白木 良一

Alanine-serine-cysteine transporter 2 (ASCT2) has been associated with increased levels of metabolism in various malignant tumors. However, its biological significance in the proliferation of prostate cancer (PCa) cells remains under investigation. We used the cBioPortal database to assess the effect of ASCT2 expression on the oncological outcomes of 108 PCa patients. To evaluate the function of ASCT2 in castration-sensitive PCa (CSPC) and castration-resistant PCa (CRPC), LNCaP cells and the ARV7-positive PCa cell line, 22Rv1, were assessed using cell proliferation assays and Western blot analyses. The ASCT2 expression level was associated with biochemical recurrence-free survival after prostatectomy in patients with a Gleason score ≥ 7. In vitro experiments indicated that the growth of LNCaP cells after combination therapy of ASCT2 siRNA and enzalutamide treatment was significantly reduced, compared to that following treatment with enzalutamide alone or ASCT2 siRNA transfection alone (p < 0.01, 0.01, respectively). After ASCT2 inhibition by siRNA transfection, the growth of 22Rv1 cells was significantly suppressed as compared with negative control siRNA via downregulation of ARV7 both in fetal bovine serum and androgen-deprivation conditions (p < 0.01, 0.01, respectively). We demonstrated that ASCT2 inhibition significantly reduced the proliferation rates of both CSPC and CRPC cells in vitro.

OBJECTIVES: Robot-assisted partial nephrectomy is widely performed for small renal masses, achieving excellent perioperative and intermediate oncological outcomes. However, long-term oncological, functional, and quality of life outcomes after robot-assisted partial nephrectomy remain unclear. In this study, we aimed to evaluate quality of life at 1 year and oncological and functional outcomes of robot-assisted partial nephrectomy after a minimum follow-up of 5 years. METHODS: Personal, perioperative, postoperative, functional, oncological, and quality of life data were evaluated. The EQ-5D-5L tool, which incorporates health profiles and a EuroQol Visual Analog Scale, was used to assess quality of life preoperatively and 365 days postoperatively. Regarding oncological and functional outcomes, overall survival, recurrence-free survival, and changes in estimated glomerular filtration rate were calculated. RESULTS: There were few changes in levels between the two time points for all EQ-5D dimensions. The mean change in EQ-5D-5L was 0.020 (95% confidence interval 0.006-0.033, P = 0.006), and in EuroQol Visual Analog Scale score 4.60 (95% confidence interval 2.17-7.02, P = 0.0003). Overall and recurrence-free survival 5 years after robot-assisted partial nephrectomy were 97.9% and 92.8%, respectively. After an early postoperative decrease, the estimated glomerular filtration rate remained stable over time. CONCLUSIONS: Robot-assisted partial nephrectomy in patients with a T1 renal tumor is safe, feasible, and effective from the perspective of quality of life and survival, even after 5 years. When making treatment decisions, perioperative and quality of life outcomes should be considered together with long-term oncological outcomes.

OBJECTIVES: To evaluate the risk factors for postoperative ileus in patients who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion. METHODS: We retrospectively analyzed 78 patients with bladder cancer who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion at Fujita Health University between 2011 and 2021. Baseline characteristics and perioperative outcomes were compared between the cohorts with and without ileus. Logistic regression analysis was used to identify the risk factors for postoperative ileus. RESULTS: Out of the 78 patients included in this study, 20 (25.6%) developed postoperative ileus. The ileus cohort was associated with a significantly lower Geriatric-8 score (P = 0.003) and a higher rate of previous abdominal/pelvic surgery (P = 0.04) compared with those of the nonileus cohort. Significantly longer intestinal tract reconstruction time, hospital stay, time to mobilization, fluid intake, solid intake, flatus, and stool were observed in the ileus cohort. According to the results of the logistic regression analysis, the Geriatric-8 sum (P = 0.009), time to mobilization (P = 0.03), and time to fluid intake (P = 0.004) were independent predictors of postoperative ileus. In the model predicting postoperative ileus, the area under the receiver operating characteristic curve was 0.716, and the cutoff value of the Geriatric-8 sum was 13. CONCLUSIONS: Early mobilization and fluid intake and low Geriatric-8 scores were significant risk factors for postoperative ileus. Preoperative Geriatric-8 evaluation is a useful tool for predicting postoperative ileus. Comprehensive enhanced recovery after surgery, including key components, may help bowel recovery and prevent subsequent ileus.

To assess the perioperative and short-term functional outcomes of robot-assisted partial nephrectomy (RAPN) with intraoperative navigation using an ultra-high-resolution computed tomography (UHR-CT) scanner, we retrospectively analyzed 323 patients who underwent RAPN using an UHR-CT or area-detector CT (ADCT). Perioperative outcomes and the postoperative preservation ratio of estimated glomerular filtration rate (eGFR) were compared. After the propensity score matching, we evaluated 99 patients in each group. Although the median warm ischemia time (WIT) was less than 25 min in both groups, it was significantly shorter in the UHR-CT group than in the ADCT group (15 min vs. 17 min, p = 0.032). Moreover, the estimated blood loss (EBL) was significantly lower in the UHR-CT group than in the ADCT group (33 mL vs. 50 mL, p = 0.028). However, there were no significant intergroup differences in the postoperative preservation ratio of eGFR at 3 or 6 months of follow-up (ADCT 91.8% vs. UHR-CT 93.5%, p = 0.195; and ADCT 91.7% vs. UHR-CT 94.0%, p = 0.160, respectively). Although no differences in short-term renal function were observed in intraoperative navigation for RAPN in this propensity score-matched cohort, this study is the first to demonstrate that UHR-CT resulted in a shorter WIT and lower EBL than ADCT.

Objective: This study aimed to compare the perioperative and long-term functional outcomes between robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN) in Japanese patients. Methods: We retrospectively analyzed 242 patients who underwent either RAPN or OPN between 2007 and 2017 at our hospital. Propensity score matching was carried out between the two groups at a ratio of 1:1. Perioperative outcomes and postoperative estimated glomerular filtration rates (eGFR) were compared at one and three years of follow-up. Results: After propensity score matching, we evaluated 39 patients from each group. The ischemia duration of the RAPN group was significantly shorter than that of the OPN group (18 vs. 24, p < 0.001). Moreover, the estimated blood loss (EBL) was significantly lower in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). However, there were no significant differences in the postoperative eGFR between the two groups at one or three years of follow-up (OPN 54.8 vs. RAPN 61.2, p = 0.109, and OPN 54.8 vs. RAPN 55.5, p = 0.262, respectively). Conclusion: RAPN resulted in shorter ischemia durations and lower rates of EBL than did OPN; however, no differences in long-term renal function were observed between RAPN and OPN in our propensity-score matched Japanese cohort.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by loss-of-function mutations in either of two tumor suppressor genes, TSC1 and TSC2. These mutations lead to the growth of benign tumors and hamartomas in many organs, including those of the central nervous system, the skin, and the kidneys. To investigate the genotype-phenotype correlation, we performed sequence analysis of the TSC1/2 genes using next-generation sequencing. We classified 30 patients with TSC whose pathogenic variants were identified into two groups: those with mutations producing premature termination codons (PTCs) and those with missense mutations. Then, we compared the phenotypes between the two groups. Patients with a PTC were significantly more likely to manifest the major symptoms of the diagnostic criteria than those without a PTC (P = 0.035). The frequencies of subependymal nodules (P = 0.026), cortical tubers (P = 0.026), and renal cysts (P = 0.026) were significantly higher in PTC-containing variants than in cases without a PTC. When the analyses were limited to renal angiomyolipoma (AML) cases with TSC2 mutations, there was no difference in tumor size between cases with and without a PTC. However, the cases with a PTC showed a trend toward disease onset at a younger age and multiple tumors, and bilateral disease was observed in their AML lesions. TSC patients with PTC-producing mutations might potentially manifest more severe TSC phenotypes than those with missense mutations. A larger-scale study with appropriate samples deserves further investigation.

The aim of the present study was to evaluate the prognosis of Japanese patients with metastatic renal cell carcinoma (mRCC) receiving nivolumab and to identify factors predicting the overall survival (OS) in this cohort of patients. This study retrospectively assessed the outcomes of 77 consecutive Japanese patients with mRCC who were treated using either 1 or 2 molecular-targeted agents followed by nivolumab in routine clinical practice. The best responses to nivolumab observed were as follows: Complete response in 3 patients, partial response in 27, stable disease in 33 and progressive disease in 14; therefore, the objective response rate in the 77 patients was 39.0%. During the median follow-up period of 11 months after the introduction of nivolumab, the median progression-free survival and OS were 7 months and not reached, respectively. On multivariate analysis of several parameters, age, Karnofsky Performance Status (KPS) and neutrophil counts were demonstrated to be independently associated with OS in the 77 patients. By dividing these patients into 3 groups according to 3 risk factors, it was possible to stratify the OS; however, the International Metastatic Renal Cell Carcinoma Database Consortium model was unable to classify the OS. These results suggested that age, KPS and neutrophil counts were useful predictors of OS in previously treated patients with mRCC who received nivolumab.

OBJECTIVE: Recently, hormonal therapy using abiraterone acetate, a second-generation androgen receptor axis-targeted agent, was reported to improve overall survival and progression-free survival in men with LATITUDE-high-risk metastatic castration-sensitive prostate cancer. This observational multicenter study aimed to assess the efficacy of upfront abiraterone acetate in Japanese patients with LATITUDE-high-risk metastatic castration-sensitive prostate cancer. METHODS: The present study included 112 Japanese patients with LATITUDE-high-risk metastatic castration-sensitive prostate cancer who received upfront abiraterone acetate at four institutions belonging to the Tokai Urologic Oncology Research Seminar group, between January 2018 and September 2020. Progression-free survival and overall survival were assessed, and Cox regression analyses were carried out to evaluate the prognostic significance of upfront abiraterone acetate for progression-free survival. RESULTS: Within a median follow-up period of 13 months, the progression-free survival and overall survival rates were 76.8% and 89.3%, respectively. Both univariate and multivariable Cox regression analyses showed that the presence of Gleason pattern 5, performance status and hemoglobin were independent predictors of progression-free survival. The patients were subsequently divided into three groups as follows: group 1, 17 patients negative for these three independent progression-free survival predictors; group 2, 49 patients with one positive independent progression-free survival predictor; and group 3, 45 patients with two or three independent progression-free survival predictors. Progression-free survival was significantly different among these three groups (P < 0.001). CONCLUSION: Upfront abiraterone acetate might provide satisfactory outcomes for Japanese patients with LATITUDE-high-risk metastatic castration-sensitive prostate cancer. Gleason pattern 5, performance status and hemoglobin are potential predictors of progression-free survival in Japanese patients with LATITUDE-high-risk metastatic castration-sensitive prostate cancer who received upfront abiraterone acetate.

BACKGROUND: Combining abiraterone (Abi) with androgen deprivation therapy (ADT) improves overall survival, compared to ADT only, in patients with metastatic castration-sensitive prostate cancer (mCSPC). In Japan, bicalutamide (Bica) and ADT (combined androgen blockade: CAB) is frequently provided for mCSPC. Because these two treatments have not been compared, mCSPC patients who received either treatment were retrospectively analyzed. METHODS: Of 178 patients with LATITUDE high-risk mCSPC, 103 had received ADT plus upfront Abi (Abi group) and 75 had received ADT plus Bica (Bica group) in multiple institutions of the Tokai Urologic Oncology Research Seminar. Kaplan-Meir curves were used to retrospectively analyze survival and cancer recurrence. Univariate and multivariate Cox regression analyses identified potential prognostic factors for progression-free survival (PFS). RESULTS: Significant differences in major clinicopathological characteristics between the two groups were not observed. The rate of castration-resistant development was higher in the Bica compared to Abi group (50.6 vs. 25.2%, p < 0.001). The median PFS in the Bica group was 13.6 months {95% confidence interval [CI] 9.2-22.2}; however, in the Abi group, PFS did not reach the median {95% CI 18.5-not assessed [NA]; p < 0.001}. Time to second progression for the Abi group was superior (p = 0.07). Univariate and multivariate analyses revealed Gleason pattern 5, high alkaline phosphatase levels, and conventional CAB using Bica as significant prognostic factors for short PFS. CONCLUSIONS: In patients with LATITUDE high-risk mCSPC, upfront use of Abi combined with ADT resulted in favorable prognostic outcomes compared with conventional ADT with Bica.

PURPOSE: The incidence of secondary bladder cancer after treatment for localized prostate cancer (PCa) remains unclear. In this study, PCa cases treated with brachytherapy (BT) were evaluated to assess the incidence of a second malignancy of bladder cancer in a Japanese cohort. MATERIALS AND METHODS: Overall, 969 patients treated with BT at our hospital between July 2006 and January 2019 were included in the study cohort. The incidence and predictors of secondary bladder cancer were also assessed. RESULTS: The incidence of secondary bladder cancer was 1.5% (n = 14). Of the seven factors (age, pretreatment PSA, Gleason score, cTNM stage, prostate volume, total activity, and combined external beam), prostate volume and total activity showed significant differences between the cohorts with and without secondary bladder cancer (P = .03 and P = .001, respectively). Upon comparison of the seven parameters for the 969 patients treated with BT, we found that only the total activity factor was affected by the incidence of secondary bladder cancer in the multivariate analysis (P = .007). CONCLUSION: The incidence of secondary bladder cancer was evaluated after BT for PCa. Total activity was associated with the incidence of secondary bladder cancer in Japanese patients who received BT.

BACKGROUND: To compare perioperative and long-term oncological outcomes and recurrence patterns between robot-assisted radical cystectomy with intra-corporeal urinary diversion (iRARC) and open radical cystectomy (ORC). METHODS: We retrospectively analyzed 177 bladder cancer patients who received iRARC or ORC at Fujita Health University between 2008 and 2020. Our primary endpoint was long-term oncological outcomes. As a secondary endpoint, we examined perioperative outcomes, complications, and recurrence patterns. These outcome measures were compared between the propensity score (PS)-matched cohorts. RESULTS: PS-matched analysis resulted in 60 matched pairs from iRARC and ORC groups. The iRARC cohort was associated with significantly longer operative time (p = 0.02), lower estimated blood loss (p < 0.001), lower blood transfusion rate (p < 0.001), shorter length of hospital stay (p < 0.001), fewer overall complications (p = 0.03), and lower rate of postoperative ileus (p = 0.02). There was no statistically significant difference between iRARC and ORC in 5-year RFS (p = 0.46), CSS (p = 0.63), and OS (p = 0.71). RFS and CSS were also comparable, even in locally advanced (≥ cT3) disease. Multivariate analysis identified lymphovascular invasion as a robust predictor of RFS, CSS, and OS. The number of recurrence was similar between the groups, while extra-pelvic lymph nodes were more frequent in iRARC than that in ORC (22.7% vs. 7.7%). CONCLUSIONS: iRARC has favorable perioperative outcomes, fewer complications, and comparable long-term survival outcomes, including locally advanced (≥ cT3) disease, compared to that in ORC. Our results need to be validated in prospective randomized clinical trials.

Objectives: To evaluate the outcomes of robot-assisted partial nephrectomy (RAPN) in cystic renal tumors. Materials and Methods: We retrospectively analyzed patients who underwent RAPN for either cystic (n = 46) or solid (n = 271) renal tumors at Fujita Health University between 2010 and 2019. Cystic renal tumors were diagnosed using cross-sectional imaging. Perioperative, oncologic, and functional outcomes were assessed. Results: The median follow-up periods were 38, 41, and 37 months in the total, cystic, and solid groups, respectively. Most patient characteristics were similar among both groups, while the median age of the cystic group was significantly lower than that of the solid group (p = 0.02). Most perioperative variables and complications were comparable between the two groups. There was no significant difference between the groups in perioperative renal function. The estimated glomerular filtration rate preservation rates were 93.1% and 89.2% in the cystic and solid groups, respectively (p = 0.17). The cystic group showed a higher benign histology rate (19.6% vs 7%) and lower Fuhrman grade than the solid group (24.3% vs 15.1% in grade 1, and 73% vs 81.3% in grade 2), although there was no statistically significant difference between the two groups. In the solid group, 10 patients (3.7%) experienced recurrence, and 2 patients (0.7%) died of renal-cell carcinoma, while none of the patients with cystic tumors experienced recurrence. There was no statistically significant difference between the cystic and solid tumors with respect to 5-year recurrence-free survival (p = 0.18), cancer-specific survival (p = 0.55), and overall survival (p = 0.35). Conclusions: RAPN for cystic renal tumors appears to be safe and feasible with perioperative, long-term functional and oncologic outcomes comparable with those in solid tumors. RAPN can be a safe and effective surgical option for cystic renal tumors.

ABSTRACT: Nivolumab has shown good prognosis in renal cell carcinoma (RCC) patients previously treated with targeted therapy. We aimed to study irAE (immune-related adverse event) due to nivolumab and numbers of previous treatment lines in RCC patients. Between October 2016 and November 2019, 114 patients were treated with nivolumab as second- and later-line therapy. Among them, 110 patients with complete data were evaluated in this retrospective observational study. The primary endpoint was the relation between irAE and numbers of previous targeted therapies. Secondary endpoints were the relation of irAE with the duration of nivolumab treatment and with best overall response. For the primary analysis, proportional odds logistic regression was used to assess the effect of the number of prior therapies on the grade of any irAE as the ordinal variable. For the secondary analysis, binomial logistic regression models adjusted for the covariates were prepared to confirm the association between the incidence of irAE and the number of courses, number of nivolumab treatments and best overall response. Overall, 69, 66, 33, 13, 9 and 9 patients were treated with sunitinib, axitinib, pazopanib, sorafenib, temsirolimus and everolimus, respectively, prior to nivolumab. In total, 60 adverse events (Grade 1, 21; Grade 2, 21; Grade 3, 14; Grade 4, 2; not evaluated, 2) were identified in the patients treated with nivolumab. Ordered logistic regression analysis showed that the adjusted odds ratios of numbers of prior treatment for grade of irAE were 1.12 (numbers of prior treatment: 2 to 1) and 1.31 (3 to 1). Odds ratios of the numbers of nivolumab treatments and best overall response for the incidence of irAE were not significant. No statistically significant relations were found between grade of irAE and numbers of treatments prior to nivolumab. Patients treated with nivolumab should be closely monitored for irAE regardless number of previous therapies.

OBJECTIVE: To investigate whether robot-assisted partial nephrectomy compared with laparoscopic partial nephrectomy is effective for renal hilar tumor removal. METHODS: This was a prospective, multicenter, single-arm, open-label trial with a 2-year enrollment period. A total of 22 academic hospitals in Japan participated in the present study. Comparison with historical control values from reported studies of laparoscopic partial nephrectomy was carried out. The warm ischemia time and positive surgical margin rate were set as primary perioperative and oncological outcomes. In the historical control group, these were 27.7 min and 13%, respectively. RESULTS: The analysis population included 105 participants. The mean warm ischemia time was 20.2 (95% confidence interval 16.7-21.8; P < 0.0001 vs 27.7). Two of 103 participants (1.9%) had a positive surgical margin (95% confidence interval 0.5-6.8%). Both results satisfy the prespecified decision criteria for the superiority of robot-assisted partial nephrectomy over the historical control of laparoscopic partial nephrectomy. Resected weight and preoperative estimated glomerular filtration rate were predictive factors of functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSION: Robot-assisted partial nephrectomy for clinical T1 renal hilar tumors results in shorter warm ischemia time than and comparable positive surgical margin rate to those reported for laparoscopic partial nephrectomy.

Background Lipid metabolism has been associated with the development of autism. The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) readily undergo lipid peroxidation and conversion to malondialdehyde (MDA). MDA-modified low-density lipoprotein (MDA-LDL) is a marker of lipid peroxidation. However, the association between PUFAs and MDA-LDL in the pathophysiology of autism spectrum disorder (ASD) is unclear. Materials and methods We studied the association between PUFAs and MDA-LDL in 16 individuals with ASD (mean age: 11.5 ± 5.7 years) and seven age- and sex-matched healthy controls (mean age: 10.0 ± 4.1 years). The Aberrant Behavior Checklist (ABC) was used to assess behavioral symptoms. We overcame the small sample size by using the adaptive LASSO for enhancing the accuracy of prediction and interpretability. We also estimated the coefficient of variation for an appropriate variable selection and compared additional prior studies to support the findings. Thus, we conducted a careful selection of appropriate candidates to account for confounding variables. Results The ASD group had significantly higher plasma MDA levels, eicosapentaenoic acid levels, and a higher ratio of plasma docosahexaenoic acid (DHA)/arachidonic acid (ARA) levels than the control group. Plasma levels of the omega-6 PUFA fraction, dihomo-γ-linolenic acid, and superoxide dismutase levels were significantly lower in the ASD group than in the control group. Total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression and adaptive LASSO indicated that plasma DHA levels and plasma DHA/ARA ratios were significantly associated with total ABC scores and plasma levels of MDA-LDL. Conclusion Increased plasma levels of DHA and DHA/ARA ratio might be related to organic pollution. These neurobiological bases may induce neuronal deficiency associated with autistic behavioral symptoms in individuals with ASD.

Background: Disease progression in castrate-resistant prostate cancer (PCa) is most commonly driven by the reactivation of androgen receptor (AR) signaling and involves AR splice variants including ARV7. Materials and methods: We used the ARV7-positive PCa cell line, 22Rv1, to study the relationship of the PCa marker α-methylacyl-CoA racemase (AMACR), AR, and ARV7 in PCa. Results: Docetaxel addition but not AMACR inhibition decreased the proliferation of 22Rv1 cells. The combination of AMACR inhibition and docetaxel treatment resulted in a maximum reduction of cell proliferation. The Western blotting analysis revealed that both AR and ARV7 expression were significantly decreased with the use of charcoal-stripped serum following AMACR inhibition and docetaxel treatment. AMACR inhibition and docetaxel treatment in the charcoal-stripped serum condition reduced the proliferation of 22Rv1, possibly via the downregulation of the heat shock protein 27. Conclusion: Using cell proliferation and Western blot analysis, we demonstrated that AMACR inhibition and docetaxel treatment, under androgen deprivation conditions, significantly reduced the proliferation of ARV7 positive cancer cells and decreased the levels of AR and ARV7 expression, possibly via downregulation of heat shock protein 27.

OBJECTIVES: To assess the impact of two cycles of neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high-risk cN0M0 upper tract urothelial carcinoma (UTUC), and to evaluate the efficacy of NAC in patients with localised disease (≤cT2). PATIENTS AND METHODS: We retrospectively analysed patients with high-risk cN0M0 UTUC who received NAC followed by surgery, compared with a matched cohort who underwent initial surgery at Fujita Health University during 2005-2019. Baseline and tumour characteristics, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the cohorts. Cox proportional hazards models were used to identify predictors of survival. RESULTS: There were 117 and 67 patients in the study group and the control group, respectively. Significantly higher pathological downstaging (pDS) and lower lymphovascular invasion (LVI) were observed in the study group than in the control group (48% vs 22%, P = 0.008 and 29% vs 46%, P = 0.045, respectively). The NAC group had significantly better 5-year OS (79% vs 53%, P = 0.003), 5-year CSS (84% vs 66%, P = 0.008), and 5-year RFS (80% vs 61%, P = 0.001) than the control group. The OS benefit of NAC was observed even in patients with localised (≤cT2) disease (P = 0.019). Patients with LVI showed significantly worse CSS both in pathologically locally advanced (≥pT3) and in localised (≤pT2) tumours (P = 0.048 and P = 0.018, respectively). Multivariate analysis identified LVI, NAC, and pDS as independent predictors of OS. Male sex and post-NAC LVI were identified as predictors of worse survival in patients who underwent NAC. CONCLUSIONS: Two cycles of NAC improved the survival of patients with high-risk UTUC, even in patients with localised disease. Although two cycles of NAC appear to be effective in cN0M0 high-risk UTUC including localised disease, additional larger sample size multicentre prospective studies comparing short-course NAC regimens followed by surgery and surgery alone are required.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme associated with immunomodulation through its regulation of the tryptophan-kynurenine (Kyn) pathway in advanced cancers, including metastatic renal cell carcinoma (mRCC). However, the failure of IDO1 inhibitors when used in combination with immune checkpoint inhibitors (ICIs), as observed in clinical trials, raises a number of questions. This study aimed to investigate the association of tryptophan 2,3-dioxygenase (TDO) and IDO1 with cancer development and resistance to immunotherapy in patients with RCC. In our analysis of RCC tissue samples, tissue Kyn levels were elevated in advanced-stage RCC and correlated well with TDO expression levels in RCC tumor cells. In patients with mRCC, TDO rather than IDO1 was expressed in RCC tumor cells, showing a strong association with Kyn expression. Furthermore, immunohistochemical staining of TDO was strongly associated with the staining intensity of forkhead box P3, as well as ICI therapy response and survival in patients with mRCC. Our study is the first to show that TDO expression in tumor tissues is associated with progression and survival, confirming its potential as a predictive biomarker of primary resistance to immunotherapy in patients with mRCC. Our findings suggest that strategies aimed at inhibiting TDO, rather than IDO1, in combination with ICI therapy may aid in the control of mRCC progression.

Objectives: To evaluate the outcomes of robot-assisted partial nephrectomy (RAPN) in cystic renal tumors. Materials and Methods: We retrospectively analyzed patients who underwent RAPN for either cystic (n = 46) or solid (n = 271) renal tumors at Fujita Health University between 2010 and 2019. Cystic renal tumors were diagnosed using cross-sectional imaging. Perioperative, oncologic, and functional outcomes were assessed. Results: The median follow-up periods were 38, 41, and 37 months in the total, cystic, and solid groups, respectively. Most patient characteristics were similar among both groups, while the median age of the cystic group was significantly lower than that of the solid group (p = 0.02). Most perioperative variables and complications were comparable between the two groups. There was no significant difference between the groups in perioperative renal function. The estimated glomerular filtration rate preservation rates were 93.1% and 89.2% in the cystic and solid groups, respectively (p = 0.17). The cystic group showed a higher benign histology rate (19.6% vs 7%) and lower Fuhrman grade than the solid group (24.3% vs 15.1% in grade 1, and 73% vs 81.3% in grade 2), although there was no statistically significant difference between the two groups. In the solid group, 10 patients (3.7%) experienced recurrence, and 2 patients (0.7%) died of renal-cell carcinoma, while none of the patients with cystic tumors experienced recurrence. There was no statistically significant difference between the cystic and solid tumors with respect to 5-year recurrence-free survival (p = 0.18), cancer-specific survival (p = 0.55), and overall survival (p = 0.35). Conclusions: RAPN for cystic renal tumors appears to be safe and feasible with perioperative, long-term functional and oncologic outcomes comparable with those in solid tumors. RAPN can be a safe and effective surgical option for cystic renal tumors.

The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.

BACKGROUND: As mutations in glucocerebrosidase 1 (GBA1) are a major risk factor for Parkinson's disease (PD), decreased GBA1 activity might play an important role in the pathogenesis of the disease. However, there are currently no reports on glucosylceramide levels in the cerebrospinal fluid (CSF) in PD. OBJECTIVE: We investigated whether glucosylceramide accumulation and abnormal immune status in the brain are associated with PD. METHODS: We measured glucosylceramide by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) as well as levels of the active fragment of complement C5, C5a, in the CSF of 33 PD, 15 amyotrophic lateral sclerosis (ALS) and 22 neurologically normal control (NNC) subjects. Serum C5a levels in all PD and ALS cases and in a limited number of NNC subjects (n = 8) were also measured. RESULTS: C5a levels in CSF were significantly downregulated in PD compared with NNC. Moreover, CSF C5a/serum C5a ratio showed pronounced perturbations in PD and ALS patients. LC-ESI-MS/MS revealed a statistically significant accumulation of a specific subspecies of glucosylceramide (d18 : 1/C23 : 0 acyl chain fatty acid) in ALS, but not in PD. Interestingly, CSF glucosylceramide (d18 : 1/C23 : 0) exhibited a significant correlation with CSF C5a levels in PD, but not ALS. No correlation was observed between C5a levels or glucosylceramide subspecies content and disease duration, levodopa equivalent daily dose or Hoehn & Yahr staging in PD. CONCLUSION: Our findings demonstrate complement dysregulation without glucosylceramide accumulation in PD CSF. Furthermore, we found an association between a specific glucosylceramide subspecies and immune status in PD.

PURPOSE: The objective of this study was to develop a novel prognostication model in patients with treatment-naïve metastatic renal cell carcinoma (mRCC). METHODS: This study included 325 consecutive mRCC patients receiving first-line molecular-targeted therapy at 4 institutions. Potential parameters associated with overall survival (OS) in these patients were investigated to develop a novel stratification model. RESULTS: Median OS of the 325 patients was 38 months. A multivariable analysis of several factors identified independent predictors associated with unfavorable OS as follows: no previous nephrectomy, Karnofsky performance status <80%, albumin (Alb) ≤3.5 g/dl, C-reactive protein (CRP) >0.5 mg/dl and neutrophil-to-lymphocyte ratio (NLR) >3. Of these 5 independent OS predictors, 3 numeric factors were used to develop the ACN (Alb, CRP, and NLR) model by dividing patients into 3 groups according to the positive numbers of these 3 numeric risk factors. Median OS durations were 63, 37, and 11 months in the favorable (n = 105, 32.3%, without risk factors), intermediate (n = 88, 27.1%, with a single risk factor), and poor (n = 132, 40.6%, with multiple risk factors) risk groups, respectively. The ACN model as a prognostication tool was shown to be superior to the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models by both the concordance index and decision curve analysis. CONCLUSIONS: The ACN model could stratify the prognostic risk of mRCC patients receiving first-line targeted therapy more accurately than the MSKCC and IMDC models.

OBJECTIVES: We evaluated the impact of discontinuation of first-line (1L) molecular-targeted therapy on prognostic outcomes among patients with metastatic renal cell carcinoma (mRCC). METHODS: Study patients with mRCC were treated with 1L molecular-targeted agents at 4 separate institutions. Prognostic outcomes in this patient cohort were analyzed retrospectively based on whether discontinuation of 1L therapy was related to adverse events (AEs) or progression of disease (PD). RESULTS: Of the 201 patients enrolled, 117 patients (58%) and 84 patients (42%) discontinued 1L targeted therapy due to PD and AEs, respectively. Second-line therapy was subsequently provided to 101 (86%) and 66 (79%) of the patients who discontinued 1L therapy secondary to PD or AEs, respectively. Patients who discontinued 1L therapy due to AEs were significantly older than those with PD. The progression-free survival and overall survival from the initiation of 1L targeted therapy were significantly longer in patients who discontinued 1L therapy due to AE than in those who discontinued 1L therapy due to PD. The OS from the initiation of second-line targeted therapy was significantly longer in patients who discontinued 1L therapy due to AE than those with PD. Furthermore, AE as a reason for discontinuation of 1L targeted therapy as opposed to PD was independently associated with longer progression-free survival and OS as determined by multivariate analysis. CONCLUSIONS: Our findings suggest that mRCC patients who discontinue 1L therapy due to AEs have a more favorable prognosis than those who discontinue therapy due to PD.

The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied association between MDA-LDL and behavioral symptoms in 11 individuals with ASD and 7 age -matched normal controls. Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). Because small sample size in this study, three measures were conducted: first, employment of adaptive Lasso for enhancing the accuracy of prediction and interpretability; second, calculation of coefficient of variation for an appropriate selection of plasma variables; and third, selection of good candidates of plasma variables. Plasma levels of MDA-LDL, eicosapentaenoic acid, docosahexaenoic acid (DHA) and DHA/arachidonic acid ratios were significantly higher, while plasma superoxide dismutase (SOD) levels were significantly lower in the ASD group than in the control group. The total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression analysis and the adaptive Lasso revealed association of increased plasma DHA levels with the ABC total scores and increased plasma MDA-LDL levels. Such association between DHA and plasma MDA-LDL levels may contribute to behavior in individuals with ASD.

OBJECTIVES: To investigate whether a deep learning model from magnetic resonance imaging information is an accurate method to predict the risk of urinary incontinence after robot-assisted radical prostatectomy. METHODS: This study included 400 patients with prostate cancer who underwent robot-assisted radical prostatectomy. Patients using 0 or 1 pad/day within 3 months after robot-assisted radical prostatectomy were categorized into the "good" group, whereas the other patients were categorized into the "bad" group. Magnetic resonance imaging DICOM data, and preoperative and intraoperative covariates were assessed. To evaluate the deep learning models from the testing dataset, their sensitivity, specificity and area under the receiver operating characteristic curve were analyzed. Gradient-weighted class activation mapping was used to visualize the regions of deep learning interest. RESULTS: The combination of deep learning and naive Bayes algorithm using axial magnetic resonance imaging in addition to clinicopathological parameters had the highest performance, with an area under the receiver operating characteristic curve of 77.5% for predicting early recovery from post-prostatectomy urinary incontinence, whereas machine learning using clinicopathological parameters only achieved low performance, with an area under the receiver operating characteristic curve of 62.2%. The gradient-weighted class activation mapping methods showed that deep learning focused on pelvic skeletal muscles in patients in the good group, and on the perirectal and hip joint regions in patients in the bad group. CONCLUSIONS: Our results suggest that deep learning using magnetic resonance imaging is useful for predicting the severity of urinary incontinence after robot-assisted radical prostatectomy. Deep learning algorithms might help in the choice of treatment strategy, especially for prostate cancer patients who wish to avoid prolonged urinary incontinence after robot-assisted radical prostatectomy.

A 69-year-old man visited a local doctor for fever, pain in the left abdomen, and macroscopic hematuria. Computed tomography (CT) revealed hydronephrosis of the left kidney, and he was referred to our hospital. Detailed examinations suggested left-side pyonephrosis due to urothelial cancer, and left-side total nephroureterectomy was performed. Pathological diagnosis was sarcomatoid renal cell carcinoma. Sunitinib administration was started postoperatively for para-aortic lymph node metastasis, which disappeared. However, metastasis to the common iliac lymph node and liver appeared newly 11 months later. Nivolumab was started in combination with radiation thepapy for the lymph node metastases. The patient remains in a stable disease state as of 21 months after nivolumab administration.

PURPOSE: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. PATIENTS AND METHODS: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). RESULTS: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with < 5 metastatic sites). SO/SU was superior to SU/SO for patients without previous nephrectomy. CONCLUSIONS: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870).

BACKGROUND/AIM: The therapeutic outcomes of patients with metastatic renal cell carcinoma (mRCC) have dramatically improved with the introduction of molecular-targeted agents. The observational multicenter study was conducted to develop a novel stratification system for the intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. PATIENTS AND METHODS: The present study included 252 Japanese patients with mRCC who received first-line molecular-targeted therapy at four institutions. RESULTS: The 252 patients were classified into the favorable, intermediate, and poor risk groups by the IMDC model. For the intermediate risk group, multivariate analysis of the six factors included in the IMDC model revealed that a low performance status, anemia, and a high platelet count were independent predictors of poor overall survival (OS). The intermediate risk group was subsequently divided into the following two groups (int -group 1 and 2) by the three independent OS predictors. Significant differences in the OS were noted among the IMDC favorable risk group, int-group 1, int-group 2, and poor risk group. CONCLUSION: The novel stratification presented in this study could be a useful tool for further prognostication of patients with mRCC classified into the intermediate risk group according to the IMDC model after first-line molecular-targeted therapy.

OBJECTIVES: To investigate whether a deep learning model from magnetic resonance imaging information is an accurate method to predict the risk of urinary incontinence after robot-assisted radical prostatectomy. METHODS: This study included 400 patients with prostate cancer who underwent robot-assisted radical prostatectomy. Patients using 0 or 1 pad/day within 3 months after robot-assisted radical prostatectomy were categorized into the "good" group, whereas the other patients were categorized into the "bad" group. Magnetic resonance imaging DICOM data, and preoperative and intraoperative covariates were assessed. To evaluate the deep learning models from the testing dataset, their sensitivity, specificity and area under the receiver operating characteristic curve were analyzed. Gradient-weighted class activation mapping was used to visualize the regions of deep learning interest. RESULTS: The combination of deep learning and naive Bayes algorithm using axial magnetic resonance imaging in addition to clinicopathological parameters had the highest performance, with an area under the receiver operating characteristic curve of 77.5% for predicting early recovery from post-prostatectomy urinary incontinence, whereas machine learning using clinicopathological parameters only achieved low performance, with an area under the receiver operating characteristic curve of 62.2%. The gradient-weighted class activation mapping methods showed that deep learning focused on pelvic skeletal muscles in patients in the good group, and on the perirectal and hip joint regions in patients in the bad group. CONCLUSIONS: Our results suggest that deep learning using magnetic resonance imaging is useful for predicting the severity of urinary incontinence after robot-assisted radical prostatectomy. Deep learning algorithms might help in the choice of treatment strategy, especially for prostate cancer patients who wish to avoid prolonged urinary incontinence after robot-assisted radical prostatectomy.

OBJECTIVES: We evaluated the impact of discontinuation of first-line (1L) molecular-targeted therapy on prognostic outcomes among patients with metastatic renal cell carcinoma (mRCC). METHODS: Study patients with mRCC were treated with 1L molecular-targeted agents at 4 separate institutions. Prognostic outcomes in this patient cohort were analyzed retrospectively based on whether discontinuation of 1L therapy was related to adverse events (AEs) or progression of disease (PD). RESULTS: Of the 201 patients enrolled, 117 patients (58%) and 84 patients (42%) discontinued 1L targeted therapy due to PD and AEs, respectively. Second-line therapy was subsequently provided to 101 (86%) and 66 (79%) of the patients who discontinued 1L therapy secondary to PD or AEs, respectively. Patients who discontinued 1L therapy due to AEs were significantly older than those with PD. The progression-free survival and overall survival from the initiation of 1L targeted therapy were significantly longer in patients who discontinued 1L therapy due to AE than in those who discontinued 1L therapy due to PD. The OS from the initiation of second-line targeted therapy was significantly longer in patients who discontinued 1L therapy due to AE than those with PD. Furthermore, AE as a reason for discontinuation of 1L targeted therapy as opposed to PD was independently associated with longer progression-free survival and OS as determined by multivariate analysis. CONCLUSIONS: Our findings suggest that mRCC patients who discontinue 1L therapy due to AEs have a more favorable prognosis than those who discontinue therapy due to PD.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted. METHODS: This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival. RESULTS: Two hundred-eighty patients received ICIs. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonitis. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P = 0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P < 0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs (P < 0.01, p < 0.01). Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy. CONCLUSION: Although the onset of irAEs was difficult to be predicted based on pre-treatment tests. It appeared that the continuation of ICI therapy, along with early detection and adequate control of irAEs, might contribute to the improved prognosis of patients.

The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied association between MDA-LDL and behavioral symptoms in 11 individuals with ASD and 7 age -matched normal controls. Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). Because small sample size in this study, three measures were conducted: first, employment of adaptive Lasso for enhancing the accuracy of prediction and interpretability; second, calculation of coefficient of variation for an appropriate selection of plasma variables; and third, selection of good candidates of plasma variables. Plasma levels of MDA-LDL, eicosapentaenoic acid, docosahexaenoic acid (DHA) and DHA/arachidonic acid ratios were significantly higher, while plasma superoxide dismutase (SOD) levels were significantly lower in the ASD group than in the control group. The total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression analysis and the adaptive Lasso revealed association of increased plasma DHA levels with the ABC total scores and increased plasma MDA-LDL levels. Such association between DHA and plasma MDA-LDL levels may contribute to behavior in individuals with ASD.

INTRODUCTION: Robot-assisted partial nephrectomy (RAPN) is emerging as an effective treatment oncologically and functionally for clinically localized renal tumors. However, RAPN in high-complexity tumors with a Preoperative Aspects and Dimensions Used for an Anatomical score ≥10 remains challenging. In this study, the feasibility of RAPN for high-complexity tumors was assessed. METHODS: The study cohort consisted of 177 cases with clinically localized renal cell carcinoma who had undergone RAPN at our hospital from July 2010 to February 2018. They were assessed for perioperative parameters and trifecta achievement (ie, negative surgical margins, warm ischemia time <25 minutes, and no complications). RESULTS: Among the 177 cases who had undergone RAPN, 60 had high-complexity tumors, and 117 had non-high-complexity (ie, intermediate- or low-complexity) tumors. There were no significant differences in the operative and console times between the cohorts, but estimated intraoperative blood loss was much lower in the non-high-complexity group. Although the average warm ischemia time was less than 25 minutes in both groups, it was significantly shorter in the non-high-complexity group. Trifecta achievement rates significantly differed between the high- and non-high-complexity groups (68.3% vs 86.3%). Comparisons of four operative parameters (ie, BMI, tumor size, endophytic properties, and hilar tumor) using univariate analysis in the 60 high-complexity tumor cases showed that BMI and tumor size were independent factors (P = 0.05 and 0.018, respectively). In multivariate analysis, tumor size was the only factor directly associated with trifecta achievement (P = 0.029). CONCLUSION: The trifecta achievement rate was significantly lower in the high-complexity group. Only tumor size affected trifecta achievement during RAPN in cases with high-complexity tumors (Preoperative Aspects and Dimensions Used for an Anatomical score ≥10).

© The Foundation Acta Radiologica 2019. Background: Evaluation of the morphology of the lower urinary tract as well as the movements associated with urination are required for the symptomatic diagnosis of lower urinary tract obstruction as well as the assessment of postoperative adaptation. However, no tool currently exists for direct and easy patient evaluation. Purpose: To evaluate lower urinary tract obstruction and postoperative adaptation using a four-dimensional (4D) virtual reality urination image (urodynamic 4D-CT image). Material and Methods: We used a 320-row area detector CT scanner and PhyZiodynamics image analysis software to perform 197 urodynamic 4D-CT examinations on 175 first-time patients between January 2014 and March 2017. Results: A comparison of the obtained images before and after holmium laser enucleation of the prostate revealed the morphological changes due to prostate enucleation and enabled visualization of the ideal urination conditions, showing that the anatomical structural changes during urination and the opening of the urethra play a major role in improving voiding function. Conclusion: Using low-dosage radiation, the sharply defined moving image obtained via urodynamic 4D-CT examination can be utilized as a physiological diagnostic tool to evaluate a series of urinary movements from any angle between the prostate, urethra, and bladder in a unitary manner with the time axis added. There was negligible patient impact. This technique could provide new opportunities for the diagnosis of lower urinary tract symptoms and post-surgical adaptation assessment.

＜文献概要＞ポイント ・出血への対応として,血管周囲の剥離に際しては常にラパロガーゼを視野内に置き圧迫止血に備える.・周囲臓器や血管の損傷に際しては,無闇に焼灼に頼らず出血点を確認し縫合止血によるコントロールを考慮する.・操作中に器材を腹腔内で紛失した際は,即座に操作を中断しマニュアルに従って探索し体位変更は慎しむ.

筋層浸潤膀胱癌に対するRARCは、RARPに習熟していれば比較的安全に施行でき出血量や合併症の低下に有用である。しかし、長時間手術に纏わる合併症もあり、体位の工夫やマニュアルを作成し可能であれば複数術者での操作が勧められる。腫瘍制御に関しては、腹膜播種や多発皮下転移、遠隔リンパ節転移等の特異な早期再発例が報告されている。再発高リスク例を予見(開腹術選択)し、手術操作の問題点を検討し腫瘍制御においても安全かつ有効な治療法を確立することが重要である。(著者抄録)