Urothelial Cancer Of Upper Urinary Tract Research Articles

Routine Surveillance of Upper Urinary Tract Imaging for Diagnosing Upper Urinary Tract Urothelial Cancer Recurrence in Patients with Nonmuscle Invasive Bladder Cancer.

Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow-up of nonmuscle invasive bladder cancer is recommended, its necessity remains invalidated. A single-institute long-term follow-up cohort study to evaluate the clinical impact of routine surveillance imaging and identify risk factors for upper urinary tract urothelial cancer recurrence after nonmuscle invasive bladder cancer treatment was conducted. A retrospective chart review of 864 patients with primary nonmuscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. The opportunities to diagnose its recurrence were examined. Moreover, oncological outcomes included upper urinary tract urothelial cancer recurrence-free survival and overall survival. Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. Among 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in 2 (10.5%), urine cytology in 2 (10.5%), and presence of gross hematuria in 1 (5.3%). All patients had high- or highest-risk NMIBC at diagnosis of primary nonmuscle invasive bladder cancer. On multivariate Fine-Gray proportional regression analyses, a tumor size of ≥30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence-free survival (P=0.040 and 0.0089, respectively). Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with nonmuscle invasive bladder cancer accompanied by a tumor size of ≥30 mm and carcinoma in situ.

Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSSafter RNUincluded male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Oncologic outcomes of patients treated with kidney-sparing surgery or radical nephroureterectomy for upper urinary tract urothelial cancer: a population-based study

PurposeAlthough kidney-sparing surgery (KSS) is a nonminor option for low-risk upper urinary tract urothelial cancer (UTUC), its oncological benefits in high-risk UTUC remain unclear when compared to radical nephroureterectomy (RNU). This study aimed to compare the oncological outcomes of RNU and KSS in patients with UTUC. MethodsWe searched the SEER database for patients treated for primary non-metastatic UTUC with either RNU or a kidney-sparing approach (segmental ureterectomy (SU) or local tumor excision (LTE)) between 2004 and 2018. ResultsThe study included 6,659 patients with primary non-metastatic UTUC treated with surgery; 2,888 (43.4%) and 3,771 (56.6%) patients presented with ureteral and renal pelvicalyceal tumors, respectively. Finally, 5,479 (82.3%) patients underwent RNU, 799 (12.0%) were treated with SU, and 381 (5.7%) patients received LTE. For confounder control, propensity score matching (PSM) of patients treated with SU and RNU was performed to adjust for T stage, grade, age, gender, tumor size, and lymphadenectomy performance. PSM analysis included 694 patients treated with RNU and 694 individuals who underwent SU. In multivariable Cox regression and Kaplan-Meier analyses, we found no difference in either CSS or OS between RNU and SU, even in the subgroup of high-grade and/or muscle-invasive UTUC including pT3-T4 tumors (all p > 0.05). ConclusionIn this population-based study, SU provides equivalent CSS and OS compared to RNU, even in high-risk and locally advanced ureteral cancer. Due to the unavoidable risk of selection bias, further prospective studies are expected to overcome the limitations of this study and support the wider implementation of KSS.

The Association between Lymph Node Dissection and Survival in Lymph Node-Negative Upper Urinary Tract Urothelial Cancer.

The benefit of lymph node dissection (LND) during radical nephroureterectomy (RNU) in lymph node (LN)-negative (cN0/pN0) UTUC remains controversial. We aimed to assess the association between LND and its extent and survival in LN-negative UTUC. The Surveillance, Epidemiology, and End Results database was searched to identify patients with non-metastatic chemotherapy-naïve cN0/pNx or pN0 UTUC who underwent RNU +/- LND between 2004 and 2019. Overall, 4649 patients with cN0/pNx or pN0 UTUC were analyzed, including 909 (19.55%) individuals who had LND. Among them, only in 368 patients (7.92%) was LND extended to at least four LNs, and the remaining 541 patients (11.64%) have had < four LNs removed. In the whole cohort, LND contributed to better cancer-specific survival (CSS) and overall survival (OS). Furthermore, a propensity score-matched analysis adjusted for confounders confirmed that improved CSS and OS was achieved only when ≥ four LNs had been removed, especially in muscle-invasive UTUC. A multivariable analysis further confirmed an association between the extent of LND and CSS. To conclude, adequate LND during RNU was associated with improved OS and CSS in LN-negative UTUC, particularly in muscle-invasive stage. This underscores that a sufficient LN yield is required to reveal a therapeutic benefit in patients undergoing RNU.

VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma.

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.

Left robot-assisted upper pole heminephrectomy for upper urinary tract urothelial cancer in lynch syndrom

Left robot-assisted upper pole heminephrectomy for upper urinary tract urothelial cancer in lynch syndrom

ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma

Introduction: Urothelial carcinoma (UC) is a common type of malignant disease, but little is known about the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) because of its rarity. To clarify the significance of ANXA10 in UTUC, we studied ANXA10 expression with immunohistochemistry (IHC). Methods: The expression of ANXA10 was analyzed in the upper and lower urinary tract of UC by IHC in combination with The Cancer Genome Atlas (TCGA) data analysis. The association between ANXA10 expression and representative cancer-related molecules was also evaluated. Results: ANXA10 expression was weak in normal upper tract urothelium but was positive in 39/117 (33%) UTUCs. ANXA10 was more frequently positive in tumors with pure UC (36%, p < 0.05), papillary morphology (50%, p < 0.01), low grade (G1/2: 57%, p < 0.01), and pTa/is/1 stage (55%, p < 0.01) than in those with histological variants (0%), nodular morphology (9%), G3 (16%), and pT2/3/4 (13%), respectively. ANXA10-positive patients showed better cancer-specific survival and progression-free survival than ANXA10-negative patients (p < 0.05). IHC showed that ANXA10 positivity was detected more in cases with the low expression of TP53 (p < 0.01) and Ki-67 labeling index <20% (p < 0.01). In TCGA dataset of muscle-invasive bladder cancer, higher ANXA10 expression correlated with papillary morphology, lower grade/stage, luminal papillary subtype, wild-type TP53, and FGFR3 gene mutation. Conclusion: We revealed that ANXA10 expression was increased during carcinogenesis and was observed more frequently in papillary UC of lower grade and stage. However, its expression decreased as cancer progressed. Therefore, the ANXA10 expression in UTUC might be clinically useful for decision-making.

The Value of Lymph Node Dissection in Patients With Node-Positive Upper Urinary Tract Urothelial Cancer: A Retrospective Cohort Study.

PurposeThe value of lymphadenectomy during radical nephroureterectomy (RNU) remains unclear. This study aimed to determine the effects of the removed lymph node (RLN) counts, positive lymph node (pLN) counts, and pLN density (pLND) on survival outcomes in patients with node-positive upper urinary tract urothelial cancer (UTUC).MethodsA total of 306 patients with node-positive UTUC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016 were identified. Multivariable Cox regression analyses were used to evaluate the effect of RLN counts, pLN counts, and pLND on survival outcomes. The maximally selected rank statistics were used to determine the most informative cutoff value for pLND on survival outcomes.ResultsThe RLN counts or pLN counts were not associated with survival outcomes, whereas higher pLND was associated with lower cancer-specific survival (CSS) and overall survival (OS) [hazard ratio (HR) 1.75, P = 0.014 and HR 1.62, P = 0.036, respectively]. The most informative cutoff value for pLND in relation to survival was 27%. Patients with pLND ≥27% had worse 5-year survival rates than those with pLND <27% (52.9% vs. 75.9% for CSS and 18.7% vs. 34.2% for OS, each P < 0.05). Furthermore, the multivariable Cox regression model with pLND could predict 5-year CSS (AUC 0.732 vs. 0.647) or OS (AUC 0.704 vs. 0.621) more accurately than the model without pLND.ConclusionsFor patients with node-positive UTUC, more lymph nodes removed do not offer a better therapeutic effect. However, pLND provides additional prognostic value.

Activated protein kinase C-alpha as a simple test for urothelial cancer screening.

e16552 Background: The development of a non-invasive, highly predictive diagnostic test for urothelial cancer (UC) would greatly benefit patients. Although numerous urine-based tests have been developed, it is not widely used, except for urine cytology, due to insufficient sensitivity, negative predictive value and high cost. Previously we reported that protein kinase C-alpha (PKCα) is overexpressed or activated in several cancer tissues but not in normal tissue, and we developed an activated PKCα-specific peptide substrate (FKKQGSFAKKK; Patent No. 5476559). The purpose of this study was to investigate the potential for UC screening of simple test detecting activated PKCα. Methods: This institutional review board-approved prospective study included patients with bladder cancer or upper urinary tract UC who underwent surgery at Kyushu University Hospital between September 2018 and December 2020. Patients with benign urologic disorders or healthy volunteers were included as a control group. Patients with prostate cancer (PC) or renal cell carcinoma (RCC) who underwent curative surgery were included as other genitourinary (GU) cancer group. Patients with other coexisting malignant tumors were excluded. Urine samples were collected prior to surgery, 20 mL of urine was centrifuged, and the pellet was lysed for analysis. We evaluated the phosphorylation status of the activated PKCα-specific peptide substrate by MALDI-TOF mass spectrometry. The utility of activated PKCα as a urinary biomarker was evaluated by its sensitivity and negative predictive value when compared to control group or other GU cancers group. Results: Urine samples were obtained from 226 individuals, which included 98 patients with UC, 51 with other GU caners, and 77 with control group. Of the 98 patients with UC, activated PKCα was detected in 75 patients, with sensitivity of 76.5%. The sensitivity in patients with high-grade and low-grade UC were 84% and 62%, respectively. The sensitivity in those with high-grade UC increased to 93% when combined with urine cytology. On the other hand, activated PKCα were rarely detected in non-UC patients which includes other GU cancers group and control group. The specificity among the non-UC patients was 74.2%. In the comparison between patients with UC and non-UC, the negative predictive value of activated PKCα was 80.5%. The area under the receiver operating characteristic curve (AUC) for detecting UC of activated PKCα was 0.80. Conclusions: This study demonstrates the utility of activated PKCα as a novel urine screening test for UC. (Patent Application No. PCT/JP2020/045257) Since this test is based on a single target, inexpensive detection devices can be developed.

Machine learning diagnosis by immunoglobulin N-glycan signatures for precision diagnosis of urological diseases.

Early diagnosis of urological diseases is often difficult due to the lack of specific biomarkers. More powerful and less invasive biomarkers that can be used simultaneously to identify urological diseases could improve patient outcomes. The aim of this study was to evaluate a urological disease‐specific scoring system established with a machine learning (ML) approach using Ig N‐glycan signatures. Immunoglobulin N‐glycan signatures were analyzed by capillary electrophoresis from 1312 serum subjects with hormone‐sensitive prostate cancer (n = 234), castration‐resistant prostate cancer (n = 94), renal cell carcinoma (n = 100), upper urinary tract urothelial cancer (n = 105), bladder cancer (n = 176), germ cell tumors (n = 73), benign prostatic hyperplasia (n = 95), urosepsis (n = 145), and urinary tract infection (n = 21) as well as healthy volunteers (n = 269). Immunoglobulin N‐glycan signature data were used in a supervised‐ML model to establish a scoring system that gave the probability of the presence of a urological disease. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). The supervised‐ML urologic disease‐specific scores clearly discriminated the urological diseases (AUC 0.78–1.00) and found a distinct N‐glycan pattern that contributed to detect each disease. Limitations included the retrospective and limited pathological information regarding urological diseases. The supervised‐ML urological disease‐specific scoring system based on Ig N‐glycan signatures showed excellent diagnostic ability for nine urological diseases using a one‐time serum collection and could be a promising approach for the diagnosis of urological diseases.

Pathological Significance and Prognostic Role of WWC1 in Upper Urinary Tract Urothelial Cancer.

WW and C2 domain-containing 1 (WWC1) protein is a suppressor of malignancies. However, there is no information on the pathological significance of WWC1 in upper urinary tract cancer (UTUC). In this study, WWC1 immunoreactivity was investigated in 152 non-metastatic UTUC samples. The relationships between WWC1 expression and grade, pT stage, proliferative index (using an antibody to Ki-67), and the immunohistochemical expression of matrix metalloproteinase (MMP)-2 and -9 were evaluated. WWC1 expression was negatively associated with tumor grade and pT stage (p<0.001). Positive expression of WWC1 was a better predictor of the UTUC recurrence and subsequent metastasis, and the multivariate analysis showed that WWC1 expression was a significant predictor of subsequent metastasis (hazard ratio=0.29, p=0.020). WWC1 expression inversely correlated with the proliferative index (odds ratio=2.59, p=0.023) and expression of MMP9 (odds ratio=2.19, p=0.040) but not with MMP2 expression, by multivariate analyses. WWC1 expression was negatively associated with malignant aggressiveness via the suppression of cancer cell proliferation and MMP9 expression in patients with UTUC. This suggests WWC1 to be a useful predictor and novel therapeutic target in patients with UTUC.

Impact of Adjuvant Chemotherapy on Variant Histology of Upper Tract Urothelial Carcinoma: A Propensity Score-Matched Cohort Analysis.

BackgroundThe advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data.Design, Setting, and ParticipantsPatients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information.InterventionThose patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not.Outcome Measurements and Statistical AnalysisPropensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival.Results and LimitationsFor the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285–0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208–0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155–0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number.ConclusionsAdjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

Is preoperative Neutrophil-Lymphocyte Ratio important in patients who undergo Radical Nephroureterectomy for Upper Urinary Tract Urothelial Cancer?

Is preoperative Neutrophil-Lymphocyte Ratio important in patients who undergo Radical Nephroureterectomy for Upper Urinary Tract Urothelial Cancer?

Comparison of Tumor Seeding and Recurrence Rate After Laparoscopic vs. Open Nephroureterectomy for Upper Urinary Tract Transitional Cell Carcinoma

Introduction: Laparoscopic surgery for Upper Urinary Tract Urothelial Cell Carcinoma (UTUC) is still debated for its possible seeding risk and thus consequent oncological recurrences, especially for atypical ones. The aim of the study is to compare recurrence and survival after Laparoscopic vs. Open Radical Nephroureterectomy (RNU) for Upper Urinary Tract Urothelial Cancer (UTUC).Method: A retrospective evaluation of UTUC consecutive surgeries from 2008 to 2019 was conducted, including pT ≥ 2, High Grade UTUC who underwent RNU with bladder cuff excision without concomitant lymphadenectomy in three urological tertiary centers. Statistical analyses compared recurrence and cancer specific survival, based on surgical approach, while logistic multivariate analyses and Kaplan Meyer survival curve analyzed possible risk factors for recurrence and survival.Results: One hundred seven cases of RNU, 47 (43.9%) laparoscopic and 60 (56.1%) open, were included in this report. Preoperative characteristics were comparable between groups. However, tumor stage was higher in the Open arm [T3–T4 in 44 (73.3%) vs. 20 (43.4%) in Laparoscopic]. Mean follow-up was 91.6 months in laparoscopy RNU vs. 93.5 months in open RNU. Recurrence rate (RR) was comparable between groups (p = 0.594), and so was the site, although 3 (6.3%) peritoneal recurrences were found only in laparoscopic group (p = 0.057). At multivariate logistic regression, tumor stage and surgical approach were independent predictors of recurrence (p < 0.05), while only tumor stage was predictor of cancer specific death (p = 0.029).Conclusion: Surgical approach has no impact on recurrence site, overall survival, and RR. Still, according to our data peritoneal carcinomatosis was present only in laparoscopic arm, despite how it didn't reach statistical significance.

The prognostic significance of controlling nutritional status (CONUT) score for surgically treated renal cell cancer and upper urinary tract urothelial cancer: a systematic review and meta-analysis.

In order to evaluate the predictive effect of the controlled nutritional status (CONUT) score on the prognosis of patients with renal cell carcinoma (RCC) and upper urinary tract urothelial carcinoma (UTUC), a meta-analysis was performed. This systematic review has been registered on PROSPERO, the registration ID is CRD42021251879. A systematic search of the published literature using PubMed, Web of Science, Cochrane Library, EMBASE, and MEDLINE was performed. The fields of "renal cell cancer," "upper tract urothelial cancer," and "controlling nutritional status" and other fields were used as search terms. STATA 16 software was used to carry out data merging and statistical analysis of binary variables, Q test and χ2 tests were used to verify the heterogeneity between the included works of studies. Subgroup analysis and sensitivity analysis were used to explain the sources of heterogeneity between studies. Begg's test was used to assess publication bias between studies. From the first 542 studies retrieved, through strict inclusion and exclusion criteria, 7 studies finally met the requirements and were included in the meta-analysis. Pooled results indicated that high CONUT indicates worse over survival (OS) [HR = 1.70, 95% CI (1.43-2.03), P = 0.02], cancer-specific survival (CSS) [HR = 1.84, 95% CI (1.52-2.23), P = 0.01], recurrence-free survival (RFS) [HR = 1.60, 95% CI (1.26-2.03), P = 0.116], and disease-free survival (DFS) [HR = 1.47, 95% CI (1.20-1.81), P = 0.03]. Based on cancer type, cutoff value, region, and sample size, a subgroup analysis was performed. The results showed that OS and CSS were not affected by the above factors, and the high CONUT score before surgery predicted worse OS and CSS. In conclusion, this meta-analysis revealed that the preoperative CONUT score is a potential independent predictor of the postoperative prognosis of RCC/UTUC patients. A high CONUT predicts worse OS/CSS/DFS and RFS in patients.

Intraoperative Mitomycin C Bladder Instillation During Radical Nephroureterectomy Is Feasible and Safe

BackgroundBladder recurrence after radical treatment of upper urinary tract urothelial cancer (UTUC) is frequent, and patients are required to undergo surveillance cystoscopies following surgery. The use of intravesical adjuvant chemotherapy is an accepted method to prevent bladder recurrence, but the timing of this method is not standardized and the concept of intraoperative use is unexplored. ObjectiveThe objective of the study is to examine the feasibility and safety of intraoperative intravesical mitomycin C (MMC) instillation using a closed-circuit system following bladder cuff excision and bladder closure. Design, setting, and participantsAll patients who underwent radical nephroureterectomy (RNU) for UTUC at the Department of Urology of Zealand University Hospital, Roskilde, Denmark from 2017 to 2020 were identified. Patient complications within 30 d and data regarding oncological outcome were registered. Outcome measurements and statistical ana lysisClavien-Dindo grade for complications and descriptive statistics were used. ResultsDuring the study period, 64 patients underwent RNU. Of these patients, 49 received bladder instillation of MMC during RNU. Complications were observed in 11 patients (21.4%), where four patients (8.2%) had Clavien-Dindo complication grade (CD) I, four patients (8.2%) had CD II, one patient (2%) had CD III, and one patient (2%) had CD IIIa. None of the complications were suspected to be related to MMC. Five of the 15 patients (33%) who did not receive MMC experienced complications. There were no significant differences in complication rates between patients who received MMC and those who did not. Study limitations include a small sample size and a single-center study. ConclusionsIntraoperative vesical instillation of MMC is feasible and was, in the present study, not associated with an increased complication rate. Patient summaryBladder recurrence after radical treatment of upper urinary tract cancer is frequent. The present study findings indicate that intraoperative bladder irrigation with the chemotherapeutic mitomycin C during surgery does not lead to excessive complications and could be a method to reduce the risk of bladder recurrence.

Simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion: step-by-step video-illustrated technique

ABSTRACTIntroduction:One of the most remarkable characteristics of urothelial carcinomas is multifocality. However, occurrence of synchronous bladder cancer and upper urinary tract urothelial cancer (UTUC) is exceptional. Minimally invasive approach for these synchronous tumors was just occasionally reported (1-4). The aim of this video article is to describe step-by-step the technique for simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion (ICUD). Patients and methods: A 66-year-old female presented with synchronous BCG refractory non-muscle invasive bladder cancer and a right-side UTUC. She was a former smoker and had previously been submitted to multiple transurethral resections of bladder tumor, BCG and right distal ureterectomy with ureteral reimplant. We performed a simultaneous laparoscopic right nephroureterectomy and robot-assisted anterior pelvic exenteration with totally intracorporeal ICUD. Combination of robot-assisted and pure laparoscopic approaches was proposed focusing on optimization of total operative time (TOT).Results:Surgery was uneventful. TOT was of 330 minutes. Operative time for nephroureterectomy, anterior pelvic exenteration and ICUD were 48, 135, 87 minutes, respectively. Estimated blood loss was 150mL. Postoperative course was unremarkable and patient was discharged after 7 days.Histopathological evaluation showed a pT1 high grade urothelial carcinoma plus carcinoma in situ both in proximal right ureter and bladder, with negative margins. Twelve lymph nodes were excised, all of them negative.Conclusion:In our preliminary experience, totally minimally invasive simultaneous nephroureterectomy and cystectomy with intracorporeal ICUD is feasible. Pure laparoscopic approach to upper urinary tract may be a useful tactic to reduce total operative time.

SC135 - Role of inflammatory markers and frailty index as predictors of adverse pathological stage andcomplications in patients with upper urinary tract urothelial cancer: a multicenter analysis

SC135 - Role of inflammatory markers and frailty index as predictors of adverse pathological stage andcomplications in patients with upper urinary tract urothelial cancer: a multicenter analysis

P0786 - Pathological significance and prognostic utility of KIBRA in upper urinary tract urothelial cancer

P0786 - Pathological significance and prognostic utility of KIBRA in upper urinary tract urothelial cancer

Transition of ANXA10 expression is a useful diagnostic and prognostic marker in upper tract urothelial carcinoma

Little is known about the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) because of its rarity. ANXA10, a calcium dependent phospholipid binding protein, is differentially expressed in several cancers. It has been reported that ANXA10 expression is a urinary mRNA biomarker for detection of bladder urothelial cancer (BUC), and loss of ANXA10 expression is associated with BUC progression. To clarify the significance of ANXA10 in UTUC, we studied ANXA10 expression with immunohistochemistry (IHC). We analyzed ANXA10 by IHC in 117 respective cases of UTUC treated by radical nephroureterectomy without neoadjuvant chemotherapy. ANXA10 positivity (ANXA10+) was defined as >10 % of nuclear staining. ANXA10 expression was weak in normal urothelium of upper tract and was positive in 39/117 (33%) of UTUC. ANXA10+ was more frequently in tumors with pure UC (36%, p<0.05), papillary morphology (50%, p<0.01), histological grade 1/2 (G1/2: 57%, p<0.01) and pTa/is/1 stage (55%, p<0.01) than in those with histological variants (0%), nodular morphology (9%), G3 (16%) and pT2/3/4 (13%), respectively. Patients with ANXA10+ showed better cancer specific survival (CSS) than those with ANXA10- (P<0.05). With IHC, ANXA10+ was detected more in TP53 negative cases (44%, P<0.01) and Uroplakin 3 (UPK3) positive cases (44%, p= 0.089) than in TP53 positive cases (6%) and UPK3 negative cases (28%), respectively. In TCGA dataset of MIBC, higher ANXA10 expression was correlated with papillary morphology, lower grade/stage, luminal papillary subtype and wild type of TP53. ANXA10 expression increases during carcinogenesis, and is observed more frequently in papillary UC with lower grade and stage. However, its expression decreases during cancer progression. Transition of ANXA10 expression in UTUC mimicking BC is clinically useful for decision-making.