Unique lipid composition maintained by extracellular blockade leads to prooncogenicity.

Lipid-mediated inflammation is involved in the development and malignancy of cancer. We previously demonstrated the existence of a novel oncogenic mechanism utilizing membrane lipids of extracellular vesicles in Epstein-Barr virus (EBV)-positive lymphomas and found that the lipid composition of lymphoma cells is skewed toward ω-3 fatty acids, which are anti-inflammatory lipids, suggesting an alteration in systemic lipid composition. The results showed that arachidonic acid (AA), an inflammatory lipid, was significantly reduced in the infected cells but detected at high levels in the sera of EBV-positive patients lead to the finding of the blockade of extracellular AA influx by downregulating FATP2, a long-chain fatty acid transporter that mainly transports AA in EBV-infected lymphoma cells. Low AA levels in tumor cells induced by downregulation of FATP2 expression confer resistance to ferroptosis and support tumor growth. TCGA data analysis and xenograft models have demonstrated that the axis plays a critical role in several types of cancers, especially poor prognostic cancers, such as glioblastoma and melanoma. Overall, our in vitro, in vivo, in silico, and clinical data suggest that several cancers exert oncogenic activity by maintaining their special lipid composition via extracellular blockade.

Predictors of surgical difficulty according to surgical proficiency in robot-assisted radical prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a standard treatment for localized prostate cancer. We previously reported that a large amount of pelvic visceral fat and a small working space, as measured by three-dimensional image analysis, were significantly associated with prolonged console time in RARP, and these factors could be alternatives to the more clinically practical body mass index (BMI) and pelvic width (PW), respectively. Herein, we further investigated whether surgical proficiency affected surgical difficulty as measured by console time. METHODS: Medical records of 413 patients who underwent RARP between 2014 and 2020 at our institution were reviewed. Surgeons who had experience with over and under 100 cases were defined as "experienced" and "non-experienced," respectively. Multivariate logistic regression analyses were performed to identify factors that prolonged console time. RESULTS: The median console times for RARP by experienced and non-experienced surgeons were 87.5 and 149.0 min, respectively; a difficult case was defined as one requiring time greater than the median. Among inexperienced surgeons, higher BMI (p < 0.001, odds ratio: 1.89) and smaller PW (p = 0.001, odds ratio: 1.86) were significant factors that increased console time; the complication rate was increased in patients with these factors. However, these factors did not significantly affect the console time or complication rate among experienced surgeons. CONCLUSION: This study demonstrates that experienced surgeons may be able to overcome obesity- and small workspace-related surgical difficulties. The current analysis may provide useful information regarding unpredictable surgical risks and identify suitable cases for novices.

A case report of a 5 mm port site hernia that occurred at the drain insertion site after laparoscopic right nephrectomy.

A 5 mm port site hernia during laparoscopic surgery is rarer than a 12 mm port site hernia. Here, we report the case of a 5 mm port site hernia in an 85-year-old woman who underwent long-term steroid therapy and laparoscopic right nephrectomy. There was also a hernia at the port site where the drain was placed. Due to the 5 mm port at the drain removal site, fascial suturing was impossible after removal of the drain, and countermeasures were difficult. However, we believe that patients at a higher risk of port need suturing wound patients like this and should be carefully observed.

Transcatheter renal arterial embolization for intractable urinary fistula occurring after robot-assisted partial nephrectomy: a case report.

Partial nephrectomy is the standard surgical procedure for small renal tumors. Since the advent of robot-assisted partial nephrectomy (RAPN), the number of cases of renal tumors undergoing the procedure has increased exponentially. Urinary fistula is a complication of partial nephrectomy. Conservative management using ureteral stents is useful in most cases of urinary fistulas. However, some patients develop intractable urinary fistulas. Herein, we report a case in which vascular embolization was useful for treating an infected and intractable urinary fistula that developed after RAPN. A 59-year-old man was accidentally found to have a right renal tumor (approximately 3 cm in diameter) during a physical examination. Pathology was clear cell carcinoma. RAPN was performed owing to the small size of the renal tumor; however, postoperatively, an intractable urinary fistula with an isolated calyx developed, which was successfully treated with transcatheter renal arterial embolization (TAE). We encountered a rare case of infected refractory urinary fistula with an isolated calyx in which TAE was successful. TAE seems useful in treating intractable urinary fistulas with an isolated calyx occurring after RAPN.

Robot-assisted radical prostatectomy in a patient with prostate cancer complicated by benign prostate hypertrophy with middle lobe hypertrophy.

Robot-assisted radical prostatectomy (RARP) is difficult in patients with benign prostatic hyperplasia (BPH), a condition causing frequent urination, because of the large prostate volume and particularly true when BPH is accompanied by an enlarged middle lobe. To overcome this difficulty, some surgeons elevate the middle lobe with a third arm or tow the urethral catheter to the edge to identify the resection line. Herein, we describe a method for lifting a prostate with an enlarged middle lobe, which was successfully applied in a patient with prostate cancer and BPH. This technique can help identify the resection line between the bladder and prostate, reducing surgical difficulty and the number of unnecessary sutures.

Variations in predictors for urinary continence recovery at different time periods following robot-assisted radical prostatectomy.

INTRODUCTION: Urinary dysfunctions are common sequelae following prostatectomy. This study aimed to discover factors that can predict urinary continence recovery at various time periods after robot-assisted laparoscopic radical prostatectomy (RARP). METHODS: This was a retrospective analysis of data of 419 consecutive patients. Only patients followed up for ≥1 year were enrolled. An answer of "zero pad per day" in the Expanded Prostate Cancer Index Composite urinary assessment (question 5) denoted continence. Possible predictors of urinary continence recovery were evaluated at 3, 3-6, and 6-12 months after the operation. RESULTS: Continence rates at 3, 6, and 12 months after RARP were 12.9%, 21.2%, and 40.2%, respectively. The proportions of patients using 0-1 pad were 54.2%, 75.7%, and 83.1% at 3, 6, and 12 months after RARP, respectively. Multivariable regression analysis revealed that a membranous urethral length (MUL) ≥11 mm was significantly associated with urinary continence recovery both within 3 months (odds ratio: 0.367, P = .003) and 3-6 months (odds ratio: 0.354, P = .001) after RARP. The analysis also revealed that, in patients with urinary continence at 6 months, a large prostate volume (odds ratio: 1.973, P = .044) and a high body mass index (odds ratio: 2.874, P = .027) were negative predictors of urinary continence recovery within 6-12 months. CONCLUSION: A longer MUL was linked to urinary continence recovery within 6 months following RARP, whereas a large prostate volume and a high body mass index were adverse predictors of urinary continence recovery beyond 6 months.

Two Cases of Intractable Radiation-Induced Hemorrhagic Cystitis Treated with Transcatheter Embolization.

Radiation-induced hemorrhagic cystitis is a late complication of radiotherapy, and in rare cases, refractory. Refractory bleeding may not be resolved by transurethral electrocoagulation (TUEC) or hyperbaric oxygen (HBO) therapy and requires transcatheter arterial embolization (TAE) or urinary diversion. Here, we report two cases of radiation-induced hemorrhagic cystitis successfully treated with TAE. Case 1 was a 61-yearold man who underwent total prostatectomy for prostate cancer followed by salvage radiation therapy. The patient developed radiation-induced hemorrhagic cystitis 2 years and 3 months after radiotherapy. After no improvement with TUEC and HBO, TAE was performed. Case 2 was a 78-year-old man who underwent total prostatectomy followed by salvage radiation therapy and developed radiation-induced hemorrhagic cystitis 12 years later. TAE was performed after no improvement with HBO. TAE proved successful in both patients, and there was no relapse. TAE is a potential treatment option for refractory radiation-induced hemorrhagic cystitis.

Current status and future outlook of ultrasound treatment for prostate cancer.

Radical prostatectomy and radiation therapy are the standard treatment options for localized prostate cancer (PC). However, radical prostatectomy may cause the deterioration of urinary and sexual function, and radiation-induced hemorrhagic cystitis and severe rectal bleeding are risk factors for fatal conditions in patients after radiation therapy. With the recent development of magnetic resonance imaging (MRI) for the localization of clinically significant PC (csPC) and treatment modalities, "focal therapy", which cures csPC while preserving anatomical structures related to urinary and sexual functions, has become a minimally invasive treatment for localized PC. Based on the clinical results of transrectal high-intensity focused ultrasound (HIFU) for localized PC in the whole gland and focal therapy, HIFU is considered an attractive treatment option for focal therapy. Recently, the short-term clinical results of transurethral high-intensity directional ultrasound (HIDU) have been reported. With the resolution of some issues, HIDU may be commonly used for PC treatment similar to HIFU. Because HIFU and HIDU have limitations regarding the treatment of patients with large prostate calcifications and large prostate volumes, the proper use of these modalities will enable the treatment of any target area in the prostate. To establish a standard treatment strategy for localized PC, pair-matched and historically controlled studies are required to verify the oncological and functional outcomes of ultrasound treatment for patients with localized PC.

Impact of tumor contact surface area on collecting system entry in robot-assisted partial nephrectomy: a retrospective analysis.

BACKGROUND: Collecting system entry in robot-assisted partial nephrectomy may occur even in cases showing a low N factor in the R.E.N.A.L nephrometry score. Therefore, in this study, we focused on the tumor contact surface area with the adjacent renal parenchyma and attempted to construct a novel predictive model for collecting system entry. METHODS: Among 190 patients who underwent robot-assisted partial nephrectomy at our institution from 2015 to 2021, 94 patients with a low N factor (1-2) were analyzed. Contact surface was measured with three-dimensional imaging software and defined as the C factor, classified as C1, < 10 cm [2]; C2, ≥ 10 and < 15 cm [2]; and C3: ≥ 15 cm [2]. Additionally, a modified R factor (mR) was classified as mR1, < 20 mm; mR2, ≥ 20 and < 40 mm; and mR3, ≥ 40 mm. We discussed the factors influencing collecting system entry, including the C factor, and created a novel collecting system entry predictive model. RESULTS: Collecting system entry was observed in 32 patients with a low N factor (34%). The C factor was the only independent predictive factor for collecting system entry in multivariate regression analysis (odds ratio: 4.195, 95% CI: 2.160-8.146, p < 0.0001). Models including the C factor showed better discriminative power than the models without the C factor. CONCLUSIONS: The new predictive model, including the C factor in N1-2 cases, may be beneficial, considering its indication for preoperative ureteral catheter placement in patients undergoing robot-assisted partial nephrectomy.

IDH2 stabilizes HIF-1α-induced metabolic reprogramming and promotes chemoresistance in urothelial cancer.

Drug resistance contributes to poor therapeutic response in urothelial carcinoma (UC). Metabolomic analysis suggested metabolic reprogramming in gemcitabine-resistant urothelial carcinoma cells, whereby increased aerobic glycolysis and metabolic stimulation of the pentose phosphate pathway (PPP) promoted pyrimidine biosynthesis to increase the production of the gemcitabine competitor deoxycytidine triphosphate (dCTP) that diminishes its therapeutic effect. Furthermore, we observed that gain-of-function of isocitrate dehydrogenase 2 (IDH2) induced reductive glutamine metabolism to stabilize Hif-1α expression and consequently stimulate aerobic glycolysis and PPP bypass in gemcitabine-resistant UC cells. Interestingly, IDH2-mediated metabolic reprogramming also caused cross resistance to CDDP, by elevating the antioxidant defense via increased NADPH and glutathione production. Downregulation or pharmacological suppression of IDH2 restored chemosensitivity. Since the expression of key metabolic enzymes, such as TIGAR, TKT, and CTPS1, were affected by IDH2-mediated metabolic reprogramming and related to poor prognosis in patients, IDH2 might become a new therapeutic target for restoring chemosensitivity in chemo-resistant urothelial carcinoma.

Usefulness of LacdiNAc-glycosylated Prostate-specific Antigen Density for Predicting Pathological Findings of Magnetic Resonance Imaging-transrectal Ultrasound Fusion Image-guided Prostate Biopsy for the Patients With Highest Prostate Imaging Reporting and Data System Category ≥3.

PURPOSE: This study aimed to evaluate the usefulness of the LDN-PSA (LacdiNAc-glycosylated-prostate specific antigen) in detecting clinically significant prostate cancer in patients suspected of having clinically significant prostate cancer on multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Patients with prostate specific antigen levels ranging between 3.0 ng/mL and 20 ng/mL and suspicious lesions with PI-RADS (Prostate Imaging-Reporting and Data System) category ≥3 were included prospectively. The LDN-PSA was measured using an automated 2-step Wisteria floribunda agglutinin lectin-anti-prostate specific antigen antibody sandwich immunoassay. RESULTS: Two hundred four patients were included. Clinically significant prostate cancer was detected in 105 patients. On multivariable logistic regression analysis, prostate specific antigen density (OR 1.61, P = .010), LDN-PSAD (OR 1.04, P = .012), highest PI-RADS category (3 vs 4, 5; OR 14.5, P < .0001), and location of the lesion with highest PI-RADS category (transition zone vs peripheral zone) (OR 0.34, P = .009) were significant risk factors for detecting clinically significant prostate cancer. Among the patients with the highest PI-RADS category 3 (n=113), clinically significant prostate cancer was detected in 28 patients. On multivariable logistic regression analysis to predict the detection of clinically significant prostate cancer in patients with the highest PI-RADS category 3, age (OR 1.10, P = .026) and LDN-PSAD (OR 1.07, P < .0001) were risk factors for detecting clinically significant prostate cancer. CONCLUSIONS: LDN-PSAD would be a biomarker for detecting clinically significant prostate cancer in patients with prostate specific antigen levels ≤20 ng/mL and suspicious lesions with PI-RADS category ≥3. The use of LDN-PSAD as an adjunct to the use of prostate specific antigen levels would avoid unnecessary biopsies in patients with the highest PI-RADS category 3. Multi-institutional studies with large population are recommended.

Risk Factors for Severe Erectile Dysfunction after Focal Therapy with High-Intensity Focused Ultrasound for Prostate Cancer.

The present study aimed to analyze the effect of predisposing clinical factors for severe erectile dysfunction (ED) in patients treated with focal therapy using high-intensity focused ultrasound (HIFU) for localized prostate cancer (PC). Patients without severe ED (International Index of Erectile Function-5 [IIEF-5] score ≥ 8) before focal HIFU therapy were included. A total of 92 of the 240 patients met the inclusion criteria and were included. The rate of severe ED (IIEF-5 ≤ 7) was 36% 12 months after treatment. Multivariable logistic regression analysis showed that the pre-procedural lower IIEF-5 score (odds ratio [OR] 0.812, p = 0.005), the pre-procedural lower score of the sexual domain of the Expanded Prostate Cancer Index Composite (OR 0.960, p = 0.038), and the treatment of the edge of the peripheral zone (PZ) in proximity to the neurovascular bundle (NVB) [treated vs. untreated, OR 8.048, p = 0.028] were significant risk factors for severe ED at 12 months after treatment. In conclusion, pre-procedural lower erectile function and treatment of the part in proximity to the NVB were significant risk factors for severe ED after focal therapy.

Preoperative factors affecting the operative outcomes of laparoscopic nephrectomy.

OBJECTIVES: Laparoscopic radical nephrectomy is the standard surgery for localized renal cell carcinoma. Both tumor and patient factors affect the difficulty of laparoscopic radical nephrectomy. Obesity is a major factor influencing technical difficulty in surgical procedures. This study examined preoperative tumor and patient factors affecting the operating time. METHODS: The data of 123 patients who underwent laparoscopic radical nephrectomy at our institution between January 2014 and December 2018 were retrospectively analyzed. The operating time was determined based on the median pneumoperitoneum time. Surgical procedures with a pneumoperitoneum time of ≥130 min were defined as having prolonged pneumoperitoneum time. Multiple logistic regression analyses were performed to identify the preoperative factors affecting the prolonged pneumoperitoneum time, and risk stratification was performed based on these factors. RESULTS: Multiple logistic regression analyses revealed that a total number of renal pedicle blood vessels ≥3 and a visceral fat volume ≥3000 cm3 were associated with prolonged pneumoperitoneum time of laparoscopic radical nephrectomy. Based on the multivariate analysis results, these factors were considered individually, and the cohort was stratified into three risk groups: low (0 point), intermediate (1 point), and high (2 points) risk groups. The pneumoperitoneum time was significantly prolonged as the number of risk factors increased. CONCLUSIONS: We developed a risk stratification model using preoperative factors to predict the prolonged pneumoperitoneum time of laparoscopic radical nephrectomy, which can help select suitable cases that are appropriate for each surgeon's skill level.

Impact of stone volume on treatment outcomes of percutaneous nephrolithotripsy.

PURPOSE: We aimed to evaluate the impact of stone volume on the surgical outcomes of patients who underwent percutaneous nephrolithotripsy, which is the preferred treatment for renal and upper ureteral stones. MATERIALS AND METHODS: This retrospective study included 37 patients who underwent percutaneous lithotripsy between 2013 and 2019. Preoperative and postoperative stone volumes were quantified using computed tomography scan data. RESULTS: The mean preoperative and postoperative stone volumes were 10.7 cm3 (1.1-50.2 cm3 ) and 2.1 cm3 (0-18.2 cm3 ), respectively. The correlation coefficient between the stone volume and maximum stone length was 0.62 (P < .01). A residual stone volume of >5 mm was observed in 17 cases (45.9%). Thirteen cases underwent secondary treatment (35.1%) who had a preoperative stone volume of >15 cm3 or a postoperative stone volume of <2 cm3 . The areas under the curve for the stone volume for treatment success and the requirement for secondary treatment were 0.701 and 0.739, respectively, and were higher than those of stone length (0.638 and 0.558) and shape (0.644 and 0.641). CONCLUSIONS: Measurement of stone volume using three-dimensional imaging is simple and greatly impacted the course of stone treatment. Information on stone volume may predict an increased likelihood of secondary treatment in patients with a preoperative stone volume of >15 cm3 .

Development and future prospective of treatment for localized prostate cancer with high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) was experimentally used for focal therapy for anti-cancer effects in prostate cancer (PC). Focal therapy is a diagnosis-based investigational treatment option for localized PC that cures clinically significant PC (csPC) while preserving the anatomical structures related to urinary and sexual function based on its spread observed using multi-parametric magnetic resonance imaging (mpMRI). The European Association of Urology indicated that the current status of focal therapy for localized PC was an investigational modality and encouraged prospective recording of outcomes and recruitment of suitable patients in 2018. During the last few years, large-population multi- and single-center prospective studies have investigated focal therapy as a treatment strategy for localized PC. In a multicenter prospective study with 5-year follow-up, failure-free survival, which was defined as avoidance of local salvage therapy (surgery or radiotherapy), systemic therapy, metastases, and prostate cancer-specific death, was 88%. In the previous studies, there was no significant influence on urinary function before and at 3 months after the treatment, although transient impairment was reported 1 month after the treatment. Pad- and leak-free continence was preserved in 80-100% of the patients after treatment. Erectile function was significantly impaired in the initial 3 months after treatment compared to the pretreatment values, but it improved 6 months after the focal therapy in the previous reports. Paired comparison studies and cohort studies with long-term follow-up will contribute to verifying this treatment's clinical outcomes for patients with localized PC.

How long should urologists observe patients with prostate cancer after radical prostatectomy? Weibull analysis.

OBJECTIVES: There is no recommended observation time for patients who have undergone radical prostatectomy for prostate cancer. This study was undertaken to determine the postoperative observation time by investigating the hazard rate for prostate-specific antigen failure and other-cause death using Weibull analysis. METHODS: We included 612 patients who underwent laparoscopic radical prostatectomy for localized prostate cancer between June 2002 and December 2017. Risk classification was categorized by the D'Amico risk classification, and the patients were divided into three age groups: <60, 60-69 and ≥70 years. The hazard rates at each point were derived using Weibull analysis. The optimal observation time after laparoscopic radical prostatectomy was determined as the intersection point at which the hazard rate of other-cause death overtakes the hazard rate of prostate-specific antigen failure. RESULTS: In all groups classified by age, the hazard rate of other-cause deaths increased over time. In contrast, the hazard rate of prostate-specific antigen failure decreased gradually. The ≥70 years age group showed the highest hazard rate. The hazard rate of prostate-specific antigen failure was highest in the high-risk group. The patients aged ≥70 and 60-69 years in the low-risk group were recommended 6 years 6 months and 14 years 8 months, respectively, for observation. The remaining patients were recommended >25 years of postsurgical observation. CONCLUSIONS: The observation time after laparoscopic radical prostatectomy could be estimated by comparing the estimated hazard rates of prostate-specific antigen failure and other-cause death based on Weibull analysis. Urologists should pay attention to age and risk classifications for optimal postoperative observation.

Effects of psoas major muscle volume in predicting the prognosis of patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

BACKGROUND: This study evaluated the impact of sarcopenia and psoas major muscle volume on the survival of patients with upper urinary tract urothelial carcinoma who had undergone radical nephroureterectomy. METHODS: We reviewed data from 110 patients treated with radical nephroureterectomy in our department between June 2007 and February 2017. Psoas major muscle volume was quantified based on computed tomography data using Synapse Vincent software. The psoas major muscle volume index was calculated as psoas major muscle volume/height squared (cm3/m2). We analysed relapse-free survival, cancer-specific survival and overall survival after radical nephroureterectomy to identify factors that predicted patient survival. RESULTS: The median psoas major muscle volume index was 121.5 cm3/m2, and the psoas major muscle volume index was <100 cm3/m2 in 34 of 110 patients (30.9%). Multivariate analysis indicated that ≥pT3-stage cancer, lymphovascular invasion and a psoas major muscle volume index of <100 cm3/m2 were independent predictors of shorter relapse-free survival, cancer-specific survival and overall survival. Using these factors, patients were stratified into three groups: low, intermediate and high risks for relapse-free survival, cancer-specific survival and overall survival. CONCLUSIONS: Low psoas major muscle volume resulting from sarcopenia, high T stage and the presence of lymphovascular invasion was associated with poor survival in patients with urinary tract urothelial carcinoma who had undergone radical nephroureterectomy, supporting the use of psoas major muscle volume as a new objective prognostic marker.

Analysis of oncological outcomes of whole-gland therapy with high-intensity focused ultrasound for localized prostate cancer in clinical and technical aspects: a retrospective consecutive case-series analysis with a median 5-year follow-up.

PURPOSE: This study aimed to analyze technical and clinical factors related to oncological outcomes in patients with localized prostate cancer (PC) who were treated with whole-gland high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: From 2007-2014, patients diagnosed with localized PC who underwent whole-gland HIFU were consecutively included retrospectively. Biochemical failure was defined according to the Phoenix ASTRO guidelines. The relationship between oncological outcomes and technical and clinical factors was evaluated. RESULTS: The study cohort included 428 patients. The median age was 67 years, and the median prostate-specific antigen level was 7.61 ng/mL. Patient risk classifications were low (n = 102), intermediate (n = 240), and high (n = 86). Biochemical disease-free survival rates of patients with HIFU for localized PC in the total, low-, intermediate-, and high-risk groups according to D'Amico risk groups over a median follow-up period of 5 years (range 9-144) were 68.4%, 80.4%, 65.6%, and 61.6%, respectively. In multivariate logistic regression analyses to predict biochemical failure of the treatment, neoadjuvant hormonal therapy (NHT) in the high-risk group (OR 0.225, p = 0.015), and compression method in the low- (OR 0.178, p = 0.030), intermediate- (OR0.291, p < 0.0001), and high-risk (OR 0.316, p = 0.049) groups were significant factors that reduced the risk of biochemical failure after treatment. There were no significant differences in complications between patients treated with compression and those treated conventionally. CONCLUSIONS: NHT may potentially improve oncological outcomes for patients in the high-risk group, and compression methods can improve the oncological outcomes of whole-gland therapy with HIFU.