Predicting Survival of Patients with Node-positive Prostate Cancer Following Multimodal Treatment

Background

According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes.

Objective

To develop and internally validate novel nomograms predicting cancer-specific mortality (CSM)–free rate in pN1 patients.

Design, setting, and participants

We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated.

Results and limitations

All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p ≤ 0.04). Based on these predictors, nomograms were developed to predict the 10-yr CSM-free rate in the overall patient population and in men with biochemical recurrence. These models showed high discrimination accuracy (79.5–83.3%) and favorable calibration characteristics. These results are limited by their retrospective nature.

Conclusions

Some patients with pN1 PCa have favorable CSM-free rates at 10 yr. We developed and internally validated the first nomograms that allow an accurate prediction of the CSM-free rate in these patients at an individual level.     

Mental health outcomes in elderly men with prostate cancer

ObjectiveTo examine the burden of mental health issues (MHI), namely anxiety, depressive disorders, and suicide, in a population-based cohort of older men with localized prostate cancer and to evaluate associations with primary treatment modality.Patients and methodsA total of 50,856 men, who were 65 years of age or older with clinically localized prostate cancer diagnosed between 1992 and 2005 and without a diagnosis of mental illness at baseline, were abstracted from the Surveillance, Epidemiology, and End Results–Medicare database. The primary outcome of interest was the development of MHI (anxiety, major depressive disorder, depressive disorder not elsewhere classified, neurotic depression, adjustment disorder with depressed mood, and suicide) after the diagnosis of prostate cancer.ResultsA total of 10,389 men (20.4%) developed MHI during the study period. Independent risk factors for MHI included age≥75 years (hazard ratio [HR] = 1.29); higher comorbidity (Charlson comorbidity index≥3, HR = 1.63); rural hospital location (HR = 1.14); being single, divorced, or widowed (HR = 1.12); later year of diagnosis (HR = 1.05); and urinary incontinence (HR = 1.47). Black race (HR = 0.79), very high-income status (HR = 0.87), and definitive treatment (radical prostatectomy [RP], HR = 0.79; radiotherapy [RT], HR= 0.85, all P<0.001) predicted a lower risk of MHI. The rates of MHI at 10 years were 29.7%, 29.0%, and 22.6% in men undergoing watchful waiting (WW), RT, and RP, respectively.ConclusionOlder men with localized prostate cancer had a significant burden of MHI. Men treated with RP or RT were at a lower risk of developing MHI, compared with those undergoing WW, with median time to development of MHI being significantly greater in those undergoing RP compared with those undergoing RT or WW.     

Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder

ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.     

The influence of CYP3A,PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients

Purpose

Tacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4 and CYP3A5. Several studies have demonstrated an association between the CYP3A5 genotype and Tac dose requirements. Recently, CYP3A4, PPARA, and POR gene variants have been shown to influence CYP3A metabolism. The present study investigated potential associations between CYP3A5*3, CYP3A4*22, PPARA c.209-1003G>A and c.208?+?3819A>G, and POR*28 alleles and dose-adjusted concentrations (C/D) of Tac and CsA in 177 renal transplant patients early post-transplant.

Methods

All patients (n?=?177) were genotyped for CYP3A4*22, CYP3A5*3, POR*28, PPARA c.209-1003G>A, and PPARA c.208?+?3819A>G using real-time polymerase chain reaction (PCR) and melting curve analysis with allele-specific hybridization probes or PCR restriction fragment length polymorphisms (RFLP) methods. Drug concentrations and administered doses were retrospectively collected from patient charts at Oslo University Hospital, Rikshospitalet, Norway. One steady-state concentration was collected for each patient.

Results

We confirmed a significant impact of the CYP3A5*3 allele on Tac exposure. Patients with POR*28 and PPARA variant alleles demonstrated 15 % lower (P?=?0.04) and 19 % higher (P?=?0.01) Tac C₀/D respectively. CsA C₂/D was 53 % higher among CYP3A4*22 carriers (P?=?0.03).

Conclusion

The results support the use of pre-transplant CYP3A5 genotyping to improve initial dosing of Tac, and suggest that Tac dosing may be further individualized by additional POR and PPARA genotyping. Furthermore, initial CsA dosing may be improved by pre-transplant CYP3A4*22 determination.     

The Preparation and Characterization of Chitosan-Based Hydrogels Cross-Linked by Glyoxal

In this study, hydrogels based on chitosan cross-linked by glyoxal have been investigated for potential medical applications. Hydrogels were loaded with tannic acid at different concentrations. The thermal stability and the polyphenol-releasing rate were determined. For a preliminary assessment of the clinical usefulness of the hydrogels, they were examined for blood compatibility and in the culture of human dental pulp cells (hDPC). The results showed that after immersion in a polyphenol solution, chitosan/glyoxal hydrogels remain nonhemolytic for erythrocytes, and we also did not observe the cytotoxic effect of hydrogels immersed in tannic acid (TA) solutions with different concentration. Tannic acid was successfully released from hydrogels, and its addition improved material thermal stability. Thus, the current findings open the possibility to consider such hydrogels in clinics.     

Phase Structure Evolution of the Fe-Al Arc-Sprayed Coating Stimulated by Annealing

The article presents the results of research on the structural evolution of the composite Fe-Al-based coating deposited by arc spray with initial low participation of in situ intermetallic phases. The arc spraying process was carried out by simultaneously melting two different electrode wires, aluminum and low alloy steel (98.6 wt.% of Fe). The aim of the research was to reach protective coatings with a composite structure consisting of a significant participation of Fe_xAl_y as intermetallic phases reinforcement. Initially, synthesis of intermetallic phases took place in situ during the spraying process. In the next step, participation of Fe_xAl_y fraction was increased through the annealing process, with three temperature values, 700 °C, 800 °C, and 900 °C. Phase structure evolution of the Fe-Al arc-sprayed coating, stimulated by annealing, has been described by means of SEM images taken with a QBSD backscattered electron detector and by XRD and conversion electron Mössbauer spectroscopy (CEMS) investigations. Microhardness distribution of the investigated annealed coatings has been presented.     

Dehydroxylation of Perlite and Vermiculite: Impact on Improving the Knock-Out Properties of Moulding and Core Sand with an Inorganic Binder

The article presents the results of research aimed at examining the type of swelling material introduced into moulding or core sand to improve their knock-out properties. Tests on Slovak perlite ore (three grain sizes), Hungarian perlite ore and ground vermiculite (South Africa) were carried out. For this purpose, thermal and structural analyses (FTIR—Fourier Transform Infrared Spectroscopy), a chemical composition test (XRF-X-Ray Fluorescence), phase analysis (XRD—X-Ray Diffraction), and scanning electron microscopy (SEM—Scanning Electron Microscope) as well as final strength tests of moulding sands with the addition of perlite ore and vermiculite were carried out. The results of thermal studies were related to IR (Infrared Spectroscopy) spectra and XRD diffractograms. It has been shown that the water content in the pearlite ore is almost three times lower than in vermiculite, but the process of its removal is different. Moreover, the chemical composition of the perlite ore, in particular the alkali content and its grain size, may influence its structure. The phenomena of expansion (perlite) and peeling (vermiculite) have a positive effect on the reduction of the final sand strength and eliminate technological inconveniences (poor knocking out) that significantly limit the wide use of moulding sands with inorganic binders.