Management of BCG failure in non-muscle-invasive bladder cancer the present and the future.

Bladder neoplasms are still among the most common cancer types in the Czech Republic. Even though the majority (more than 90%) of bladder tumours are of urothelial origin, the group is vastly heterogeneous in terms of biological behaviour and thus also progression of the disease. Adequate adjuvant treatment is the cornerstone of the therapy in high-risk patients for disease recurrence, particularly those with a high risk of progression to a muscle-invasive disease (T2 and higher). Intravesical BCG immunotherapy still remains such a therapy. It is a standard therapy with well-established efficacy as regards the recurrence rate and a reduced risk of progression. Nevertheless, radical cystectomy is recommended in patients in whom this therapy fails. Considering the non-negligible morbidity and mortality associated with this type of surgery, intensive research efforts have been put forth to develop new bladder preserving strategies. This article outlines the main bladder preserving strategies that are currently explored.

Prognostic factors of early second transurethral resection of non-muscle invasive bladder cancer 10 years of experience of a referral center.

INTRODUCTION: Urothelial bladder cancer invading the submucosal layer (T1) is a tumor with a high risk of progression to invasive disease. In case of pT1 histology or absence of detrusor muscle in the specimen, an early second resection of the bladder tumor (reTUR) is indicated. According to retrospective studies, the histology finding of reTUR has a prognostic value. The aim of this study is to present the outcomes of second resection at a tertiary referral center. METHODS: In total, 146 patients with non-muscle invasive bladder cancer (NMIBC) were analyzed retrospectively. These patients underwent (the first) transurethral resection of their bladder tumor and an early reTUR between 3/2010 and 2/2021. Recurrence, progression and cystectomy free survival rates (RFS, PFS, CFS) were calculated using the Kaplan-Meier curves and the correlation of 7 clinical and pathologic factors (age, gender, muscle in specimen, presence of residual tumor and carcinoma in situ in reTUR, intravesical chemotherapy and BCG therapy) was evaluated using univariate and multivariate analyses. RESULTS: Median RFS was 2.15 years, 1-year RFS was 66.9% and 3-year RFS was 43.4%. One-year and 3-year PFS was 93.5% and 88.4%, respectively. One-year and 3-year CFS was 91.0% and 82.4%, respectively. Based on the multivariate analysis, presence of any residual tumor in reTUR was a negative prognostic marker for RFS, while intravesical chemotherapy and BCG therapy were positive prognostic markers. Presence of any residual tumor in reTUR was the only negative prognostic marker for PFS and CFS. CONCLUSION: The quality of the first resection of bladder tumor as determined by its completeness and presence of detrusor muscle in the histology specimen is the cornerstone of an adequate diagnosis and proper treatment. If an early reTUR is indicated, presence of any residual tumor in the histology specimen is a significant prognostic marker according to our findings.

MicroRNAs in urine supernatant as potential non-invasive markers for bladder cancer detection.

Urinary bladder carcinoma contributes to 4% of newly diagnosed oncological diseases in the Czech Republic. Biomarkers for its early non-invasive detection are therefore highly desirable. Urine seems to be an ideal source of such biomarkers due to the content of cell-free nucleic acids, especially microRNAs (miRNAs).To find potential biomarkers among miRNAs in urine supernatant, we examined in total 109 individuals (36 controls and 73 bladder cancer patients) in three phases. In the first - discovery - phase, microarray cards with 381 miRNAs were used for miRNA analysis of 13 controls and 46 bladder cancer patients. In the second - verification - phase, the results of this first phase were verified on the same groups of subjects by single-target qPCR assays for the selected miRNAs. For the third - validation - phase, new independent samples of urine supernatant (23 controls and 27 bladder cancer patients) were analyzed using single-target qPCR assays for 13 verified in the previous phase. The results of all phases were normalized to miR-191, miR-28-3p, and miR-200b, which were selected as suitable for our study by the qBase+®.We found that miR-125b, miR-30b, miR-204, miR-99a, and miR-532-3p are significantly down-regulated in patients' urine supernatant. In our experiments, the analysis of miR-125 levels provided the highest AUC (0.801) with 95.65% specificity and 59.26% sensitivity, the analysis of miR-99a lead to AUC (0.738) with 82.61% specificity and 74.07% sensitivity. We demonstrate that levels of these miRNAs could potentially serve as promising diagnostic markers for the non-invasive diagnostics of bladder cancer.

Positron emission tomography and clinical predictors of survival in primary extragonadal germ cell tumors.

BACKGROUND: Primary extragonadal germ cell tumors (EGTs) are an uncommon malignancy -accounting for 2-4% of all germ cell neoplasms in adult males. Their prognosis is worse than that for testicular germ cell tumors because of their relative chemoresistance and frequent presentation with widely disseminated metastases. We have studied the role of fluorodeoxyglucose positron emission tomography (FDG-PET) for outcome prediction of patients with EGTs. PATIENTS AND METHODS: We have retrospectively analysed 36 men with germ cell tumors originating in the mediastinum or the retroperitoneum. All patients were treated between 1994 and 2010. Negative result of testicular ultrasonographic examination and/or testicular biopsy was required for diagnosis of EGT. Platinum-based systemic therapy was used in all cases, and resectable residual tumor masses were removed surgically. RESULTS: Overall survival at one and three years was 81% (95% confidence interval [CI]: 68-94%) and 55% (CI: 38-71%), respectively. None of the patients who had positive FDG-PET findings after first line chemotherapy survived at three years after diagnosis. In contrast, 69% and 20% of patients with positive tumor markers, and 90% and 67% of patients with negative tumor markers after first line chemotherapy survived at one and three years, respectively. Negative FDG-PET after completion of treatment was also a powerful predictor of long-term survival with 100% patients surviving three years and 89% surviving five years after diagnosis. CONCLUSIONS: Negative FDG-PET after first-line chemotherapy or after the completion of systemic treatment and resection of residual tumor masses strongly predicts long-term event-free survival in patients with EGTs.

Search for a low-mass standard model Higgs boson in the ττ decay channel in pp collisions at sqrt[s]=1.96 TeV.

We report on a search for the standard model Higgs boson decaying into pairs of τ leptons in pp collisions produced by the Tevatron at sqrt[s]=1.96 TeV. The analyzed data sample was recorded by the CDFII detector and corresponds to an integrated luminosity of 6.0 fb(-1). The search is performed in the final state with one τ decaying leptonically and the second one identified through its semihadronic decay. Since no significant excess is observed, a 95% credibility level upper limit on the production cross section times branching ratio to the ττ final state is set for hypothetical Higgs boson masses between 100 and 150 GeV/c2. For a Higgs boson of 120 GeV/c2 the observed (expected) limit is 14.6 (15.3) the predicted value.

Measurements of the angular distributions in the decays B→K(*)µ(+)µ(-) at CDF.

We report an indirect search for nonstandard model physics using the flavor-changing neutral current decays B→K(*)µ(+)µ(-). We reconstruct the decays and measure their angular distributions, as a function of q(2)=M(µµ)(2)c(2), where M(µµ) is the dimuon mass, in pp¯ collisions at √s=1.96 TeV using a data sample corresponding to an integrated luminosity of 6.8 fb(-1). The transverse polarization asymmetry A(T)(2) and the time-reversal-odd charge-and-parity asymmetry A(im) are measured for the first time, together with the K* longitudinal polarization fraction F(L) and the muon forward-backward asymmetry A(FB) for the decays B(0)→K(*0)µ(+)µ(-) and B(+)→K(*+)µ(+)µ(-). The B→K*µ(+)µ(-) forward-backward asymmetry in the most sensitive kinematic regime, 1≤q(2)<6 GeV(2)/c(2), is measured to be A(FB)=0.29(-0.23)(+0.20)(stat)±0.07(syst), the most precise result to date. No deviations from the standard model predictions are observed.

Search for a Higgs boson in the diphoton final state in pp collisions at sqrt[s]=1.96 TeV.

A search for a narrow Higgs boson resonance in the diphoton mass spectrum is presented based on data corresponding to 7.0 fb{-1} of integrated luminosity from pp collisions at sqrt[s]=1.96 TeV collected by the CDF experiment. No evidence of such a resonance is observed, and upper limits are set on the cross section times branching ratio of the resonant state as a function of Higgs boson mass. The limits are interpreted in the context of the standard model and one fermiophobic benchmark model where the data exclude fermiophobic Higgs bosons with masses below 114 GeV/c{2} at a 95% Bayesian credibility level.

Search for B(s)(0) → µ+ µ- and B(0) → µ+ µ- decays with CDF II.

A search has been performed for B(s)(0) → µ+ µ- and B(0) → µ+ µ- decays using 7 fb(-1) of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron collider. The observed number of B(0) candidates is consistent with background-only expectations and yields an upper limit on the branching fraction of B(B(0) → µ+ µ-) < 6.0 × 10(-9) at 95% confidence level. We observe an excess of B(s)(0) candidates. The probability that the background processes alone could produce such an excess or larger is 0.27%. The probability that the combination of background and the expected standard model rate of B(s)(0) → µ+ µ- could produce such an excess or larger is 1.9%. These data are used to determine B(B(s)(0)→ µ+ µ-) = (1.8(-0.9) (+1.1)) × 10(-8) and provide an upper limit of B(B(s)(0) → µ+ µ-) < 4.0 × 10(-8) at 95% confidence level.

Search for New T' particles in final states with large jet multiplicities and missing transverse energy in p p collisions at sqrt[s] = 1.96 TeV.

We present a search for a new particle T' decaying to a top quark via T' → t + X, where X goes undetected. We use a data sample corresponding to 5.7 fb(-1) of integrated luminosity of p p collisions with sqrt[s] = 1.96 TeV, collected at Fermilab Tevatron by the CDF II detector. Our search for pair production of T' is focused on the hadronic decay channel, pp → T'T' → tt + XX → bqq b qq + XX. We interpret our results in terms of a model where T' is an exotic fourth generation quark and X is a dark matter particle. The data are consistent with standard model expectations. We set a limit on the generic production of T'T' → tt + XX, excluding the fourth generation exotic quarks T' at 95% confidence level up to m(T') = 400 GeV/c(2) for m(X) ≤ 70 GeV/c(2).

Observation of the baryonic flavor-changing neutral current decay Λb(0)â†’Λµ+µ-.

We report the first observation of the baryonic flavor-changing neutral current decay Λ(b)(0)â†’Λµ(+)µ(-) with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses a pp collisions data sample corresponding to 6.8 fb(-1) at √s = 1.96 TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Λ(b)(0)â†’Λµ(+)µ(-) are measured. We find B(Λ(b)(0)â†’Λµ(+)µ(-))=[1.73 ± 0.42(stat) ± (syst)] × 10(-6). We also report the first measurement of the differential branching ratio of B(s)(0)→ϕµ(+)µ(-), using 49 signal events. In addition, we report branching ratios for B(+)→K(+)µ(+)µ(-), B(0)→K(0)µ(+)µ(-), and B→K(*)(892)µ(+)µ(-) decays.

Top-quark mass measurement using events with missing transverse energy and jets at CDF.

We present a measurement of the top-quark mass using a sample of t ̄t events in 5.7 fb(-1) of integrated luminosity from p ̄p collisions at the Fermilab Tevatron with √s=1.96 TeV and collected by the CDF II Detector. We select events having large missing transverse energy, and four, five, or six jets with at least one jet tagged as coming from a b quark, and reject events with identified charged leptons. This analysis considers events from the semileptonic t ̄t decay channel, including events that contain tau leptons. The measurement is based on a multidimensional template method. We fit the data to signal templates of varying top-quark masses and background templates, and measure a top-quark mass of M(top)=172.32±2.4(stat)±1.0(syst) GeV/c(2).

Search for new physics in high pT like-sign dilepton events at CDF II.

We present a search for new physics in events with two high pT leptons of the same electric charge, using data with an integrated luminosity of 6.1 fb(-1). The observed data are consistent with standard model predictions. We set 95% C.L. lower limits on the mass of doubly charged scalars decaying to like-sign dileptons, m(H±±) > 190-245 GeV/c(2), assuming 100% BR to ee, µµ or eµ.

Observation of the Ξ(b)(0) baryon.

The observation of the bottom, strange baryon Ξ(b)(0) through the decay chain Ξ(b)(0)→Ξ(c)(+)π-, where ΞΞ(c)(+)→Ξ- π+ π+, Ξ-→Λπ-, and Λ→pπ-, is reported by using data corresponding to an integrated luminosity of 4.2 fb(-1) from pp collisions at square root(s)=1.96 TeV recorded with the Collider Detector at Fermilab. A signal of 25.3(-5.4)(+5.6) candidates is observed whose probability of arising from a background fluctuation is 3.6×10(-12), corresponding to 6.8 gaussian standard deviations. The Ξ(b)(0) mass is measured to be 5787.8±5.0(stat)±1.3(syst) MeV/c2. In addition, the Ξ(b)- baryon is observed through the process Ξ(b)-→Ξ(c)(0)π-, where Ξ(c)(0)→Ξ- π+, Ξ-→Λπ-, and Λ→pπ-.

Measurement of the cross section for prompt isolated diphoton production in pp collisions at square root(s) = 1.96 TeV.

This Letter reports a measurement of the cross section of prompt isolated photon pair production in pp collisions at a total energy square root(s)=1.96 TeV using data of 5.36 fb(-1) integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. The measured cross section, differential in basic kinematic variables, is compared with three perturbative QCD predictions, a leading order parton shower calculation and two next-to-leading order calculations. The next-to-leading order calculations reproduce most aspects of the data. By including photon radiation from quarks before and after hard scattering, the parton shower prediction becomes competitive with the next-to-leading order predictions.

Search for a very light CP-odd Higgs boson in top quark decays from pp collisions at sqrt(s)]=1.96 TeV.

We present the results of a search for a very light CP-odd Higgs boson a(1)(0) originating from top quark decays t → H(±)b → W(±(*)) a(1)(0)b, and subsequently decaying into τ+ τ-. Using a data sample corresponding to an integrated luminosity of 2.7 fb(-1) collected by the CDF II detector in pp collisions at 1.96 TeV, we perform a search for events containing a lepton, three or more jets, and an additional isolated track with transverse momentum in the range 3 to 20 GeV/c. Observed events are consistent with background sources, and 95% C.L. limits are set on the branching ratio of t → H(±)b for various masses of H(±) and a(1)(0).

First search for multijet resonances in sqrt(s) = 1.96 TeV pp collisions.

We present the first model independent search for three-jet hadronic resonances within multijet events in sqrt(s) = 1.96 TeV pp collisions at the Fermilab Tevatron using the CDF II detector. Pair production of supersymmetric gluinos and squarks with hadronic R-parity violating decays is employed as an example of a new physics benchmark for this signature. Selection criteria based on the kinematic properties of an ensemble of jet combinations within each event help to extract signal from copious QCD background. No significant excess outside the top quark mass window is observed in data with an integrated luminosity of 3.2 fb(-1). We place 95% confidence level limits on the production cross section σ(pp → XX')×BR(gg → 3 jet + 3 jet) where X, X' = g, q, or q, with q, q → g + jet, as a function of gluino mass, in the range of 77 GeV/c2 to 240 GeV/c2.

Limits on anomalous trilinear gauge couplings in Zγ events from pp¯ collisions at √s=1.96 TeV.

Using Zγ candidate events collected by the CDF detector at the Tevatron Collider, we search for potential anomalous (non-standard-model) couplings between the Z boson and the photon. Zγ couplings vanish at tree level and are heavily suppressed at higher orders; hence any evidence of couplings indicates new physics. Measurements are performed using data corresponding to an integrated luminosity of 4.9 fb(-1) in the Z→νν¯ decay channel and 5.1 fb(-1) in the Z→l(+)l(-) (l=µ, e) decay channels. The combination of these measurements provides the most stringent limits to date on Zγ trilinear gauge couplings. Using an energy scale of Λ=1.5 TeV to allow for a direct comparison with previous measurements, we find limits on the CP-conserving parameters that describe Zγ couplings to be |h(3)(γ,Z)|<0.022 and |h(4)(γ,Z)|<0.0009. These results are consistent with standard model predictions.

Search for new dielectron resonances and Randall-Sundrum gravitons at the collider detector at Fermilab.

A search for new dielectron-mass resonances using data recorded by the CDF II detector and corresponding to an integrated luminosity of 5.7 fb(-1) is presented. No significant excess over the expected standard model prediction is observed. In this data set, an event with the highest dielectron mass ever observed (960 GeV/c(2)) was recorded. The results are interpreted in the Randall-Sundrum (RS) model. Combined with the 5.4 fb(-1) diphoton analysis, the RS-graviton lower-mass limit for the coupling k/M¯(Pl)=0.1 is 1058 GeV/c(2), making it the strongest limit to date.

First measurement of the angular coefficients of Drell-Yan e(+)e(-) pairs in the Z mass region from pp¯ collisions at √s=1.96 TeV.

We report on the first measurement of the angular distributions of final state electrons in pp¯ → γ*/Z → e(+)e(-) + X events produced in the Z boson mass region at √s1.96 TeV. The data sample collected by the CDF II detector for this result corresponds to 2.1 fb(-1) of integrated luminosity. The angular distributions are studied as a function of the transverse momentum of the electron-positron pair and show good agreement with the Lam-Tung relation, consistent with a spin-1 description of the gluon, and demonstrate that, at high values of the transverse momentum, Z bosons are produced via quark-antiquark annihilation and quark-gluon Compton processes.

Invariant mass distribution of jet pairs produced in association with a W boson in pp collisions at sqrt[s]=1.96 TeV.

We report a study of the invariant mass distribution of jet pairs produced in association with a W boson using data collected with the CDF detector which correspond to an integrated luminosity of 4.3 fb(-1). The observed distribution has an excess in the 120-160 GeV/c(2) mass range which is not described by current theoretical predictions within the statistical and systematic uncertainties. In this Letter, we report studies of the properties of this excess.