Comparison of Biochemical Recurrence After Robot-assisted Laparoscopic Radical Prostatectomy with Volatile and Total Intravenous Anesthesia

Aims: Recurrence after cancer surgery is a major concern in patients with cancer. Growing evidence from preclinical studies has revealed that various anesthetics can influence the immune system in different ways. The current study compared the long-term biochemical recurrence of prostate cancer after robot-assisted laparoscopic radical prostatectomy (RALP) in terms of selection of anesthetic agent between total intravenous anesthesia (TIVA) with propofol/remifentanil and volatile anesthetics (VA) with sevoflurane or desflurane/remifentanil. Methods: We followed up oncologic outcomes of patients who underwent RALP from two previous prospective randomized controlled trials, and the outcomes of those who received TIVA (n = 64) were compared with those who received VA (n = 64). The follow-up period lasted from November 2010 to March 2019. Results: Both TIVA and VA groups showed identical biochemical recurrence-free survivals at all-time points after RALP. The following predictive factors of prostate cancer recurrence were determined by Cox regression: colloid input [hazard ratio (HR)=1.002, 95% confidence interval (CI): 1.000-1.003; P = 0.011], initial prostate-specific antigen level (HR=1.025, 95% CI: 1.007-1.044; P = 0.006), and pathological tumor stage 3b (HR=4.217, 95% CI:1.207-14.735; P = 0.024), but not the anesthetic agent. Conclusions: Our findings demonstrate that both TIVA with propofol/remifentanil and VA with sevoflurane or desflurane/remifentanil have comparable effects on oncologic outcomes in patients undergoing RALP.ope

Urethral realignment with maximal urethral length and bladder neck preservation in robot-assisted radical prostatectomy: Urinary continence recovery

PURPOSE: To evaluate early recovery of urinary continence after robot-assisted radical prostatectomy (RARP) with urethral realignment using bladder neck preservation (BNP) and maximal urethral length preservation (MULP). METHODS: Patients who underwent RARP between 2014 and 2017 owing to prostate cancer with a Gleason score ≤ 7 (3+4), ≤ cT2c stage, and prostate-specific antigen level < 20 ng/ml were investigated. Patients with tumors of the bladder neck or apex on magnetic resonance imaging were excluded. A total of 266 patients underwent the operation using the standard method between 2014 and 2015 (group 1), while 305 patients underwent urethral realignment between 2016 and 2017 (group 2). Continence was defined as wearing no pad or one security pad. RESULTS: The continence rates immediately after Foley catheter removal, at 2 weeks, and at 1, 3, 6, and 12 months after operation in group 2 were 46.9%, 63.0%, 73.4%, 90.1%, 94.8%, and 98.7%, respectively. The continence rate at 1 month in group 2 was significantly higher than that in group 1 (65.4% versus 73.4%, p = 0.037). The multivariate regression analysis showed that age and surgical method were factors affecting early continence recovery. The positive surgical margin rates were 18.0% and 14.8% in groups 1 and 2, respectively (p = 0.288). Biochemical recurrence occurred in 14.7% and 8.2% in groups 1 and 2, respectively (p = 0.015). CONCLUSION: Urethral realignment using BNP and MULP resulted in rapid continence recovery and good oncological results after RARP in young patients with a Gleason score ≤ 7 and organ-confined disease.ope

Prognostic value of prostate volume in non-muscle invasive bladder cancer

There is evidence that a history of benign prostatic hyperplasia increases the incidence of bladder cancer, and treatment with 5-alpha reductase inhibitor or androgen deprivation therapy reduces recurrence of non-muscle invasive bladder cancer. We aimed to evaluate whether prostate volume affects its prognosis. We reviewed medical records of men who underwent transurethral resection of bladder tumor due to non-muscle invasive bladder cancer from January 2012 to December 2017. Patients were divided into two groups based on prostate volume measured by computed tomography (group 1: 264 patients with ≤ 30 mL, group 2: 124 patients with > 30 mL). Propensity score matching analysis was used for adjust selection bias, and then assessed recurrence-free survival and progression-free survival. With a median follow up duration of 52 months, group 1 showed higher 5-year recurrence-free and progression-free survival (69.3% vs 47.0%, p = 0.001; 96.7% vs 87.7%, p = 0.002). Further, cox-regression analysis showed that tumor size (HR = 1.292 p < 0.001), multifocal tumor (HR = 1.993, p < 0.001), adjuvant intravesical therapy (chemotherapy: HR = 0.580, p = 0.037 and bacillus Calmette-Guérin: HR = 0.542, p = 0.004) and prostate volume (HR = 2.326, p < 0.001) were significant predictors of recurrence-free survival. Prostate volume (HR = 2.886, p = 0.014) was also associated with PFS with age (HR = 1.043, p = 0.044) and tumor grade (HR = 3.822, p = 0.013). We conclude higher prostate volume is associated with worse recurrence and progression-free survival in non-muscle invasive bladder cancer.ope

Effect of prostate gland weight on the surgical and oncological outcomes of extraperitoneal robot-assisted radical prostatectomy

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is performed by urologists as one of the surgical procedures for treating prostate cancer. Numerous studies have been published with regard to the impact of prostate weight on performing RARP but were limited by the insufficient number of patients and use of the transperitoneal approach. This study aimed to determine the effect of prostate gland weight on the surgical and short-term oncological outcomes of RARP using the extraperitoneal approach. METHODS: In total, 1168 patients who underwent extraperitoneal RARP (EP-RARP) performed by a single surgeon at Yonsei University Severance Hospital between May 2009 and May 2016 were included in the study. The patients were divided into 4 groups according to the prostate weight measured by transrectal ultrasonography preoperatively. Intraoperative and postoperative outcomes were analyzed retrospectively. One-way analysis of variance and the chi-square test were used in the statistical analyses. RESULTS: Age, the Gleason score, clinical stage, and pathological stage were significantly different. Patients with a larger prostate size had a longer console time and higher estimated blood loss (P < 0.05). There were no significant differences between the 4 groups in length of hospital stay, duration of catheterization, blood transfusion, body mass index, prostate-specific antigen (PSA) level, history of abdominal surgery, intraoperative complications, positive surgical margin, incidence of lymphocele, and PSA recurrence after 1 year. CONCLUSIONS: The console time and estimated blood loss were significantly increased with a larger prostate size. However, there were no significant differences in the oncologic outcome and intraoperative complications, suggesting that EP-RARP requires meticulous bleeding control in patients with a prostate weighing > 75 g, and if appropriate management is implemented for blood loss intraoperatively, EP-RARP can be performed regardless of the prostate size.ope

Effect of Dexmedetomidine on Biochemical Recurrence in Patients after Robot-Assisted Laparoscopic Radical Prostatectomy: A Retrospective Study

The usage of dexmedetomidine during cancer surgery in current clinical practice is debatable, largely owing to the differing reports of its efficacy based on cancer type. This study aimed to investigate the effects of dexmedetomidine on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer, who have undergone robot-assisted laparoscopic radical prostatectomy (RALP). Using follow-up data from two prospective randomized controlled studies, BCR and radiographic progression were compared between individuals who received dexmedetomidine (n = 58) and those who received saline (n = 56). Patients with complete follow-up records between July 2013 and June 2019 were enrolled in this study. There were no significant between-group differences in the number of patients who developed BCR and those who showed positive radiographic progression. Based on the Cox regression analysis, age (p = 0.015), Gleason score ≥ 8 (p < 0.001), and pathological tumor stage 3a and 3b (both p < 0.001) were shown to be significant predictors of post-RALP BCR. However, there was no impact on the dexmedetomidine or control groups. Low-dose administration of dexmedetomidine at a rate of 0.3-0.4 μg/kg/h did not significantly affect BCR incidence following RALP. In addition, no beneficial effect was noted on radiographic progression.ope

Gene Expression Analysis of Aggressive Clinical T1 Stage Clear Cell Renal Cell Carcinoma for Identifying Potential Diagnostic and Prognostic Biomarkers

The molecular characteristics of early-stage clear cell renal cell carcinomas (ccRCCs) measuring ≤7 cm associated with poor clinical outcomes remain poorly understood. Here, we sought to validate genes associated with ccRCC progression and identify candidate genes to predict ccRCC aggressiveness. From among 1069 nephrectomies performed on patients, RNA sequencing was performed for 12 ccRCC patients with aggressive characteristics and matched pairs of 12 ccRCC patients without aggressive characteristics. Using a prospective cohort (ClinicalTrials.gov Identifier: NCT03694912), the expression levels of nine genes (PBRM1, BAP1, SETD2, KDM5C, FOXC2, CLIP4, AQP1, DDX11, and BAIAP2L1) were measured by reverse-transcription polymerase chain reaction from frozen tissues, and their relation to Fuhrman grade was investigated in 70 patients with small ccRCC (≤4 cm). In total, 251 genes were differentially expressed and presented fold changes with p-values < 0.05; moreover, 10 genes with the greatest upregulation or downregulation in aggressive ccRCC remained significant even after adjustment. We validated previously identified genes that were associated with ccRCC progression and identified new candidate genes that reflected the aggressiveness of ccRCC. Our study provides new insight into the tumor biology of ccRCC and will help stratify patients with early-stage ccRCC by molecular subtyping.ope

Comparison of intraoperative and short-term postoperative outcomes between robot-assisted laparoscopic multi-port pyeloplasty using the da Vinci Si system and single-port pyeloplasty using the da Vinci SP system in children

Purpose: We compared the intraoperative and postoperative outcomes of single-port robot-assisted laparoscopic pyeloplasty (S-RALP) using the da Vinci SP® system and conventional multi-port robot-assisted laparoscopic pyeloplasty (M-RALP) in pediatric patients. Materials and methods: Multi-port and single-port pyeloplasty have been performed in pediatric patients in our institution since October 2015 and February 2019, respectively. We conducted an entire cohort comparison. Considering the learning curve of M-RALP, we defined the last 15 cases of M-RALP as a subgroup of M-RALP and compared this subgroup with the entire cohort of S-RALP patients. Results: Thirty-one patients who underwent multi-port pyeloplasty and 15 patients who underwent single-port pyeloplasty were enrolled in this study. Age, height, body weight, laterality, surgical indication, and ipsilateral differential renal function were statistically similar in the M-RALP and S-RALP groups. The median operative time (3.0 h vs. 2.4 h; p=0.01) and the median console time (2.2 h vs. 1.5 h; p<0.001) were longer in the M-RALP group than in the S-RALP group. There was no significant difference in operative time or console time between the M-RALP subgroup and the S-RALP group. There were no significant differences in the length of hospitalization, pain score, morphine-equivalent use of analgesics, or postoperative differential renal function in all comparisons. Conclusions: This study confirmed that pyeloplasty using the da Vinci® SP system can be started by robotic surgeons who can overcome the learning curve. Robot-assisted laparoscopic single-port pyeloplasty is feasible in noninfant pediatric patients.ope

Nephron-Sparing Approaches in Upper Tract Urothelial Carcinoma: Current and Future Strategies

Upper tract urothelial carcinoma (UTUC) is a relatively rare cancer, and much of the approach to treatment has been derived from strategies employed in treating bladder cancer. Radical nephroureterectomy (RNU) is regarded as the gold standard treatment for UTUC. However, due to potential complications, such as renal function impairment, that can affect oncologic outcomes, the demand for nephron-sparing treatment to effectively treat cancer while preserving renal function has increased. As a result, various treatment methods for low-grade, low-volume UTUC, such as segmental ureterectomy, endoscopic resection, and intraluminal therapy, have been attempted and reported. Although these treatment modalities have exhibited acceptable oncological results, further studies are required. In the future, the introduction of new technologies, such as improved diagnostic and surgical equipment, and new drug delivery systems, could enhance the effectiveness of nephron-sparing strategies in the treatment of UTUC. Additionally, understanding the biological and genetic characteristics of UTUC that distinguish it from those of bladder cancer will also aid in establishing strategies for nephron-sparing.ope

Predictive Factors and Oncologic Outcome of Downgrade to Pathologic Gleason Score 6⁻7 after Radical Prostatectomy in Patients with Biopsy Gleason Score 8⁻10

Gleason score (GS) 8⁻10 is associated with adverse outcomes in prostate cancer (PCa). However, biopsy GS (bGS) may be upgraded or downgraded post-radical prostatectomy (RP). We aimed to investigate predictive factors and oncologic outcomes of downgrade to pathologic GS (pGS) 6⁻7 after RP in PCa patients with bGSs 8⁻10. We retrospectively reviewed clinical data of patients with bGS ≥ 8 undergoing RP. pGS downgrade was defined as a pGS ≤ 7 from bGS ≥ 8 post-RP. Univariate and multivariate cox regression analysis, logistic regression analysis, and Kaplan⁻Meier curves were used to analyze pGS downgrade and biochemical recurrence (BCR). Of 860 patients, 623 and 237 had bGS 8 and bGS ≥ 9, respectively. Post-RP, 332 patients were downgraded to pGS ≤ 7; of these, 284 and 48 had bGS 8 and bGS ≥ 9, respectively. Prostate-specific antigen (PSA) levels; clinical stage; and adverse pathologic features such as extracapsular extension, seminal vesicle invasion and positive surgical margin were significantly different between patients with pGS ≤ 7 and pGS ≥ 8. Furthermore, bGS 8 (odds ratio (OR): 0.349, p < 0.001), PSA level < 10 ng/mL (OR: 0.634, p = 0.004), and ≤cT3a (OR: 0.400, p < 0.001) were identified as significant predictors of pGS downgrade. pGS downgrade was a significant positive predictor of BCR following RP in patients with high bGS (vs. pGS 8, hazard radio (HR): 1.699, p < 0.001; vs. pGS ≥ 9, HR: 1.765, p < 0.001). In addition, the 5-year BCR-free survival rate in patients with pGS downgrade significantly differed from that in patients with bGS 8 and ≥ 9 (52.9% vs. 40.7%, p < 0.001). Among patients with bGS ≥ 8, those with bGS 8, PSA level < 10 ng/mL, and ≤cT3a may achieve pGS downgrade after RP. These patients may have fewer adverse pathologic features and show a favorable prognosis; thus we suggest that active treatment is needed in these patients. In addition, patients with high-grade bGS should be managed aggressively, even if they show pGS downgrade.ope

Gene Expression Analysis of Aggressive Adult Xp11.2 Translocation Renal Cell Carcinoma at Clinical Stage T1N0M0 to Identify Potential Prognostic and Therapeutic Biomarkers

Xp11.2 translocation renal cell carcinoma (tRCC), involving transcription factor E3 (TFE3) gene fusions, is a rare and aggressive RCC variant when present in adults and has been recently recognized as a unique entity in RCC. Biomarkers and treatment guidelines do not exist for patients with aggressive Xp11.2 tRCC. The aim was to identify and evaluate therapeutic biomarkers for aggressive Xp11.2 tRCC. RNA sequencing was performed using formalin-fixed, paraffin-embedded tissues from 11 adult patients with clinical T1N0M0 Xp11.2 tRCC, including three patients with aggressive characteristics (recurrence or cancer-specific death after nephrectomy). Thirty genes were differentially expressed between the aggressive and non-aggressive groups, even after adjustment, and were associated with KEGG pathways related to the aggressiveness of Xp11.2 tRCC. PIK3R2, involved in various KEGG pathways, including the PI3K/AKT/mTOR pathway, was overexpressed in the Xp11.2 tRCC cell lines UOK120 and UOK146. The PI3K pathway inhibitor LY294002 showed a significant therapeutic benefit. This study provides the first candidate biomarker, PIK3R2, for aggressive clinical T1N0M0 Xp11.2 tRCC. Furthermore, this study is the first to recommend a targeted drug, LY294002, for aggressive Xp11.2 tRCC based on the molecular pathophysiology.ope