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

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

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

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

Near-infrared fluorescence imaging of thoracic duct in minimally invasive esophagectomy.

Chylothorax is a serious complication after esophagectomy and there are unmet needs for new intraoperative navigation tools to reduce its incidence. The aim of this study is to explore the feasibility and effectiveness of near-infrared fluorescence imaging (NIR-FI) with indocyanine green (ICG) to identify thoracic ducts (TDs) and chyle leakage during video-assisted thoracoscopic esophagectomy. We recruited 41 patients who underwent thoraco-laparoscopic minimally invasive esophagectomy (MIE) for esophageal cancer in this prospective, open-label, single-arm clinical trial. ICG was injected into the right inguinal region before operations, after which TD anatomy and potential chyle leakage were checked under the near-infrared fluorescence intraoperatively. In 38 of 41 patients (92.7%) using NIR-FI, TDs were visible in high contrast. The mean signal-to-background ratio (SBR) value of all fluorescent TDs was 3.05 ± 1.56. Fluorescence imaging of TDs could be detected 0.5 hours after ICG injection and last up to 3 hours with an acceptable SBR value. The optimal observation time window is from about 1 to 2 hours after ICG injection. Under the guidance of real-time NIR-FI, three patients were found to have chylous leakage and the selective TD ligations were performed intraoperatively. No patient had postoperative chylothorax. NIR-FI with ICG can provide highly sensitive and real-time assessment of TDs as well as determine the source of chyle leakage, which might help reduce TD injury and direct selective TD ligation. It could be a promising navigation tool to reduce the incidence of chylothorax after minimally invasive esophagectomy.

Identification of an IDO1-based immune classifier for survival prediction of upper tract urothelial carcinoma.

The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1-based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease-free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+ , CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD-L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65-0.93) in the discovery cohort, 0.75 (95% CI 0.58-0.92) and 0.78 (95% CI 0.65-0.92) in the internal and external validation cohorts, respectively. The high-risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1-based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.

Clinical characteristics and surgical treatment of ureteral endometriosis: our experience with 40 cases.

BACKGROUND: To present the experience with the surgical management of ureteral endometriosis (UE) in our single center. METHODS: To present the experience with the surgical management of ureteral endometriosis (UE) in our single center. A retrospective analysis of 40 patients with UE who presented with intraoperative surgical findings of endometriosis involving the ureter and pathology-proven UE was performed. RESULTS: Forty patients (median age, 42.5 years) with histological evidence of UE were included. Six (15%) patients had a history of endometriosis. Twenty-one (52%) patients had urological symptoms, and 19 (48%) patients were asymptomatic. All patients had hydronephrosis. The mean glomerular filtration rate (GFR) of the ipsilateral kidney was significantly worse than that of the contralateral kidney (23.4 vs 54.9 ml/min; P < 0.001). Twelve (30%) patients were treated with ureteroureterostomy (11 open approaches and 1 robotic approach). Twenty-two (55%) patients underwent ureteroneocystostomy (17 open approaches, 4 laparoscopic approaches and 1 robotic approach). Five patients underwent nephroureterectomy. One patient refused aggressive surgery and received ureteroscopic biopsy and ureteral stent placement. Thirteen (33%) patients required gynecological operations. Three (8%) patients in the open group suffered from major surgical complications. Nine (24%) patients received postoperative endocrine therapy. Twenty-eight (70%) patients were followed up (median follow-up time, 71 months). Twenty-four patients received kidney-sparing surgeries. The success rate for these 24 patients was 21/24 (87.5%). The success rates of ureteroneocystostomy and ureteroureterostomy were 15/16 (93.8%) and 5/7 (71.4%), respectively. CONCLUSIONS: Although UE is rare, we should remain vigilant for the disease among female patients with silent hydronephrosis. Typically, a multidisciplinary surgical team is necessary. For patients with severe UE, segmental ureteral resection with ureteroureterostomy (UU) or ureteroneocystostomy may be a preferred choice.

Comparison of functional and oncological outcomes of innovative "three-port" and traditional "four-port" laparoscopic radical prostatectomy in patients with prostate cancer.

BACKGROUND: To compare the functional and oncological outcomes between innovative "three-port" and traditional "four-port" laparoscopic radical prostatectomy (LRP) in patients with prostate cancer (PCa). METHODS: We retrospectively collected the data of PCa patients treated at our institutions from June 2012 to May 2016. According to the inclusion criteria, a total of 234 patients were included in the study, including 112 in group A (four-port) and 122 in group B (three-port). The perioperatively surgical characteristics, functional and oncological outcomes were compared between groups. RESULTS: There were no statistical differences in the baseline parameters between these two groups. Compared with group A, the operative time (OT) and estimated blood loss (EBL) were significantly less in group B. On follow-up, the rate of positive surgical margin (PSM), prostate specific antigen (PSA) biochemical recurrence and continence after LRP did not show any statistically significant difference between the groups. An identical conclusion was also received in comparison of overall survival (OS) and biochemical recurrence-free survival (BRFS) between both groups. CONCLUSIONS: Innovative "three-port" LRP can significantly shorten the OT and reduce the EBL compared with the traditional "four-port" LRP. Meanwhile, it does not increase the rate of PSM and PSA biochemical recurrence. "Three-port" LRP could be popularized in the future in view of its superior surgical technique, considerably better functional outcomes and remarkable oncological control.

Modified Laparoscopic and Robotic Flap Pyeloplasty for Recurrent Ureteropelvic Junction Obstruction with a Long Proximal Ureteral Stricture: The "Wishbone" Anastomosis and the "Ureteral Plate" Technique.

OBJECTIVES: The aim of the study was to present our modified flap pyeloplasty techniques for recurrent ureteropelvic junction obstruction (UPJO) with a long proximal ureteral stricture and compare outcomes of laparoscopic and robotic procedures. MATERIALS AND METHODS: Between March 2018 and January 2020, 21 patients underwent modified laparoscopic or robotic flap pyeloplasty for recurrent UPJO with a long proximal ureteral stricture. Our surgical modifications included the "wishbone" anastomosis and "ureteral plate" technique. Demographic, perioperative, and follow-up data were recorded and compared retrospectively between the groups. Success was defined as subjective pain alleviation and hydronephrosis improvement. RESULTS: Thirteen modified laparoscopic flap pyeloplasty (mLFP) and 8 modified robotic flap pyeloplasty (mRFP) were performed successfully without conversion. mRFP tended to have shorter overall operative time (142.4 vs. 179.1 min, p = 0.122) and anastomosis time (43.1 vs. 61.0 min, p = 0.093) than mLFP. No difference was found in estimated blood loss (p = 0.723) and pararenal draining time (p = 0.175) between the groups. The mean postoperative hospital stay of mRFP was significantly shorter than that of mLFP (5.0 vs. 8.2 days, p = 0.015). No major complications occurred. During the mean follow-up of 17.9 months, the overall success rate was 90.5%, and there was no significant difference between 2 groups. CONCLUSIONS: The modified flap pyeloplasty could be considered a practical and effective treatment option with a high success rate for recurrent UPJO with a long proximal ureteral stricture, and the robotic procedures showed advantages of higher efficiency and faster recovery.

Artificial-intelligence-based computed tomography histogram analysis predicting tumor invasiveness of lung adenocarcinomas manifesting as radiological part-solid nodules.

Background: Tumor invasiveness plays a key role in determining surgical strategy and patient prognosis in clinical practice. The study aimed to explore artificial-intelligence-based computed tomography (CT) histogram indicators significantly related to the invasion status of lung adenocarcinoma appearing as part-solid nodules (PSNs), and to construct radiomics models for prediction of tumor invasiveness. Methods: We identified surgically resected lung adenocarcinomas manifesting as PSNs in Peking University People's Hospital from January 2014 to October 2019. Tumors were categorized as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) by comprehensive pathological assessment. The whole cohort was randomly assigned into a training (70%, n=832) and a validation cohort (30%, n=356) to establish and validate the prediction model. An artificial-intelligence-based algorithm (InferRead CT Lung) was applied to extract CT histogram parameters for each pulmonary nodule. For feature selection, multivariate regression models were built to identify factors associated with tumor invasiveness. Logistic regression classifier was used for radiomics model building. The predictive performance of the model was then evaluated by ROC and calibration curves. Results: In total, 299 AIS/MIAs and 889 IACs were included. In the training cohort, multivariate logistic regression analysis demonstrated that age [odds ratio (OR), 1.020; 95% CI, 1.004-1.037; p=0.017], smoking history (OR, 1.846; 95% CI, 1.058-3.221; p=0.031), solid mean density (OR, 1.014; 95% CI, 1.004-1.024; p=0.008], solid volume (OR, 5.858; 95% CI, 1.259-27.247; p = 0.037), pleural retraction sign (OR, 3.179; 95% CI, 1.057-9.559; p = 0.039), variance (OR, 0.570; 95% CI, 0.399-0.813; p=0.002), and entropy (OR, 4.606; 95% CI, 2.750-7.717; p<0.001) were independent predictors for IAC. The areas under the curve (AUCs) in the training and validation cohorts indicated a better discriminative ability of the histogram model (AUC=0.892) compared with the clinical model (AUC=0.852) and integrated model (AUC=0.886). Conclusion: We developed an AI-based histogram model, which could reliably predict tumor invasiveness in lung adenocarcinoma manifesting as PSNs. This finding would provide promising value in guiding the precision management of PSNs in the daily practice.

Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis.

BACKGROUND: The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In the current study, the authors aim to compare the long-term oncological outcomes of POPRC versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort. PATIENTS AND METHODS: Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival and recurrence-free survival. To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching was performed. RESULTS: Among the 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After propensity score matching, each cohort included 99 matched patients. The OS ( P =0.940), cancer-specific survival ( P =0.957), and recurrence-free survival ( P =0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (Hazard ratio 0.874, 95% CI 0.592-1.290; P =0.498). CONCLUSIONS: The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.

Interferon gamma-related gene signature based on anti-tumor immunity predicts glioma patient prognosis.

Background: Glioma is the most common primary tumor of the central nervous system. The conventional glioma treatment strategies include surgical excision and chemo- and radiation-therapy. Interferon Gamma (IFN-γ) is a soluble dimer cytokine involved in immune escape of gliomas. In this study, we sought to identify IFN-γ-related genes to construct a glioma prognostic model to guide its clinical treatment. Methods: RNA sequences and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and the China Glioma Genome Atlas (CGGA). Using univariate Cox analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, IFN-γ-related prognostic genes were selected to construct a risk scoring model, and analyze its correlation with the clinical features. A high-precision nomogram was drawn to predict prognosis, and its performance was evaluated using calibration curve. Finally, immune cell infiltration and immune checkpoint molecule expression were analyzed to explore the tumor microenvironment characteristics associated with the risk scoring model. Results: Four out of 198 IFN-γ-related genes were selected to construct a risk score model with good predictive performance. The expression of four IFN-γ-related genes in glioma tissues was significantly increased compared to normal brain tissue (p < 0.001). Based on ROC analysis, the risk score model accurately predicted the overall survival rate of glioma patients at 1 year (AUC: The Cancer Genome Atlas 0.89, CGGA 0.59), 3 years (AUC: TCGA 0.89, CGGA 0.68), and 5 years (AUC: TCGA 0.88, CGGA 0.70). Kaplan-Meier analysis showed that the overall survival rate of the high-risk group was significantly lower than that of the low-risk group (p < 0.0001). Moreover, high-risk scores were associated with wild-type IDH1, wild-type ATRX, and 1P/19Q non-co-deletion. The nomogram predicted the survival rate of glioma patients based on the risk score and multiple clinicopathological factors such as age, sex, pathological grade, and IDH Status, among others. Risk score and infiltrating immune cells including CD8 T-cell, resting CD4 memory T-cell, regulatory T-cell (Tregs), M2 macrophages, resting NK cells, activated mast cells, and neutrophils were positively correlated (p < 0.05). In addition, risk scores closely associated with expression of immune checkpoint molecules such as PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT, CD48, CD226, and CD96. Conclusion: Our risk score model reveals that IFN-γ -associated genes are an independent prognostic factor for predicting overall survival in glioma, which is closely associated with immune cell infiltration and immune checkpoint molecule expression. This model will be helpful in predicting the effectiveness of immunotherapy and survival rate in patients with glioma.

Aberrant methylation of the 16q23.1 tumor suppressor gene ADAMTS18 promotes tumorigenesis and progression of clear cell renal cell carcinoma.

BACKGROUND: The 16q23.1 tumor suppressor gene (TSG) of ADAMTS18 has been identified to be aberrant methylated in clear cell renal cell carcinoma (ccRCC), and there still exists an unclear situation between its methylation and the progression of ccRCC. OBJECTIVE: To analyze the biological function and mechanism of ADAMTS18 gene in the tumorigenesis and progression of ccRCC. METHODS: We examined ADAMTS18 gene methylation using methylation- specific polymerase chain reaction (MSP) in 92 ccRCC primary tumors from September 2017 to May 2018. Using reverse transcriptase PCR (RT-PCR) and immunohistochemical (IHC) assay, the relative expression level of ADAMTS18 was measured in the representative tumor samples with their adjacent normal tissues. Meanwhile, colony formation, cell viability, wound healing, transwell chamber, flow cytometry, and PI staining were performed to confirm the tumor-suppressive function and mechanism of ADAMTS18 gene. RESULTS: Aberrant methylation was further detected in 47 of the 92 (51.1%) primary tumors and in 8 of the 92 (8.7%) adjacent normal tissues (p < 0.05). Due to the phenomenon of aberrant methylation, ectopic low-level expression of ADAMTS18 gene could result in the promotion of tumorigenesis and progression in ccRCC. CONCLUSION: The aberrantly methylated ADAMTS18 gene may be involved in the tumorigenesis and progression of ccRCC.

Curcumin reverses the sunitinib resistance in clear cell renal cell carcinoma (ccRCC) through the induction of ferroptosis via the ADAMTS18 gene.

BACKGROUND: To explore the possible mechanism by which curcumin reverses the sunitinib resistance in clear cell renal cell carcinoma (ccRCC). METHODS: A sunitinib-resistant ccRCC cell model was established. The MTT assay was used to determine the half maximal inhibitory concentration (IC50) and drug resistance (DR) index. The effects of curcumin plus sunitinib or sunitinib alone on drug-resistant cell lines were verified by the cell counting kit-8 (CCK-8)assay, colony formation assay, and apoptosis assay. The concentration of iron ions in the cell lines was analyzed using an Abcam Iron Assay Kit. The expressions of ADAMTS18 gene and ferroptosis-related proteins (NCOA4, FTH1 and p53) after curcumin plus sunitinib treatment were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. After transfection of curcumin plus sunitinib/sunitinib alone-treated drug-resistant cell lines with si-ADAMTS18, cell proliferation activity was assessed by the CCK-8 assay, and the protein expression levels of ADAMTS18, NCOA1, FTH1 and p53 were analyzed by Western blotting. After treatment with ferroptosis-1 (Fer-1; a ferroptosis inhibitor), the cell proliferation activity of drug-resistant cell lines treated with curcumin plus sunitinib/sunitinib alone was reassessed using the CCK-8 assay. RESULTS: Curcumin plus sunitinib inhibited the proliferation of sunitinib-resistant ccRCC cells (P<0.05). Curcumin significantly decreased the concentration of iron ions and increased the expression of ADAMTS18 gene, while significantly inhibited ferroptosis-related protein expression (P<0.05). After silencing the ADAMTS18 gene, there was no significant difference in cell proliferation or ferroptosis-related protein expression between curcumin plus sunitinib and sunitinib-treated drug-resistant cell lines (P>0.05). Ferroptosis inhibitors reversed the inhibitory effect of curcumin on sunitinib-resistant ccRCC cell lines. CONCLUSIONS: Curcumin can reverse the sunitinib resistance in ccRCC, possibly by upregulating the expression of the ADAMTS18 gene to induce ferroptosis.

Experience managing distal ureteral strictures with Boari flap-psoas hitch and comparison of open and laparoscopic procedures.

BACKGROUND: To summarize our experience with the Boari flap-psoas hitch and compare the indications, perioperative data and outcomes between open and laparoscopic procedures. METHODS: This study retrospectively reviewed 35 patients with complex distal ureteral stricture between January 2015 and April 2019. All patients were treated with Boari flap-psoas hitch by either an open or a laparoscopic procedure. Selection criteria were based on the etiology, comorbidities, medical history, and patient preference. RESULTS: All surgeries were performed successfully. The median operation time was 201 min (range, 120 to 300 min), and the median estimated blood loss was 50 mL (range, 20 to 400 mL). The median postoperative hospitalization was 9 days (range, 3 to 46 days). Nineteen patients were treated by the open procedure, and 16 were treated by the transperitoneal laparoscopic procedure. The surgical indication of open surgery was broader than that for laparoscopic surgery. For patients experiencing iatrogenic injury and ureterovesical reimplantation failure, no significant differences in sex, laterality, operative time, ASA score or postoperative hospitalization stay were observed between the two groups. The median estimated blood loss was lower in the laparoscopic group than in the open group (P=0.047). Patients in the open group had more surgical complications than patients in the laparoscopic group (P=0.049). The postoperative follow-up showed the radiological resolution of hydronephrosis in 33 patients. CONCLUSIONS: With the appropriate surgical considerations, Boari flap-psoas hitch is a valid method to bridge distal ureteral defects. For select patients, laparoscopic surgery had advantages being a minimal invasive surgery with less estimated blood loss and fewer surgical complications.

Real-time navigation by three-dimensional virtual reconstruction models in robot-assisted laparoscopic pyeloplasty for ureteropelvic junction obstruction: our initial experience.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of real-time surgical navigation by three-dimensional (3D) virtual reconstruction models in robot-assisted laparoscopic pyeloplasty (RALP). METHODS: Between November 2018 and January 2020, 38 patients with ureteropelvic junction obstruction (UPJO) who underwent RALP were retrospectively enrolled. The operations were assisted in real time by 3D models in 16 patients, while 22 patients underwent surgery without navigation. Based on whether patients had a prior intervention history, crossing vessels or congenital deformities, we further divided them into the "complicated UPJO" cohort and the "regular UPJO" cohort for subgroup analysis. The demographic characteristics, intraoperative parameters, perioperative data and follow-up data were recorded and compared between the groups. RESULTS: All of the procedures were successfully performed without open or laparoscopic conversion. The mean dissection time to the UPJ was shorter in the navigation group than in the non-navigation group, both in the whole cohort (15.3 vs. 24.8 min, P=0.011) and in the complicated cohort (15.4 vs. 27.5 min, P=0.004), while there was no significant difference in the regular cohort. The overall operative time and estimated blood loss in the navigation group tended to be less, although the difference was not statistically significant. No difference in anastomosis time, postoperative hospital stay or complications was noted between the two groups in either cohort. At a mean follow-up of 11.2 months, the overall success rate was 94.7% (36/38), and there was no significant difference between the two groups. CONCLUSIONS: Real-time navigation by 3D virtual reconstruction models might be helpful to improve surgical efficiency and safety of RALP by facilitating the dissection around the UPJ, especially for cases of complicated UPJO. However, the prospective study with larger sample size is further needed to confirm the results.

The application of the "omental wrapping" technique with autologous onlay flap/graft ureteroplasty for the management of long ureteral strictures.

BACKGROUND: To present our experience with the "omental wrapping" technique in laparoscopic and robotic ureteroplasty using onlay flaps or grafts for the management of long proximal or middle ureteral strictures. METHODS: This is a retrospective review of 25 patients with long proximal or middle ureteral strictures who underwent laparoscopic and robotic onlay flaps or grafts ureteroplasty using an omental flap to reinforce an anastomosis site between August 2018 and November 2019. Perioperative and follow-up data were collected. RESULTS: Sixteen laparoscopic procedures and nine robotic procedures were performed successfully. Sixteen patients underwent ureteroplasty with lingual mucosal graft (LMG), and nine patients with appendiceal onlay flap (AOF). The median stricture length was 4 cm (range, 2-6 cm). The mean operative time (OT) was 220.5±50.6 min, the estimated blood loss (EBL) was 66.0±38.9 mL, and the length of hospital stay (LHS) was 8.0±3.6 days. In the LMG group, four patients had tongue numbing and one had an oral ulcer, which relieved itself gradually without intervention. Two patients in the LMG group and four patients in the AOF group experienced urinary tract infection, and all responded well to antibiotic treatment. There were no complications attributed to "omental wrapping". The mean follow-up was 16.3±4.8 months. According to the standards regarding improvement in clinical symptoms, relief of obstruction radiologically and a stable estimate glomerular filtration rate, our surgical success rate was 100%. CONCLUSIONS: The "omental wrapping" technique in laparoscopic and robotic onlay flaps or grafts ureteroplasty for long proximal or middle ureteral strictures is an efficient, safe, reproducible and simple technique.

Robotic ureteral reimplantation for the management of ureterovaginal fistula: four cases at a single center.

BACKGROUND: To describe our initial experience with robotic ureteral reimplantation for the management of ureterovaginal fistulas. METHODS: Between January 2018 and January 2020, four patients received robotic ureteral reimplantation for ureterovaginal fistulas. All patients were diagnosed based on anterograde urography and computed tomography urography (CTU). Follow-up was performed with magnetic resonance urography and renal ultrasound as well as the clinical assessment of symptoms. RESULTS: The mean age of all patients was 50.3 (range, 37-65) years. The cause of the ureterovaginal fistula in four patients was due to a previous hysterectomy. The mean time from fistula diagnosis to robotic repair surgery was 14.5 (range, 3-36) months. All robotic procedures were successfully performed without intraoperative complications or open conversion. The mean operative time was 137 (range, 116-171) minutes, and the mean estimated blood loss was 25 (range, 10-50) mL. No postoperative complications that were high grade (grade III and IV) occurred within one month of surgery. Patients had the double-J (D-J) stents removed 2 months after surgery and the nephrostomy tubes removed 3 months after the operation. There was a 100% success rate without serious complications, such as the leakage of urine and side progressive hydronephrosis, during the 6 to 24 months of follow-up. CONCLUSIONS: Our initial results and experience showed that robotic ureteral reimplantation for the management of ureterovaginal fistula is safe and feasible.

Prognostic role of stromal tumor-infiltrating lymphocytes in locally advanced upper tract urothelial carcinoma: A retrospective multicenter study (TSU-02 study).

Locally advanced upper urinary tract urothelial carcinoma (UTUC) exhibits high recurrence and metastasis rates even after radical nephroureterectomy. Adjuvant immunotherapy can be a reasonable option, and a simple, low-cost, and effective biomarker is further needed. Stromal tumor-infiltrating lymphocytes (sTILs) has been demonstrated as a prognostic and predictive biomarker in various tumor types, but not yet in locally advanced UTUC. In this multicenter, real-world and retrospective study, we tried to investigate the prognostic role of sTIL and its correlation with the PD-L1/PD-1/CD8 axis by reviewing the clinicopathologic variables of 398 locally advanced UTUC patients at four high-volume Chinese medical centers. sTIL density was evaluated with standardized methodology on H&E sections, and patients were stratified by the cutoff of sTIL (50%). Results showed that high sTIL indicated improved survival (CSS, p = .022; RFS, p = .015; DFS, p = .004), and was an independent predictor of better CSS (HR, 0.577; 95% CI, 0.391-0.851; p = .006), RFS (HR, 0.613; 95% CI 0.406-0.925; p = .020) and DFS (HR, 0.609; 95% CI, 0.447-0.829; p = .002). A strongly positive correlation between sTIL density and the expression level of PD-1/PD-L1/CD8 axis was observed. We also found that aristolochic acid (AA) exposure was associated with increased sTIL and elevated PD-L1 expression, indicating that AA-related UTUC might be a distinct subgroup with unique tumor microenvironment characteristics. Our results show that sTIL can be an easily acquired biomarker for prognostic stratification in locally advanced UTUC.

Laparoscopic and robotic ureteroplasty using onlay flap or graft for the management of long proximal or middle ureteral strictures: our experience and strategy.

PURPOSE: To present our experience of laparoscopic and robotic ureteroplasty using onlay flap or graft for the management of long proximal or middle ureteral strictures and summarize our treatment strategies for these challenging scenarios. METHODS: From March 2018 to January 2020, 53 patients with long proximal/middle ureteral strictures (2-6 cm) who underwent laparoscopic or robotic onlay flap/graft ureteroplasty were retrospectively enrolled. Different reconstruction techniques were chosen based on our management strategy: pelvic flap (PF) was the first choice for proximal stricture if pelvic tissue was sufficient for repair, while appendiceal flap (AF) was preferred over oral mucosa graft for both proximal and middle strictures. RESULTS: A total of 28 PFs, 9 AFs and 16 lingual mucosa grafts (LMGs) onlay ureteroplasty were performed successfully, with 33 laparoscopic procedures and 20 robotic procedures being undertaken. No intraoperative complications or conversion occurred. The median stricture length was 4 cm (range 2-6 cm). Compared with laparoscopic procedures, robotic procedures showed significantly shorter operative time (P = 0.008), shorter postoperative hospital stay (P = 0.011) but higher hospital cost (P < 0.001). At a mean follow-up of 12.8 months, the overall success rate was 94.3%. There was no difference in postoperative complications or the success rate between the approaches. CONCLUSION: Laparoscopic and robotic onlay flap/graft ureteroplasty can be safe and feasible to repair long proximal/middle ureteral strictures while robotic procedures showed higher efficiency, faster recovery but higher cost. Our algorithmic strategies may provide beneficial references for their standardization and dissemination into clinical care.

Clinical Characteristics and Surgical Management of Adult Adrenal Teratoma: A 15-year Experience and Systematic Review of the Literature.

OBJECTIVE: To summarize the clinical characteristics and surgical management of adrenal teratoma in adults. PATIENTS AND METHODS: We retrospectively reviewed 14 patients with adrenal teratoma from January 2002 to June 2017, at 2 large centers in China and performed a systematic review of 39 patients from our series and published literatures. The clinicopathological characteristics, imaging features, surgical management and outcomes of this rare disease were analyzed. RESULTS: Our series includes 12 females and 2 males with the median age of 35. Seven patients were treated by open adrenalectomy (OA) and 7 by laparoscopic adrenalectomy (LA) without perioperative complications. All patients were alive without recurrence or canceration over a mean follow-up of 77.1 months. In the systemic review, the male-female ratio was nearly 1:3, with a median age of 29 years. Mean tumor size was 9.4 cm and the distribution was almost the same between left and right side (53.8% vs 46.2%). The most common symptoms were flank or abdominal pain (46.2%), whereas 53.8% patients were asymptomatic. Tumors were often cystic (63.9%) with intratumoral fat (91.7%) and calcifications (80.6%). All patients underwent surgery including 17 (43.6%) OA and 22 (56.4%) minimally invasive surgery. All tumors were pathologically confirmed mature teratoma except for one. CONCLUSION: Adrenal teratoma is an extremely rare entity, frequently found to be large, benign and cystic. The patient's prognosis is generally good. As for its large volume, OA is the first choice for teratoma in most cases, while the LA can be an option in the small one.