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41 result(s) for "Kaczmarek, Krystian"
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Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
Neoadjuvant chemotherapy has become standard of care for cisplatin-eligible patients with muscle-invasive bladder cancer qualified to radical cystectomy, providing a modest increase in 5-year overall survival rate. Several regimens are being employed for neoadjuvant treatment, largely because of their efficacy in metastatic setting. There is however a scarcity of evidence on the optimal cytotoxic regimen for neoadjuvant chemotherapy. We evaluated the efficacy of different protocols of neoadjuvant chemotherapy amongst patients who underwent radical cystectomy at our institution. This is a single-center, retrospective, observational study including a cohort of 220 patients who underwent radical cystectomy between 2014 and 2020. The neoadjuvant chemotherapy cohort included 79 patients and was compared to the cohort of historical controls including 141 patients operated prior to routine administration of neoadjuvant chemotherapy and those who opted for upfront surgery. Administration of neoadjuvant chemotherapy decreased the risk of overall and cancer-specific mortality HR = 0.625 (95% CI 0.414-0.944), p = 0.025 and HR = 0.579 (95% CI 0.348-0.964), p = 0.036. Rates of downstaging, complete responses, lymph node metastasis, extravesical extension and positive surgical margins significantly favored neoadjuvant chemotherapy. Out of cytotoxic regimens, dose-dense MVAC and gemcitabine-cisplatin were similarly efficacious providing 46.9% and 50% of downstaging to
The influence of temperature on the biological activity of selected nematode species (Steinernematidae and Heterorhabditidae) under the conditions of their coexistence
The presented study is concerned with infectivity of select entomopathogenic nematode species under different temperature conditions (15, 20 and 25 °C) in the presence of competing species. Two species of nematodes of the genus Steinernema (S. kraussei, S. feltiae) and two of the genus Heterorhabditis (H. bacteriophora and H. megidis) were included in the analysis. Different experimental variants were adopted in which the selected two entomopathogenic nematode species were mixed between Steinernemaand Heterorhabditis. The study showed that Heterorhabditis and Steinernema cannot coexist together in a single host and one genus will always prevail. H. megidis, under co-occurrence with S. feltiae separately infected Galleria mellonella larvae most commonly at 15 °C, while H. bacteriophora at 20 °C. The study showed that the main determinant of nematode activity towards the host is not temperature, but the presence of co-existing nematode species. The results of the experiment encourage further research to determine the effects of a variety of concurrent biotic and abiotic factors on entomopathogenic nematodes and their biological activity.
Biomechanical Examination of Wrist Flexors and Extensors with Biodex System Dynamometer—Isometric, Isokinetic and Isotonic Protocol Options
Background and Objectives: Biodex System® is an advanced dynamometer used for testing various biomechanical parameters of muscles. Test outcomes allow for the identification of muscle pathology and consequently lead to a clinical diagnosis. Despite being widely used for the testing and rehabilitation of the human musculoskeletal system, no universal and acceptable protocol for wrist examination has been proposed for patients with wrist pathology. In this study, the authors aim to identify the most appropriate protocol for testing the biomechanical parameters of flexors and extensors of the wrist. Materials and Methods: A group of 20 patients with symptomatic tennis elbow and 26 healthy volunteers were examined using three different protocols: isokinetic, isometric and isotonic. Protocol order for each study participant was assigned at random with a minimum of a 24 h break between protocols. All protocol parameters were set according to data obtained from a literature review and an earlier pilot study. Following completion of each protocol, participants filled out a questionnaire-based protocol, assessing pain intensity during the exam, difficulty with exam performance and post-exam muscle fatigue. Results: The isotonic protocol showed the best patient tolerance and the highest questionnaire score. There was a significant difference (p < 0.05) between the three protocols in average pain intensity reported by study participants. All participants completed the isotonic protocol, but not all patients with symptomatic tennis elbow were able to complete the isometric and isokinetic protocols. The isotonic protocol was deemed “difficult but possible to complete” by study participants. Conclusions: The isotonic protocol is most suitable for testing the flexors and extensors of the wrist. It gives the most biomechanical data of all protocols, is well tolerated by patients and rarely causes pain during examination even in symptomatic participants.
Loss of chromosome Y is unrelated to the composition of the tumor microenvironment and patient prognosis in muscle-invasive urothelial bladder cancers
Background Loss of chromosome Y (LOY) has recently been proposed to be associated with cancer aggressiveness, altered T-cell function, and poor prognosis in bladder carcinomas. Methods Chromosome Y was analyzed using fluorescence in-situ hybridization on a tissue microarray containing 2,071 urothelial carcinomas of the urinary bladder from male patients, including 487 patients who had undergone cystectomy for muscle-invasive disease and for whom follow-up data were available. Data on tumor microenvironment were obtained from a previous study. Results LOY was found in 26.0% of 1,704 analyzable cancers. In non-invasive cancers, LOY frequency was comparable in pTa G2 (22.8%) and pTa G3 (24.1%, p  = 0.8036) carcinomas and slightly increased from pTa to pT2 - 4 carcinomas (23.1% for pTa and 27.2% for pT2 - 4) but these differences were not significant ( p = 0.0794). In muscle-invasive cancers, LOY frequency slightly increased from pT2 (25.5%) to pT4 cancers (33.0%), but this association was not significant ( p = 0.1814). Among pT2 - 4 cancers, LOY was associated with venous invasion ( p = 0.0010) but unrelated to pT, pN, and L-status, as well as to overall, recurrence-free, and cancer-specific survival. Muscle-invasive urothelial carcinomas with and without LOY did not show significant differences in the number of CD8 positive lymphocytes, fraction of CD8 positive intraepithelial lymphocytes, number of macrophages and dendritic cells, and fraction of T helper and T regulatory cells. Conclusion The lack of a clear association of LOY with histopathological parameters of cancer aggressiveness, patient prognosis, and parameters describing the tumor microenvironment strongly argues against the driving role of LOY in bladder cancer progression and cancer-associated immune reactions.
Differential Androgen Receptor Expression Across Bladder Cancer Stages and Its Link to Poor Outcomes
Bladder cancer is more common in men than in women, and sex hormones such as testosterone may influence how the disease develops and progresses. The androgen receptor is a protein that allows cells to respond to these hormones and is well known in prostate cancer, but its role in bladder cancer has been unclear. In this study, we analyzed 2710 bladder cancer samples to find out whether the amount of androgen receptor in tumor cells is linked to patient outcomes. We discovered that men whose tumors had high levels of this receptor lived shorter after surgery than those with little or no receptor expression. These results suggest that the androgen receptor could help identify patients at higher risk and might become a new target for personalized treatment in bladder cancer.
Surface-Active Ionic Liquids and Surface-Active Quaternary Ammonium Salts from Synthesis, Characterization to Antimicrobial Properties
The present work provides new evidence of the ongoing potential of surface-active ionic liquids (SAILs) and surface-active quaternary ammonium salts (surface-active QASs). To achieve this, a series of compounds were synthesized with a yield of ≥85%, and their thermal analyses were studied. Additionally, antimicrobial activity against both human pathogenic and soil microorganisms was investigated. Subsequently, their surface properties were explored with the aim of utilizing SAILs and surface-active QASs as alternatives to commercial amphiphilic compounds. Finally, we analyzed the wettability of the leaves’ surface of plants occurring in agricultural fields at different temperatures (from 5 to 25 °C) and the model plant membrane of leaves. Our results show that the synthesized compounds exhibit higher activity than their commercial analogues such as, i.e., didecyldimethylammonium chloride (DDAC) and dodecyltrimethylammonium bromide (C12TAB), for which the CMC values are 2 mM and 15 mM. The effectiveness of the antimicrobial properties of synthesized compounds relies on their hydrophobic nature accompanied by a cut-off effect. Moreover, the best wettability of the leaves’ surface was observed at 25 °C. Our research has yielded valuable insights into the potential effectiveness of SAILs and surface-active QASs as versatile compounds, offering a promising alternative to established antimicrobials and crop protection agents, all the while preserving substantial surface activity.
GATA3 amplification is associated with high grade disease in non-invasive urothelial bladder cancer but unrelated to patient prognosis
Purpose We aimed to assess the impact of GATA3 binding protein (GATA3) gene copy number alterations on tumor aggressiveness, patient prognosis, and GATA3 protein expression in a large urothelial bladder cancer cohort. Methods A tissue microarray containing over 2,700 urothelial bladder cancers (pTa-pT4) was analyzed retrospectively using dual-labeling fluorescence in-situ hybridization (FISH) with probes for GATA3 (10p14) and centromere 10. GATA3 copy number gains were categorized as GATA3 elevation (ratio GATA3 /centromere ≥ 2/≤4), low-level amplification (ratio > 4/≤12), and high-level amplification (ratio > 12) and deletions were divided between homozygous and heterozygous. Results GATA3 copy number gain was detected in 9.9% of 2,213 interpretable tumors, including 2.0% with GATA3 elevation, 3.2% with low-level amplification, and 4.7% with high-level amplification. The frequency of high-level amplification increased from pTa G2 low (0%) to pTa G3 tumors (12% [CI 0.07;0.21]; p  < 0.0001 pTa G2 low vs. pTaG2 high) but decreased in advanced-stage carcinomas pT2-4 with 5.4% [CI 0.07;0.21] ( p  < 0.0001, pTa vs. pT2-4). In muscle-invasive carcinomas, GATA3 amplification was not linked to tumor aggressiveness or patient survival. Overall, no homozygous GATA3 deletion was detected and heterozygous GATA3 deletion was only observed in 1.1%; of 1,432 pT2-4 tumors without any association to cancer progression. While GATA3 copy number was significantly correlated with GATA3 expression ( p  < 0.0001), the relationship was not strong. Only 2.3% of GATA3 -negative cancers had a deletion, and 42.1% of strong GATA3-expressing cancers exhibited high-level amplification. Conclusion High-level GATA3 amplification is common in urothelial bladder cancer and correlates with grade progression in pTa tumors, while GATA3 deletion is rare. Neither amplification nor deletion appears to be the primary driver of GATA3 expression dysregulation. Clinical trial number Not applicable.
18F-choline positron emission tomography/computed tomography guided laparoscopic salvage lymph node dissection in patients after radical prostatectomy
Salvage lymph node dissection (sLND) using novel imaging methods is an interesting alternative to treat lymph node (LN) metastasis after radical prostatectomy (RP); however, recommendations for using sLND as such are still being developed. To assess the clinical outcomes of prostate cancer (PCa) after fluorine-18-choline (18F-choline) positron emission tomography/computed tomography (PET/CT) guided sLND. Ten patients who had undergone sLND under 18F-choline PET/CT guidance (positive nodes: median 1, range 1-3) and had biochemical recurrence or persistence of prostate-specific antigen (PSA: median PSA 2.05 ng/ml, range: 0.8-8.4) after RP were enrolled in this retrospective study. Complete biochemical response (cBCR) after salvage surgery was defined as PSA < 0.2 ng/ml. The median follow-up time after salvage surgery was 33 months. The median PSA level 6 weeks after sLND and at the end of follow-up was 0.93 and 2.95 ng/ml, respectively. At 6 weeks after targeted sLND only 1 patient had cBCR, whereas a PSA decrease was noted in 7 patients. No patient had cBCR at the end of follow-up. Laparoscopic sLND in cases of LN metastatic PCa after RP is a feasible option with low morbidity. However, an initial cBCR occurs in a negligible proportion of patients, and a long-term response is unlikely to be achieved.
PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors
Background A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. Methods To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. Results Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p  = 0.0255) and was even higher in muscle-invasive (pT2–4) carcinomas (29.3%; p  < 0.0001). However, within pT2–4 carcinomas, PD-L1 positivity was linked to low pT stage ( p  = 0.0028), pN0 (p < 0.0001), L0 status ( p  = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs ( p  = 0.0073 for tumor cells and p  = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells ( p  < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). Conclusion It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.
Loss of MTAP expression is strongly linked to homozygous 9p21 deletion, unfavorable tumor phenotype, and noninflamed microenvironment in urothelial bladder cancer
Homozygous 9p21 deletions usually result in a complete loss of S‐methyl‐5′‐thioadenosine phosphorylase (MTAP) expression visualizable by immunohistochemistry (IHC). MTAP deficiency has been proposed as a marker for predicting targeted treatment response. A tissue microarray including 2,710 urothelial bladder carcinomas were analyzed for 9p21 deletion by fluorescence in situ hybridization and MTAP expression by IHC. Data were compared with data on tumor phenotype, patient survival, intratumoral lymphocyte subsets, and PD‐L1 expression. The 9p21 deletion rate increased from pTaG2 low (9.2% homozygous, 25.8% heterozygous) to pTaG2 high (32.6%, 20.9%; p < 0.0001) but was slightly lower in pTaG3 (16.7%, 16.7%) tumors. In pT2–4 carcinomas, 23.3% homozygous and 17.9% heterozygous deletions were found, and deletions were tied to advanced pT (p = 0.0014) and poor overall survival (p = 0.0461). Complete MTAP loss was seen in 98.4% of homozygous deleted while only 1.6% of MTAP negative tumors had retained 9p21 copies (p < 0.0001). MTAP loss was linked to advanced stage and poor overall survival in pT2–4 carcinomas (p < 0.05 each). The relationship between 9p21 deletions/MTAP loss and poor patient prognosis was independent of pT and pN (p < 0.05 each). The 9p21 deletions were associated with a noninflamed microenvironment (p < 0.05). Complete MTAP loss is strongly tied to homozygous 9p21 deletion, aggressive disease, and noninflamed microenvironment. Drugs targeting MTAP‐deficiency may be useful in urothelial bladder carcinoma. MTAP IHC is a near perfect surrogate for MTAP deficiency in this tumor type.