Background
The decline of health-related quality-of-life (QOL) during the year after radical prostatectomy is severe. General self-efficacy (GSE) is an effective psychological factor for long-term ...regulation of patient behavior and emotions. GSE is expected to facilitate enhanced health-related quality of life. We evaluated changes in GSE and analyzed the relationship between GSE and prostate cancer-specific and general health-related QOL.
Methods
We conducted a longitudinal survey with 104 patients who underwent radical prostatectomy and administered the General Self-efficacy Scale (GSES), Expanded Prostate Cancer Index Composite (EPIC), and SF8 Health Survey (SF-8). ANCOVA was performed to compare EPIC and SF-8 between GSES high and low-medium groups.
Results
GSES scores increased significantly after 6 months. Regarding EPIC urinary summary scores, high GSES group was significantly higher than low-medium group at 1 month (mean score difference MSD, 7.3; 95% CI 1.1–13.2,
P
= 0.016), 3 months (MSD, 6.8; 95% CI 0.7–12.8,
P
= 0.028), and 6 months (MSD, 6.3; 95% CI 0.9–11.7,
P
= 0.022). High GSES group had significantly higher SF-8 physical component summary score at 6 months (MSD, 3.2; 95% CI 1.4–5.0,
P
= 0.001), and significantly higher SF-8 mental component summary score at 1 month (MSD, 2.6; 95% CI 0.4–4.9,
P
= 0.022), 3 months (MSD, 2.7; 95% CI 0.8–4.6,
P
= 0.007), and 6 months (MSD, 2.8; 95% CI 1.0–4.6,
P
= 0.003).
Conclusion
This study suggests that high GSE was associated with better prostate cancer-specific and general health-related QOL after radical prostatectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine ...the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Objectives
This study aimed to evaluate whether oncological outcomes of radical prostatectomy differ depending on adherence to the criteria in patients who opt for active surveillance.
...Materials and methods
We retrospectively reviewed the data of 1035 patients enrolled in a prospective cohort of the PRIAS-JAPAN study. After applying the exclusion criteria, 136 of 162 patients were analyzed. Triggers for radical prostatectomy due to pathological reclassification on repeat biopsy were defined as on-criteria. Off-criteria triggers were defined as those other than on-criteria triggers. Unfavorable pathology on radical prostatectomy was defined as pathological ≥T3, ≥GS 4 + 3 and pathological N positivity. We compared the pathological findings on radical prostatectomy and prostate-specific antigen recurrence-free survival between the two groups. The off-criteria group included 35 patients (25.7%), half of whom received radical prostatectomy within 35 months.
Results
There were significant differences in median prostate-specific antigen before radical prostatectomy between the on-criteria and off-criteria groups (6.1 vs. 8.3 ng/ml, P = 0.007). The percentage of unfavorable pathologies on radical prostatectomy was lower in the off-criteria group than that in the on-criteria group (40.6 vs. 31.4%); however, the differences were not statistically significant (P = 0.421). No significant difference in prostate-specific antigen recurrence-free survival was observed between the groups during the postoperative follow-up period (median: 36 months) (log-rank P = 0.828).
Conclusions
Half of the off-criteria patients underwent radical prostatectomy within 3 years of beginning active surveillance, and their pathological findings were not worse than those of the on-criteria patients.
Criteria adherence was not associated with unfavorable pathology with regard to radical prostatectomy in patients who opt for active surveillance.
We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second ...vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm
were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm
were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.
Background
Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable complications of this procedure. We ...retrospectively evaluated whether adjuvant systemic heparinization just before arterial manipulation could reduce early failure of primary AVF.
Methods
Three hundred and fifty-six patients with end-stage renal failure who underwent primary AVF surgery from April 2009 to September 2020 were enrolled in this study. The patients were divided into two groups based on whether they received adjuvant heparinization or not. Patient backgrounds, frequency of early AVF failure, and bleeding events were compared between the two groups. Multivariate Cox regression analysis identified risk factors for early AVF failure.
Results
Early failure of AVF was observed in only 2 of 157 patients (1.2%) in the adjuvant group, and the incident was significantly lower than observed in the non-adjuvant group, i.e., 17 of 199 patients (8.5%) (
p
= 0.002). Bleeding events were not significantly different between the two groups. Seven of 157 patients (4.5%) in the adjuvant group and 7 of 199 patients (3.5%) in the non-adjuvant group experienced bleeding events (
p
= 0.785). Female sex, use of steroids, hypoalbuminemia, venous stenosis in pre-surgical evaluation, arterial spasm in the perioperative period, new-onset venous stenosis after AVF anastomosis, technical failure of surgery, no early cannulation after surgery, and non-adjuvant heparinization were related to early AVF failure in the multivariate regression analysis.
Conclusion
Adjuvant systemic heparinization therapy just before arterial manipulation reduced early failure of primary AVF without increasing bleeding events.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Metabolic syndrome is a long-term complication of systemic chemotherapy for testicular germ cell tumor (TGCT). It is believed to be caused by secondary hypogonadism or toxic medicines because of ...orchidectomy followed by systemic chemotherapy. In this study, changes in the body composition of patients over time were quantitatively analyzed up to 24 months after chemotherapy. This study retrospectively analyzed 44 patients with TGCT who underwent chemotherapy at our institution from January 2008 to December 2016. Subcutaneous and visceral fat areas and psoas and skeletal muscle areas were measured by computed tomography before and immediately after chemotherapy as well as 3 months, 6 months, 12 months, and 24 months after chemotherapy. The subcutaneous and visceral fat indices and psoas and skeletal muscle indices were calculated as each area divided by body height squared. The total fat area had already significantly increased 3 months after the initiation of chemotherapy (P = 0.004). However, it did not return to prechemotherapeutic levels even at 24 months after chemotherapy. The skeletal muscle area was significantly decreased at the end of chemotherapy (P < 0.001); however, the value returned to baseline within 12 months. In multivariable analysis, the prechemotherapeutic skeletal muscle index and number of chemotherapy cycles were independently associated with the reduction of skeletal muscle at the end of chemotherapy (P = 0.001 and P = 0.027, respectively). In patients with TGCT, skeletal muscle mass decreased during chemotherapy and recovered within 12 months, whereas fat mass progressively increased from the initiation of chemotherapy until 24 months after chemotherapy.
Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA ...(ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%.
This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied.
One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious
,
, and
variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in
or
HR, 2.52; 95% confidence interval (CI), 1.24-5.11;
= 0.0091 and
(HR, 3.74; 95% CI, 1.60-8.71;
= 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable.
Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.
Objectives
We evaluated whether the treatment history of low‐dose rituximab affected safety profiles, and humoral and cellular responses induced by severe acute respiratory syndrome coronavirus 2 ...messenger ribonucleic acid vaccine in healthy controls and kidney transplant recipients.
Methods
We enrolled 10 healthcare workers as controls, 22 kidney transplant recipients with rituximab, and 36 kidney transplant recipients without rituximab without history of coronavirus disease 2019 who received two doses of vaccine. We assessed anti‐severe acute respiratory syndrome coronavirus 2 spike antibody and the antigen‐specific T cells using enzyme‐linked immunospot against spike protein at baseline and after two doses of vaccine.
Results
All controls showed anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion and enzyme‐linked immunospot positivity. Only 19/58 (33%) kidney transplant recipients experienced anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion and 31/58 (53%) kidney transplant recipients developed enzyme‐linked immunospot assay positivity after vaccination. The anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion rate and enzyme‐linked immunospot assay positivity rate after vaccination were not significantly different between kidney transplant recipients with or without rituximab. Multivariate regression analysis demonstrated rituximab was not associated with a lack of humoral and cellular responses to the vaccine.
Conclusions
Low‐dose rituximab in kidney transplant recipients did not affect humoral or cellular responses to the severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine without severe systemic adverse events including the deterioration of kidney function.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with ...LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis‐free survival (MFS) was the primary outcome. Patients were stratified by prostate‐specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan‐Meier method and log‐rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15‐0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) among patients with persistent prostate‐specific antigen (PSA) after RP has not been established. Here, the outcomes of various management strategies among patients with LNI after RP were investigated. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to androgen deprivation therapy (ADT) might improve survival.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives
To create a new model for the prediction of overall survival in synchronous metastatic renal cell carcinoma.
Methods
Medical records of 158 patients with metastatic renal cell carcinoma ...diagnosed at the Yamagata University Hospital from August 2007 to February 2018 were reviewed. Among them, 77 with synchronous metastatic renal cell carcinoma were retrospectively analyzed using the univariate and multivariate analyses. A new prognostic model was constructed, followed by a bootstrap validation to estimate the model fitting. In addition, these prognostic factors were estimated in 67 metachronous metastatic renal cell carcinoma patients.
Results
Five independent prognostic factors were identified in synchronous metastatic renal cell carcinoma: cT3/4, cN1, high corrected calcium, >3.6 neutrophil‐to‐lymphocyte ratio and central nerve system metastasis. The number (%) and overall survival (95% confidence interval) in the favorable‐ (0 or 1 risk factor), intermediate‐ (2 risk factors) and poor‐risk (≥3 risk factors) groups were 29 (45.3%) and 67.4 (31.8–NA), 21 (32.8%) and 16.8 (10.0–27.6), and 14 (21.9%) and 9.1 (7.3–13.7) months, respectively. The C‐index was 0.72. Patients in the favorable‐risk group had better overall survival with nephrectomy than without nephrectomy (hazard ratio 0.29, 95% confidence interval 0.09–0.91 with nephrectomy). In metachronous metastatic renal cell carcinoma, these prognostic factors showed no statistical differences in the overall survival.
Conclusions
Prognostic factors are completely different between synchronous and metachronous metastatic renal cell carcinoma. The new model for synchronous metastatic renal cell carcinoma can predict a good candidate for cytoreductive nephrectomy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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