A Refinement of Clinical Tumor Marker Monitoring: Why Not Use an Inverse Value of Doubling Time?

OBJECTIVES: The aim of this study was to compare prostate-specific antigen (PSA) kinetics - half-life time (HT), doubling time (DT), and elimination rate PSA (ePSA) in prostate cancer (PCa) monitoring. Implementation of ePSA in clinical practice could help simplify patient monitoring in the remission phase. MATERIALS AND METHODS: A total of 49 PCa patients were examined by their PSA tests before prostatectomy and after 30 days, 91 days, and 24 months. Conventional PSA rate of change parameters (HT and DT) were compared to a new clinically understandable ePSA parameter. RESULTS: We observed that implementation of inverse value (ePSA) rather than HT or DT has distinct advantages: (1) values are valid when PSA is unchanged (ePSA equals zero), (2) the concept of ePSA can be easily understood, as it is a growth fraction, (3) ePSA fluctuates within a narrow range and is thus easy to interpret, and (4) there are no mathematical flaws (no positive skewing). CONCLUSION: Exploring ePSA norm as ≤0% could help spot biochemical recurrence in a timely manner. Primary health care providers tend to use an irrelevant PSA threshold, that is, 4.0 ng/mL, in postoperative follow-up. The delayed referrals of patients in remission might be reduced if ePSA testing is adopted.

Atezolizumab Retains Cellular Binding to Programmed Death Ligand 1 Following Aerosolization via Mesh Nebulizer.

BACKGROUND/AIM: Cytotoxic inhalable drugs were shown to be advantageous in treating malignancies of the respiratory tract. However, these drugs have not always presented a safe profile and were reported to induce local adverse events. Protein-based anticancer drugs, such as immune checkpoint and vascular endothelial growth factor inhibitors, do not induce tissue injury, nor do they exhibit vesicant properties upon direct contact with tissues. Protein drugs are susceptible to the heat and stress encountered during droplet generation for delivery by nebulization. The aim of this study was to investigate the capacity of atezolizumab, an antibody to programmed death ligand 1, to bind target cells after nebulization with a vibrating mesh (VM) nebulizer. MATERIALS AND METHODS: We compared Fourier-transformed infrared (FTIR) and Raman spectra of native atezolizumab (60 mg/ml) and its nebulized form following 10-min nebulization in a piezoceramic VM nebulizer. The binding of atezolizumab to DU-145 prostate cancer cells was evaluated using competitive blocking of anti-CD274 staining. RESULTS: Nebulization did not induce Raman or FTIR spectral modification nor did it affect the binding capacity of atezolizumab. Conversely, heat-inactivated atezolizumab lost its cell-binding capacity and did not reduce anti-CD274 immunostaining. Native and nebulized atezolizumab displayed identical spectra, whereas the FTIR spectra of the heat-inactivated drug was significantly altered. CONCLUSION: VM nebulization does not obliterate the functionality of the drug atezolizumab. The integrity of a nebulized form can be rapidly assessed by FTIR and Raman spectrometry.

Immunophenotype Rearrangement in Response to Tumor Excision May Be Related to the Risk of Biochemical Recurrence in Prostate Cancer Patients.

BACKGROUND: Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients. METHODS: Radical prostatectomy (RP) was performed on 108 PCa stage pT2-pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups. RESULTS: The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = -2.0% d-1 (AUC = 0.85 (95% CI, 0.78-0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 - CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL (p < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients (p = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16). CONCLUSION: Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period.

[Incidence of varicocele measured by echoscopy]. / Varikoceles daznumas vyrams po echoskopijos.

UNLABELLED: Varicocele should be diagnosed and treatment should be started in boys under 10-14, because at an older age it will interfere with the development of the testicle. The objective of the study is to establish the rate of varicocele. The study material and methods. One hundret of patients aged from 20 to 87 (SD=17) have been studied: the thickness of veins of plexus pampiniformis was measured by echoscopy, funiculus spermaticus was palpated. RESULTS: Varicocele was diagnosed in 24 (24%) of patients. CONCLUSION: The incidence rate of this disease is high.

[Penis deviation correction using Schröder's method and patients' postoperative quality of life]. / Varpos deviacijos korekcija pagal Srioderi (Schröder) ir pacientu pooperacinio gyvenimo kokybe.

Most frequent methods of penis deviation operative treatment are penis corporoplastics after Schröder and Nesbit. The penis corporoplastics can be followed by early complications (bleeding from the penis, recrudescent deviation due to suture cut-out, reduced or extinct sensitivity of the penis head as a result of n. dorsalis penis injury, etc.) or tardy ones (scarring phymosis, recrudescent deviation due to the scar, etc.). The objective of the study is to assess the quality of the patients' life after the operation (penis corporoplastics after Schröder) and any possible post-operative complications. The medical documentation of twelve patients, who were operated in the aforesaid manner at Kaunas 2(nd) Clinical Hospital and Kaunas Clinics of General Medical Practice in 1994-2001, was checked. Before the operation all the patients had penis deviation diagnosed (two ventral, two lateral and five mixed) resulting from congenital penis curvature. The indication for the operation of all the patients was aggravated intercourse. None of the patients showed early post-operative complications. When the patients were checked 6 months and 1 year later there were no tardy post-operative complications, either. All the patients were satisfied with the quality of life after the operation - there was no deviation, the erection and intercourse were normal. Penis corporoplastics after Schröder is a proper method to be used for correction of inherent penis deviations.

[Percutaneous nephrostomy at the Second Kaunas Clinical Hospital]. / Perkutanine nefrostomija Kauno 2-ojoje klinikineje ligonineje.

From 1996 to 2000 in urology department of 2(nd) Kaunas Clinical Hospital, 343 percutaneous interventions were performed, 250 of which was percutaneous nephrostomy. Urinary flowing was disturbed to 171 patients with urinary obstruction and 79 with malignant tumor. Death related to operation was not noticed in all patients. One of the patient had undergone surgery. PCN was successfully performed in 97.5% of all the cases.