Introduction Patients with localized high-risk urothelial carcinoma of the upper urinary tract are advised radical nephroureterectomy, the surgical removal of the kidney and ureter, utilizing robot-assisted versus laparoscopic methods. This study aims to compare the surgical and oncological results of robot-assisted and laparoscopic radical nephroureterectomy for upper-tract urothelial carcinoma. Methods An observational retrospective cohort study compared 14 patients who had robotic-assisted nephroureterctomy (RAN) to 16 patients who had laparoscopic assisted nephroureterctomy (LAN). Results There was no significant difference in age, sex, glomerular filtration rate (GFR), creatinine, Charlson comorbidity score, length of hospital stays, or the need to convert to an open approach. However, there was a statistical difference between the two procedures in terms of lymph dissection (p-value of 0.037) and the length of the procedure (p-value of 0.09). Conclusions The robotic approach has significantly higher use for lymph node dissection, while laparoscopic radical nephroureterectomy has a shorter operation time.

UNASSIGNED: The possible negative impact of radical surgery on patients\' health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes.
UNASSIGNED: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds.
UNASSIGNED: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning.
UNASSIGNED: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery.
UNASSIGNED: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery.

OBJECTIVE: Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow-up.
METHODS: An institutional database was reviewed for the UUT biopsy/resection histopathologic specimens, and we included 52 UUT cytology specimens pertinent to these cases in the study. These specimens were blindly reviewed and reclassified using TPS 2.0. The correlation between TPS 2.0, ORS and histopathologic follow-up was assessed.
RESULTS: The UUT cytology specimens corresponded to 21 (40.4%) high-grade urothelial carcinoma (HGUC), 27 (51.9%) low-grade urothelial carcinoma (LGUC) and 4 (7.7%) benign cases on follow-up. For HGGC cases, the associated TPS categories included unsatisfactory (n = 1, 4.8%), negative for HGUC (NHGUC; n = 3, 14.3%), atypical urothelial cells (AUC; n = 6, 28.6%), suspicious for HGUC (SHGUC; n = 3, 14.3%) and HGUC (n = 8, 38.1%), while ORS categorised the specimens as unsatisfactory (n = 1, 4.8%), negative for malignant cells (NFMC; n = 3, 14.3%), AUC (n = 5, 23.8%), low-grade urothelial carcinoma (LGUC; n = 0, 0%), SHGUC (n = 5, 23.8%) and HGUC (n = 7, 33.3%). The risks of high-grade malignancy among cytologic categories were similar between ORS and TPS (p > 0.05). The majority of LGUC were classified as AUC similarly by ORS and TPS (55.6% vs. 59.3%).
CONCLUSIONS: Our study demonstrated comparable performance between TPS 2.0 and ORS for UUT cytology specimens. Cytological diagnosis of UUT specimens remains challenging, especially for LGUC.

Nested urothelial carcinoma (NUC) and large nested urothelial carcinoma (LNUC) of the upper urinary tract are exceedingly rare. This has contributed to the paucity of information regarding their clinicopathological and molecular characteristics. To address this knowledge gap, we explored the largest cohort to date of these rare tumors, comprising resection specimens of 10 LNUC and 7 NUC, from 7 participating institutions. Clinicopathological data were retrieved and documented. Whole exome sequencing and RNA sequencing were performed on the Illumina NovaSeq 6000 sequencer. The data generated were analyzed using the genome analysis toolkit pipeline. Somatic mutations were annotated using funcotator tool to identify pathogenic/likely pathogenic variants. Tumor mutational burden was calculated using python-based \"pyTMB\" tool. Microsatellite instability analysis was done using MSIsensor2 and the Idylla platform. Differential expression analysis of genes in LNUC and NUC along with mRNA expression-based molecular subtyping was performed by analyzing expression pattern of markers used in The Cancer Genome Atlas subclassification of bladder carcinoma. Both tumor types were more common in older males, were unifocal, and occurred more commonly mixed with minor components of predominantly conventional urothelial carcinoma. Overlying low-grade papillary urothelial carcinoma was significantly more common in LNUC (P = .034). On follow-up (LNUC: median, 10 months; range, 3-84 months; NUC: median, 9 months; range, 2-48 months), LNUC had better clinical outcomes (P = .031). Pathogenic mutations in FGFR3 and PIK3CA were significantly more common in LNUC (P = .049 and P = .044, respectively), with the latter present exclusively in LNUC. Seventy-five percent of the cases showed tumor mutational burden of <10, and all cases were microsatellite-stable. FGFR3 mutations were also more common in low-stage tumors. This study expands on the clinicopathological spectrum of NUC and LNUC of the upper urinary tract and is the first to comprehensively analyze the molecular profile of these tumors, highlighting pathogenic genetic alterations of potential therapeutic and prognostic value.

BACKGROUND: To explore the application value of intraoperative imaging by indocyanine green (ICG) injection through the collection system of the urinary tract for Da Vinci Xi robot navigation in complex surgeries on the upper urinary tract.
METHODS: Data of 14 patients who underwent complex surgeries of the upper urinary tract post-ICG injection through the collection system of the urinary tract in combination with Da Vinci Xi robot navigation in the Tianjin First Central Hospital between December 2019 and October 2021 were analyzed in this retrospective study. The operation duration, estimated blood loss, and exposure time of ureteral stricture to ICG were evaluated. The renal functions and tumor relapse were evaluated after surgery.
RESULTS: Of the fourteen patients, three had distal ureteral stricture, five had ureteropelvic junction obstruction, four presented duplicate kidney and ureter, one had a giant ureter, and one presented an ipsilateral native ureteral tumor after renal transplantation. The surgeries in all patients were successful, with no conversion to open surgery. In addition, no injury to the surrounding organs, anastomotic stenosis or leakage, or ICG injection-related side effects were detected. Imaging at 3 months post-operatively revealed improved renal functions compared to those before the operation. No tumor recurrence or metastasis was observed in patient 14.
CONCLUSIONS: Fluorescence imaging compensating for the inadequacy of tactile feedback in the surgical operating system has advantages in identifying the ureter, determining the site of ureteral stricture, and protecting the blood flow for the ureter.

BACKGROUND: Noninvasively urine-based diagnostic modalities for upper urinary tract urothelial carcinoma (UTUC) were still lacking. We evaluated the diagnostic value of our previously developed urine-based assay (UTC assay) in UTUC.
METHODS: We retrospectively analyzed 90 patients with suspected UTUC and 40 donors without UTUC. Voided urine specimens were analyzed by UTC assay and fluorescence in situ hybridization (FISH). The performance of UTC assay and FISH was compared among the 60 histologically proven UTUC patients and the 40 donors with benign disease.
RESULTS: Of the 60 UTUCs, there were 8 low-grade and 52 high-grade cases. Overall sensitivity for UTC assay and FISH were 85% and 73.3%, respectively (P = 0.116). Specificities for UTC assay and FISH were 92.5% and 95%, respectively (P = ns.). By grade, sensitivities of UTC assay and FISH were 87.5% vs. 37.5% for low-grade (P = 0.119), and 84.6% vs. 78.8% for high- grade UTUC (P = 0.446), respectively. By stage, UTC assay showed significantly higher sensitivity than FISH for detecting non-muscle-invasive UTUC, which were 88.5% vs. 61.5%, respectively (P = 0.025).
CONCLUSIONS: UTC assay has good performance for the non-invasive diagnosis of UTUC. UTC assay may improve the diagnosis and surveillance of low-grade or superficial UTUC.

During endoscopic procedures for suspected urothelial tumors of the upper urinary tract, radiographic imaging using an iodinated contrast medium is often required. However, following ureteropyelography, we detected changes in cytology characteristics not correlating with real cytology findings in naive urine. The aim of our study was to assess cytology changes between naive and postcontrast urine according to The Paris System of cytology classification. Methods: We prospectively assessed urine samples from 89 patients (23 patients with histologically proven urothelial cancer and 66 healthy volunteers). The absence of malignancy was demonstrated by CT urography and/or ureteroscopy. The study was single blind (expert cytopathologist) and naïve Paris system for urine cytology assessment was used. Furthermore, additional cytological parameters were analyzed (e.g., specimen cellularity, degree of cytolysis, cytoplasm and nucleus color, chromatin and nucleo-cytoplasmic ratio). Results: Our study showed statistically significant differences when comparing naïve and postcontrast urine in healthy volunteers (only 51 % concordance, p = 0.001) versus malignant urine specimens (82 % concordance). The most important differences were in the shift from The Paris System category 2 (negative) to 1 (non-diagnostic) and from category 2 (negative) to 3 (atypia). Other significant changes were found in the assessment of specimen cellularity (p = 0.0003), degree of cytolysis (p = 0.001), cytoplasm color (p = 0.003), hyperchromasia (p = 0.001), course chromatin (p = 0.002), nucleo-cytoplasmatic ratio (p = 0.001) and nuclear borders\' irregularity (p = 0.01). Conclusion: Our unique study found crucial changes in the cytological assessment of naive and postcontrast urine and we confirm that postcontrast urine is more often assessed as abnormal, suspect or non-diagnostic. Therefore, before urine collection for cytology, the clinician should avoid administration of iodinated contrast into the urinary tract.

OBJECTIVE: Urinary culture sensitivity after antibiotics administration is unknown. This study aimed to describe the diagnostic sensitivity of urine cultures from patients\' first, second, and third micturition samples after a single dose of empirical antibiotics given for upper and/or febrile urinary tract infections, as well as searched for factors influencing diagnostic sensitivity over time.
METHODS: We collected consecutive urine samples from adult patients with an upper or febrile urinary tract infection diagnosed at four secondary hospital emergency rooms. One sample was collected before a first dose of empirical antibiotic treatment and up to three samples were collected from consecutive postadministration micturition. The main outcome was the number of positive cultures growing uropathogens with ≥103 colony forming units (CFUs) for men and ≥104 for women. Identical analyses were performed for any identified CFU and ≥105 CFU cut-off points. Time between antibiotic administration and first negative urinary culture was noted, which could have been at the time of any of the three postantibiotic urine samples. We used a Cox regression analysis for age- and sex-adjusted analyses.
RESULTS: A total of 86 of 87 patients\' preantibiotic cultures (99%) were positive compared with 26 of 75 (35%; p < 0.001), 15 of 50 (30%; p < 0.001), and 1 of 15 (7%; p < 0.001) of the first, second, and third postantibiotic samples, respectively, and missing 14 of 21 (67%), 13 of 17 (76%), and 7 of 7 (100%) of uropathogens with antibiotic resistance, respectively. The times needed for 25%, 50%, and 75% of cultures to be negative were 1.5, 2.9, and 9 hours, respectively, after antibiotic administration. Older age, male sex, non-Escherichia coli pathogens, urinary tract disease, comorbidity burdens, and urinary catheters prolonged time to negative culture, but were not significantly associated after adjustment. Uropathogens were found at ≥105 CFU in 15 of 75 (20%), 7 of 50 (14%), and 0 of 15 (0%) of the three postantibiotic micturition samples, respectively, and in any identified CFU in 48 of 75 (64%), 23 of 50 (46%), and 1 of 15 (7%), respectively.
CONCLUSIONS: Urinary culture sensitivity decreases rapidly after administering antibiotics.

UNASSIGNED: To determine the safety and feasibility of extraperitoneal laparoscopic extended lymph node dissection (LND) at the time of extraperitoneal laparoscopic radical nephroureterectomy (RNU).
UNASSIGNED: Between May 2018 and March 2019, 39 patients with upper tract urothelial carcinoma (UTUC) received extraperitoneal laparoscopic RNU and concomitant extraperitoneal laparoscopic extended LND. All patients were followed for at least 90 days. Perioperative and pathological data including nodal status and perioperative complications were collected.
UNASSIGNED: Among all 39 patients, 12 patients had pT1, 6 had pT2, 20 had pT3 disease, and 1 had T4 disease. The median (range) lymph node count was 10 (5-22), with 8 patients having pathologically proven lymph node metastasis. The median (range) operating time was 225 (165-430) min, and the median estimated blood loss was 200 (60-800) ml. The median postoperative hemoglobin loss was 1.6 (0-4.2) g/dl. The median (range) postoperative hospital stays were 6 (3-26) days. Overall, 7 patients experienced minor (Clavien Grade I-II) postoperative complications with five patients having Clavien Grade I complications and two patients having Clavien Grade II complications. No major complication (Clavien grade III-IV) occurred. With a median follow-up of 38 months, a total of 8 patients (20.5%) developed local or distant recurrence and no regional LNs where extended LND were performed had recurrence.
UNASSIGNED: The present prospective study demonstrated that extraperitoneal laparoscopic extended LND during extraperitoneal laparoscopic RNU for UTUC is a feasible and safe procedure which provides minimal invasion, rapid recovery, and potentially lower risk of regional LN recurrence. Larger prospective clinical trials with survival endpoints are needed to further determine its potential therapeutic benefits.
UNASSIGNED: ClinicalTrials.gov identifier NCT03544437 www.clinicaltrials.gov.

To assess trends in the incidence, disease management and survival rates for upper urinary tract urothelial carcinoma (UTUC) in the Netherlands.
Patients diagnosed with primary UTUC in the Netherlands between 1993 and 2017 were identified through the population-based Netherlands Cancer Registry (NCR). Patient and tumour characteristics, as well as information on treatment and vital status, were retrieved from the NCR. Age-standardized incidence rates were calculated, stratified by age, gender, calendar period and disease stage. Relative survival served as an approximation for cancer-specific survival.
We identified 13 314 patients with primary UTUC. The age-standardized incidence rate increased from 2.0 in 1993 to 3.2 per 100 000 person-years in 2017, without change in gender distribution. The increase in incidence held for all disease stages except organ-confined (T1-T2) disease. The most prominent increase was in superficial (Tis/Ta) and metastatic (M+) UTUC, which increased from 0.6 to 1.2 and 0.1 to 0.4 per 100 000 person-years, respectively. The 5-year relative survival did not change over time: 57.0% (95% confidence interval 55.9-58.1). Applied treatments were largely the same over the study period, although fewer radical nephroureterectomies and more kidney-sparing surgeries were performed in the most recent years. The use of peri-operative intravesical chemotherapy modestly increased.
Between 1993 and 2017, the age-standardized incidence of primary UTUC in the Netherlands has increased by more than 50%, but the relative survival of UTUC patients remained unchanged. Preventive measures against exposure to risk factors, early detection of disease, and more efficacious treatment methods are needed to improve outcomes of patients with UTUC.