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Background: Up- and/or downgrading rates in single intermediate-risk positive biopsy core are unknown.
Methods: We identified single intermediate-risk (Gleason grade group (GGG) 2/GGG3) positive biopsy core prostate cancer patients (≤ cT2c and PSA ≤ 20 ng/mL) within the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). Subsequently, separate uni- and multivariable logistic regression models tested for independent predictors of up- and downgrading.
Results: Of 1,328 assessable patients with single core positive intermediate-risk prostate cancer at biopsy, 972 (73%) harbored GGG2 versus 356 (27%) harbored GGG3. Median PSA (5.5 vs 5.7; p = 0.3), median age (62 vs 63 years; p = 0.07) and cT1-stage (77 vs 75%; p = 0.3) did not differ between GGG2 and GGG3 patients. Of individuals with single GGG2 positive biopsy core, 191 (20%) showed downgrading to GGG1 versus 35 (4%) upgrading to GGG4 or GGG5 at RP. Of individuals with single GGG3 positive biopsy core, 36 (10%) showed downgrading to GGG1 versus 42 (12%) significant upgrading to GGG4 or GGG5 at RP. In multivariable logistic regression models, elevated PSA (10–20 ng/mL) was an independent predictor of upgrading to GGG4/GGG5 in single GGG3 positive biopsy core patients (OR:2.89; 95%-CI: 1.31–6.11; p = 0.007).
Conclusion: In single GGG2 positive biopsy core patients, downgrading was four times more often recorded compared to upgrading. Conversely, in single GGG3 positive biopsy core patients, up- and downgrading rates were comparable and should be expected in one out of ten patients.
The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium–aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1–38) vs. a median of 15 (range 2–74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.
Bone-seeking 223Radium-dichloride (223Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has been increasingly implemented in patients with mCRPC failing conventional treatment options. In this study, the safety and efficacy of 177Lu-PSMA-617 in patients with progressive bone involvement under treatment with 223Ra was assessed. Twenty-eight men (median age 73 years, range 63–89 years) with progressive mCRPC, who started 177Lu-PSMA-617 within 8 weeks after the last 223Ra administration, received a median of 4 (IQR 3–6) and a total of 120 cycles of 223Ra and a median of 4 (IQR 2–7) cycles 177Lu-PSMA-617 with a mean treatment activity of 6.5 ± 1.2 GBq per cycle, reaching a mean cumulative activity of 30.7 ± 23.4 GBq. A PSA response (≥50% PSA decline 12 weeks after the first 177Lu-PSMA-617 cycle) was observed in 18/28 (64.3%) patients and imaging-based partial remission (PR) was observed in 11/28 (39.3%) patients. Median imaging-based progression-free survival (PFS) was 10 (95% CI, 6–14) months and median overall survival (OS) was 18 (95% CI, 14–22) months. Patients with low bone tumor burden (2–20 lesions) had a significantly longer OS (28 vs. 14 months, p < 0.045) compared to patients with a high tumor burden (>20 lesions). Grade ≥ 3 hematological toxicity was observed in six patients after their last treatment cycle with anemia, leukopenia and thrombocytopenia in 5/28 (17.9%), 4/28 (14.3%) and 6/28 (21.4%) patients, respectively. In progressive bone-metastatic mCRPC patients, prompt initiation of 177Lu-PSMA-617 after failing 223Ra is effective with an acceptable toxicity profile.
The production of baryons and K0 S mesons (V0 particles) was measured in p–Pb collisions at √sNN = 5.02 TeV and pp collisions at √s = 7 TeV with ALICE at the LHC. The production of these strange particles is studied separately for particles associated with hard scatterings and the underlying event to shed light on the baryon-to-meson ratio enhancement observed at intermediate transverse momentum (pT) in high multiplicity pp and p–Pb collisions. Hard scatterings are selected on an eventby-event basis with jets reconstructed with the anti-kT algorithm using charged particles. The production of strange particles associated with jets pch T, jet > 10 and pch T, jet > 20 GeV/c in p–Pb collisions, and with jet pch T, jet > 10 GeV/c in pp collisions is reported as a function of pT. Its dependence on angular distance from the jet axis, R(V0, jet), for jets with pch T, jet > 10 GeV/c in p–Pb collisions is reported as well. The pT-differential production spectra of strange particles associated with jets are found to be harder compared to that in the underlying event and both differ from the inclusive measurements. In events containing a jet, the density of the V0 particles in the underlying event is found to be larger than the density in the minimum bias events. The /K0 S ratio associated with jets in p–Pb collisions is consistent with the ratio in pp collisions and follows the expectation of jets fragmenting in vacuum. On the other hand, this ratio within jets is consistently lower than the one obtained in the underlying event and it does not show the characteristic enhancement of baryons at intermediate pT often referred to as “baryon anomaly” in the inclusive measurements.
The production of Λ baryons and K0S mesons (V0 particles) was measured in p-Pb collisions at sNN−−−√=5.02 TeV and pp collisions at s√=7 TeV with ALICE at the LHC. The production of these strange particles is studied separately for particles associated with hard scatterings and the underlying event to shed light on the baryon-to-meson ratio enhancement observed at intermediate transverse momentum (pT) in high multiplicity pp and p-Pb collisions. Hard scatterings are selected on an event-by-event basis with jets reconstructed with the anti-kT algorithm using charged particles. The production of strange particles associated with jets pchT,jet>10 and pchT,jet>20 GeV/c in p-Pb collisions, and with jet pchT,jet>10 GeV/c in pp collisions is reported as a function of pT. Its dependence on angular distance from the jet axis, R(V0,jet), for jets with pchT,jet>10 GeV/c in p-Pb collisions is reported as well. The pT-differential production spectra of strange particles associated with jets are found to be harder compared to that in the underlying event and both differ from the inclusive measurements. In events containing a jet, the density of the V0 particles in the underlying event is found to be larger than the density in the minimum bias events. The Λ/K0S ratio associated with jets in p-Pb collisions is consistent with the ratio in pp collisions and follows the expectation of jets fragmenting in vacuum. On the other hand, this ratio within jets is consistently lower than the one obtained in the underlying event and it does not show the characteristic enhancement of baryons at intermediate pT often referred to as "baryon anomaly" in the inclusive measurements.
The production of Λ baryons and K0S mesons (V0 particles) was measured in p-Pb collisions at sNN−−−√=5.02 TeV and pp collisions at s√=7 TeV with ALICE at the LHC. The production of these strange particles is studied separately for particles associated with hard scatterings and the underlying event to shed light on the baryon-to-meson ratio enhancement observed at intermediate transverse momentum (pT) in high multiplicity pp and p-Pb collisions. Hard scatterings are selected on an event-by-event basis with jets reconstructed with the anti-kT algorithm using charged particles. The production of strange particles associated with jets pchT,jet>10 and pchT,jet>20 GeV/c in p-Pb collisions, and with jet pchT,jet>10 GeV/c in pp collisions is reported as a function of pT. Its dependence on angular distance from the jet axis, R(V0,jet), for jets with pchT,jet>10 GeV/c in p-Pb collisions is reported as well. The pT-differential production spectra of strange particles associated with jets are found to be harder compared to that in the underlying event and both differ from the inclusive measurements. In events containing a jet, the density of the V0 particles in the underlying event is found to be larger than the density in the minimum bias events. The Λ/K0S ratio associated with jets in p-Pb collisions is consistent with the ratio in pp collisions and follows the expectation of jets fragmenting in vacuum. On the other hand, this ratio within jets is consistently lower than the one obtained in the underlying event and it does not show the characteristic enhancement of baryons at intermediate pT often referred to as "baryon anomaly" in the inclusive measurements.
The production of K∗(892)0 and ϕ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at sNN−−−√=5.02 TeV has been measured using the ALICE detector at the Large Hadron Collider (LHC). The transverse momentum (pT) distributions of K∗(892)0 and ϕ(1020) mesons have been measured at midrapidity (|y|<0.5) up to pT=20 GeV/c in inelastic pp collisions and for several Pb-Pb collision centralities. The collision centrality and collision energy dependence of the average transverse momenta agree with the radial flow scenario observed with stable hadrons, showing that the effect is stronger for more central collisions and higher collision energies. The K∗0/K ratio is found to be suppressed in Pb-Pb collisions relative to pp collisions: this indicates a loss of the measured K∗(892)0 signal due to rescattering of its decay products in the hadronic phase. In contrast, for the longer-lived ϕ(1020) mesons, no such suppression is observed. The nuclear modification factors (RAA) of K∗(892)0 and ϕ(1020) mesons are calculated using pp reference spectra at the same collision energy. In central Pb-Pb collisions for pT>8 GeV/c, the RAA values of K∗(892)0 and ϕ(1020) are below unity and observed to be similar to those of pions, kaons, and (anti)protons. The RAA values at high pT (>~8 GeV/c) for K∗(892)0 and ϕ(1020) mesons are in agreement within uncertainties for sNN−−−√=5.02 and 2.76 TeV.
The production of K∗(892)0 and ϕ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at sNN−−−√=5.02 TeV has been measured using the ALICE detector at the Large Hadron Collider (LHC). The transverse momentum (pT) distributions of K∗(892)0 and ϕ(1020) mesons have been measured at midrapidity (|y|<0.5) up to pT=20 GeV/c in inelastic pp collisions and for several Pb-Pb collision centralities. The collision centrality and collision energy dependence of the average transverse momenta agree with the radial flow scenario observed with stable hadrons, showing that the effect is stronger for more central collisions and higher collision energies. The K∗0/K ratio is found to be suppressed in Pb-Pb collisions relative to pp collisions: this indicates a loss of the measured K∗(892)0 signal due to rescattering of its decay products in the hadronic phase. In contrast, for the longer-lived ϕ(1020) mesons, no such suppression is observed. The nuclear modification factors (RAA) of K∗(892)0 and ϕ(1020) mesons are calculated using pp reference spectra at the same collision energy. In central Pb-Pb collisions for pT>8 GeV/c, the RAA values of K∗(892)0 and ϕ(1020) are below unity and observed to be similar to those of pions, kaons, and (anti)protons. The RAA values at high pT (>~8 GeV/c) for K∗(892)0 and ϕ(1020) mesons are in agreement within uncertainties for sNN−−−√=5.02 and 2.76 TeV.
Background and Objectives: To test for differences in perioperative outcomes and total hospital costs (THC) in nonmetastatic bladder cancer patients undergoing open (ORC) versus robotic-assisted radical cystectomy (RARC).
Methods: We relied on the National Inpatient Sample database (2016–2019). Statistics consisted of trend analyses, multivariable logistic, Poisson, and linear regression models.
Results: Of 5280 patients, 1876 (36%) versus 3200 (60%) underwent RARC versus ORC. RARC increased from 32% to 41% (estimated annual percentage change [EAPC]: + 8.6%; p = 0.02). Rates of transfusion (8% vs. 16%), intraoperative (2% vs. 3%), wound (6% vs. 10%), and pulmonary (6% vs. 10%) complications were lower in RARC patients (all p < 0.05). Moreover, median length of stay (LOS) was shorter in RARC (6 vs. 7days; p < 0.001). Conversely, median THC (31,486 vs. 27,162$; p < 0.001) were higher in RARC. Multivariable logistic regression-derived odds ratios addressing transfusion (0.49), intraoperative (0.53), wound (0.68), and pulmonary (0.71) complications favored RARC (all p < 0.01). In multivariable Poisson and linear regression models, RARC was associated with shorter LOS (Rate ratio:0.86; p < 0.001), yet higher THC (Coef.:5,859$; p < 0.001). RARC in-hospital mortality was lower (1% vs. 2%; p = 0.04).
Conclusions: RARC complications, LOS, and mortality appear more favorable than ORC, but result in higher THC. The favorable RARC profile contributes to its increasing popularity throughout the United States.
Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro. The cells were treated with different dilutions of OMWW, and tumor growth and clone formation were evaluated. Possible mechanisms of action were investigated by evaluating cell cycle phases and cell cycle-regulating proteins. OMWW profoundly inhibited the growth and proliferation of chemo-sensitive as well as gemcitabine- and cisplatin-resistant bladder cancer cells. Depending on the cell line and on gemcitabine- or cisplatin-resistance, OMWW induced cell cycle arrest at different phases. These differing phase arrests were accompanied by differing alterations in the CDK-cyclin axis. Considerable suppression of the Akt-mTOR pathway by OMWW was observed in all three cell lines. Since OMWW blocks the cell cycle through the manipulation of the cyclin-CDK axis and the deactivation of Akt-mTOR signaling, OMWW could become relevant in supporting bladder cancer therapy.