Functional status recovery trajectories in hospitalised older adults with pneumonia.

BACKGROUND AND OBJECTIVES: Pneumonia is associated with significant mortality and morbidity in older adults. We investigated changes in functional status over 6 months after pneumonia hospitalisation by frailty status. METHODS AND MEASUREMENTS: This single-centre prospective cohort study enrolled 201 patients (mean age 79.4, 37.3% women) who were hospitalised with pneumonia. A deficit-accumulation frailty index (range: 0-1; robust <0.15, pre-frail 0.15-0.24, mild-to-moderately frail 0.25-0.44, severely frail ≥0.45) was calculated on admission. Functional status, defined as self-reported ability to perform 21 activities and physical tasks independently, was measured by telephone at 1, 3 and 6 months after discharge. Group-based trajectory model was used to identify functional trajectories. We examined the probability of each trajectory based on frailty levels. RESULTS: On admission, 51 (25.4%) were robust, 43 (21.4%) pre-frail, 40 (20.0%) mild-to-moderately frail and 67 (33.3%) severely frail patients. Four trajectories were identified: excellent (14.4%), good (25.4%), poor (28.9%) and very poor (31.3%). The trajectory was more strongly correlated with frailty level on admission than pneumonia severity. The most common trajectory was excellent trajectory (59.9%) in robust patients, good trajectory (74.4%) in pre-frail patients, poor trajectory (85.0%) in mild-to-moderately frail patients and very poor trajectory (89.6%) in severely frail patients. The risk of poor or very poor trajectory from robust to severely frail patients was 11.8%, 25.6%, 92.5% and 100%, respectively. CONCLUSIONS: Frailty was a strong determinant of lack of functional recovery over 6 months after pneumonia hospitalisation in older adults. Our results call for hospital-based and post-acute care interventions for frail patients.

Comparison of Frailty Index to Pneumonia Severity Measures in Older Patients With Pneumonia.

OBJECTIVES: Risk stratification tools are useful to provide appropriate clinical care for older patients with pneumonia. This study aimed to compare a Frailty Index (FI) with pneumonia severity measures, CURB-65, and the Pneumonia Severity Index (PSI), for predicting mortality and persistent disability after pneumonia. DESIGN: Single-center prospective cohort study. SETTING AND PARTICIPANTS: The study included 190 patients aged ≥65 years who were hospitalized with pneumonia at a university hospital in Korea between October 2019 and September 2020. METHODS: At admission, a 50-item deficit-accumulation FI (range: 0-1), CURB-65 (range: 0-5), and PSI (range: 0-395) scores were calculated. The outcomes were death and a composite outcome of death or decline in ability to perform daily activities and physical task 6 months later. RESULTS: The median age was 79 years (interquartile range: 74-85), and 70 (36.8%) patients were women. The patients who died (n = 53) had higher FI (median, 0.46 vs 0.20; P < .011), CURB-65 score (median, 3 vs 2; P = .001), and PSI score (median, 149 vs 116; P < .001) than those who did not. The C-statistics (95% confidence intervals) for 6-month mortality were 0.69 (0.61-0.77) for the FI, 0.62 (0.53-0.71) for CURB-65, and 0.71 (0.62-0.79) for the PSI (P = .019). The C-statistics for the 6-month composite outcome were 0.73 (0.65-0.81) for the FI, 0.64 (0.55-0.73) for CURB-65, and 0.69 (0.60-0.77) for the PSI (P = .096). The C-statistics improved when the FI was added to CURB-65 (from 0.64 to 0.74; P = .003) and to the PSI (from 0.69 to 0.75; P = .044) for the composite outcome. CONCLUSIONS AND IMPLICATIONS: Measuring frailty provides additive value to widely used pneumonia severity measures in predicting death or persistent hospitalization-associated disability in older adults after pneumonia hospitalization. Early recognition of frailty may be useful to identify those who require in-hospital and post-acute care interventions for functional recovery.

Comparison of radical prostatectomy and external beam radiotherapy in high-risk prostate cancer.

PURPOSE: We evaluated clinical outcomes of high-risk prostate cancer patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). MATERIALS AND METHODS: Patients were classified as high-risk prostate cancer and received definitive treatment between 2005 and 2015. Patients with previous pelvic radiotherapy, positive lymph node or distant metastasis were excluded. The primary outcomes were prostate cancer-specific survival (PCSS) and distant metastasis-free survival (DMFS). RESULTS: Of 583 patients met the inclusion criteria (77 EBRT and 506 RP). The estimated 10-year PCSS was 97.0% in the RP and 95.9% in the EBRT (p = 0.770). No significant difference was seen in the DMFS (p = 0.540), whereas there was a trend in favor of RP over EBRT in overall survival (OS) (p = 0.068). Propensity score matching analysis with confounding variables was done, with 183 patients (66 EBRT and 117 RP) were included. No significant difference in DMFS, PCSS or OS was found. CONCLUSION: Our data demonstrated similar oncologic PCSS, OS, and DMFS outcomes between EBRT and RP patients.

Frailty and hospitalization-associated disability after pneumonia: A prospective cohort study.

BACKGROUND: Pneumonia is a major cause of morbidity and mortality in older adults. The role of frailty assessment in older adults with pneumonia is not well defined. Our purpose of the study was to investigate 30-day clinical course and functional outcomes of pneumonia in older adults with different levels of frailty. METHODS: A prospective cohort was conducted at a university hospital in Seoul, Korea with 176 patients who were 65 years or older and hospitalized with pneumonia. A 50-item deficit-accumulation frailty index (FI) (range: 0-1; robust < 0.15, pre-frail 0.15-0.24, mild-to-moderately frail 0.25-0.44, and severely frail ≥ 0.45) and the pneumonia severity CURB-65 score (range: 0-5) were measured. Primary outcome was death or functional decline, defined as worsening dependencies in 21 daily activities and physical tasks in 30 days. Secondary outcomes were intensive care unit admission, psychoactive drug use, nasogastric tube feeding, prolonged hospitalization (length of stay > 15 days), and discharge to a long-term care institution. RESULTS: The population had a median age 79 (interquartile range, 75-84) years, 68 (38.6 %) female, and 45 (25.5 %) robust, 36 (47.4 %) pre-frail, 37 (21.0 %) mild-to-moderately frail, and 58 (33.0 %) severely frail patients. After adjusting for age, sex, and CURB-65, the risk of primary outcome for increasing frailty categories was 46.7 %, 61.1 %, 83.8 %, and 86.2 %, respectively (p = 0.014). The risk was higher in patients with frailty (FI ≥ 0.25) than without (FI < 0.25) among those with CURB-65 0-2 points (75 % vs. 52 %; p = 0.022) and among those with CURB-65 3-5 points (93 % vs. 65 %; p = 0.007). In addition, patients with greater frailty were more likely to require nasogastric tube feeding (robust vs. severe frailty: 13.9 % vs. 60.3 %) and prolonged hospitalization (18.2 % vs. 50.9 %) and discharge to a long-term care institution (4.4 % vs. 59.3 %) (p < 0.05 for all). Rates of intensive care unit admission and psychoactive drug use were similar. CONCLUSIONS: Older adults with frailty experience high rates of death or functional decline in 30 days of pneumonia hospitalization, regardless of the pneumonia severity. These results underscore the importance of frailty assessment in the acute care setting.

Reactive-oxygen-species-mediated mechanism for photoinduced antibacterial and antiviral activities of Ag3PO4.

Cubic-shaped Ag3PO4 crystals with a mean size of 1 µm were synthesized by a precipitation method from a mixed solution of AgNO3, Na2HPO4, and triethanolamine. The antibacterial activities against Escherichia coli, Listeria innocua, and Pseudomonas syringae DC3000 in both the absence and presence of Ag3PO4 under dark conditions and in the presence of Ag3PO4 under red-light (625 nm) and blue-light (460 nm) irradiation were examined. The concentrations of reactive oxygen species (ROS) were also measured in the antibacterial action of the Ag3PO4 against Escherichia coli. The photoinduced enhancement of the Ag3PO4 antibacterial activity under blue-light irradiation is explained by the formation of ROS during the antibacterial action of the Ag3PO4. Moreover, the antiviral activity of Ag3PO4 against amphotropic 10A1 murine leukemia virus enhanced under blue-light irradiation via ROS production. These results provide an insight into extended bio-applications of Ag3PO4.

Construction of replication-competent oncolytic retroviral vectors expressing R peptide-truncated 10A1 envelope glycoprotein.

Replication-deficient retroviral (RDR) vectors have been generally used for gene therapy, but clinically beneficial transduction efficiency is difficult to achieve with these vectors. In recent times, attention has been focused on the use of murine leukemia virus (MLV)-based replication-competent retroviral (RCR) vectors. RCR vectors have been shown to achieve efficient tumor reduction in a wide variety of cancer models. Most RCR vectors have been developed from amphotropic 4070 A MLV env, which is broadly applied in basic research. In this study, we generated RCR vectors based on Moloney MLV by replacing the native env gene in a full-length viral genome with the 10A1 env gene. 10A1 MLV can infect a wide variety of cells. Unlike amphotropic MLV, the 10A1 MLV can use amphotropic MLV receptor Pit2 or gibbon ape leukemia virus (GaLV) receptor Pit1. The resulting construct MoMLV-10A1-EGFP was able to replicate in 293 T, NIH3T3, and Mus dunni cells. To evaluate the potential of MoMLV-10A1 vector as a therapeutic agent, we incorporated the yeast cytosine deaminase (CD) suicide gene into vectors. The resulting vector MoMLV-10A1-CD could inhibit the growth of human 293T cells upon 5-fluorocytosine (5-FC) administration. In addition, to lyse tumor cells by syncytium, MoMLV-10A1-R(-)-EGFP was generated by replacing wild-type 10A1 env with the 16-amino acid R peptide-truncated 10A1 env gene. Syncytium formation was observed in the TE671 human tumor cells, 293 T and PG13 cells upon transfection of the MoMLV-10A1-R(-)-EGFP vector. This result suggests that replication of this vector could be oncolytic in itself. We also found that syncytium could contribute to enhance cell-to-cell transmission of the retroviral vectors. Our results thus show that the MoMLV-10A1 vectors can be potentially useful for cancer gene therapy.

Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines.

PURPOSE: The mechanism of resistance to cisplatin during treatment of bladder cancer (BC) has been a subject of intense investigation in clinical research. This study aims to identify candidate genes associated with resistance to cisplatin, in order to understand the resistance mechanism of BC cells to the drug, by combining the use of microarray profiling, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. MATERIALS AND METHODS: The cisplatin sensitive human BC cell line (T24) and the cisplatin resistant BC cell line, T24R2, were used for microarray analysis to determine the differential expression of genes that are significant in cisplatin resistance. Candidate upregulated genes belonging to three well-known cancer-related KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (p53 tumor suppressor, apoptosis, and cell cycle) were selected from the microarray data. These candidate genes, differentially expressed in T24 and T24R2, were then confirmed by quantitative RT-PCR and western blot. A fold change ≥2 with a p-value <0.05 was considered significant. RESULTS: A total of 18 significantly upregulated genes were detected in the three selected cancer-related pathways in both microarray and RT-PCR analyses. These genes were PRKAR2A, PRKAR2B, CYCS, BCL2, BIRC3, DFFB, CASP6, CDK6, CCNE1, STEAP3, MCM7, ORC2, ORC5, ANAPC1, and ANAPC7, CDC7, CDC27, and SKP1. Western blot analyses also confirmed the upregulation of BCL2, MCM7, and CCNE1 at the protein level, indicating their crucial association with cisplatin resistance. CONCLUSIONS: The BCL2, MCM7, and CCNE1 genes might play distinctive roles in cisplatin resistance in BC.

Effect of preoperative urodynamic detrusor overactivity on post-prostatectomy incontinence: a systematic review and meta-analysis.

PURPOSE: To investigate whether preoperative urodynamic detrusor overactivity (DO) contributes to post-prostatectomy incontinence (PPI). METHODS: We systematically searched the online PubMed, Embase, and Cochrane Library databases spanning the period of January 1989 to December 2014. RESULTS: A total of nine articles met the eligibility criteria for this systematic review. The eligible studies included a total of 457 patients with a median number of 58 patients per study (range 17-92). Of the nine studies, five conducted open retropubic radical prostatectomy (RRP), two performed robot-assisted laparoscopic prostatectomy (RALP), and two others utilized multiple modalities. PPI was more likely to occur in patients with preoperative DO [pooled odds ratio (OR) 2.30; 95 % confidence interval (CI) 1.39-3.82; studies 9; participants 419], as compared to patients who were DO negative. Sensitivity analysis using the subgroups of RRP (OR 2.32; 95 % CI 1.11-4.85), RALP (OR 3.41; 95 % CI 1.55-7.47), DO defined as any amplitude of involuntary contraction (OR 2.32; 95 % CI 1.11-4.85), no postoperative intervention (OR 2.32; 95 % CI 1.11-4.85), and outcome evaluation after 6 months (OR 2.32; 95 % CI 1.11-4.85) demonstrated consistent results. Although some comparisons showed inter-study heterogeneity, there was no clear evidence of publication bias in this meta-analysis. CONCLUSIONS: Our meta-analysis results suggest that preoperative DO is another possible underlying mechanism for PPI.

A Study of Relationship of Atheroembolic Risk Factors with Postoperative Recovery in Renal Function after Partial Nephrectomy in Patients Staged T1-2 Renal Cell Carcinoma during Median 4-Year Follow-up.

PURPOSE: The objective of this study is to evaluate the relationship of atheroembolic risk factors with postoperative recovery of renal function after on-clamp partial nephrectomy (PN) with warm ischemia in patients with staged T1-2 renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 234 patients from 2004 to 2012 were included, and their clinicopathologic and operative parameters, including atheroembolic risk factors were reviewed retrospectively. Renal function, as determined by estimated glomerular filtration rate (eGFR) and measurement of serum creatinine level (Cr) at each scheduled follow-up for a median four years, was compared between the high-risk (HR) group (n=49, ≥ five risk factors) and the low-risk (LR) group (n=185, < five risk factors). RESULTS: Except for baseline renal function and number of risk factors for atheroembolism, differences in characteristics between groups were comparatively insignificant. At 3 months after the operation, Cr and eGFR differed significantly between the two groups (p < 0.05), but no differences were observed afterward. Significant deterioration from baseline in Cr and eGFR was observed in both groups at 1 month after the operation, with a greater change in the HR group (p < 0.05). From measurement to measurement, significantly faster deterioration in Cr and eGFR was observed in the HR group than in the LR group until 6 months after the operation (Cr: LR, 0.02 mg/dL and HR, 0.13 mg/dL; eGFR: LR, 1.50 mL/min/1.73 m(2) and HR, 6.38 mL/min/1.73 m(2); p < 0.05). CONCLUSION: The presence of atheroembolic risk factors may negatively influence postoperative recovery of renal function after PN in patients with localized RCC.

The Quantified Level of Circulating Prostate Stem Cell Antigen mRNA relative to GAPDH Level Is a Clinically Significant Indictor for Predicting Biochemical Recurrence in Prostate Cancer Patients after Radical Prostatectomy.

The study quantified the relative absolute PSCA level in relation to the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) level in the peripheral blood of 478 hormone-naive prostate cancer (PC) patients who underwent radical prostatectomy from 2005 to 2012 and evaluated its prognostic significance as a risk factor for predicting biochemical recurrence (BCR), compared to known parameters. Nested real-time polymerase chain reaction (RT-PCR) and gel electrophoresis detected PSCA levels and measured the PSCA/GAPDH ratio. Clinicopathological data from the institutional database were examined to determine the adequate cut-off level to predict postoperative BCR. A total of 110 patients had a positive PSCA result (23.0%) via RT-PCR (mean blood ratio 1.1 ± 0.4). The BCR was significantly higher in the PSCA-positive detection group (p = 0.009). A multivariate model was created to show that a PSCA/GAPDH ratio between 1.0 and 1.5 (HR 12.722), clinical T2c stage (HR 0.104), preoperative PSA (HR 1.225), extraprostatic capsule extension (HR 0.006), lymph node dissection (HR 16.437), and positive resection margin (HR 27.453) were significant predictive factors for BCR (p < 0.05). The study showed successful quantification of PSCA with its significance for BCR-related risk factor; however, further studies are needed to confirm its clinical predictive value.

A propensity-matched comparison of perioperative complications and of chronic kidney disease between robot-assisted laparoscopic partial nephrectomy and radiofrequency ablative therapy.

OBJECTIVE: The study presents a matched-pair analysis of robot-assisted laparoscopic partial nephrectomy (RALPN) versus radiofrequency ablation (RFA) to compare the perioperative incidence of complications and chronic kidney disease (CKD). METHODS: All 46 RFA and 206 RALPN cases from June 2005 to December 2011 were retrospectively reviewed from the medical records and were matched 1:1 based on propensity scores by sex, tumor size, tumor laterality of kidney, tumor location within the kidney, and clinical T stage. Hilar vessel clamping was performed in all RALPN patients. The estimated glomerular filtration rate was used to define the CKD of < 60 mL/minute/1.73 m(2) by the Modification of Diet in Renal Disease equation. All patients with baseline CKD or solitary kidney were excluded prior to the matching analysis. The complication was noted with modified Clavien grades ≥ 3. Statistical analysis was performed to compare the perioperative incidence of complications and CKD. RESULTS: A total of 27 matched pairs of RFA and RALPN patients were enrolled for analyzing CKD and perioperative complications. The better general conditions, higher estimated blood loss and transfusion rates, and longer operative time and hospital stay were observed significantly in RALPN patients (p < 0.05). Matched analysis demonstrated that the incidences of both perioperative complications (p = 0.434) and of CKD (p = 0.500) were not significantly different. No complication higher than Grade 4 was detected in either group. CONCLUSION: Despite the intraoperative renal ischemia and invasiveness of the procedure associated with RALPN, the incidence of perioperative complication and of CKD developing rates were statistically similar.

Long-term oncologic outcomes of hand-assisted laparoscopic radical nephrectomy for clinically localized renal cell carcinoma: a multi-institutional comparative study.

BACKGROUND: We aimed to assess the long-term oncologic outcome of hand-assisted laparoscopic radical nephrectomy (HLRN) compared with open radical nephrectomy (ORN) in patients with clinically localized renal cell carcinoma (RCC). PATIENTS AND METHODS: We retrospectively reviewed the data from 1098 patients who underwent radical nephrectomy at five institutions in Korea between 2000 and 2011 for clinically localized RCC. One hundred ninety-seven patients in the HLRN group were compared with 901 patients in the ORN group. Univariate and multivariate analysis assessed the effects of operative method on oncologic outcomes. RESULTS: The median duration of follow-up was 69 months for the HLRN group and 63 months for the ORN group. No statistically significant difference was found in the operative time (170.2 minutes versus 168.9 minutes, P=.793) between the HLRN and ORN groups. However, estimated blood loss was significantly lower in the HLRN group than in the ORN group (245.9 mL versus 422.4 mL, P<.001). The pathological T stage was significantly higher in patients in the ORN group: 79.9% of patients in the HLRN group derived from pT1, versus 54.7% of those in the ORN group (P<.001). A statistically significant difference was found in the 5-year disease-free (90.6% versus 79.6%, P<.001), cancer-specific (95.7% versus 91.1%, P=.019), and overall (93.4% versus 85.4%, P<.001) survival between the HLRN and ORN groups. However, multivariate analysis by Cox's proportional hazards model does not retain surgical methods as an independent predictive factor for cancer-related death or recurrence. CONCLUSIONS: HLRN may be a preferable minimally invasive surgical treatment for clinically localized RCC with comparable long-term oncologic outcomes.

A retrospective analysis of incidence and its associated risk factors of upper urinary tract recurrence following radical cystectomy for bladder cancer with transitional cell carcinoma: the significance of local pelvic recurrence and positive lymph node.

OBJECTIVE: The aim of this study is to examine the incidence and risk factors of upper urinary tract recurrence (UUTR) following radical cystectomy (RC) in bladder cancer and to evaluate its relationship with neobladder (Neo) or ileal conduit (IC). MATERIALS AND METHODS: All clinicopathologic parameters and perioperative parameters of 311 patients who underwent RC with either Neo or IC by a single surgeon from 1999 to 2012 were retrospectively included in this study. Patients with a history of renal surgery, concomitant UUTR, or a histopathology of non-transitional cell carcinoma were excluded. For statistical analyses of predictive risk factors of UUTR, a multivariate analysis was performed with known risk factors of UUTR, including type of urinary diversion with significance defined as P < 0.05. RESULTS: During the median follow-up period of 53 months, 143 (46.0%) IC and 168 (54.0%) Neo were performed, resulting in 11 (3.5%) cases of UUTR (Neo 7 and IC 4) after RC and all patients then underwent nephroureterectomy. No significant differences in incidence and overall survival in UUTR were observed according different types of urinary diversion (p = 483), and the prognosis for survival of Neo was insignificantly better than that of IC (5-year overall survival 78% vs 74%, respectively, p>0.05). Higher number of positive lymph nodes (HR 9.03) and the presence of pelvic local recurrence (HR 7286.08) were significant predictive factors of UUTR (p<0.05). CONCLUSION: This study reports a UUTR rate of 3.5%, and positive lymph nodes and presence of local recurrence at the pelvis as important risk factors. No significant differences in incidence and survival were observed between Neo and IC.

Incidence and risk factors of 30-day early and 90-day late morbidity and mortality of radical cystectomy during a 13-year follow-up: a comparative propensity-score matched analysis of complications between neobladder and ileal conduit.

OBJECTIVE: We report on the short and late morbidity and mortality of ileal conduit and neobladder after radical cystectomy with their associated risk factors. METHODS: We retrospectively collected data on 308 non-metastatic bladder cancer patients who underwent radical cystectomy with either ileal conduit or neobladder for a curative intent from January 1999 to December 2011. Post-operative morbidity and mortality of 30-day (early) and 90-day (late) complication with their risk factors were examined in association with different types of urinary diversion. A comparative analysis using propensity-score matching was performed with matching variables of age, sex, number of underlying diseases and pathologic T and N stages, lymph node dissection, operative time and time of surgical year for comparison of the early and late morbidities between ileal conduit and neobladder. RESULTS: During the median follow-up of 46.6 months, early and late morbidities were 29.5% (n=91) and 19.8% (n=61), and complication-related mortalities were 2.2 and 6.6%, respectively. The type of urinary diversion significantly affected only the late complications (early: neobladder 57 vs. ileal conduit 47, P=0.096; late: neobladder 67 vs. ileal conduit 37, P<0.001). However, after propensity-score matching, no significant differences in early and late morbidities were observed between neobladder and ileal conduit. For risk factors of morbidity, number of removed lymph node states and hypertension were independently significant for both early and late complications (P<0.05). CONCLUSIONS: The type of urinary diversion affected only late complication, however, results of the matching analysis showed no significant differences in early and late morbidities between neobladder and ileal conduit.

Is high-dose leuprorelin acetate effective and safe in asian men with prostate cancer? An open-label, non-comparative, multi-center clinical trial.

PURPOSE: Leuprorelin is a well known luteinizing hormone releasing hormone agonist. However, there are insufficient data on the efficacy and safety of high dose leuprorelin acetate, especially in Asian patients with prostate cancer. We aimed to investigate the safety and efficacy of leuprorelin acetate 22.5 mg administered at three-month intervals in patients with prostate cancer. MATERIALS AND METHODS: In an open, prospective clinical trial enrolling 47 patients, we aimed to assess the efficacy and safety of leuprorelin acetate 22.5 mg in treating patients with histologically confirmed prostate cancer. The primary objective of this study was to evaluate the efficacy of the leuprorelin acetate 22.5 mg in producing and maintaining castration levels of testosterone over a 6-month follow-up period and to determine its safety profile. RESULTS: All 42 patients achieved serum testosterone levels within the castration range by 4 weeks. A breakthrough response was observed in one of 36 patients by 8 weeks. However, this patient was medically castrated by 12 weeks. There were no significant prostate-specific antigen (PSA) or testosterone changes according to clinical stage or body mass index. Twenty adverse events (AEs) in 15 of 42 patients (35.7%) were observed during this study. The most common AEs were hot flushes (n=4, 20.0%) with mild intensity, pain (n=2, 10.0%), and infection (n=2, 10.0%). No patient withdrew from the study due to AEs. CONCLUSION: Leuprorelin acetate 22.5 mg was shown to be effective and safe in Asian patients with prostate cancer, even though sexual function decreased.

Partial nephrectomy versus radical nephrectomy for non-metastatic pathological T3a renal cell carcinoma: a multi-institutional comparative analysis.

OBJECTIVES: To compare the recurrence-free survival of partial nephrectomy and radical nephrectomy in patients with non-metastatic pathological T3a renal cell carcinoma. METHODS: We reviewed the records of 3567 patients who had undergone a nephrectomy for renal cell carcinoma at five institutions in Korea from January 2000 to December 2010. The clinical data of 45 patients with pathological T3a renal cell carcinoma in the partial nephrectomy group were compared with 298 patients with pathological T3a renal cell carcinoma in the radical nephrectomy group. The effects of surgical methods on recurrence-free survival were assessed by a multivariate Cox proportional hazard analysis. All comparisons were repeated in subgroup analysis on 63 clinical T1a patients with tumors ≤4 cm. RESULTS: During a median 43-month follow-up period, disease recurrence occurred in two patients (4.4%) in the partial nephrectomy group, and 94 patients (31.5%) in the radical nephrectomy group. The results from a multivariate model showed that radical nephrectomy was a significant predictor of recurrence. However, in subgroup analysis that included 63 clinical T1a pathological T3a patients, the recurrence-free survival rates were not significantly different between the two cohorts. The renal function was significantly better preserved in the partial nephrectomy cohort than in the radical nephrectomy cohort. CONCLUSIONS: Partial nephrectomy provides similar recurrence-free survival outcomes compared with radical nephrectomy in patients with clinical T1a pathological T3a renal cell carcinoma. However, there seems to be a higher risk of recurrence for large pathological T3a tumors treated by radical nephrectomy compared with small tumors treated by partial nephrectomy. Thus, large tumors with the same pathological T3a renal cell carcinoma grade could have hidden aggressive features.

Localized non-conventional renal cell carcinoma: prediction of clinical outcome according to histology.

OBJECTIVE: A wide variety of parameters have been investigated in the prognostic significance of non-conventional clear cell renal cell carcinoma. Aim of the present study was to compare its clinical outcome and to determine the independent prognostic factors according to the histology. METHODS: This retrospective study enrolled localized non-conventional clear cell renal cell carcinomas (T1a-T4N0M0), including Xp11.2 translocation (Xp11.2t), all surgically treated in a single institution between 1988 and 2011. The study statistically analyzed the clinicopathological parameters to compare the prognostic outcomes among the different histological subtypes of non-conventional clear cell renal cell carcinoma and to define any independent prognostic factors. RESULTS: A total of 374 cases were examined, including 126 papillary (33.7%), 164 chromophobe (43.9%), eight collecting duct (2.1%), 40 unclassified (10.7%), 16 Xp11.2t (4.3%), seven mucinous tubular and spindle cell (1.8%) renal cell carcinomas and 13 oncocytomas (3.5%). The mean follow up was 56.4 months, with s mean tumor size of 4.9 ± 3.4 cm. The 4-year recurrence-free survival, overall survival and cancer-specific survival were inversely related to the increase of pathological T stages (P < 0.001). For histological type other than 13 oncocytomas and seven mucinous tubular and spindle cell renal cell carcinomas, the chromophobe showed the best prognosis of survival, followed by papillary, Xp11.2t, unclassified and collecting duct renal cell carcinomas, in this order. All survival rates were significantly different, as according to the histology (P = 0.009). The significant prognostic factors were preoperative body mass index (hazard ratio 0.76), serum albumin (hazard ratio 0.64), T stage (hazard ratio 2.28), the sarcomatoid differentiation (hazard ratio 33.45) and lymphovascular invasion (hazard ratio 12.40) in pathology (P < 0.05). CONCLUSIONS: Different non-conventional clear cell renal cell carcinoma subtypes have significantly different clinical characteristics of prognosis with many suggestive predictive factors of survival.

Clinical significance of a large difference (≥ 2 points) between biopsy and post-prostatectomy pathological Gleason scores in patients with prostate cancer.

We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure.

The histone deacetylase inhibitor trichostatin A synergistically resensitizes a cisplatin resistant human bladder cancer cell line.

PURPOSE: Cisplatin is the mainstay of treatment for advanced bladder cancer. However, intrinsic or acquired resistance to cisplatin is common, which severely limits its therapeutic potential. We determined the synergistic antitumor effect of cisplatin and the histone deacetylase inhibitor trichostatin A in cisplatin resistant human bladder cancer cells. MATERIALS AND METHODS: The cisplatin resistant human bladder cancer cell line T24R2 was exposed to cisplatin and/or trichostatin A. Tumor cell proliferation was examined by cell counting kit assay. Synergism between 2 drugs was examined by the combination index. Changes in cell cycle and apoptosis were determined by flow cytometry. We analyzed the expression of caspase-3, 8 and 9, poly(adenosine diphosphate-ribose) polymerase, p21WAF1/CIP1, cyclin A, B1 and D1, Cdc2c, p-Cdc2c, Cdc25c, p-Cdc25c, cytochrome c, p-Akt, t-Akt, Bcl-2, Bax, Bad, vascular endothelial growth factor and fetal liver kinase-1 by Western blot and colorimetric assay. RESULTS: Based on the combination index and isobole analysis of the Cell Counting Kit-8 assay we observed a strong synergistic antitumor effect between cisplatin and trichostatin A, allowing a 3.5 and 4.9-fold dose reduction in cisplatin and trichostatin A, respectively, while achieving an estimated 90% kill of T24R2 cells. The underlying mechanism could be synergistic cell cycle arrest, induction of caspase mediated apoptosis or up-regulated expression of pro-apoptotic Bad and Bax. CONCLUSIONS: Results indicate that trichostatin A may synergistically enhance the antitumor effect of cisplatin and resensitize cisplatin resistant bladder cancer cells. These findings suggest the potential use of histone deacetylase inhibitor as a combination agent to enhance the antitumor effect of cisplatin in patients with advanced bladder cancer.

Nomogram to predict insignificant prostate cancer at radical prostatectomy in Korean men: a multi-center study.

PURPOSE: Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC. MATERIALS AND METHODS: The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort. RESULTS: Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827. CONCLUSION: Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.