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Background & Aims A detailed understanding of antitumor immunity is essential for optimal cancer immune therapy. Although defective mutations in the B2M and HLA-ABC genes, which encode molecules essential for antigen presentation, have been reported in several studies, the effects of these defects on tumor immunity have not been quantitatively evaluated. Methods Mutations in HLA-ABC genes were analyzed in 114 microsatellite instability–high colorectal cancers using a long-read sequencer. The data were further analyzed in combination with whole-exome sequencing, transcriptome sequencing, DNA methylation array, and immunohistochemistry data. Results We detected 101 truncating mutations in 57 tumors (50%) and loss of 61 alleles in 21 tumors (18%). Based on the integrated analysis that enabled the immunologic subclassification of microsatellite instability–high colorectal cancers, we identified a subtype of tumors in which lymphocyte infiltration was reduced, partly due to reduced expression of HLA-ABC genes in the absence of apparent genetic alterations. Survival time of patients with such tumors was shorter than in patients with other tumor types. Paradoxically, tumor mutation burden was highest in the subtype, suggesting that the immunogenic effect of accumulating mutations was counterbalanced by mutations that weakened immunoreactivity. Various genetic and epigenetic alterations, including frameshift mutations in RFX5 and promoter methylation of PSMB8 and HLA-A, converged on reduced expression of HLA-ABC genes. Conclusions Our detailed immunogenomic analysis provides information that will facilitate the improvement and development of cancer immunotherapy.

Background Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used in chemotherapy-naive patients with metastatic castration-resistant prostate cancer owing to efficacy and favorable toxicity. However, the order in which they should be administered has not been determined. Patients and Methods We retrospectively reviewed the records of chemotherapy-naive patients with metastatic castration-resistant prostate cancer who had received sequential treatment with either AA followed by ENZA (AA-ENZA) or the converse (ENZA-AA). Prostate-specific antigen (PSA) response rates (defined as ≥ 50% PSA decline from baseline), first-line progression-free survival (PFS), second-line PFS, combined PFS (defined as first-line PFS plus second-line PFS), and overall survival are compared between the 2 sequence groups. Results A total of 97 patients received sequential treatment with AA and ENZA; 50 patients were in the AA-ENZA group, and 47 patients were in the ENZA-AA group. The PSA response rate to first-line treatment was not significantly different between AA (48%) and ENZA (51%) ( P = .840). However, a significant difference was observed in the PSA response rate to second-line treatment (AA, 6.4% vs. ENZA, 30%; P = .004). The median combined PFS was not significantly different between sequence groups (hazard ratio, 0.71; 95% confidence interval, 0.46-1.08; log-rank P = .105). The order of addition also had no significant effect on median overall survival (hazard ratio, 0.98; 95% confidence interval, 0.64-1.52; log-rank P = .834). Conclusion With the exception of the second-line PSA response, there was no significant difference in clinical outcomes between the AA-ENZA and ENZA-AA groups. Our results might be useful reference in daily practice, especially for patients who do not have a suitable general condition for chemotherapy.

To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.

Background The effectiveness of cancer control is unclear after radical prostatectomy for patients with clinical T3 prostate cancer. Methods We retrospectively reviewed 1409 patients who underwent radical prostatectomy between April 2007 and December 2014, including 210 patients with cT3 prostate cancer. Nine patients who received neoadjuvant hormonal therapy and three patients who were lost to follow-up were excluded from the analysis. Clinical staging was performed by an experienced radiologist using preoperative magnetic resonance imaging findings. We analyzed the predictors of biochemical recurrence using Cox proportional hazard analyses. Results A total of 113 patients (57%) underwent radical retropubic prostatectomy and 85 patients (43%) underwent robot-assisted radical prostatectomy. The median follow-up period was 36 months. Downstaging occurred for 60 patients (30%), positive surgical margins were identified in 117 patients (59%), and biochemical recurrence was observed for 89 patients (45%). In the multivariate analyses, the independent preoperative predictors of biochemical recurrence were ≥50% proportion of positive biopsy cores [hazard ratio (HR): 2.858, P < 0.0001] and a biopsy Gleason score of ≥8 (HR: 1.800, P = 0.0093). The independent post-operative predictors of biochemical recurrence were positive surgical margins (HR: 2.490, P = 0.0018) and seminal vesicle invasion (HR: 2.750, P < 0.0001). Conclusions Among patients with cT3 prostate cancer, the percentage of positive biopsy cores and the biopsy Gleason score should be considered to select treatment. Compared with radical retropubic prostatectomy, robot-assisted radical prostatectomy may be a feasible treatment option in this setting.

A 25 year-old man was admitted to our hospital with a left swelling testis. We diagnosed as left testicular tumor by ultrasound sonography and magnetic resonance imaging (MRI). Computed tomography (CT) showed no metastasis and tumor makers, βHCG, AFP, LDH, were normal. A tumor was removed by left radical high orchiectomy and histological examination revealed large cell calcifying Sertoli cell tumor. He was given no adjuvant therapy. Neither recurrence nor metastasis has been found for 4 months after the operation.

The patient is a 43-year-old male, presented with numbness of the left lower extremities. Imaging studies showed a pelvic tumor 20 cm in diameter, involving the left ureter, left common iliac vessels, left internal and external iliac vessels, and inferior mesenteric artery, which was deemed unresectable. Tumor biopsy confirmed liposarcoma. As chemotherapy was not effective, he was referred to us. Following femoral-femoral artery bypass in advance, the tumor was resected with the sigmoid colon, left kidney, ureter, left iliac vessels, and interior mesenteric artery. Removal of the tumor caused massive venous hemorrhage from the pre-sacral plexus, which was scarcely managed by gauze packing. Open abdominal management was selected to avoid abdominal compartment syndrome by severe intestinal edema. The packed gauze was retrieved on the fourth post-operative day, with laparotomy closed. The postoperative course was uneventful.

An important clinical question of great interest to clinicians is how to best sequence androgen receptor targeted agents (ARTAs) and chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), but the answer is still unclear.To evaluate and compare the clinical outcomes of ARTA and docetaxel (DTX) as second-line treatment in the post first-line ARTA, we conducted a retrospective analysis of chemotherapy-naive mCRPC patients who had received sequential treatment with ARTA followed by another ARTA (ARTA-ARTA) or ARTA followed by DTX (ARTA-DTX).A total of 97 patients were treated with the ARTA-ARTA sequence and 42 with the ARTA-DTX sequence. A prostate-specific antigen (PSA) response to the second-line treatment was observed in 18.6% in the ARTA-ARTA and in 33.3% in the ARTA-DTX sequence, but the difference in PSA response was not statistically significant (P = .057). The median progression-free survival (PFS) was significantly different between ARTA and DTX in the second-line treatment (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.24-0.59; P .001). The favorable outcome in the ARTA-DTX sequence compared with the ARTA-ARTA sequence remained (HR, 0.51, 95% CI, 0.33-0.80; P = .004) in the combined PFS (first-line PFS + second-line PFS). However, no statistically significant difference in overall survival (OS) between the 2 groups was observed (HR, 0.60; 95% CI, 0.34-1.09; P = .095). In multivariate analysis, the ARTA-DTX sequence was identified as an independent prognostic factor for combined PFS, but not OS.ARTA-DTX might improve clinical outcomes in terms of second-line PFS and combined PFS, compared with the ARTA-ARTA sequence. However, this significance was not observed for OS.

This work targets a novel self-powered Smart Circuit Breaker (SCB) for monitoring and controlling power in emerging small-scale AC nano-grids. The SCB concept is intended as a direct replacement of standard(120 Vac, 15 Arms) household circuit breakers, which imposes several challenging constraints. The SCB must therefore generate its own internal supply from the small AC voltage drop across the main switch when the breaker is closed. The SCB is composed of the following key blocks: 1) back-to-back 900 V Silicon Carbide (SiC) MOSFETs as the main power switches, 2) a low-voltage energy harvesting circuit, 3) a high-voltage step-down converter, and 4) low-power digital controller and wireless communication circuits. In order to stabilize the internal supply voltage under a wide range of AC load currents, a novel approach of dynamic on-resistance control is implemented, through adaptive gate-drive and MOSFET segmentation. The fabricated SCB prototype dissipates only 7.4 W for a 13 Arms AC load, corresponding to an efficiency of 99.5%.

In sensor-node applications, the auxiliary power is drawn from the ac mains to supply the mixed-signal sensor components. There is therefore a need for low-cost, sub-1W, miniature non-isolated ac-dc down-converters. In this work, a new two-chip architecture is proposed to implement a high-voltage quasi-resonant buck converter with peak current-mode control. The current and voltage control loops are implemented in the high-side (HS) and low-side (LS) IC, respectively. Each IC includes a 700V power transistor, sensing and control circuits. The LS IC transmits the digital peak current command, along with mode selection information, to the HS IC using a low-power 20 MHz isolated communication interface. The architecture achieves a peak simulated efficiency of 85.6% when converting from 339 V to 12 V and allows the size of the input filter to be greatly reduced due to the current-mode operation. State-of-the-art UHV BCD technologies offer a unique opportunity to increase the level of integration and reduce the system cost in the targeted sensor node applications, despite the relatively poor figure-of-merit of the HV devices compared to discrete Silicon super-junction or GaN alternatives.

We evaluated short- and long-term renal function in patients after radical cystectomy with urinary diversion and identified risk factors for the deterioration of renal function. This retrospective study comprised 91 patients who underwent radical cystectomy and urinary diversion for bladder cancer and survived ≥3 years after surgery. The estimated glomerular filtration rate (eGFR) was calculated, and longitudinal changes of eGFR were assessed. Deterioration in renal function in early and late postoperative years was defined as a ≥25 % decrease in the eGFR from preoperative to postoperative year one, and a reduction in the eGFR of >1 mL/min/1.73 m2 annually in subsequent years, respectively. Univariate and multivariate logistic regression analyses were used to evaluate its association with clinicopathologic features. The median follow-up period after surgery was 7 years (range 3–26). The mean eGFR decreased from preoperative 65.1 to 58.9 mL/min/1.73 m2 1 year after the surgery, followed by a continuous decline of ~1.0 mL/min/1.73 m2 per year thereafter. Multivariate analyses identified ureteroenteric stricture as the sole risk factor associated with early renal function deterioration [odds ratio (OR) 4.22, p = 0.037]. Diabetes mellitus (OR 8.24, p = 0.015) and episodes of pyelonephritis (OR 4.89, p = 0.038) were independently associated with the gradual decline in the late postoperative period. In cystectomy patients with urinary diversion, the rapid deterioration of renal function observed during the first year after surgery and the gradual but continuous decline in function thereafter were found to be associated with different risk factors.

Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed. In this study, employing microwave technology as a new means to improve solubility, we established a method for preparing solid dispersions using hydroxypropyl methylcellulose acetate succinate as a polymeric carrier and urea as a third component. This effective method has a treatment time of several minutes (simple) and does not require the use of organic solvents (low environmental impact). The third component, urea, acts to lower the melting point of NZ-105, which promotes amorphization. This greatly improves the solubility compared with the microwave-treated product of NZ-105/HPMC-AS binary system. The solid dispersion prepared with this method, in addition to evaluation in vitro, was tested in vivo using beagle dogs and shown to be effective from the eightfold improvement in absorption compared with NZ-105 alone based on the area under the curve.

This paper explores the multi-disciplinary design challenges in building a 240 VAC, 2 kVA modular single-phase inverter with high power-density using wide-bandgap transistors. The compromise between the electrical and mechanical design is extremely important in any high-density power converter. In this work the electrical and mechanical systems were iteratively co-designed using detailed 3D thermal and air-flow simulations. Custom copper heat-sinks and heat-pipes were developed for optimal thermal management. The inverter uses three soft-switching sub-inverters in parallel, which are controlled using a novel digital Hysteretic Current Mode Control (HCMC) scheme. To achieve a flat high efficiency curve with low THD over a wide load range, two operating modes are used: 1) Boundary Conduction Mode (BCM) with a slight negative inductor valley current for soft-switching, and 2) Continuous Conduction Mode (CCM) to limit the required saturation current in the inductors. The design of an active power decoupling scheme to minimize input capacitance is also discussed. The designed single-phase inverter has a volume of 33.1 in3 and resulting theoretical power-density of 60.3 W/in3 at 2 kW load. A measured efficiency of 97.7% is achieved for a single sub-inverter with 4.5% THD at 632.7 W.

Retroperitoneal tumors present diagnostic challenges, although a definitive diagnosis can be established based on a histopathological analysis. We herein report the case of a 62-year-old woman with a massive retroperitoneal tumor who was referred to our department for surgery. Although we initially planned to perform an incisional biopsy, we unexpectedly detected gingival swelling, and a gingival biopsy subsequently confirmed a pathological diagnosis of Burkitt's lymphoma (BL). We successfully avoided the use of more invasive diagnostic procedures and were able to promptly initiate chemotherapy. Obtaining an immediate pathological diagnosis is essential for providing successful treatment in such cases, as the disease is potentially curable with chemotherapy. BL should therefore be considered in the differential diagnosis of massive retroperitoneal tumors, highlighting the importance of routine systemic screening.

Objective To elucidate whether the lower ureteral lesion can predict subsequent intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). Patients and methods We retrospectively reviewed 186 consecutive patients with UTUC who underwent RNU at our institution between 1996 and 2013. Associations of various clinicopathological factors with subsequent IVR were assessed. Lower ureteral lesion was defined as the pathologically confirmed lowest carcinoma component within 5 cm from the lower end of the ureter. The log-rank test and Cox proportional hazards model were used for univariable and multivariable analysis, respectively. Results Overall, 86 patients (46%) developed IVR during the follow-up, with a median follow-up period of 43 months (interquartile range: 17–79 mo). In all, 53 patients (28%) had lower ureteral lesions, and 34 (64%) of them developed IVR. Univariable analysis demonstrated that lower ureteral lesion was significantly associated with IVR, as well as tumor multifocality, lymphatic invasion, and history of bladder cancer. Multivariable analysis identified the lower ureteral lesion as a sole independent predictor of IVR ( P = 0.0304, hazard ratio = 1.74). Conclusions Lower ureteral lesion was an independent predictor of IVR in patients with UTUC treated with RNU. Such patients may deserve prophylactic treatment and intensive follow-up.