Trends of First-Line Targeted Therapy in Korean Patients With Metastatic Clear Cell Renal Cell Carcinoma: Sunitinib Versus Pazopanib, a Multicenter Study

Purpose@#There have been few reports on comparison between sunitinib and pazopanib as first-line targeted therapy in Korean metastatic clear cell renal cell carcinoma (ccRCC). We sought to analyze the treatment trends of metastatic ccRCC by comparing the effects and adverse events of sunitinib and pazopanib. @*Materials and Methods@#Data of 357 metastatic RCC patients who received the sunitinib or pazopanib as the first-line targeted therapy from the Daegyeong Oncology Study Group database was obtained and analyzed. Among these patients, patients who only clear cell type was confirmed after needle biopsy or nephrectomy were included, and patients who underwent target therapy for less than 3 months were excluded. @*Results@#Of 251 patients who met the inclusion criteria, sunitinib and pazopanib group were identified in 156 (62%) and 95 patients (38%), respectively. Pazopanib group was older (66 years vs. 61 years, p=0.001) and more symptomatic (65% vs. 52%, p=0.037) and had more patients with Karnofsky performance status <80 (20% vs. 11%, p=0.048) and fewer number of organ metastases (p=0.004) compared to sunitinib group. There was no significant difference in disease control rate (88.5% vs. 87.3%, p=0.744), the median progression-free survival (19 months vs. 15 months, p=0.444) and overall survival (25 months vs. 19 months, p=0.721) between sunitinib and pazopanib. The most common grade 3/4 adverse events with sunitinib and pazopanib were anemia (5%) and hand-foot syndrome (3%), respectively. There was no significant difference between sunitinib and pazopanib in number of patients who experienced grade 3/4 adverse events (15% vs. 11%, p=0.275). However, there were more patients who discontinued treatment due to only adverse events in sunitinib group compared to pazopanib group (12% vs. 3%, p=0.020). @*Conclusions@#In Korean metastatic ccRCC, pazopanib tended to be used in patients with poorer health status compared to sunitinib. Sunitinib and pazopanib had no significant difference in treatment effect and survival, but pazopanib had more tolerable adverse events.

Impact of Multiple Prostate Biopsies: Risk of Perioperative Complications and Biochemical Recurrence After Radical Prostatectomy

Purpose@#The aim of this study was to analyze the perioperative complications and oncological outcomes of radical prostatectomy (RP) in patients who underwent multiple prostate biopsies. @*Materials and Methods@#A total of 1,112 patients who underwent RP between January 2009 and April 2016 at 4 different centers were included in this study. We divided these patients into 2 groups: patients who underwent only 1st biopsy, and those who underwent 2nd or more repeated biopsies. The association between the number of prior biopsies and perioperative complications and biochemical recurrence (BCR) was analyzed. @*Results@#Of 1,112 patients, 1,046 patients (94.1%) underwent only 1st biopsy, and 66 (5.9%) underwent 2nd or more repeated biopsies. There were no significant differences in preoperative prostate-specific antigen levels, operation times, blood loss volumes, or hospital stay durations (all p＞0.05). Patients who underwent multiple prostate biopsies presented with a localized tumor significantly more often (p＜0.05). The Gleason score and rate of positive surgical margins were significantly lower in patients with multiple biopsies (all p＜0.05). The Cox proportional hazards model analysis indicated that there was no association between the number of prior prostate biopsies and BCR (p＞0.05). Kaplan-Meier curve analysis indicated that BCR-free survival rates between the 2 groups were similar (p＞0.05). @*Conclusions@#Multiple prostate biopsies are not associated with an increased risk of perioperative complications, adverse pathological outcomes, or higher rates of BCR in patients who have undergone RP. (Korean J Urol Oncol 2020;18:24-31)

Initial Experiences of Retropubic Radical Prostatectomy Including Antegrade Nerve Sparing, Continuous Anastomosis, and Preservation of Endopelvic Fascia

Purpose@#We compared retropubic radical prostatectomy (RRP) with various laparoscopic radical prostatectomy procedures with RRP as previous performed in our institution. @*Materials and Methods@#Demographics, perioperative and functional outcomes of 78 patients that underwent modified RRP (mRP; N=53) or established RRP (eRP; N=25) at our institution from January 2013 to December 2018 were evaluated retrospectively. Postoperative incontinence and erectile dysfunction are involved functional outcomes. During the modified procedure, with preserving endopelvic fascia, the prostate was dissected in an antegrade fashion with bilateral nerve sparing, and then urethrovesical anastomosis was performed with continuous suture. @*Results@#The mean age was older in mRP (68.7±5.3 years) than mRP (65.9±5.0 years) and mean prostate volume was larger in mRP (40.1±18.6 mL) than eRP (30.4±14.0 mL). Mean operative time was longer in eRP (227.0±111.1 minutes) than mRP (154.6±31.6 minutes) and estimated blood loss and complicate rate were similar in 2 groups. The pathologic stage was all T2 stage in eRP, however, in mRP T2 stage was 31 and T3 stage was 22. The pathologic Gleason score was higher in mRP than eRP (p=0.001). Positive surgical margin was significantly higher in mRP, however, biochemical recurrence was insignificantly higher in mRP. Incontinence rates at 3 and 12 months after eRP decreased from 96.0% to 28.0% and after mRP decreased from 49.1% to 7.5%. Overall postoperative potency rate at 12 months was significant different in eRP and mRP groups (8.0% and 34.0%). @*Conclusions@#The mRP was found to have favorable functional outcome and short operative time. This technique might be adopted by inexperienced urologic surgeons as a standard procedure. (Korean J Urol Oncol 2020;18:47-52)

Erectile Function and Long-term Oncologic Outcomes of Nerve-Sparing Robot-Assisted Radical Cystectomy: Comparison With Open Radical Cystectomy

PURPOSE: We performed nerve-sparing robot-assisted radical cystectomy (nsRARC) and compared the operative outcomes of nsRARC and open radical cystectomy (ORC). MATERIALS AND METHODS: The data of 38 patients that underwent ORC or nsRARC for bladder cancer between July 2009 and April 2014 (23 ORC and 15 RARC) were retrospectively analyzed. Data were collected on patient demographics, pathologic stages, perioperative outcomes, and oncologic outcomes as well as on erectile function. Five-year overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Erection function recovery was defined as the ability to achieve penetration ≥50% of the time and to maintain an erection sufficient enough for penetration ≥50% of the time at 12 months after surgery. RESULTS: No significant differences were found between the nsRARC and ORC groups in terms of age, sex, body mass index, American Society of Anesthesiologists physical status, or clinical stage. Mean estimated blood loss was significantly less in the nsRARC group (205.3 mL vs. 394 mL, p=0.011), but mean operative time was significantly greater (520.3 minutes vs. 415.0 minutes, p=0.004). Five-year overall survival and cancer-specific survival were 86.7% and 86.7%, respectively, for nsRARC, and 77.7% and 86.7% for ORC. With respect to erectile function, the overall postoperative potency rate at 12 months was 40.0% in the RARC group and 9.5% in the ORC group, and this difference was significant (p=0.021). CONCLUSIONS: Our clinical experiences indicate nsRARC in selected patients is a feasible procedure in terms of oncologic outcome and that it preserves erectile function relatively effectively.

Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells

Atmospheric (in vitro) oxygen pressure is around 150 mm Hg (20% O₂), whereas physiologic (in vivo) oxygen pressure ranges between 5 and 50 mm Hg (0.7–7% O₂). The normoxic environment in cell culture does not refer to a physiological stem cell niche. The aim of this study is to investigate the effect of oxygen concentration on cell properties of human mesenchymal stem cells (MSCs). We analyzed cell proliferation rate, senescence, immunophenotype, stemness gene expression and differentiation potency with human urine stem cells (USCs), dental pulp stem cells (DPSCs), amniotic fluid stem cells (AFSCs), and bone marrow stromal cells (BMSCs). USCs, DPSCs, AFSCs and BMSCs were cultured under either 5% O₂ hypoxic or 20% O₂ normoxic conditions for 5 days. MSCs cultured under hypoxia showed significantly increased proliferation rate and high percentage of S-phase cells, compared to normoxic condition. In real-time PCR assay, the cells cultured under hypoxia expressed higher level of Oct4, C-Myc, Nanog, Nestin and HIF-1α. In immunophenotype analysis, MSCs cultured under hypoxia maintained higher level of the MSC surface markers, and lower hematopoietic markers. Senescence was inhibited under hypoxia. Hypoxia enhances osteogenic differentiation efficiency compared to normoxia. Hypoxia showed enhanced cell proliferation rate, retention of stem cell properties, inhibition of senescence, and increased differentiation ability compared to normoxia.

Visible Angle on Magnetic Resonance Imaging Can Be Considered Indicator of Postoperative Outcome in Retropubic Radical Prostatectomy

PURPOSE: We aimed to measure the visible angle (VA) outside the surgical field of view using preoperative magnetic resonance imaging (MRI), and to relate structural data to clinical outcome. MATERIALS AND METHODS: We retrospectively analyzed data obtained from 322 consecutive patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP) or radical retropubic prostatectomy (RRP) for prostate cancer from January 2011 to June 2013, with at least 1 year of follow-up. Patients were divided into 4 groups, according to median VA values and surgical approach. VA was defined as the angle between the horizontal line on view, rotated to 90∘ from the midsagittal T2-weighted sequence image, and the tangent line of the highest protruding surface of the symphysis pubis. RESULTS: The larger VA was, the shorter mean operative time (213.2 minutes vs. 174.2 minutes, p=0.002) was significantly and the smaller VA was, the higher complication rate (10.8% vs. 1.6%, p=0.043) was in RRP patients. There were no significant differences in operative outcomes in RALP patients. CONCLUSIONS: VA in midsagittal T2-weighted sequence predict operative time and complication rates in retropubic radical prostatectomy, and thus, the value may be used as surgical indications for retropubic radical prostatectomy.

The Efficacy and Safety of Collagen-I and Hypoxic Conditions in Urine-Derived Stem Cell Ex Vivo Culture

Upper urinary tract-derived urine stem cells (USCs) are considered a valuable mesenchymal stem cell source for autologous cell therapy. However, the reported culture condition for USCs is not appropriate for large-quantity production, because cells can show limited replicativity, senescence, and undesirable differentiation during cultivation. These drawbacks led us to reconstitute a culture condition that mimics the natural stem cell niche. We selected extracellular matrix protein and oxygen tension to optimize the ex vivo expansion of USCs, and compared cell adhesion, proliferation, gene expression, chromosomal stability, differentiation capacity, immunity and safety. Culture on collagen type I (ColI) supported highly enhanced USC proliferation and retention of stem cell properties. In the oxygen tension analysis (with ColI), 5% O₂ hypoxia showed a higher cell proliferation rate, a greater proportion of cells in the S phase of the cell cycle, and normal stem cell properties compared to those observed in cells cultured under 20% O₂ normoxia. The established reconstituted condition (ColI/hypoxia, USCs(recon)) was compared to the control condition. The expanded USCs(recon) showed highly increased cell proliferation and colony forming ability, maintained transcription factors, chromosomal stability, and multi-lineage differentiation capacity (neuron, osteoblast, and adipocyte) compared to the control. In addition, USCs(recon) retained their immune-privileged potential and non-tumorigenicity with in vivo testing at week 8. Therefore, reconstituted condition allows for expanded uUSC cell preparations that are safe and useful for application in stem cell therapy.

Extra-gastrointestinal Stromal Tumor on the Inner Urinary Bladder Wall

A gastrointestinal stromal tumor is the most common mesenchymal tumor of the gastrointestinal tract, and is diagnosed on the basis of the combined expression of CD34 and CD117 (C-kit protein). An extragastrointestinal stromal tumor of the urinary bladder is a very rare neoplasm. In this report, we describe a case of an extragastrointestinal stromal tumor originating from the inner surface of the urinary bladder. A 46-year-old man presented with an incident bladder mass, and he was diagnosed with an extragastrointestinal stromal tumor after transurethral resection of the bladder tumor. A tumor on the inner urinary bladder wall is an unusual presentation of an extragastrointestinal stromal tumor. The patient is doing well with no recurrence at 18 months after surgery.

Clinical Significance of the Resistive Index of Prostatic Blood Flow According to Prostate Size in Benign Prostatic Hyperplasia / 대한배뇨장애요실금학회지

PURPOSE: The authors evaluated the relationships between the clinical factors and resistive indexes (RIs) of prostate and urethral blood flows by using power Doppler transrectal ultrasonography (PDUS) in men with benign prostatic hyperplasia (BPH). METHODS: The data of 110 patients with BPH and lower urinary tract symptoms (LUTS) treated between January 2015 and July 2015 were prospectively collected. PDUS was used to identify the capsular and urethral arteries of the prostate in order to measure RIs. International Prostate Symptom Score (IPSS), maximal flow rate (Qmax), total prostate volume (TPV), transition zone volume (TZV), transition zone index (=TZV/TPV), presence of intravesical prostatic protrusion (IPP), and the RIs of capsular and urethral arteries were evaluated for all of the patients by one urologist. RESULTS: The 110 patients were categorized according to IPSS (mild symptoms, 0-7; moderate symptoms, 8-19; and severe symptoms, 20-35), Qmax (<10 and ≥10 mL/sec), TPV (<30 and ≥30 mL), and presence or absence of IPP. No significant relationship was found between the mean RI of any artery and IPSS or Qmax. The mean RIs of the urethral artery, and left and right capsular arteries were significantly dependent on prostate size and the presence of IPP. CONCLUSIONS: RI obtained by using PDUS correlated with the presence of IPP and prostate size. The RI of prostate blood flow can be used as a noninvasive diagnostic tool for BPH with LUTS.

Urethroplasty Using Autologous Urethral Tissue-embedded Acellular Porcine Bladder Submucosa Matrix Grafts for the Management of Long-Segment Urethral Stricture in a Rabbit Model

We conducted this study to evaluate the combined effect of acellular bladder submucosa matrix (BSM) and autologous urethral tissue for the treatment of long segment urethral stricture in a rabbit model. To prepare the BSM, porcine bladder submucosa was processed, decellularized, configured into a sheet-like shape, and sterilized. Twenty rabbits were randomized to normal control, urethral stricture, urethroplasty using BSM only or BSM/autologous urethral tissue (n=5 per group). Retrograde urethrography was performed at 4, 8, and 12 weeks postoperatively, and the grafted specimens were harvested at week 12 to evaluate urethral reconstruction through histopathologic and immunohistochemical analysis. The mean urethral width of the control, stricture, BSM, and BSM/autologous urethral tissue groups at week 12 was 10.3+/-0.80, 3.8+/-1.35, 8.8+/-0.84, and 9.1+/-1.14 mm, respectively. The histopathologic study revealed that the BSM/autologous urethral tissue graft had a normal area of urethral lumen, compact muscular layers, complete epithelialization, and progressive infiltration by vessels in the regenerated urethra. In contrast, the BSM grafts revealed keratinized epithelium, abundant collagenized fibrous connective tissue, and were devoid of bundles of circular smooth muscle. Nontransected ventral onlay-augmented urethroplasty using an acellular BSM scaffold combined with an autologous urethral tissue graft represents a feasible procedure for urethral reconstruction.

Urethroplasty Using Autologous Urethral Tissue-embedded Acellular Porcine Bladder Submucosa Matrix Grafts for the Management of Long-Segment Urethral Stricture in a Rabbit Model

We conducted this study to evaluate the combined effect of acellular bladder submucosa matrix (BSM) and autologous urethral tissue for the treatment of long segment urethral stricture in a rabbit model. To prepare the BSM, porcine bladder submucosa was processed, decellularized, configured into a sheet-like shape, and sterilized. Twenty rabbits were randomized to normal control, urethral stricture, urethroplasty using BSM only or BSM/autologous urethral tissue (n=5 per group). Retrograde urethrography was performed at 4, 8, and 12 weeks postoperatively, and the grafted specimens were harvested at week 12 to evaluate urethral reconstruction through histopathologic and immunohistochemical analysis. The mean urethral width of the control, stricture, BSM, and BSM/autologous urethral tissue groups at week 12 was 10.3+/-0.80, 3.8+/-1.35, 8.8+/-0.84, and 9.1+/-1.14 mm, respectively. The histopathologic study revealed that the BSM/autologous urethral tissue graft had a normal area of urethral lumen, compact muscular layers, complete epithelialization, and progressive infiltration by vessels in the regenerated urethra. In contrast, the BSM grafts revealed keratinized epithelium, abundant collagenized fibrous connective tissue, and were devoid of bundles of circular smooth muscle. Nontransected ventral onlay-augmented urethroplasty using an acellular BSM scaffold combined with an autologous urethral tissue graft represents a feasible procedure for urethral reconstruction.

Efficacy of Percutaneous Nephrostomy During Flexible Ureteroscopy for Renal Stone Management

PURPOSE: Preoperative percutaneous nephrostomy (PCN) can be applied to urinary stone patients with pyelonephritis as well as obstructive uropathy; thus, some patients undergo flexible ureteroscopy (fURS) in the presence of a PCN tube. We evaluated the effectiveness of PCN during fURS for the management of renal stones. MATERIALS AND METHODS: We retrospectively analyzed 130 consecutive patients who underwent fURS for renal stones between January 2009 and December 2011. All fURS procedures were performed by a single experienced surgeon. The patients were divided into two groups depending on the presence of PCN during the surgery: patients with PCN (group 1, n=41) and patients without PCN (group 2, n=89). To evaluate operative outcomes, we compared success rates, operative times, and complication rates. We defined success as the absence of any residual stones in the kidney or stone fragments less than 2 mm that were too small to be extracted during follow-up. RESULTS: There were no significant differences in age, sex, body mass index, stone laterality, burden, or location between the two groups. The mean operative times of groups 1 and 2 were 50.1 and 58.3 minutes, respectively (p=0.102). The success rates of groups 1 and 2 were 95.1% and 82.0%, respectively (p=0.044). There was no statistically significant difference in the complication rate between groups 1 and 2 (p=0.888). CONCLUSIONS: Flexible ureteroscopy in the presence of PCN produced a superior outcome in terms of the success rate without increasing the operative time or complication rate. PCN may be helpful to induce better outcomes of fURS.

Obesity Is an Adverse Factor on Laparoscopic Radical Nephrectomy for T2 but Not T1 Renal Cell Carcinoma

PURPOSE: Laparoscopic radical nephrectomy (LRN) is more challenging with increases in body mass index (BMI). Several recent studies have shown, however, that LRN can be safely performed even in obese patients. The influence of obesity on the perioperative outcomes of LRN has not been well elucidated for large renal tumors (>7 cm), however. We estimated the impact of obesity on LRN for stage T1 and T2 renal cell carcinoma (RCC). MATERIALS AND METHODS: From January 2004 to March 2011, 266 patients underwent LRN (T1: 195, T2: 71). These patients were subdivided into the following two groups according to BMI: the nonobese group (BMI less than 25 kg/m2) and the obese group (BMI greater than 25 kg/m2). Perioperative outcomes were retrospectively compared between these two groups in T1 and T2 RCC patients. RESULTS: There were no significant differences in perioperative outcomes between the obese and nonobese groups of T1 RCC patients. However, in T2 RCC patients, operative time and complication rate were significantly increased in the obese group. CONCLUSIONS: Our results suggest that LRN can be safely performed in Korean patients with T1 RCC regardless of obesity. In T2 RCC patients, however, LRN may become more difficult with increasing BMI considering a longer operation time as well as a higher complication rate. We suggest that LRN for obese patients with T2 RCC be carefully considered.

Solitary Testicular Metastasis of Prostate Cancer Mimicking Primary Testicular Cancer

We report a rare case of testicular metastasis from prostate cancer. A 68-year-old patient presented with a right testicular mass with discomfort. He had a history of robot-assisted laparoscopic radical prostatectomy and had received adjuvant radiation therapy and had been treated with androgen deprivation therapy continuously at another institution. We performed a right inguinal orchiectomy. The testicular mass was diagnosed as a metastasis from prostate carcinoma.

Laparoscopic versus Open Radical Nephrectomy in T2 Renal Cell Carcinoma: Long-Term Oncologic Outcomes

PURPOSE: Laparoscopic radical nephrectomy (LRN) has become the standard technique for radical nephrectomies for T1 renal tumors (7 cm or less). We extended our experience with LRN to T2 renal tumors (greater than 7 cm) and compared the efficacy and long-term oncologic outcomes with those of open radical nephrectomy (ORN) for T2 clear renal cell carcinoma (RCC) in the same period. MATERIALS AND METHODS: We retrospectively analyzed the data from 33 patients who underwent LRN and 35 patients who underwent ORN in our institution from January 2003 to June 2006 for T2N0M0 RCC. We compared long-term oncologic outcomes between the two groups. RESULTS: The median follow-up periods were 60.0 months (range, 48.0-77.0 months) and 65.6 months (range, 56.0-77.0 months) in the LRN and ORN groups, respectively. There were no statistically significant differences between the two groups in the patients' demographic data. There were no significant differences in the 5-year overall survival rate, the cancer-specific survival rate, or the recurrence-free survival rate. CONCLUSIONS: Our results suggest that LRN for the management of T2 RCC is feasible and efficacious and that the long-term oncologic outcomes of LRN are comparable to those of ORN.

Initial Experiences with Robot-Assisted Laparoscopic Radical Cystectomy

PURPOSE: Robot-assisted laparoscopic radical cystectomy (RLRC) is a new option for the treatment of muscle-invasive bladder cancer, and case series for RLRC have been increasing recently. We report our operative technique and initial experiences with RLRC with extracorporeal urinary diversion. MATERIALS AND METHODS: Between October 2008 and November 2009, 17 consecutive patients with muscle-invasive bladder cancer underwent RLRC, pelvic lymph node dissection, and extracorporeal urinary diversion. Urinary diversion included 13 ileal conduits and 4 orthotopic neobladders (Studer method). Data were collected prospectively on patient demographics, intraoperative parameters, pathologic staging, and postoperative outcomes. RESULTS: The mean patient age was 63.7 years. The mean body mass index was 22.6 kg/m2. No patients had a history of previous abdominal surgery. The mean operative time was 379.1 minutes, including 32.6 minutes for pelvic lymph node dissection, 185.2 minutes for RLRC, and 159.4 minutes for urinary diversion. The mean estimated blood loss was 210.5 ml. The mean hospital stay was 20.7 days and the mean time to oral intake and ambulation was 5.0 and 1.3 days, respectively. There were no major perioperative complications. The pathologic reports showed urothelial cell carcinomas in all cases. CONCLUSIONS: Our initial clinical experiences indicate that RLRC with pelvic lymph node dissection and extracorporeal urinary diversion is a safe and feasible procedure with minimal blood loss and rapid recovery. Long-term follow up in a larger patient population is needed to determine the true oncological and functional benefit of this procedure.