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1.
Ann Surg Oncol ; 30(12): 7903-7909, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37689608

ABSTRACT

BACKGROUND: This study aimed to investigate the role of radical prostatectomy (RP) among clinical nodal metastasis prostate cancer and whether histological confirmation of lymph node metastasis through surgery can help with treatment. PATIENTS AND METHODS: After excluding patients with distant metastatic prostate cancer or neoadjuvant androgen deprivation therapy, 42 patients with clinical nodal metastasis who underwent RP at our institution were included in the study. We classified them as having or not having pathological lymph node metastasis. Clinicopathologic data were analyzed in this retrospective chart review. Kaplan-Meier analysis was used to calculate the estimated castration-resistant prostate cancer (CRPC)-free survival, biochemical recurrence (BCR)-free survival, and cancer-specific survival (CSS). RESULTS: There is no significant difference in age, presence of diabetes mellitus, hypertension, BCR time, CRPC time, overall survival, salvage RT rate, and initial prostate-specific antigen level between the two groups. However, there is a significant difference in the pathology N1 group in terms of pathological T stage, pathologic Gleason score, BCR rate, CRPC rate, and CSS. A multivariate Cox proportional hazard regression analysis was used to identify predictors of CRPC-free survival. Patients with pathological lymph node metastasis had a shorter CRPC-free survival [hazard ratio (HR) 4.87; 95% confidence interval (CI) 1.25-19.00, p = 0.02]. CONCLUSION: Radical prostatectomy can confirm lymph node metastasis. Although pathologic diagnosis has no effect on time to BCR and CPRC, because it affects BCR rate, CRPC rate, and CSS, an accurate pathological diagnosis obtained through surgery is beneficial in the treatment of clinical lymph node metastasis prostate cancer.

2.
Ann Surg Oncol ; 29(4): 2473-2479, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34625877

ABSTRACT

BACKGROUND: We aimed to describe the effect of preoperative sarcopenia on oncologic outcomes of organ-confined renal cell carcinoma (RCC) after radical nephrectomy. PATIENTS AND METHODS: A total of 632 patients with pT1-2 RCC who underwent radical nephrectomy between 2004 and 2014 were retrospectively analyzed. From preoperative computerized tomography (CT) scans, skeletal muscle index (SMI) was measured and gender-specific cutoff values at third lumbar vertebra of 52.4 cm2/m2 for men and 38.5 cm2/m2 for women were used to define sarcopenia. Survivals were compared and associations with sarcopenia were analyzed using Kaplan-Meier log rank tests and Cox proportional hazard regression models. Median follow-up was 83 months. RESULTS: Of 632 patients, 268 (42.4%) were classified as sarcopenic. The sarcopenic group was more advanced in age (57 versus 53 years) and more predominantly male (71.3% versus 59.9%). Sarcopenic patients had lower body mass index (BMI, 23.0 versus 25.9 kg/m2), but there was no difference in tumor size, stage, or nuclear grade. Sarcopenia was associated with poorer overall survival (OS) and cancer-specific survival (CSS; OS 94.0% versus 82.1%; p < 0.001 and CSS 97.5% versus 91.8%; p < 0.001). On multivariate analysis, sarcopenia was an independent risk factor for all-cause mortality [hazard ratio (HR) 2.58; 95% CI 1.02-6.54] and cancer-specific mortality (HR 3.07; 95% CI 1.38-6.83). CONCLUSIONS: Sarcopenia at diagnosis was an independent risk factor for all-cause and cancer-specific mortality after radical nephrectomy for pT1-2 RCC. These findings underscore the importance of assessing presence of sarcopenia for risk stratification even among surgical candidates.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Sarcopenia , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/surgery , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Muscle, Skeletal/pathology , Nephrectomy/methods , Prognosis , Retrospective Studies , Sarcopenia/complications , Sarcopenia/surgery
3.
BMC Urol ; 22(1): 44, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35337318

ABSTRACT

BACKGROUND: Solo-surgery can be defined as a practice of a surgeon operating alone using a camera holder, without other surgical members except for a scrub nurse. This study was designed to evaluate the feasibility and safety of solo-surgeon pure laparoscopic donor nephrectomy. METHODS: The study protocol was approved by the Institutional Review Board of Asan Medical Center, Seoul, Korea. The brief study protocol was registered on the Clinical Research Information Service site of the Korea Centers for Disease Control and Prevention. Candidates fulfilling all inclusion and exclusion criteria were enrolled in the clinical trial and underwent solo-surgeon pure laparoscopic donor nephrectomy. The feasibility was assessed by the proportion of subjects who could undergo solo-surgeon pure laparoscopic donor nephrectomy without difficulty. The perioperative complications were identified to assess the safety of solo-surgeon pure laparoscopic donor nephrectomy. RESULTS: Of the 47 potential candidates from November 2018 to August 2019, 40 were enrolled in the clinical trial and seven excluded due to declining participation. The feasibility of solo-surgeon pure laparoscopic donor nephrectomy was 100%, without an occasion of any difficulty requiring conversion to the human assisted pure laparoscopic donor nephrectomy. Fourteen intraoperative complications occurred in 10 patients. The most common intraoperative complication was spleen injury. Two of three cases classified as the Satava classification grade II were due to the incomplete stapling of endoscopic stapler. Seventy-eight postoperative complications occurred in 34 patients. The most common postoperative complication was nausea/vomiting and followed by aspartate aminotransferase/alanine aminotransferase elevation. Most postoperative complication was independent of the solo-surgery itself. CONCLUSIONS: Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder is technically feasible. In terms of safety, it is necessary to adjust the scope of surgery performed alone. Trial Registration CRIS, KCT0003458. Registered 30/01/2019, Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/15868 .


Subject(s)
Kidney Transplantation , Laparoscopy , Surgeons , Humans , Kidney , Kidney Transplantation/methods , Laparoscopy/methods , Nephrectomy/methods
4.
Cytotherapy ; 23(10): 931-938, 2021 10.
Article in English | MEDLINE | ID: mdl-34326007

ABSTRACT

BACKGROUND AIMS: The efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM). Pre-clinical studies using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED have shown promising results. The authors conducted a phase 1 clinical trial with autologous BMSCs in patients with ED due to radical prostatectomy or DM. METHODS: Ten patients (five with post-prostatectomy ED and five with DM-associated ED) who could not perform sexual activity despite taking the maximum dose of a PDE5I were enrolled. The brief clinical trial protocol was registered with the US National Institutes of Health on ClinicalTrials.gov (NCT02344849). The primary outcome was the safety of stem cell therapy, and the secondary outcome was the improvement of erectile function. RESULTS: Of the 13 patients screened, 10 were registered in the clinical trial and received autologous BMSCs and nine completed the clinical trial. One patient with post-prostatectomy ED experienced two treatment-emergent adverse events (TEAEs) (pyrexia and back pain), and two patients with DM-associated ED experienced a total of five TEAEs (one case each of viral upper respiratory tract infection, prostatitis and pruritus and two cases of hyperglycemia). Of these patients, one with DM-associated ED experienced two serious TEAEs (two instances of hyperglycemia). All TEAEs were considered not to be related to autologous BMSC therapy. In addition, no clinical significance was identified related to other safety measures, such as laboratory tests and vital signs. The mean International Index of Erectile Function score increased significantly at 1 month versus baseline (24.9 versus 18.1, P = 0.0222). CONCLUSIONS: This phase 1 clinical trial confirmed the safety and potential efficacy of autologous BMSC therapy in patients with ED. The authors' results need to be confirmed by a phase 2 clinical trial.


Subject(s)
Erectile Dysfunction , Mesenchymal Stem Cells , Bone Marrow , Erectile Dysfunction/etiology , Erectile Dysfunction/therapy , Humans , Male , Penile Erection , Prostatectomy/adverse effects , Treatment Outcome
5.
BMC Urol ; 21(1): 92, 2021 Jun 11.
Article in English | MEDLINE | ID: mdl-34116662

ABSTRACT

PURPOSE: We report our preliminary experience of using a hybrid ileal pouch, assessing oncologic outcomes, complications, voiding, and renal function. METHODS: The study included 25 patients with bladder cancer treated with radical cystectomy with a hybrid ileal pouch with concomitant anti-refluxing and refluxing anastomosis, performed by a single surgeon. The patients were divided into two groups (first and last cases) according to the surgery date. Postoperative complications, separate renal function by renal scan, voiding function by uroflowmetry with residual urine, and oncologic outcomes were assessed. RESULTS: The surgery duration was shorter in the last cases than the first cases. The voiding volume increased with time. There were 23 cases of grade 3 complication in 12 patients and one case of grade 4 complication (sepsis). In the first cases, ureterovesical stenosis occurred in five cases, whereas in the last cases, there were no cases of stenosis. In separate renal function, there was no difference between the left and right side or between the first and last cases. CONCLUSIONS: The hybrid ileal pouch showed acceptable oncologic and functional outcomes and complications; therefore, it can be used according to the appropriate surgical situation with a relatively short bowel segment during neobladder construction.


Subject(s)
Colonic Pouches , Cystectomy , Ileum/surgery , Ureter/surgery , Urinary Bladder Neoplasms/surgery , Aged , Anastomosis, Surgical/methods , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
6.
J Urol ; 202(3): 525-532, 2019 09.
Article in English | MEDLINE | ID: mdl-30916628

ABSTRACT

PURPOSE: Although muscle mass has been associated with survival in patients with various types of solid tumors, the relationship between muscle mass and survival in patients with prostate cancer remains unclear. We retrospectively investigated the association of muscle mass with survival after radical prostatectomy in patients with prostate cancer. MATERIALS AND METHODS: We reviewed the records of 2,042 patients who underwent radical prostatectomy of prostate cancer between 1998 and 2013. Muscle mass was evaluated by measuring the psoas muscle index on preoperative computerized tomography images. RESULTS: In the lowest, second, third and highest psoas muscle index quartiles the 10-year distant metastasis-free survival rate was 72.5%, 83.8%, 92.3% and 93.7% (p <0.001), the 10-year cancer specific survival rate was 85.7%, 92.1%, 96.8% and 97.6%, and the 10-year overall survival rate was 74.5%, 79.6%, 89.8% and 90.6%, respectively (each p <0.001). The psoas muscle index positively correlated with the body mass index, serum concentrations of IGFBP-3 and bioavailable testosterone, and inversely correlated with patient age, the serum SHBG concentration and the neutrophil-to-lymphocyte ratio. On multivariable analysis the psoas muscle index was independently associated with increased risks of biochemical recurrence, distant metastasis, and cancer specific and overall death. CONCLUSIONS: Low muscle mass may be associated with increased risks of recurrence and mortality in patients who undergo radical prostatectomy of prostate cancer regardless of the body mass index. Large-scale prospective studies are warranted.


Subject(s)
Neoplasm Recurrence, Local/epidemiology , Prostatectomy , Prostatic Neoplasms/mortality , Psoas Muscles/anatomy & histology , Age Factors , Aged , Body Mass Index , Disease-Free Survival , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Organ Size , Preoperative Period , Prostatic Neoplasms/surgery , Psoas Muscles/diagnostic imaging , Retrospective Studies , Risk Factors , Survival Rate , Tomography, X-Ray Computed
7.
J Surg Oncol ; 119(7): 1016-1023, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30820951

ABSTRACT

OBJECTIVES: To compare the functional outcomes of open, laparoscopic, and robot-assisted partial nephrectomy (OPN, LPN, and RAPN, respectively) using diethylene triamine penta-acetic acid (DTPA). METHODS: We identified 610 patients who underwent partial nephrectomy for renal cell carcinoma (285 open partial nephrectomy [OPN], 96 laparoscopic partial nephrectomy [LPN], and 229 robot-assisted partial nephrectomy [RAPN]) with preoperative and postoperative DTPA within 1 year. We excluded multiple renal masses and history of immunotherapy or chemotherapy. Predictive factors for glomerular filtration rate (GFR) reduction were assessed using multivariate linear regression. RESULTS: Postoperative complications and disease-free survival were similar in the three groups. Within 1 postoperative year, OPN showed a significantly lower mean ipsilateral GFR than LPN and RAPN (28.9 versus 32.4 versus 32.7 mL/min/1.73 m 2 , respectively; P < 0.001). RAPN was associated with a significantly higher total GFR than OPN within 1 year (76.6 versus 71.2 mL/min/1.73 m 2 , respectively; P = 0.001). On multivariate analysis within 1 year, operation type (OPN versus RAPN: ß = 2.82; 95% confidence interval, 1.17-4.48; P = 0.001) was significantly associated with GFR reduction. CONCLUSION: There was no difference in postoperative complications and disease-free survival among operation types. RAPN could help to promote earlier recovery of ipsilateral GFR than OPN.


Subject(s)
Carcinoma, Renal Cell/physiopathology , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/physiopathology , Kidney Neoplasms/surgery , Nephrectomy/methods , Carcinoma, Renal Cell/diagnostic imaging , Disease-Free Survival , Female , Glomerular Filtration Rate , Humans , Kidney Neoplasms/diagnostic imaging , Laparoscopy/methods , Male , Middle Aged , Pentetic Acid , Retrospective Studies , Robotic Surgical Procedures/methods , Young Adult
8.
Int J Clin Oncol ; 24(10): 1238-1246, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31087170

ABSTRACT

BACKGROUND: To investigate the prognostic and therapeutic implications of time to biochemical relapse (BCR) in patients with prostate cancer after radical prostatectomy. METHODS: The records of 3210 consecutive men with prostate cancer who underwent radical prostatectomy between January 1998 and June 2013 were retrospectively reviewed. Patients with BCR were divided into three groups based on quartiles of time to BCR, namely an early group (first quartile), an intermediate group (second and third quartiles) and late group (fourth quartile). RESULTS: 817 (25.5%) patients experienced BCR at a median of 24.9 months after surgery. The 8-year rate of distant metastasis-free survival (64.3% vs. 41.3%, p = 0.002) and cancer-specific survival (86.6% vs. 63.4%, p < 0.001) was higher in the salvage radiotherapy (SRT) group than the androgen deprivation therapy (ADT) group in patients with early BCR, whereas those rates (91.3% vs. 87.9%, p = 0.607 and 100.0% vs. 93.1%, p = 0.144, respectively) were similar in patients with late BCR. In the intermediate BCR group, the impact of SRT over ADT on 8-year cancer-specific survival was modest (91.9% vs. 82.3%, p = 0.057) and was limited to patients with pT2 or pT3a disease. CONCLUSIONS: SRT may decrease the risk of distant metastasis and cancer-specific mortality in patients with early BCR. However, a survival benefit for those with late BCR was not apparent. For patients with intermediate BCR, SRT was associated with a cancer-specific survival benefit in patients with pT2 or pT3a disease. Novel genomic tests and imaging modalities may support clinical decision-making in these patients.


Subject(s)
Androgen Antagonists/therapeutic use , Neoplasm Recurrence, Local/radiotherapy , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Radiotherapy/methods , Salvage Therapy/methods , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/etiology , Prognosis , Prostatic Neoplasms/pathology , Retrospective Studies , Survival Rate , Time Factors
9.
Int J Urol ; 26(1): 62-68, 2019 01.
Article in English | MEDLINE | ID: mdl-30238513

ABSTRACT

OBJECTIVES: To investigate the progression to castration-resistant prostate cancer after primary androgen deprivation therapy, and to build a simple risk prediction model for primary androgen deprivation therapy patients based on the Japan Cancer of the Prostate Risk Assessment criteria. METHODS: A total of 602 patients who received primary androgen deprivation therapy were entered into the Korean Cancer Study of the Prostate database. The effect of prognostic factors was determined by multivariate analysis. For each patient, the weight of all factors was totaled to give Korean Cancer Study-prostate scores; patients were divided into three risk groups according to their score. The probability of castration-resistant prostate cancer, cancer-specific survival and overall survival was estimated by Kaplan-Meier analysis. RESULTS: On multivariate analysis for castration-resistant prostate cancer, the significant variables were initial prostate-specific antigen (>40 ng/mL; 1 point), biopsy Gleason score (≥9; 1 point), clinical N1 (1 point), and non-regional lymph node (1 point), bone (1 point) and visceral (1 point) metastasis. The Korean Cancer Study-prostate scoring model was calculated on a scale of 0-6 (0: low, 1-2: intermediate, ≥3: high risk). The risk groups stratified castration-resistant prostate cancer (P < 0.0001), cancer-specific survival (P < 0.0001) and overall survival (P < 0.0001) by Kaplan-Meier curve. The Korean Cancer Study-prostate model predicted castration-resistant prostate cancer with a c-index of 0.7242, cancer-specific survival with a c-index of 0.7036 and overall survival with a c-index of 0.5890. The 5-year estimated castration-resistant prostate cancer/cancer-specific death rates were 10.3%/6.3% in the low-risk group, 48.4%/22.2% in the intermediate-risk group and 81.7%/53.1% in the high-risk group. CONCLUSIONS: The Korean Cancer Study-prostate risk classification, a modified Japan Cancer of the Prostate Risk Assessment model, is a simple scoring model for predicting oncological outcomes after primary androgen deprivation therapy.


Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/mortality , Aged , Disease Progression , Humans , Japan , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Prognosis , Prostate/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Risk Assessment , Survival Analysis
10.
BMC Cancer ; 18(1): 271, 2018 03 09.
Article in English | MEDLINE | ID: mdl-29523103

ABSTRACT

BACKGROUND: Here we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer. METHODS: Patients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression. RESULTS: Of the 227 patients who underwent post-prostatectomy RT, 95 (41.9%) received concurrent ADT for a median of 17.0 months. Despite more aggressive disease characteristics in the concurrent ADT group than in the RT-only group, the former had a better 5-year BCR-free survival rate than the latter (66.1 vs. 53.9%; p = 0.016), whereas the radiographic progression rate was not significantly different between two groups. On the other hand, salvage ADT after post-RT BCR significantly delayed radiographic progression (5-year radiographic progression-free survival; 75.2 vs. 44.5%; p = 0.002). CONCLUSIONS: Concurrent ADT improved BCR-free survival, and salvage ADT after post-RT BCR improved radiographic progression-free survival. To maximize the oncological benefit, ADT of sufficient duration should be implemented.


Subject(s)
Androgen Antagonists/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Prostatectomy , Prostatic Neoplasms/drug therapy , Salvage Therapy , Aged , Case-Control Studies , Combined Modality Therapy , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Prognosis , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Radiotherapy Dosage , Retrospective Studies , Survival Rate
11.
Urol Int ; 101(3): 269-276, 2018.
Article in English | MEDLINE | ID: mdl-30179882

ABSTRACT

INTRODUCTION: Primary carcinoma in situ (P-CIS) of the bladder is rare and its clinical behavior and predictive features have not been well described. The purpose of this study was to evaluate the effects of various factors including angiotensin-2 converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) on recurrence-free survival (RFS)-related prognosis in patients with P-CIS. MATERIALS AND METHODS: In our medical center, 5,945 patients were diagnosed with bladder cancer from January 1999 to January 2014. Of these, 64 patients were diagnosed with CIS and were treated with at least 6 cycles of Bacillus Calmette-Guérin (BCG). We accessed variables including patient age, sex, initial presenting symptoms, smoking history, P-CIS descriptions, urine cytology, and medication history related to hypertension. RESULTS AND CONCLUSIONS: We evaluated the use of anti-hypertensive medications (ACEIs/ARBs, p = 0.028), the symptom of non-gross hematuria (p = 0.028), and older age (p = 0.015) as significant factors related to RFS. Older age was also a significant factor for influencing the RFS rate. We found that the use of anti-hypertensive medications (ACEIs/ARBs) improves RFS in patients with P-CIS after BCG therapy. The prognosis was poor when there was no gross hematuria and if patients were at older ages at the time of diagnosis of P-CIS.


Subject(s)
BCG Vaccine/therapeutic use , Carcinoma in Situ/diagnosis , Carcinoma in Situ/drug therapy , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/drug therapy , Aged , Antihypertensive Agents/therapeutic use , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome , Urinary Bladder/pathology
12.
Am J Physiol Renal Physiol ; 313(2): F192-F198, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28404588

ABSTRACT

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1: <30 ml·min-1·1.73 m-2, group 2: 30-45 ml·min-1·1.73 m-2, and group 3: ≥45 ml·min-1·1.73 m-2). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1, 2, and 3, respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [ß: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (ß: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function.


Subject(s)
Glomerular Filtration Rate , Kidney Neoplasms/surgery , Kidney/physiopathology , Nephrectomy/adverse effects , Adaptation, Physiological , Age Factors , Contrast Media/administration & dosage , Female , Humans , Kidney/diagnostic imaging , Kidney Neoplasms/pathology , Kidney Neoplasms/physiopathology , Linear Models , Male , Middle Aged , Multivariate Analysis , Nephrectomy/methods , Predictive Value of Tests , Radioisotope Renography/methods , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
13.
Prostate ; 77(10): 1128-1136, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28556958

ABSTRACT

BACKGROUND: Androgen and androgen receptor (AR) play essential roles in the development and maintenance of prostate cancer. The recently identified AR splice variants (AR-Vs) have been considered as a plausible mechanism for the primary resistance against androgen deprivation therapy (ADT) in castration-resistant prostate cancer (CRPC). Sodium meta-arsenite (NaAsO2 ; KML001; Kominox), a trivalent arsenical, is an orally bioavailable and water soluble, which is currently in phase I/II clinical trials for the treatment of prostate cancer. It has a potent anti-cancer effect on prostate cancer cells and xenografts. The aim of this study was to examine the effect of NaAsO2 on AR signaling in LNCaP and 22Rv1 CRPC cells. METHODS: We used hormone-sensitive LNCaP cells, hormone-insensitive 22Rv1 cells, and CRPC patient-derived primary cells. We analyzed anti-cancer effect of NaAsO2 using real-time quantitative reverse transcription-PCR, Western blotting, immunofluorescence staining and CellTiter Glo® luminescent assay. Statistical evaluation of the results was performed by one-way ANOVA. RESULTS: NaAsO2 significantly reduced the translocation of AR and AR-Vs to the nucleus as well as their level in LNCaP and 22Rv1 cells. Besides, the level of the prostate-specific antigen (PSA), downstream target gene of AR, was also decreased. This compound was also an effective modulator of AKT-dependent NF-κB activation which regulates AR. NaAsO2 significantly inhibited phosphorylation of AKT and expression and nuclear translocation of NF-κB. We then investigated the effect of NaAsO2 on AR stabilization. NaAsO2 promoted HSP90 acetylation by down-regulating HDAC6, which reduces the stability of AR in prostate cancer cells. CONCLUSIONS: Here, we show that NaAsO2 disrupts AR signaling at multiple levels by affecting AR expression, stability, and degradation in primary tumor cell cultures from prostate cancer patients as well as CRPC cell lines. These results suggest that NaAsO2 could be a novel therapeutics for prostate cancer.


Subject(s)
Arsenites/pharmacology , Prostate , Prostatic Neoplasms, Castration-Resistant , Receptors, Androgen/metabolism , Signal Transduction/drug effects , Sodium Compounds/pharmacology , Cell Line, Tumor , Down-Regulation , Enzyme Inhibitors/pharmacology , HSP90 Heat-Shock Proteins/metabolism , Humans , Male , NF-kappa B/metabolism , Prostate/drug effects , Prostate/metabolism , Prostate/pathology , Prostate-Specific Antigen/analysis , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Proto-Oncogene Proteins c-akt/metabolism , Treatment Outcome
14.
J Urol ; 198(1): 71-78, 2017 07.
Article in English | MEDLINE | ID: mdl-28161349

ABSTRACT

PURPOSE: We investigated the influence of obesity on unfavorable disease in men with low risk prostate cancer eligible for active surveillance and verified the underlying relationship with tumor location. MATERIALS AND METHODS: We analyzed the records of 890 patients with biopsy Gleason score 6 who underwent radical prostatectomy for prostate cancer via multicore (12 or more) biopsy at our institution. Unfavorable disease was defined as primary Gleason pattern 4 or greater, or pathological stage T3 or greater. Multivariate logistic regression analysis was performed to identify factors associated with unfavorable disease. The association of unfavorable disease with anatomical location of the index tumor was assessed. RESULTS: Overall 216 (24.3%), 544 (61.1%) and 130 men (14.6%) had a body mass index of less than 23 (normal), 23 to 27.5 (overweight) and 27.5 kg/m2 or greater (obese), respectively, according to established cutoff points for Asian men. Multivariate analysis showed that age, prostate volume and body mass index were independent factors for predicting unfavorable disease regardless of the various active surveillance criteria used. For Johns Hopkins Hospital criteria the risk of unfavorable disease was higher in obese patients than in normal weight patients (OR 3.30, p = 0.022). Unfavorable disease was more frequent in cases of transition zone cancer than nontransition zone cancer across all criteria for active surveillance (all p <0.01). Among men fulfilling Johns Hopkins Hospital criteria the proportion of transition zone cancer was 4.2% for normal weight, 11.6% for overweight and 16.7% for obesity, respectively (p = 0.022). CONCLUSIONS: Obese men with low risk prostate cancer who are eligible for active surveillance are at higher risk for unfavorable pathological features. Obese men more frequently had transition zone cancer, which was associated with unfavorable pathology findings in those with very low risk prostate cancer.


Subject(s)
Obesity/complications , Prostatic Neoplasms/complications , Prostatic Neoplasms/pathology , Aged , Humans , Male , Middle Aged , Prostatic Neoplasms/therapy , Retrospective Studies , Risk Assessment , Risk Factors , Watchful Waiting
15.
Cell Tissue Res ; 368(3): 603-613, 2017 06.
Article in English | MEDLINE | ID: mdl-28283911

ABSTRACT

Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P < 0.001). TUNEL labeling showed significantly decreased apoptosis in both the renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P < 0.001). Thus, renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.


Subject(s)
Acute Kidney Injury/therapy , Adipose Tissue/cytology , Stromal Cells/transplantation , Acute Kidney Injury/etiology , Animals , Antioxidants , Apoptosis , Cell Fractionation , Cell Proliferation , Cell- and Tissue-Based Therapy , Disease Models, Animal , Flow Cytometry , Kidney/pathology , Kidney/physiopathology , Kidney Function Tests , Male , Rats , Rats, Sprague-Dawley , Reperfusion Injury/complications
16.
World J Urol ; 35(4): 665-673, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27502934

ABSTRACT

PURPOSE: This study aimed to investigate the effects of lymph node dissection (LND) on upper tract urothelial carcinoma (UTUC) without suspicious lymph node (LN) metastasis on preoperative imaging studies. METHODS: From 1998 to 2012, 418 UTUC patients without suspicious LN metastasis on preoperative imaging studies were included. Patients were divided into two groups according to the performance of LND. The effects of LND on oncological outcomes were assessed after adjusting other variables. The mean follow-up duration was 69 months. RESULTS: Among the 132 patients who underwent LND, LN metastasis was pathologically identified in 16 patients (12.1 %). The median number of resected LNs for patients who underwent LND was 7. On multivariate analysis, the number of resected LNs and pathologic T stage was significant predictors of LN metastasis. The 5-year recurrence-free survival was 76.4 % for patients without LND and 65.4 % for patients with LND (p = 0.126). In addition, there was no difference in 5-year overall survival between the 2 groups (without LND; 71.7 % vs. with LND; 72.1 %, p = 0.756). Multivariate analysis showed that pathologic T stage, tumor grade, and lymphovascular invasion were risk factors for recurrence. Age at surgery, tumor size, pathologic T stage, tumor grade, and lymphovascular invasion were significantly associated with overall survival. However, performance of LND was not associated with recurrence and survival. CONCLUSIONS: LND could be selectively performed in patients with clinically LN-negative UTUC based on patient/tumor characteristics and operative findings although sufficient LNs should be removed if LND is to be performed.


Subject(s)
Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/surgery , Lymph Node Excision/methods , Lymph Nodes/pathology , Nephrectomy/methods , Ureter/surgery , Ureteral Neoplasms/surgery , Aged , Carcinoma, Transitional Cell/diagnostic imaging , Carcinoma, Transitional Cell/pathology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Preoperative Care , Retrospective Studies , Tumor Burden , Ureteral Neoplasms/diagnostic imaging , Ureteral Neoplasms/pathology , Urologic Surgical Procedures/methods
17.
Urol Int ; 99(4): 406-413, 2017.
Article in English | MEDLINE | ID: mdl-29020683

ABSTRACT

INTRODUCTION: To assess the value of androgen deprivation therapy (ADT) on salvage radiotherapy (RT) in post-prostatectomy recurrent prostate cancer patients, we compared the oncologic outcomes between patients receiving RT + ADT and those receiving RT alone. MATERIALS AND METHODS: We reviewed the records of patients diagnosed with prostate cancer between 1995 and 2011, including 93 patients who underwent salvage RT and 69 patients who underwent salvage RT + ADT. The ADT-free duration after withdrawal was calculated to verify testosterone recovery. RESULTS: Presalvage prostate serum antigen (PSA) was the only significantly different characteristic between the 2 groups (p < 0.001). The ADT-free duration was greater than 6 months in >80% of patients. Presalvage PSA ≥0.6 ng/mL, pathologic stage ≥T3b, and RT + ADT were significantly associated with biochemical progression after salvage treatment. RT + ADT reduced biochemical progression in patients with seminal vesicle invasion or presalvage PSA ≥0.6 ng/mL (p = 0.001) compared to RT alone; biochemical progression-free probability was unchanged in seminal vesicle noninvasive prostate cancer patients with presalvage PSA <0.6 ng/mL (p = 0.541). CONCLUSIONS: RT + ADT reduced the risk of biochemical progression after salvage treatment in patients with seminal vesicle invasion or presalvage PSA ≥0.6 ng/mL, but had no effect in patients with seminal vesicle noninvasive disease and presalvage PSA <0.6 ng/mL.


Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Chemoradiotherapy , Neoplasm Recurrence, Local/therapy , Prostatectomy , Prostatic Neoplasms/therapy , Salvage Therapy/methods , Aged , Androgen Antagonists/adverse effects , Antineoplastic Agents, Hormonal/adverse effects , Chemoradiotherapy/adverse effects , Disease Progression , Disease-Free Survival , Humans , Kallikreins/blood , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatectomy/adverse effects , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Retrospective Studies , Risk Factors , Salvage Therapy/adverse effects , Time Factors , Treatment Outcome
18.
J Korean Med Sci ; 32(3): 495-501, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28145654

ABSTRACT

This study aimed to determine patients with T1b renal cell carcinoma (RCC) who could benefit from partial nephrectomy (PN) and method to identify them preoperatively using nephrometry score (NS). From a total of 483 radical nephrectomy (RN)-treated patients and 40 PN-treated patients who received treatment for T1b RCC between 1995 and 2010, 120 patients identified through 1:2 propensity-score matching were included for analysis. Probability of chronic kidney disease (CKD) until postoperative 5-years was calculated and regressed with respect to the surgical method and NS. Median follow-up was 106 months. CKD-probability at 5-years was 40.7% and 13.5% after radical and PN, respectively (P = 0.005). While PN was associated with lower risk of CKD regardless of age, comorbidity, preoperative estimated renal function, the effect was observed only among patients with NS ≤ 8 (P < 0.001) but not in patients with NS ≥ 9 (P = 0.746). Percent operated-kidney volume reduction and ischemia time were similar between the patients with NS ≥ 9 and ≤ 8. In the stratified Cox regression accounting for the interaction observed between the surgical method and the NS, PN reduced CKD-risk only in patients with NS ≤ 8 (hazard ratio [HR], 0.054; P = 0.005) but not in ≥ 9 (HR, 0.996; P = 0.994). In T1b RCC with NS ≥ 9, the risk of postoperative CKD was not reduced following PN compared to RN. Considering the potential complications of PN, minimally invasive RN could be considered with priority in this subgroup of patients.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Kidney/physiopathology , Nephrectomy/methods , Adult , Aged , Area Under Curve , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/surgery , Creatinine/blood , Disease-Free Survival , Female , Glomerular Filtration Rate , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/surgery , Male , Middle Aged , Nephrectomy/adverse effects , Postoperative Period , Propensity Score , Proportional Hazards Models , ROC Curve , Renal Insufficiency, Chronic/etiology , Retrospective Studies
19.
Ann Surg Oncol ; 23(2): 686-93, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26442922

ABSTRACT

PURPOSE: The aim of this study was to investigate the prevalence of acute kidney injury (AKI) after radical cystectomy, and evaluate its impact on chronic kidney disease (CKD) and mortality. METHODS: The medical records of 866 patients who underwent radical cystectomy for bladder cancer were reviewed. AKI was assessed within 7 days after surgery according to the Acute Kidney Injury Network criteria. The prevalence of AKI after surgery was examined, and the significance of AKI for CKD and mortality was analyzed. RESULTS: Of 866 patients, 269 (31.1 %) developed AKI in the first week after surgery. Of these, 231 (85.9 %) were at stage 1, 32 (11.9 %) at stage 2, and 6 (2.2 %) at stage 3. Of 722 patients with a preoperative Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m(2), CKD developed in 23.0 % (118/513) of patients in the non-AKI group and 32.5 % (68/209) of patients in the AKI group. Independent factors predicting new-onset CKD were a preoperative eGFR (p < 0.001), age (p = 0.011), urinary tract complication (p < 0.001) and AKI (p = 0.015). In all, 297 patients died (191 in the non-AKI group and 106 in the AKI group). AKI also correlated significantly with overall survival (p = 0.001). CONCLUSIONS: AKI is not only commonly encountered after radical cystectomy but is also associated with higher CKD rates and mortality. There is a critical need for strategies to increase the identification of patients at risk of postoperative AKI, and to improve the management of patients, with an aim toward preventing AKI and improving the treatment of AKI once it occurs.


Subject(s)
Acute Kidney Injury/etiology , Carcinoma in Situ/surgery , Cystectomy/adverse effects , Cystectomy/mortality , Postoperative Complications , Renal Insufficiency, Chronic/mortality , Urinary Bladder Neoplasms/surgery , Acute Kidney Injury/epidemiology , Carcinoma in Situ/pathology , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Retrospective Studies , Risk Factors , Survival Rate , Urinary Bladder Neoplasms/pathology
20.
Cytotherapy ; 18(7): 870-80, 2016 07.
Article in English | MEDLINE | ID: mdl-27260208

ABSTRACT

BACKGROUND AIMS: Although clinical studies using stem cells to treat erectile dysfunction have been performed or are ongoing, there is little consensus on the optimal protocol. We aimed to develop a protocol optimizing human bone marrow-derived mesenchymal stromal cell (hBMSC) therapy in a rat model of cavernous nerve injury. METHODS: We performed, in order, a dose-finding study, a toxicokinetic study of hBMSCs, and a study to determine the timing and number of cell injections. RESULTS: From the dose-finding study, 1 × 10(6) cells were selected as the dose per hBMSC injection. From the toxicokinetic study, 14 days was selected as the interval between repeat treatments. In the final study, the ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (23.4% vs. 55.1%, P <0.001). An immediate single injection of hBMSCs significantly improved erectile function compared with the control group (39.8%, P = 0.035), whereas a delayed single injection showed improvement with a marginal trend (38.1%, P = 0.079). All histomorphometric changes were significantly more improved in the immediate or delayed single injection groups than in the control group. Repeat treatments did not provide any benefit for the recovery of erectile function and histomorphometric changes. CONCLUSIONS: Intracavernous injection of 1 × 10(6) hBMSCs results in a recovery of penile erection and histomorphometric changes in a rat model of cavernous nerve injury, even when treatment was delayed until 4 weeks after cavernous nerve injury.


Subject(s)
Bone Marrow Cells/cytology , Drug Approval , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Penis/injuries , Penis/innervation , Animals , Cell Survival , Disease Models, Animal , Humans , Immunophenotyping , Injections , Male , Rats, Sprague-Dawley , Time Factors , Tissue Distribution
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