Zusammenhang zwischen der Aquaporinexpression auf mRNA Ebene und Grading, Staging sowie deren Einfluss auf die Prognose von Patienten mit nicht-muskelinvasivem Blasenkarzinom (NMIBC)

Unter Einschluss von 130 Patienten mit nicht muskelinvasivem Urothelkarzinom (NMIBC) im Stadium pT1 sollte der Zusammenhang zwischen der Aquaporinexpression auf mRNA Ebene und Grading, Staging sowie deren Einfluss auf die Prognose von Patienten mit nicht-muskelinvasivem Blasenkarzinom (NMIBC) der Patienten untersucht werden. Ziel war es, Aquaporine als mögliche prognostische Biomarker in der sehr heterogenen Tumorentität NMIBC zu identifizieren. Nach positivem Ethikvotum der Universität Regensburg (Nr.: 16-321-101) wurden 130 Proben von Patienten mit pT1 NMIBC, die Im Zeitraum von 2007 bis 2015 einer TUR-B unterzogen wurden, sowie 5 Proben von normaler Blasenschleimhaut (Normalgewebe in Zystektomiepräparaten) untersucht. Bei 13 Proben war nicht genügend Tumorgewebe vorhanden, weshalb letztendlich 117 Patienten ausgewertet werden konnten. 19 klinische und pathologische Parameter wurden erhoben. Es handelt sich um Erstbefunde. Nach primärer TUR erhielten alle Patienten eine Nachresektion oder eine Frühzystektomie. Das resezierte Blasentumorgewebe der initialen TUR-B wurde als Formalin-fixiertes Paraffin-eingebettetes Gewebe (FFPE) gelagert. Die retrospektive Erhebung des Follow-up erfolgte zwischen April und Oktober 2017. Im Labor wurde die Aquaporin 3, 4, 7 und 9 Expression, sowie die Expression der Houskeepinggene CALM 2 und TBP1 der pT1 Tumorzellen auf mRNA Ebene durch RTqPCR und Immunfluoreszenz bestimmt. Die statistische Auswertung erfolgte mit Hilfe von IBM SPSS Version 25 (2017). Mittels der Spearman-Korrelation erfolgte die Korrelation der mRNA-Expressionen mit den klinischen und pathologischen Parametern. Mit Hilfe der Kaplan-Meier-Überlebenszeitanalyse wurde das Karzinomspezifische Überleben (cancer-specific survival, CSS), das progressionsfreie Überleben (progression-free survival, PFS) und das rezidivfreie Überleben (recurrence-free survival, RFS) analysiert. Bei allen statistischen Tests wurde das Signifikanzniveau α=0,05 festgesetzt. P-Werte <0,05 wurden als statistisch signifikant und p-Werte <0,001 als statistisch hochsignifikant gewertet. Insgesamt zeigte sich bei AQP3-mRNA-Expression im Tumorgewebe besseres Grading, sowie weniger konkomittantes Cis. Allerdings zeigte sich eine Korrelation mit Tumoren >3cm und schlechteres CSS bei Patienten mit Tumoren >3cm, die keiner Frühzystektomie unterzogen wurden. AQP7-mRNA-Expression ging mit schlechterem Grading und CSS einher. Dies bestätigte sich in der Hochrisikogruppe der pT1G3 Tumoren. Bei Patienten, die blasenerhaltend therapiert wurden, konnte zudem schlechteres PFS nachgewiesen werden. AQP9-mRNA-Expression korrelierte mit vermehrter Multifokalität, konkomittantem Cis und erhöhtem EORTC Progression Score. Bei Patienten mit pT1G3 Tumoren zeigte sich zudem schlechteres PFS. AQP4-mRNA-Expression zeigte keine signifikanten Korrelationen. Vor allem AQP7 und AQP9-mRNA-Expression zeigen bei Hochrisiko Patienten mit pT1G3 Tumoren schlechteres Outcome und könnten als potenzielle Biomarker in Frage kommen

Ureteroplasty with buccal mucosa graft without omental wrap: an effective method to treat ureteral strictures

Purpose Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. Methods In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. Results Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. Conclusions Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair

A novel grading approach predicts worse outcomes in stage pT1 non‐muscle‐invasive bladder cancer

Objective To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. Patients and Methods The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. Results The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. Conclusions We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02–3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18–3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification

Prognostic Role of mRNA-Expression of Aquaporins (AQP) 3, 4, 7 and 9 in Stage pT1 Non-Muscle-Invasive Bladder Cancer

BACKGROUND: AQP proteins show a variety of functions in human cell metabolism. The role of different AQP subtypes in tumor metabolism and prognosis are subject of ongoing research. OBJECTIVE: To investigate the mRNA expression of Aquaporin (AQP) 3, 4, 7 and 9 in pT1 non-muscle-invasive bladder cancer (NMIBC) and its prognostic value in therapeutic decision making. METHODS: Formalin-fixed-paraffin-embedded (FFPE) tissues from transurethral resection of the bladder (TURB) from 112 patients with initial diagnosis of stage pT1 NMIBC were analyzed retrospectively together with clinical data and therapeutic approaches. mRNA expression of AQP3, 4, 7 and 9 was measured and quantified using RT-qPCR. RESULTS: Of the 112 patients (83.9% male, median age 72 years), 40 had a recurrence (35.7%), 16 a progression (14.3%) and 14 patients (12.5%) died tumor-related. mRNA expression for AQP3 was detected in 99.1%, AQP4 in 46.4%, AQP7 in 86.6% and AQP9 in 97.3%. Spearman analysis revealed statistically significant correlations between AQP3, AQP7 and AQP9 mRNA expression with adverse clinical and histopathological parameters (WHO1973 grade 3, concomitant Cis or multifocality). High AQP9 mRNA expression was associated with worse PFS in the total cohort (p = 0.034) and in Grade 3 tumors (p = 0.003) in Kaplan-Meier analysis. In patients with bladder sparing approach, high AQP3 mRNA expression was significantly associated with worse CSS in patients receiving BCG therapy (p = 0.029). CONCLUSIONS: mRNA expression of AQP3, 7 and 9 correlates with adverse clinical and pathological parameters. AQP3 and 9 may help to identify a subgroup of highest risk patients who may be considered for early cystectomy