Jan Doležel

Clinically node-positive bladder cancer: Oncological results of induction chemotherapy and consolidative surgery

Patients with clinically node-positive bladder cancer have a poor prognosis, with many receiving only palliative chemotherapy. We evaluated oncological results in bladder cancer patients with clinically regional and supraregional lymphadenopathy treated with induction chemotherapy (IC) and consolidative cystectomy. Twenty-five patients with clinically node-positive bladder cancer (including pelvic and retroperitoneal nodes) were treated with 2-4 cycles of IC followed by consolidative cystectomy between 2010 and 2016. Pathologic complete response (pCR) was defined as no residual tumor in the final specimen (ypT0N0). The 3-year cancer-specific (CSS) and recurrence-free survival (RFS) for the whole cohort were 52% and 39%, respectively. The 3-year RFS differed according to volume of nodal metastases, the rates were 56% for minimal nodal disease (cN1) versus 33% for cN2-3 and 0% for cM1 disease (p<0.001). pCR was seen in 7 (28%) patients; 50% in cN1 versus 13% in cN3-M1. pCR associated with 3-year CSS of 80% versus 45% in patients with persistent disease aft er IC. In conclusion, a multimodal approach to patients with clinically node-positive bladder cancer, consisting of IC followed by consolidative surgery, may achieve long-term survival in selected patients. Better results may be expected in patients with initially minimal nodal burden and complete pathologic response to chemotherapy. Further studies are warranted to improve patient selection for consolidative surgery, especially with supra-regional metastases.

Abstract 3979: Urinary cell-free microRNAs as potential biomarkers of urothelial carcinoma of the urinary bladder

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Introduction: Urothelial carcinoma of the urinary bladder (UCUB) is the most common malignancy of the urinary system. UCUB is divided into muscle invasive and non-muscle invasive bladder cancer (superficial), which represents approximately 80% of cases. Despite the relatively high degree of superficial tumors is UCUB associated with high local recurrence rate and approximately 20% of non-muscle invasive tumors progress to invasive form. Although cystoscopy remains a fundamental investigative tool in the detection and surveillance of urothelial bladder cancer, carcinoma in situ (CIS) or small papillary tumors can be with this method easily missed. This has led to the development of newer technologies and several molecular urinary tests, but currently there is no sensitive biomarker enabling early detection of relapse, which occurs in almost 70% of cases of superficial UCUB or biomarker with ability to predict the risk of progression of non-invasive to invasive form of UCUB. Such requirements could fit with diagnostic approach based on the detection of microRNAs (miRNAs) in urine, where have already showed remarkably high stability and good analytical properties. Patients and methods: Using Affymetrix miRNA microarrays we have analyzed expression profiles of 1733 miRNAs in urine supernatant of 16 UCUB patients (6 invasive, 5 high-grade non-invasive, 5 low-grade non-invasive), 17 controls, 10 RCC patients and 4 urinary tract infections (UTI). Ability of selected miRNAs to identify UCUB from urine was confirmed in the validation phase based on independent cohort of 80 UCUB patients using qRT-PCR method. Results: Global expression profiling revealed set of 76 miRNAs significantly differentially expressed in urine of UCUB patients (P < 0,01) compared to healthy controls, thereof 64 highly up-regulated and 12 down-regulated. These miRNAs were specific for UCUB also when compared to other examined cohorts of patients (RCC, UTI). Moreover 23 miRNAs were able distinguish invasive and non-invasive forms of UCUB (P < 0,01) and 18 miRNAs high-grade and low-grad non-invasive (p < 0,01). Subsequent validation on larger independent cohort of UCUB patients lead to definition of urinary miRNA panel enabling sensitive and highly specific diagnosis of UCUB from urine. Conclusion: Our data have shown that urinary miRNAs could serve as sensitive and specific biomarkers of UCUB and after further independent validations could be useful tool to increase sensitivity of standard cytological examination potentially decreasing high costs for long-term follow-up of UCUB patients. This work has been supported by IGA MZCR: NT/13860-4/2012. Citation Format: Jaroslav Juracek, Hana Mlcochova, Michal Stanik, Barbora Peltanova, Robert Iliev, Taňa Machackova, Jitka Mlcochova, Renata Hežova, Jan Doležel, Ondřej Slabý. Urinary cell-free microRNAs as potential biomarkers of urothelial carcinoma of the urinary bladder. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3979. doi:10.1158/1538-7445.AM2015-3979

Effect of ureterointestinal anastomosis on renal function and morbidity in intestinal urinary diversion

Abstract Objective.The authors previously successfully applied the “flap-and-trough” (FT) method of antireflux ureterointestinal anastomosis (UIA) in a pilot set of 81 patients. This randomized prospective trial tested the effectiveness of this method in protecting the upper urinary tract from obstruction, reflux and infections. Material and methods.Forty-nine patients indicated for cystectomy and intestinal urinary diversion were randomly split into two groups, A and B. The FT antireflux UIA was applied in group A (n = 20), and refluxing direct elliptical UIA in group B (n = 29). Both groups were divided into two subcategories according to the type of diversion used: Ar (n = 10) and Br (n = 16) with low-pressure reservoirs and Ac (n = 10) and Bc (n = 13) with conduits. The follow-up evaluation compared the groups regarding perioperative complications, antireflux efficiency of FT, occurrence of obstruction and urinary infection, kidney morphology and glomerular filtration rate. Results.During the follow-up period (median 31 months), the obstruction occurred only in group Br (insignificant difference compared to Ar). A significant decrease in glomerular filtration rate and shortening of the left kidney occurred in group Br during the period and in comparison with Ar. There were no other considerable divergences in other studied parameters. Conclusions.The antireflux FT anastomosis represents a low risk for stenosis. The reduced occurrence of obstructive complications in comparison with direct UIA was statistically insignificant. Its construction did not increase the frequency of complications; on the contrary, it guarantees a better protection of renal morphology and function.

Ureteral incarceration in the symptomatology of hydronephrosis

Renal colic symptoms may be caused by an aberrant vascular bundle that intermittently incarcerates the pyeloureteral junction. The authors describe 6 patients who were complaint free except for the period of fits and routine urological examinations showed normal findings. The patients had no subjective complaints after open surgery.