Evaluation of the Surgical Margin Threshold for Avoiding Recurrence after Partial Nephrectomy in Patients with Renal Cell Carcinoma

Purpose@#An adequate minimal surgical margin for partial nephrectomy (PN) has not yet been conclusively established. Therefore, we aimed to compare PN recurrence rates according to surgical margin status and to establish an adequate minimal surgical margin. @*Materials and Methods@#We retrospectively studied patients with clinically localized renal cell carcinoma who underwent PN between 2005 and 2014. Surgical margin width (SMW) was assessed for all surgical tissues and divided into three groups: SMW <1 mm, SMW ≥1 mm, and positive surgical margin (PSM). The data were analyzed using the Kaplan-Meier method with log-rank tests and multivariate Cox regression models. @*Results@#Of 748 patients (median age, 55 years; interquartile range, 46–64 years; 220 female), 704 (94.2%) and 44 (5.8%) patients had negative and PSMs, respectively. Recurrence-free survival was significantly lower in patients with PSMs (p<0.001) and was not significantly different between SMW ≥1 mm and <1 mm groups (p=0.604). PSM was a significant predictor of recurrence (hazard ratio: 8.03, 95% confidence interval: 2.74–23.56, p<0.001), in contrast to SMW <1 mm (p=0.680). @*Conclusion@#A PSM after PN significantly increases the risk of recurrence. We discovered that even a submillimeter safety surgical margin may be enough to prevent recurrence. To maximize normal renal parenchyma preservation and to avoid cancer recurrence in renal parenchymal tumor patients, PN may be a safe treatment, except for those with a PSM in the final pathology.

Subcutaneous Interleukin-2 Monotherapy for Metastatic Renal Cell Carcinoma in Korean Patients

Purpose@#This study was a prospective single-arm clinical trial aimed at assessing the efficacy and toxicity of subcutaneous interleukin (IL)-2 monotherapy in patients with metastatic renal cell carcinoma (RCC). @*Materials and Methods@#We enrolled 26 patients with metastatic RCC in this multicenter controlled trial. The patients received subcutaneous injections of recombinant IL-2 (BMI-rh-IL2, an aldesleukin biosimilar, BMIKOREA Co., Ltd.) in 5-week cycles. In the first week, the patients received a subcutaneous IL-2 loading dose of 18×106 IU once on treatment days 1–5, followed by 2 days of rest. In the following 3 weeks, they received a dose of 18×106 IU via subcutaneous injection once on treatment days 1 and 2. Then, the patients received a dose of 9×106 IU via subcutaneous injection once on treatment days 3, 4, and 5, followed by 2 days of rest. The primary end point was the objective response rate; the secondary end points were progressionfree survival (PFS) and safety. @*Results@#Overall, 22 patients were included in the final per-protocol analysis. The objective response and the disease control rates were 13.64% (3 of 22), and 90.9% (20 of 22), respectively. The mean PFS was 5.55 months (95% confidence interval, 2.71–8.4). The proportion of patients who experienced a treatment-related grade 3 or 4 adverse event was 3.85% (1 of 26). There were no treatment-related deaths. @*Conclusions@#In this study, the subcutaneous IL-2 monotherapy regimen demonstrated efficacy and safety comparable to those reported in previous studies of subcutaneous IL-2 monotherapy and was effective in Korean patients with metastatic RCC.

Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs. @*Materials and Methods@#All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation. @*Results@#FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival. @*Conclusion@#FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

Association Between Prostate Cancer and 25-Hydroxyvitamin D2 Levels: National Health and Nutrition Examination Survey 2007−2008 Results

Purpose@#To report an association between prostate cancer and vitamin D levels among different races in a single population in the United States. @*Materials and Methods@#We investigated whether there was an association between vitamin D level and prostate cancer in different races in the United States. We used data collected from 1,363 men during the National Health and Nutrition Examination Survey 2007–2008. Multivariate logistic regression analysis was used to evaluate the independent associations between vitamin D levels (not only 25-hydroxyvitamin D [25(OH)D], but also 25(OH)D2 and D3) and prostate cancer. Association between vitamin D levels and prostate specific antigen level was also analyzed in non-Hispanic white males without prostate cancer. @*Results@#Older age was significantly associated with prostate cancer in all races (p＜0.05), whereas vitamin D (p=0.024), especially 25(OH)D2 (p=0.027) was significantly higher only in non-Hispanic white males. There was no difference in vitamin D levels between non-Hispanic white males with a prostate specific antigen concentration ＞3 ng/mL and ≤3 ng/mL. @*Conclusions@#This study revealed a positive association between vitamin D, especially 25(OH)D2, and prostate cancer only in non-Hispanic white males. And vitamin D was not associated with prostate specific antigen level causing detection bias. (Korean J Urol Oncol 2020;18:32-39)

Synergistic Antitumor Effects of Combined Treatment with HSP90 Inhibitor and PI3K/mTOR Dual Inhibitor in Cisplatin-Resistant Human Bladder Cancer Cells

Purpose@#The current study aimed to investigate the synergistic antitumor effect of combined treatment with 17-DMAG (HSP90 inhibitor) and NVP-BEZ235 (PI3K/mTOR dual inhibitor) on cisplatin-resistant human bladder cancer cells. @*Materials and Methods@#Human bladder cancer cells exhibiting cisplatin resistance (T24R2) were exposed to escalating doses of 17-DMAG (2.5–20 nM) with or without NVP-BEZ236 (0.5–4 μM) in combination with cisplatin. Antitumor effects were assessed by CCK-8 analysis. Based on the dose-response study, synergistic interactions between the two regimens were evaluated using clonogenic assay and combination index values. Flow cytometry and Western blot were conducted to analyze mechanisms of synergism. @*Results@#Dose- and time-dependent antitumor effects for 17-DMAG were observed in both cisplatin-sensitive (T24) and cisplatin- resistant cells (T24R2). The antitumor effect of NVP-BEZ235, however, was found to be self-limiting. The combination of 17- DMAG and NVP-BEZ235 in a 1:200 fixed ratio showed a significant antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range, and clonogenic assay showed compatible results with synergy tests. Three-dimensional analysis revealed strong synergy between the two drugs with a synergy volume of 201.84 μM/mL2%. The combination therapy resulted in G1-phase cell cycle arrest and caspase-dependent apoptosis confirmed by the Western blot. @*Conclusion@#HSP90 inhibitor monotherapy and in combination with the PI3K/mTOR survival pathway inhibitor NVP-BEZ235 shows a synergistic antitumor effect in cisplatin-resistant bladder cancers, eliciting cell cycle arrest at the G1 phase and induction of caspase-dependent apoptotic pathway.

The Relationships between Survivals and Early Salvage Androgen Deprivation Therapy for Non-Organ Confined Prostate Cancer after Radical Prostatectomy / 전남의대학술지

Androgen deprivation therapy (ADT) is one salvage treatment used when prostate-specific antigen (PSA) recurs after radical prostatectomy (RP), especially in high-risk prostate cancer (PC) patients. However, the optimal timing for salvage ADT (SADT) is still unclear. In this study, we analyzed the efficacy of early SADT for non-organ confined PC. We investigated pathologically confirmed, non-organ confined PC patients who received SADT for PSA recurrence after RP. Patients with distant metastasis, those with lymph node involvement confirmed by lymph node dissection, and those who received neo-adjuvant or adjuvant therapy were excluded. Early SADT was defined as ADT initiated before PSA levels reached 0.5 ng/ml from the nadir PSA level after RP. Univariable and multivariable Cox regression analyses were performed for distant metastasis-free, PC-specific, and overall survival. Data from 345 patients were analyzed. The median follow-up duration was 82 months. The median PSA level was 10.9 ng/ml. Patients with T3b or T4 stage cancers represented 24.9% of the cohort; those with a Gleason score ≥9 represented 15.1%. The 10-year distant metastasis-free survival, PC-specific survival and overall survival were 87.1%, 92.0%, 80.9%, respectively. In univariable and multivariable Cox regression analyses, SADT that was initiated when PSA levels were less than 0.5 ng/mL was significantly associated with improved distant metastasis-free survival, PC-specific survival, and overall survival in non-organ confined PC. Early SADT initiated in patients with PSA levels <0.5 ng/mL was associated with increased distant metastasis-free survival, PC-specific survival, and overall survival in non-organ confined PC after RP.

Neutrophil-to-Lymphocyte Ratio Predicts Pathological Renal Sinus Fat Invasion in Renal Cell Carcinomas of ≤7 cm with Presumed Renal Sinus Fat Invasion

PURPOSE: Computed tomography (CT) is the most useful diagnostic modality for staging renal cell carcinoma (RCC). However, CT is limited in its ability to predict renal sinus fat invasion (SFI). Here, we aimed to evaluate whether preoperative neutrophil-to-lymphocyte ratio (NLR) could predict pathological SFI in patients with RCC of ≤7 cm for whom preoperative imaging reveals potential renal SFI. MATERIALS AND METHODS: We reviewed the medical records of 1311 patients who underwent extirpative renal surgery for non-metastatic RCC of ≤7 cm between November 2005 and December 2014. After excluding patients with no SFI in preoperative imaging, unavailable preoperative data, and morbidity affecting inflammatory markers, a total of 476 patients were included in this study. Multivariate logistic regression analysis was used to evaluate predictors of pathological SFI. RESULTS: We implemented a cut-off value of 1.98, which was calculated by ROC analysis to obtain high (≥1.98) and low (<1.98) NLR groups. A total of 93 patients with pathological SFI had larger clinical tumor size, higher preoperative NLR, larger pathological tumor size, more frequent renal vein involvement, and higher Fuhrman nuclear grade. Multivariate analysis indicated that high NLR [odds ratio (OR) 2.032, p=0.004], clinical tumor size (OR 1.586, p<0.001), and collecting system involvement on preoperative imaging (OR 3.957, p=0.011) were significantly associated with pathological SFI in these tumors. CONCLUSION: Preoperative high NLR was associated with pathological SFI in patients with RCC of ≤7 cm and presumed SFI on preoperative imaging. Greater surgical attention is needed to obtain negative margins during partial nephrectomy in these patients.

Surgical Treatment of Chronic Tophaceous Gout in the 1st Metatarso-Phalangeal Joint / 대한족부족관절학회지

PURPOSE: Chronic tophaceous gout is a painful and disabling inflammatory disease. Surgical treatment for chronic tophaceous gout is very difficult with many complications. This study evaluated the efficacy of shortening scarf osteotomy on the treatment of chronic tophaceous gout in the 1st metatarso-phalangeal (MTP) joint. MATERIALS AND METHODS: From January 2006 to December 2015, 14 patients (19 cases) who underwent axial shortening scarf osteotomy for chronic tophaceous gout were reviewed. All patients were male. The average age at the time of surgery was 59.6 years (42~66 years). The minimum follow-up was 24 months. Total removal of the tophi mass with the adhered medial capsule of the 1st MTP joint was attempted. Axial shortening scarf osteotomy was done on the 1st metatarsal shaft. The visual analogue scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was assessed preoperatively and postoperatively. The range of motion (ROM) of the 1st MTP joint was also compared pre- and postoperatively. RESULTS: The average size of the extracted tophaceous mass was 32 mm. The mean amount of the length of metatarsal shortening was 4.9 mm. The mean ROM of the 1st MTP joint was improved from 30.4° to 62.3°. The mean AOFAS forefoot score improved from 51.4 to 86.6 points. The mean VAS for pain improved from 4.6 to 0.3 points. CONCLUSION: The axial shortening scarf osteotomy used on chronic tophaceous gout could reconstruct the 1st MTP joint with an improved ROM and was free of pain. Axial shortening scarf osteotomy is suggested as a useful and effective method for the treatment of chronic tophaceous gout.

Efficacy and Safety of Robotic Procedures Performed Using the da Vinci Robotic Surgical System at a Single Institute in Korea: Experience with 10000 Cases

PURPOSE: To evaluate the efficacy and safety of robotic procedures performed using the da Vinci Robotic Surgical System at a single institute. MATERIALS AND METHODS: We analyzed all robotic procedures performed at Severance Hospital, Yonsei University Health System (Seoul, Korea). Reliability and mortality rates of the robotic surgeries were also investigated. RESULTS: From July 2005 to December 2013, 10267 da Vinci robotic procedures were performed in seven different departments by 47 surgeons at our institute. There were 5641 cases (54.9%) of general surgery, including endocrine (38.0%), upper (7.7%) and lower gastrointestinal tract (7.5%), hepato-biliary and pancreatic (1.2%), and pediatric (0.6%) surgeries. Urologic surgery (33.0%) was the second most common, followed by otorhinolaryngologic (7.0%), obstetric and gynecologic (3.2%), thoracic (1.5%), cardiac (0.3%), and neurosurgery (0.1%). Thyroid (40.8%) and prostate (27.4%) procedures accounted for more than half of all surgeries, followed by stomach (7.6%), colorectal (7.5%), kidney and ureter (5.1%), head and neck (4.0%), uterus (3.2%), thoracic (1.5%), and other (2.9%) surgeries. Most surgeries (94.5%) were performed for malignancies. General and urologic surgeries rapidly increased after 2005, whereas others increased slowly. Thyroid and prostate surgeries increased rapidly after 2007. Surgeries for benign conditions accounted for a small portion of all procedures, although the numbers thereof have been steadily increasing. System malfunctions and failures were reported in 185 (1.8%) cases. Mortality related to robotic surgery was observed for 12 (0.12%) cases. CONCLUSION: Robotic surgeries have increased steadily at our institution. The da Vinci Robotic Surgical System is effective and safe for use during surgery.

Impact of Early Salvage Androgen Deprivation Therapy in Localized Prostate Cancer after Radical Prostatectomy: A Propensity Score Matched Analysis

PURPOSE: Androgen deprivation therapy (ADT) is used as a salvage treatment for men with biochemical recurrence (BCR) of prostate cancer (PCa) following initial radical prostatectomy (RP). The optimal time at which to begin salvage ADT (sADT) remains controversial. In this retrospective study, we evaluated the efficacy of initiating sADT in patients before prostate-specific antigen (PSA) values met the clinical definition of BCR. MATERIALS AND METHODS: We identified 484 PCa patients who received sADT for BCR after RP. Median follow-up was 82 months. Propensity score matching was performed based on preoperative PSA level, pathologic T stage, and Gleason score. Patients were assigned to two groups of 169 patients each, based on PSA levels at the time of sADT: Group A (without meeting of the definition of BCR) and Group B (after BCR). Kaplan-Meier survival analyses and Cox regression analyses were performed. RESULTS: The median PSA level at sADT initiation was 0.12 ng/mL in group A and 0.42 ng/mL in group B. Kaplan-Meier analyses showed that group A had favorable disease progression-free survival (DPFS) and distant metastasis-free survival (DMFS), but did not have better cancer-specific survival (CSS) than group B. In subgroup analyses, group A showed better CSS rates in the non-organ confined PCa group. In Cox regression analyses, early sADT was associated significantly with DPFS and DMFS rates, however, did not correlate with CSS (p=0.107). CONCLUSION: Early sADT after RP improved DPFS and DMFS. Furthermore, early sADT patients demonstrated better CSS in non-organ confined PCa.

The Within-Group Discrimination Ability of the Cancer of the Prostate Risk Assessment Score for Men with Intermediate-Risk Prostate Cancer

BACKGROUND: Significant clinical heterogeneity within contemporary risk group is well known, particularly for those with intermediate-risk prostate cancer (IRPCa). Our study aimed to analyze the ability of the Cancer of the Prostate Risk Assessment (CAPRA) score to discern between favorable and non-favorable risk in patients with IRPCa. METHODS: We retrospectively reviewed the data of 203 IRPCa patients who underwent extraperitoneal robot-assisted radical prostatectomy (RARP) performed by a single surgeon. Pathologic favorable IRPCa was defined as a Gleason score ≤ 6 and organ-confined stage at surgical pathology. The CAPRA score was compared with two established criteria for the within-group discrimination ability. RESULTS: Overall, 38 patients (18.7% of the IRPCa cohort) had favorable pathologic features after RARP. The CAPRA score significantly correlated with established criteria I and II and was inversely associated with favorable pathology (all P < 0.001). The area under the receiver operating characteristic curve for the discriminative ability between favorable and non-favorable pathology was 0.679 for the CAPRA score and 0.610 and 0.661 for established criteria I and II, respectively. During a median 37.8 (interquartile range, 24.6–60.2) months of follow-up, 66 patients (32.5%) experienced biochemical recurrence (BCR). Cox regression analysis revealed that the CAPRA score, as a continuous sum score model or 3-group risk model, was an independent predictor of BCR after RARP. CONCLUSION: The within-group discrimination ability of preoperative CAPRA score might help in patient counseling and selecting optimal treatments for those with IRPCa.

An Intrarenal Adrenocortical Carcinoma Arising in an Adrenal Rest

We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.

Prognostic Factors of Penile Cancer and the Efficacy of Adjuvant Treatment after Penectomy: Results from a Multi-institution Study

BACKGROUND: Penile cancer is a rare malignancy associated with high rates of mortality and morbidity. Currently, the efficacy of adjuvant treatment (AT), including radiotherapy and chemotherapy, for penile cancer remains unclear. Therefore, we investigated the prognostic factors for treatment outcomes and the efficacy of AT in consecutive patients who underwent penectomy for penile cancer at multiple Korean institutions between 1999 and 2013. METHODS: AT was defined as the administration of chemotherapy, radiotherapy, or both within 12 months after initial treatment. All patients were divided into two groups according to the AT status. RESULTS: Forty-three patients (median age 67.0 years) with a median follow-up after penectomy of 26.4 (interquartile range: 12.0–62.8) months were enrolled. Patients with AT had a significantly higher pathologic stage. However, no differences in age, histologic grade, or type of surgery were identified according to the presence of AT. The 3- and 5-year cancer-specific survival (CSS) rates were 79.0% and 33.0%, respectively. In a multivariate analysis, American Joint Committee on Cancer (AJCC) stage ≥ III disease was an independent predictor of CSS and recurrence-free survival (RFS). However, AT was not associated with CSS and RFS. The type of primary surgical treatment and inguinal lymph node dissection at diagnosis were also not significantly associated with overall survival, CSS, or RFS. CONCLUSION: AJCC stage ≥ III disease, which mainly reflects lymph node positivity, is a significant prognosticator in patients with penile cancer. By contrast, AT does not seem to affect CSS and RFS.

Effects and Satisfaction of Medical Device Safety Information Reporting System Using Electronic Medical Record / 대한의료정보학회지

OBJECTIVES: This paper describes an evaluation study on the effectiveness of developing an in-hospital medical device safety information reporting system for managing safety information, including adverse incident data related to medical devices, following the enactment of the Medical Device Act in Korea. METHODS: Medical device safety information reports were analyzed for 190 cases that took place prior to the application of a medical device safety information reporting system and during a period when the reporting system was used. Also, questionnaires were used to measure the effectiveness of the medical device safety information reporting system. The analysis was based on the questionnaire responses of 15 reporters who submitted reports in both the pre- and post-reporting system periods. RESULTS: Sixty-two reports were submitted in paper form, but after the system was set up, this number more than doubled to 128 reports in electronic form. In terms of itemized reporting, a total of 45 items were reported. Before the system was used, 23 items had been reported, but this increased to 32 items after the system was put to use. All survey variables of satisfaction received a mean of over 3 points, while positive attitude, potential benefits, and positive benefits all exceeded 4 points, each receiving 4.20, 4.20, and 4.13, respectively. Among the variables, time-consuming and decision-making had the lowest mean values, each receiving 3.53. Satisfaction was found to be high for system quality and user satisfaction, but relatively low for time-consuming and decision-making. CONCLUSIONS: We were able to verify that effective reporting and monitoring of adverse incidents and the safety of medical devices can be implemented through the establishment of an in-hospital medical device safety information reporting system that can enhance patient safety and medical device risk management.

Preoperative Lymphocyte-Monocyte Ratio Ameliorates the Accuracy of Differential Diagnosis in Non-Metastatic Infiltrative Renal Masses

PURPOSE: Distinguishing infiltrative renal cell carcinoma (RCC) from transitional cell carcinoma (TCC) is a challenging issue due to their radiologic similarities. We evaluated systemic inflammatory biomarkers as parameters for distinguishing tumor types. MATERIALS AND METHODS: A computerized search of medical records from November 2005 to October 2015 identified 116 patients with infiltrative renal masses who were difficult to diagnose confirmatively in radiological study. We investigated the diagnostic efficacy among these patients with their preoperative absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), absolute monocyte counts (AMC), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). RESULTS: The infiltrative RCC group demonstrated significantly lower ALC {1449/µL (1140–1896), median [interquartile range (IQR)]} than the TCC group [1860/µL (1433–2342), p=0.016]. LMR [median (IQR)] also was lower in the infiltrative RCC group [2.98 (2.32–4.14) vs. TCC group 4.10 (2.86–6.09); p=0.011]. In subgroup analysis, non-metastatic infiltrative RCC showed lower ALC and LMR and higher NLR than non-metastatic TCC. Within non-metastatic infiltrative renal masses, multivariate logistic regression analysis revealed that younger patient age and lower LMR were associated with infiltrative RCC [odds ratios (OR) 0.874, p=0.024 and OR 0.461, p=0.048, respectively]. Receiver operating characteristic curve analysis showed that younger age and lower LMR were highly predictive of non-metastatic RCC (area under the curve=0.919, p<0.001). CONCLUSION: Age and LMR were significantly different between patients with infiltrative renal mass. These are potential markers for distinguishing between infiltrative RCC and TCC without metastasis.

Impact of the ASA Physical Status Score on Adjuvant Chemotherapy Eligibility and Survival of Upper Tract Urothelial Carcinoma Patients: a Multicenter Study

The aim of the present multi-institutional study was to assess the influence of the American Society of Anesthesiologists Physical Status (ASA-PS) classification on adjuvant chemotherapy eligibility and survival in a multi-institutional cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We retrospectively reviewed data from 416 patients who underwent RNU for UTUC at four Korean institutions between 2001 and 2013. The ASA-PS classification was obtained from the anesthesia chart. Locally advanced UTUC was defined as ≥ pT3 and/or pN1 disease. The influence of ASA-PS score on survival was evaluated by Kaplan-Meier analyses and a multivariate Cox regression model. Patients with a higher ASA-PS class were less likely to be eligible for adjuvant chemotherapy in locally advanced UTUC (P = 0.016). Kaplan-Meier estimates showed that the high-risk ASA-PS group has a poorer overallsurvival (OS) and cancer-specific survival (CSS) compared to low risk ASA-PS groups in both the total and locally advanced UTUC cohorts. Based on multivariate Cox regression analysis, the high-risk ASA-PS category was an independent predictor for overall mortality (OM) (hazard ratio [HR], 1.919; 95% confidence interval [CI], 1.017–3.619; P = 0.044) and cancer-specific mortality (CSM) (HR, 2.120; 95% CI, 1.023–4.394; P = 0.043). In conclusion, high-risk ASA-PS score was independently associated with a lower survival rate in patients with UTUC after RNU. However, the influence of ASA-PS classification on survival was limited to locally advanced UTUC. The lower eligibility of patients in the high-risk ASA category for adjuvant chemotherapy may contribute to the lower survival rate in this group.

A Systematic Review and Meta-Analysis of Functional Outcomes and Complications Following the Photoselective Vaporization of the Prostate and Monopolar Transurethral Resection of the Prostate

PURPOSE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing monopolar transurethral resection of the prostate (MTURP) and photoselective vaporization of the prostate (PVP) in order to provide the most up-to-date and reliable recommendations possible. MATERIALS AND METHODS: Relevant RCTs were identified from electronic databases for meta-analysis of the surgical outcomes and complications of MTURP and PVP. Meta-analytical comparisons were made using qualitative and quantitative syntheses. The outcome variables are presented as odds ratios with 95% confidence intervals (CIs). RESULTS: In total, 11 articles were included in this comparative analysis of PVP versus MTURP. Most of the recently published studies exhibited low risk in terms of quality assessment. MTURP was superior to PVP regarding operative time; however, with regard to catheterization and hospitalization time, the mean differences were -1.39 (95% CI=-1.83~-0.95, p<0.001) and -2.21 (95% CI=-2.73~-1.69, p<0.001), respectively, in favor of PVP. PVP was superior to MTURP with regard to transfusion rate and clot retention, but no statistically significant differences were found with regard to acute urinary retention and urinary tract infection. The long-term complications of bladder neck contracture and urethral stricture showed no statistically significant differences between PVP and MTURP. Long-term functional outcomes, including the International Prostate Symptom Score and maximum flow rate, likewise did not display statistically significant differences between PVP and MTURP. CONCLUSIONS: Based on our findings, we believe that PVP should be considered as an alternative surgical procedure for treating male lower urinary tract symptoms secondary to benign prostatic hyperplasia.

The Effect of Tumor-Prostate Ratio on Biochemical Recurrence after Radical Prostatectomy

PURPOSE: Prostate tumor volume calculated after surgery using pathologic tissue has been shown to be an independent risk factor for biochemical recurrence. Nonetheless, prostate size varies among individuals, regardless of the presence or absence of cancer. We assumed to be lower margin positive rate in the surgical operation, when the prostate volume is larger and the tumor lesion is same. Thus, we defined the tumor-prostate ratio in the ratio of tumor volume to prostate volume. In order to compensate the prostate tumor volume, the effect of tumor-prostate ratio on biochemical recurrence was examined. MATERIALS AND METHODS: This study included 251 patients who underwent open retropubic radical prostatectomy for prostate cancer in a single hospital. We analyzed the effects of tumor volume and tumor-prostate ratio, as well as the effects of known risk factors for biochemical recurrence, on the duration of disease-free survival. RESULTS: In the univariate analysis, the risk factors that significantly impacted disease-free survival time were found to be a prostate-specific antigen level ≥10 ng/mL, a tumor volume ≥5 mL, tumor-prostate ratio ≥10%, tumor capsular invasion, lymph node invasion, positive surgical margins, and seminal vesicle invasion. In the multivariate analysis performed to evaluate the risk factors found to be significant in the univariate analysis, positive surgical margins (hazard ratio=3.066) and a tumor density ≥10% (hazard ratio=1.991) were shown to be significant risk factors for biochemical recurrence. CONCLUSIONS: Tumor-prostate ratio, rather than tumor volume, should be regarded as a significant risk factor for biochemical recurrence.

Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma

PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.

Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls

PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.