objective@#To compare the reproducibility and performance of quantitative metrics between ZOOMit and conventional intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the diagnosis of early- and mid-stage Sjögren’s syndrome (SS). @*Materials and Methods@#Twenty-two patients (mean age ± standard deviation, 52.0 ± 10.8 years; male:female, 2:20) with early- or mid-stage SS and 20 healthy controls (46.9 ± 14.6 years; male:female, 7:13) were prospectively enrolled in our study.ZOOMit IVIM and conventional IVIM MRI were performed simultaneously in all individuals using a 3T scanner. Quantitative IVIM parameters - including tissue diffusivity (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) - inter- and intra-observer reproducibility in measuring these parameters, and their ability to distinguish patients with SS from healthy individuals were assessed and compared between ZOOMit IVIM and conventional IVIM methods, appropriately. MR gland nodular grade (MRG) was also examined. @*Results@#Inter- and intra-observer reproducibility was better with ZOOMit imaging than with conventional IVIM imaging (ZOOMit vs. conventional, intraclass correlation coefficient of 0.897–0.941 vs. 0.667–0.782 for inter-observer reproducibility and 0.891–0.968 vs. 0.814–0.853 for intra-observer reproducibility). Significant differences in ZOOMit f, ZOOMit D*, conventional D*, and MRG between patients with SS and healthy individuals (all p < 0.05) were observed. ZOOMit D* outperformed conventional D* in diagnosing early- and mid-stage SS (area under receiver operating curve, 0.867 and 0.658, respectively; p = 0.002). The combination of ZOOMit D*, MRG, and ZOOMit f as a new diagnostic index for SS, increased diagnostic area under the curve to 0.961, which was higher than that of any single parameter (all p < 0.01). @*Conclusion@#Considering its better reproducibility and performance, ZOOMit IVIM may be preferred over conventional IVIM MRI, and may subsequently improve the ability to diagnose early- and mid-stage SS.

Three dimensional nephrometry system for partial nephrectomy: Our initial exploration / 北京大学学报(医学版)

OBJECTIVE@#To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value.@*METHODS@#The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed.@*RESULTS@#A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm3 and (33.0±36.4) cm3, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation.@*CONCLUSION@#Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC).@*METHODS@#Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed.@*RESULTS@#There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic.@*CONCLUSION@#Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Expression and clinical significance of visfatin, hsa-miR-199a and extracellular signal regulating protein kinase 1/2 in colorectal cancer / 解剖学报

Objective To investigate the expression and correlation of visfatin, hsa-miR-199a and extracellular regulated protein kinase 1/2 (ERK1/2) in colorectal cancer (CRC) tissues. Methods The expression levels of visfatin mRNA and hsa-miR-199a were detected by Real-time PCR in 64 primary cases of radical resection of colorectal cancer who underwent pathological clinical examination in the clinicopathological examination in our hospital center from January 2017 to December 2017, the protein expression levels of visfatin and ERK1/2 were detected by immunohistochemistry and Western blotting. The relative expression levels of hsa-miR-199a in each group were compared according to the expression levels of visfatin and ERK1/2. Results The levels of visfatin gene and protein in colorectal cancer tissue (observation group, 64 cases) were higher than those in normal colorectal cancer (control group, 64 cases), and the expression was consistent. The colorectal cancer tissue(observation group) expression level of hsa-miR-199a was lower than that of normal colorectal tissue(control group), and visfatin mRNA was significantly negatively correlated. The colorectal cancer tissue (observation group) expression of ERK1/2 was higher than normal colorectal tissue (control group) and visfatin was significantly positively correlated. The relative expression of hsa-miR-199a in the visfatin and ERK1/2 positive group was significantly different from that in the test variables. Conclusion The overexpression of visfatin in colorectal cancer affects the down-regulation of hsa-miR-199a and is related to the ERK signaling pathway.

Automatic Detection and Classification of Rib Fractures on Thoracic CT Using Convolutional Neural Network: Accuracy and Feasibility

Objective@#To evaluate the performance of a convolutional neural network (CNN) model that can automatically detect and classify rib fractures, and output structured reports from computed tomography (CT) images. @*Materials and Methods@#This study included 1079 patients (median age, 55 years; men, 718) from three hospitals, between January 2011 and January 2019, who were divided into a monocentric training set (n = 876; median age, 55 years; men, 582), five multicenter/multiparameter validation sets (n = 173; median age, 59 years; men, 118) with different slice thicknesses and image pixels, and a normal control set (n = 30; median age, 53 years; men, 18). Three classifications (fresh, healing, and old fracture) combined with fracture location (corresponding CT layers) were detected automatically and delivered in a structured report. Precision, recall, and F1-score were selected as metrics to measure the optimum CNN model. Detection/diagnosis time, precision, and sensitivity were employed to compare the diagnostic efficiency of the structured report and that of experienced radiologists. @*Results@#A total of 25054 annotations (fresh fracture, 10089; healing fracture, 10922; old fracture, 4043) were labelled for training (18584) and validation (6470). The detection efficiency was higher for fresh fractures and healing fractures than for old fractures (F1-scores, 0.849, 0.856, 0.770, respectively, p = 0.023 for each), and the robustness of the model was good in the five multicenter/multiparameter validation sets (all mean F1-scores > 0.8 except validation set 5 [512 x 512 pixels; F1-score = 0.757]). The precision of the five radiologists improved from 80.3% to 91.1%, and the sensitivity increased from 62.4% to 86.3% with artificial intelligence-assisted diagnosis. On average, the diagnosis time of the radiologists was reduced by 73.9 seconds. @*Conclusion@#Our CNN model for automatic rib fracture detection could assist radiologists in improving diagnostic efficiency, reducing diagnosis time and radiologists’ workload.

Application of indocyanine green in complex upper urinary tract repair surgery / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery.@*METHODS@#This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty.@*RESULTS@#All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal.@*CONCLUSION@#The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.

Application of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction / 北京大学学报(医学版)

OBJECTIVE@#To investigate the value of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction (UPJO).@*METHODS@#We reviewed data on 40 patients (22 male cases, and 18 female cases) diagnosed with UPJO in Peking University First Hospital from May 2017 to April 2019. The median age was 26.5 years (IQR 23.25-38.75) years. There were 11 patients complicated with ectopic vessels, 14 patients with kidney stones, 3 patients with horseshoe kidney, and 6 patients with obstruction after pyeloplasty. All the patients underwent preoperative enhanced CT scan, and the CT data were reconstructed into three-dimensional image models. The obstruction position of ureteropelvic junction and the relationship between ureteropelvic junction and blood vessels and organs were observed by three-dimensional models to assist planning surgery. Thirty-seven patients underwent laparoscopic pyeloplasty (including 3 cases combined with pyelolithotomy with flexible cystoscope, 1 case combined with pyelolithotomy by sun-style cystoscope, 1 case with laparoscopic ureter resection and anastomosis, 3 cases of laparoscopic pyeloplasty of horseshoe kidney), 2 patients underwent laparoscopic ventral onlay lingual mucosal graft ureteroplasty, and 1 patient underwent robot-assisted laparoscopic pyeloplasty.@*RESULTS@#Three-dimensional CT image clearly showed the relationship between the obstruction of ureteropelvic junction and blood vessels and organs after three-dimensional reconstruction. The type, diameter, position and direction of the ectopic vessels could be observed clearly before operation according to the three-dimensional reconstruction model, and the number, size, location and shape of renal calculi or other masses, the number of involved renal calyces and the anatomical distribution in the renal pelvis and calyces could be also evaluated preoperatively. After comprehensive analysis of the above information, individualized operation plans were performed on the patients, all the 40 cases were successfully completed with the surgery without any transfer to open surgery. The average operative time was (129.91±37.90) min (range: 75 to 273), the average blood loss was (48.1±78.0) mL (range: 10 to 400), the average hospitality was (5.04±1.99) d (range: 2 to 10), and the average postoperative drainage time was (3.8±1.4) d (range: 2 to 8).@*CONCLUSION@#The preoperative three-dimensional image reconstruction has a high clinical value in the treatment of ureteropelvic junction obstruction, and it is of great help to assist surgery planning and is worthy of further clinical promotion and application.

Robot-assisted laparoscopic upper urinary tract reconstruction surgery: A review of 108 cases by a single surgeon / 北京大学学报(医学版)

OBJECTIVE@#To summarize the experiences and outcomes of 108 robot-assisted laparoscopic upper urinary tract reconstruction surgeries conducted by a single surgeon.@*METHODS@#We consecutively and retrospectively reviewed 108 patients who underwent robot-assisted laparoscopic upper urinary tract reconstruction surgeries by a single surgeon from November 2018 to January 2020. The patient demographics, perioperative variables, postoperative complications and follow-up data were recorded. Fifty-three modified dismembered pyeloplasties (MDP), 11 spiral flap pyeloplasties (SFP), 11 ure-teroureterostomies (UUT), 4 lingual mucosal onlay graft ureteroplasties (LMU), 5 appendiceal onlay flap ureteroplasties (AU), 11 ureteral reimplantations (UR), 6 Boari flap-Psoas hitch surgeries (BPS) and 7 ileal ureter replacements (IUR) were enrolled finally. The success was defined as the improvement in subjective pain levels, and the improvement in the degree of hydronephrosis at ultrasound.@*RESULTS@#All the surgeries were successfully completed without open or laparoscopic conversion. The median operative time was 141 min (range: 74-368 min), median blood loss was 20 mL (range: 10-350 mL) and median hospital stay was 4 d (range: 3-19 d) in MDP group, with the success rate of 94.3%. The median operative time was 159 min (range: 110-222 min), median blood loss was 50 mL (range: 20-150 mL) and median hospital stay was 5 d (range: 3-8 d) in SFP group, with the success rate of 100%. The median operative time was 126 min (range: 76-160 d), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 5 d (range: 4-9 d) in UUT group, with the success rate of 100%. The median operative time was 204 min (range: 154-250 min), median blood loss was 30 mL (range: 10-100 mL) and median hospital stay was 6 d (range: 4-7 d) in LMU group, with the success rate of 100%. The median operative time was 164 min (range: 135-211 min), median blood loss was 75 mL (range: 50-200 mL) and median hospital stay was 8.5 d (range: 6-12 d) in AU group, with the success rate of 100%. The median operative time was 149 min (range: 100-218 min), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 7 d (range: 5-10 d) in UR group, with the success rate of 90.9%. The median operative time was 166 min (range: 137-205 min), median blood loss was 45 mL (range: 20-100 mL) and median hospital stay was 5 d (range: 4-41 d) in BPS group, with the success rate of 83.3%. The median operative time was 270 min (range: 227-335 min), median blood loss was 100 mL (range: 10-100 mL) and median hospital stay was 7 d (range: 5-26 d) in IUR group, with the success rate of 85.7%.@*CONCLUSIONS@#The surgeon performed and modified numerous complicated upper urinary tract reconstruction surgeries by the robotic platform, which facilitated the development of the standardized upper urinary tract reconstruction surgical technique.

Advance in re-do pyeloplasty for the management of recurrent ureteropelvic junction obstruction after surgery / 北京大学学报(医学版)

Ureteropelvic junction obstruction (UPJO) is characterized by decreased flow of urine down the ureter and increased fluid pressure inside the kidney. Open pyeloplasty had been regarded as the standard management of UPJO for a long time. Laparoscopic pyeloplasty reports high success rates, for both retroperitoneal and transperitoneal approaches, which are comparable to those of open pyeloplasty. However, open and laparoscopic pyeloplasty have yielded disappointing failure rates of 2.5%-10%. The main causes for recurrent UPJO are severe peripelvic and periureteric fibrosis due to urinary extravasation, ureteral ischemia, and inadequate hemostasis. In addition, failing to diagnose lower pole crossing vessels before or during the primary procedure is also responsible for recurrent UPJO. In addition, poor preoperative split renal function, hydronephrosis, presence of renal stones, patient age, diabetes, prior endopyelotomy history, and retrograde pyelography history were considered as predictors of pyeloplasty failure. The failure is usually defined by persistent pain, persistent radiographic obstruction (infection or stones), continued decline in split renal function, or a combination of the above. And the failure of pye-loplasty often occurs in the first 2 years after the surgery. The available options for managing recurrent UPJO with a salvageable renal unit include endopyelotomy, re-do pyeloplasty, stent implantation, percutaneous nephrostomy, ureterocalicostomy, and nephrectomy. Re-do pyeloplasty has such merits as high successful rates and rare complications, compared with endopyelotomy or ureterocalicostomy. And some investigators think that re-do pyeloplasty should be regarded as the gold standard for secondary therapy if feasible. Open pyeloplasty can enlarge the operating field, facilitate the exposure of the ureteropelvic junction, reduce the difficulty of operation, and thus reduce the occurrence of complications. There are no significant differences among the success rates of re-do pyeloplasty under open approach, traditional laparoscopy and robot-assisted laparoscopy, according to previous reports. However, traditional laparoscopic and robot-assisted pyeloplasty give advantages of cosmetology, small trauma, less postoperative pain, speedy recovery and shorter hospitalization, fewer complications and lower recurrent rates. If the primary pyeloplasty is an open operation in retroperitoneal approach, the traditional laparoscopic and robotic operation with retroperitoneal approach should be considered for secondary repair. The cause of recurrent UPJO should be evaluated before surgery and identified intraoperatively to minimize the possibility of recurrence.

Review of upper urinary modified minimal invasive surgical technology / 北京大学学报(医学版)

Upper urinary surgery is an important area of urology surgery. Open surgery used to be the gold standard of upper urinary surgery. With the development of medical techniques, minimal invasive surgeries including laparoscopic and robot assisted-laparoscopic surgery have gradually replaced the open surgery. Because of the complexity and diversity of upper urinary diseases, surgeries sometimes are difficult, and minimal invasive surgeries require higher surgical abilities of urologists than open surgeries. In recent years, depending on our surgical experience and international reports, our team from three Chinese medical centers summarizes techniques of upper urinary minimal invasive surgeries. For malignant diseases, such as renal and ureteral carcinomas, it's important to totally remove the tumor first, and then to avoid the surgical injuries. We summarize surgical experience of retroperitoneal laparoscopic partial nephrectomy for moderately complex renal hilar tumors. Our team modified minimal invasive techniques for some complex tumors, including ring suture technique for renal hilar tumors, internal suspension technique for renal ventral tumors, and combination retroperitoneal laparoscopic surgery with mini-flank incision for complex renal tumors. While for begin diseases, urologists should focus on the resections and surgical injuries at the same time. We have reported the novel technique of laparoscopic aspiration for central renal angiomyolipoma, making the surgery simple and available. For reconstruction surgeries, operations should be based on several principals. We generalize it as "4TB principals", which include "tension-free", "water-tight", "thin suture", "no touch of the key area" and "protecting the blood supply". Depending on the localization, length, and etiology of the strictures, different techniques are required. Our team summarize the pyeloplasty, ureteral reimplantation and ileal ureter replacement based on our surgical experience. For infant upper urinary surgeries, our team has made invasive surgeries that can be used in complex diseases, such as duplex kidney. Based on years of surgical techniques, our modified surgeries achieve a better subjective cosmetic result than the traditional surgeries. In the future, the standardized, practical, simple and individual minimal invasive surgical technique will become the main direction in the future researches.

Clinicopathologic features and prognostic analyses of locally recurrent renal cell carcinoma patients after initial surgery / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinicopathologic features and potential prognostic predictors of locally recurrent renal cell carcinoma patients after initial surgery.@*METHODS@#Authors retrospectively analyzed data extracted from 81 patients who were treated for postoperative locally recurrence of renal cell carcinoma from January 2006 to June 2016 in the Department of Urology, Peking University First Hospital. Postoperative locally recurrence of renal cell carcinoma was defined as disease recurring in the remnant kidney, renal fossa, adjacent abdomen, ipsilateral adrenal and retroperitoneal lymph nodes.@*RESULTS@#In the study, 81 patients were finally included, of whom 43 were initially treated in our hospital and 38 were initially treat in other centers. Partial nephrectomy (PN) was performed for 38 cases (26 in our hospital and 12 in other hospitals) as initial treatment and radical nephrectomy (RN) was conducted for the remnant 43 cases (17 in our hospital and 26 in other hospitals). Overall median recurrence time was 26 months (range: 3-164 months), in which 26 months (range: 3-55 months) for PN cases and 30 months (range: 4-164 months) for RN cases (P=0.009). Sixty-nine patients had single site recurrence, including remnant kidney (n=29), renal fossa (n=20), abdomen (n=4), ipsilateral lymph nodes (n=5), ipsilateral adrenal (n=11), while 12 patients had multiple sites recurrence. Seventy-eight patients were managed by complete surgical resection, while three patients were managed by radiofrequency ablation. Postoperative pathological diagnoses included clear cell carcinoma (n=72), papillary renal cell carcinoma (n=8, 7 cases with type 1, 1 case with type 2) and Xp11 translocation/TFE3 gene fusion renal cell carcinoma (n=1). Complete pathologic information of the initial surgery could be extracted from 43 patients who were initially treated in our hospital. Seventeen patients with initial radical nephrectomy were staged as T1a (n=4), T1b (n=2), T2a (n=1), T3a (n=8), and T3b (n=2). Twenty-six patients with initial partial nephrectomy were staged as T1a (n=18), T1b (n=7), and T3a (n=1). For PN cohort, the patients with T1a stage disease had longer median recurrence time than those with beyond T1a stage disease, and the difference was significant (29 months vs. 18 months, P=0.041). At the end of the follow-up, 58 patients were alive, 4 died and 19 lost the follow-up. Overall, 3-year and 5-year disease free survival rates were 81.9%, and 53.6%, respectively.@*CONCLUSION@#The present research reported a large-scale single central experience of locally recurrent renal cell carcinoma. The recurrence time of the PN group is shorter than that of the RN group. For patients after PN surgery, median recurrence time is longer for patients with T1a stage tumor when compared with those with stage beyond T1a. Patients can obtain relative long-term survival after complete secondary surgery resection.

Comparison of efficacy and safety between two different methods of nephroureterectomy in two centers / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC).@*METHODS@#We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries.@*RESULTS@#Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups.@*CONCLUSION@#CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.

Application of totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis in upper urinary tract urothelial carcinomas treatment / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the feasibility and effectiveness of the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis in the treatment of upper urinary tract urothelial carcinoma (UTUC), and to review the experience of renal autotransplantation for UTUC treatment.@*METHODS@#One case of applying the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis to the UTUC treatment was reported, and related literature was reviewed. The patient was a sixty-four-year old man who received right radical nephroureterectomy for right ureteral carcinoma 1 year before and diagnosed as left ureteral carcinoma(G2, high grade) this time. In order to preserve his renal function and avoid the shortness of common kidney-sparing surgery, a totally extraperitoneal procedure, including retroperitoneoscopic nephrectomy, ureterectomy, renal autotransplantation and Boari flap-pelvis anastomosis, was performed to the patient.@*RESULTS@#The operation was completed successfully without perioperative complications. The renal function recovered to preoperative level within 1 week. No deterioration of renal function during the follow-up and no tumor recurrence was observed under cystoscopy at the 3-month postoperative consult.@*CONCLUSION@#The totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis is a feasible and effective treatment for UTUC. The innovative procedure has several advantages compared to the former ones. The extraperitoneal procedure results in significantly less pain, shorter hospital stay, decreased overall time to recovery and lower bowel complications risk without warm ischemia time extension. Meanwhile, the Boari flap-pelvis anastomosis simplifies the follow -up protocols and creates an easy route for cystoscopy and topical therapy. From the systematic clinical analysis, as well as the related literature review, it's been concluded that the renal autotransplantation can be a reasonable option for the patients who have UTUC in solitary kidney or have bilateral UTUC. This type of treatment possesses advantages of preservation of renal function and total resection of malignant lesions. But long-term data and large cohort study on renal function or tumor recurrence are still absent which will be necessary to confirm the advantages of this approach.

Advances in surgical repair of ureteral injury / 北京大学学报(医学版)

Ureteral injury can be classified as iatrogenic or traumatic, which represents a rare but challenging field of reconstructive urology. Due to their close proximity to vital abdominal and pelvic organs, the ureters are highly susceptible to iatrogenic injury, while ureteral injury caused by external trauma is relatively rare. The signs of ureteric injury are difficult to identify initially and often present after a delay. The treatment of ureteral injury, which is depended on the type, location, and degree of injury, the time of diagnosis and the patient's overall clinical condition, ranges from simple endoscopic management to complex surgical reconstruction. And long defect of the ureter presents much greater challenges to urologists. Ureterotomy under endoscopy using laser or cold-knife is available for the treatment of 2-3 cm benign ureteral injuries or strictures. Pyeloplasty is an effective treatment for ureteropelvic junction obstruction and some improved methods showed the possibility of repairing long-segment (10-15 cm) stenosis. Proximal and mid-ureteral injuries or strictures of 2-3 cm long can often be managed by primary ureteroureterostomy. When not feasible due to ureteral defects of longer segment, mobilization of the kidney should be considered, and transureteroureterostomy is alternative if the proximal ureter is of sufficient length. And autotransplantation or nephrectomy is regarded as the last resorts. Most of the injuries or strictures are observed in the distal ureter, below the pelvic brim, and are usually treated with ureteroneocystostomy. A non-refluxing technique together with a ureteral nipple or submucosal tunnel method, is preferable as it minimizes vesico-ureteral reflux and the risk of infection. In order to cover a longer distance, ureteroneocystostomy in combination with a psoas hitch (covering 6-10 cm of defect) or a Boari flap (covering 12-15 cm) is often adopted. Among various ureteral replacement procedures, only intestinal ureteral substitution, which includes ileal ureter, appendiceal interposition and reconfigured colon substitution, has gained wide acceptance when urothelial tissue is insufficient. Ileal ureter can be used to replace the ureter of >15 cm defect and even to replace the entire unbilateral ureter or bilateral ureter. Laparoscopic and robotic-assisted techniques are increasingly being employed for ureteral reconstruction and adopted with encouraging results.

Evaluating the impact of preoperative anemia on the prognosis of upper tract urothelial carcinoma following radical nephroureterectomy: A single-center retrospective study of 686 patients / 北京大学学报(医学版)

OBJECTIVE@#To identify the effect of preoperative anemia on the prognosis of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy.@*METHODS@#Clinicopathological and prognosis data on 686 patients with UTUC who underwent RNU at Peking University First Hospital between January 2000 and December 2013 were retrospectively analyzed. Preoperative anemia was defined as hemoglobin <130 g/L in men and <120 g/L in women based on the World Health Organization classification. The Kaplan-Meier method with log-rank test was applied to estimate the effect of anemia on survival. The associations of clinicopathologic features with overall survival and cancer-specific survival were evaluated using univariate and multivariate Cox regression models.@*RESULTS@#There were 303(44.2%, 303/686) male and 383(55.8%, 383/686) female patients, and the median age was 68 years (interquartile range: 60-74 years). In all, 320 (46.6%, 320/686) patients were anemic before surgery. The median follow-up duration was 47 months. In all, 160 (23.3%) patients died, 141 (20.6%) died of cancer and 19 (2.7%) died of other disease or accidents. Preoperative anemia was associated with gender (P=0.002), age (P<0.001), lymph node positive (P=0.026), increased tumor grade (P=0.018), concomitant carcinoma in situ (P=0.038), tumor necrosis (P=0.007) and poor renal function (P<0.001). In univariate analysis, overall mortality was correlated with pre-operative anemia (P<0.001), gender (P=0.009), hydronephrosis (P=0.024), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture(P<0.001), sarcomatoid differentiation (P=0.013), history of ureteroscope (P=0.033) and tumor hemorrhage (P<0.001); cancer-specific mortality was correlated with preoperative anemia (P=0.001), gender (P=0.001), hydronephrosis (P=0.043), tumor stage (P<0.001), lymph node positive (P<0.001), tumor grade (P<0.001), tumor architecture (P<0.001), sarcomatoid differentiation (P=0.016), history of ureteroscope (P=0.028) and tumor hemorrhage (P=0.003). A multivariate Cox proportional hazards model indicated that preoperative anemia was an independent prognositic predictor for overall mortality (P<0.001, HR=1.861) and cancer-specific mortality (P=0.003, HR=1.688).@*CONCLUSION@#The preoperative anemia is an independent risk factor for cancer-specific survival and overall survival. Hemoglobin levels should be considered during patient counseling and in decision-making for further therapy.

Doxorubicin induces stemness of mouse TNBC 4T1 cells through Stat3-Oct-4/CD44 signaling pathway / 中国病理生理杂志

AIM:To investigate the stemness of mouse triple-negative breast cancer (TNBC) 4T1 cells induced by doxorubicin (DOX) and the underlying mechanism.METHODS:The 4T1 cells and MDA-MB-468 cells were treated with DOX at different concentrations (0, 0.05, 0.1 and 0.5μmol/L) for 24 h, and the shape and viability of the cells were observed.The concentration of DOX at 0.1μmol/L was chosen as the optimal concentration for the following experiments.The 4T1 cells and MDA-MB-468 cells resistant to DOX were established by continuous stimulation with DOX for 4 weeks, and named as 4T1-DOX and MDA-MB-468-DOX.Sphere formation assay was used to detect the stemness of 4T1cells and MDA-MB-468 cells.The expression of CD133 was observed by immunofluorescence staining.The expression of CD44 was analyzed by flow cytometry.The protein levels of Stat3, phosphorylated Stat3 (p-Stat3) and Oct-4 were determined by Western blot.RESULTS:The sphere formation ability of the 4T1-DOX cells was stronger than that of the 4T1control cells.The 4T1-DOX cells expressed high levels of the stemness markers CD133 and CD44 as compared with the 4 T1 cells (P<0.05).Furthermore, the 4T1-DOX cells exhibited enhanced activation of Stat3 (p-Stat3) and increased expression of Oct-4 (P<0.05) , while the expression of total Stat3 had no obvious variation.In addition, when activation of Stat3 was inhibited by WP1066, the protein levels of p-Stat3, Oct-4 and CD44 were down-regulated (P<0.05).Furthermore, inhibition of Stat3 phosphorylation reduced the sphere formation ability of the 4T1-DOX cells (P<0.05).CONCLUSION:DOX induces the stemness of mouse TNBC 4T1 cells through Stat3-Oct-4 signaling pathway.

Prognostic role of chromogranin A in castration-resistant prostate cancer: A meta-analysis / 亚洲男科学杂志(英文版)

We aimed to investigate the prognostic value of chromogranin A (CgA) in castration-resistant prostate cancer (CRPC). We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows: progression-free survival (PFS) was associated with CgA level (hazard ratio [HR] = 2.47, 95% confidence interval [CI]: 1.47-4.14, P = 0.0006); PFS was relative to CgA change (HR = 9.22, 95% CI: 3.03-28.05, P < 0.0001); and overall survival (OS) was relative to CgA level (HR = 1.47, 95% CI: 1.15-1.87, P = 0.002). When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 (95% CI: 1.09-1.45, P = 0.001) in the first-line hormonal therapy group, and an HR of 2.33 (95% CI: 1.40-3.89, P = 0.001) in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.