Search

Introduction: Durable techniques that prevent postoperative inguinal hernia (IH) after robot-assisted radical prostatectomy (RARP) have not been established. This study evaluated the long-term efficacy of a postoperative IH prevention technique that uses no artificial agents to assess the characteristics of IH occurrence after introducing this technique., Patients and Methods: We retrospectively analyzed 201 consecutive patients who underwent RARP at our institution between September 2011 and February 2014. In total, 189 cases were eligible for the study. The non-IH prevention and IH prevention groups comprised 72 and 117 cases, respectively. We compared the incidence of IH between the two groups using Kaplan-Meier curves. Risk factors for IH in the prevention group were determined via multivariable logistic regression analysis., Results: The rate of IH occurrence was 20.8% (15 cases) in the nonprevention group and 8.5% (10 cases) in the prevention group, with median follow-up periods of 99.5 and 89.9 months, respectively. The Kaplan-Meier curves indicated a significant difference between the two groups (p = 0.011). Only cutting of the vas deferens significantly contributed to reduced occurrence of IH in multivariable analysis (p = 0.047). After reviewing the intraoperative videos, insufficient separation of the vas deferens was considered the main cause of IH in the prevention group., Conclusion: Our simple prevention technique with no artificial agents had a durable effect on IH prevention after RARP over a median follow-up period of more than 7 years. Cutting the vas deferens effectively prevented IH after RARP., (© 2022 The Japanese Urological Association.)

Scribble (Scrib) is a conserved polarity protein acting as a scaffold involved in multiple cellular and developmental processes. Recent evidence from our group indicates that Scrib is also essential for brain development as early global deletion of Scrib in the dorsal telencephalon induced cortical thickness reduction and alteration of interhemispheric connectivity. In addition, Scrib conditional knockout (cKO) mice have behavioral deficits such as locomotor activity impairment and memory alterations. Given Scrib broad expression in multiple cell types in the brain, we decided to determine the neuronal contribution of Scrib for these phenotypes. In the present study, we further investigate the function of Scrib specifically in excitatory neurons on the forebrain formation and the control of locomotor behavior. To do so, we generated a novel neuronal glutamatergic specific Scrib cKO mouse line called Nex -Scrib -/- cKO. Remarkably, cortical layering and commissures were impaired in these mice and reproduced to some extent the previously described phenotype in global Scrib cKO. In addition and in contrast to our previous results using Emx1-Scrib -/- cKO, the Nex-Scrib -/- cKO mutant mice exhibited significantly reduced locomotion. Altogether, the novel cKO model described in this study further highlights an essential role for Scrib in forebrain development and locomotor behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ezan, Moreau, Mamo, Shimbo, Decroo, Sans and Montcouquiol.)

This study aimed to evaluate the robustness against geometric uncertainties in the hybrid intensity-modulated radiation therapy (IMRT) plans generated by commercially available software for automated breast planning (ABP). The ABP plans were compared with commonly used forward-planned field-in-field (FIF) technique plans. The planning computed tomography datasets of 20 patients who received left-sided breast-conserving surgery were used for both the ABP and FIF plans. Geometric uncertainties were simulated by shifting beam isocenters by 2, 3, 5, and 10 mm in the six directions: anterior/posterior, left/right, and superior/inferior. A total of 500 plans (20 patients and 25 scenarios, including the original plan) were created for each of the ABP and FIF plans. The homogeneity index of the target volume in the ABP plans was significantly better (p < 0.001) than the value in the FIF plans in the scenarios of shifting beam isocenters by 2, 3, and 5 mm. Mean heart dose and percentage volume of lungs receiving a dose more than 20 Gy were clinically acceptable in all scenarios. The hybrid IMRT plans generated by commercially available ABP software provided better robustness against geometric uncertainties than forward-planned FIF plans., (© 2022. The Author(s).)

Purpose: The purpose of this study is to evaluate the prediction and classification performances of the gamma passing rate (GPR) for different machine learning models and to select the best model for achieving machine learning-based patient-specific quality assurance (PSQA)., Methods: The measurement verification of 356 head-and-neck volumetric modulated arc therapy plans was performed using a diode array phantom (Delta4 Phantom), and GPR values at 2%/2 mm with global normalization and 3%/2 mm with local normalization were calculated. Machine learning models, including ridge regression (RIDGE), random forest (RF), support vector regression (SVR), and stacked generalization (STACKING), were used to predict the GPR. Each machine learning model was trained using 260 plans, and the prediction accuracy was evaluated using the remaining 96 plans. The prediction error between the measured and predicted GPR was evaluated. For the classification evaluation, the lower control limit for the measured GPR and lower control limit for predicted GPR (LCL p ) was defined to identify whether the GPR values represent a "pass" or a "fail." LCL p values with 99% and 99.9% confidence levels were calculated as the upper prediction limits for the GPR estimated from the linear regression between the measured and predicted GPR., Results: There was an overestimation trend of the low measured GPR. The maximum prediction errors for RIDGE, RF, SVR, and STACKING were 3.2%, 2.9%, 2.3%, and 2.2% at the global 2%/2 mm and 6.3%, 6.6%, 6.1%, and 5.5% at the local 3%/2 mm, respectively. In the global 2%/2 mm, the sensitivity was 100% for all the machine learning models except RIDGE when using 99% LCL p . The specificity was 76.1% for RIDGE, RF, and SVR and 66.3% for STACKING; however, the specificity decreased dramatically when 99.9% LCL p was used. In the local 3%/2 mm, however, only STACKING showed 100% sensitivity when using 99% LCL p . The decrease in the specificity using 99.9% LCL p was smaller than that in the global 2%/2 mm, and the specificity for RIDGE, RF, SVR, and STACKING was 61.3%, 61.3%, 72.0%, and 66.8%, respectively., Conclusions: STACKING had better prediction accuracy for low GPR values than other machine learning models. Applying LCL p to a regression model enabled the consistent evaluation of quantitative and qualitative GPR predictions. Adjusting the confidence level of the LCL p helped improve the balance between the sensitivity and specificity. We suggest that STACKING can assist the safe and efficient operation of PSQA., (© 2021 American Association of Physicists in Medicine.)

Optimization process in treatment planning for intensity-modulated radiation therapy varies with the treatment planner. Therefore, a large variation in the quality of dose distribution is usually observed. To reduce variation, an automatic optimizing toolkit was developed for the Monaco treatment planning system (Elekta AB, Stockholm, Sweden) for prostate cancer using volumetric-modulated arc therapy (VMAT). This toolkit was able to create plans automatically. However, most plans needed two arcs per treatment to ensure the dose coverage for targets. For prostate cancer, providing a plan with a single arc was advisable in clinical practice because intrafraction motion management must be considered to irradiate accurately. The purpose of this work was to develop an automatic treatment planning system with a single arc per treatment for prostate cancer using VMAT. We designed the new algorithm for the automatic treatment planning system to use one arc per treatment for prostate cancer in Monaco. We constructed the system in two main steps: (1) Determine suitable cost function parameters for each case before optimization, and (2) repeat the calculation and optimization until the conditions for dose indices are fulfilled. To evaluate clinical suitability, the plan quality between manual planning and the automatic planning system was compared. Our system created the plans automatically in all patients within a few iterations. Statistical differences between the plans were not observed for the target and organ at risk. It created the plans with no human input other than the initial template setting and system initiation. This system offers improved efficiency in running the treatment planning system and human resources while ensuring high-quality outputs., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Conventional group-based outpatient cardiac rehabilitation through monitoring and center-based approaches for patients in the recovery phase has shown strong evidence for the prevention of cardiovascular diseases. However, there are some cases in which maintaining attendance of center-based cardiac rehabilitation is difficult., Objective: This study aims to ascertain the safety and efficacy of remote cardiac rehabilitation (RCR) in the recovery phase in patients with cardiovascular disease., Methods: Patients satisfying the study criteria will be recruited from multiple institutions (approximately 30) across Japan. In total, 75 patients (approximately 2 or 3 patients from each institution) are proposed to be recruited. Patients enrolled in the RCR group will be lent devices necessary for RCR (including calibrated ergometers and tablets). Patients will perform anaerobic exercise at home using ergometer for 30-40 minutes at least 3 times weekly. During exercise, an instructor will monitor the patient in real time (using interactive video tools and monitoring tools for various vital data). Moreover, educational instructions will be given 3 times weekly using e-learning methods., Results: The primary endpoint is the peak oxygen uptake 2-3 months from the start of exercise or 6-min walk test. The extracted data will be compared between RCR patients and controls without RCR., Conclusions: The establishment of the system of RCR proposed in this study will lead to the development of more extensive applications, which have been insufficient through conventional interventions., Trial Registration: University Hospital Medical Information Network-Clinical Trials Registry UMIN-CTR UMIN000042942; https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000048983., International Registered Report Identifier (irrid): DERR1-10.2196/30725., (©Hidetaka Itoh, Eisuke Amiya, Koichi Narita, Mai Shimbo, Masanobu Taya, Issei Komuro, Takashi Hasegawa, Shigeru Makita, Yutaka Kimura. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.10.2021.)

Aim To investigate the variation of tumor volume during moderate hypo-fractionated stereotactic body radiation therapy (SBRT). Patients and Methods Twenty patients, who received SBRT at our institution, were included in the analysis. A prescribed dose was 56 Gy at iso-center in seven fractions. Tumor volumes before and during SBRT were calculated. In order to investigate factors affecting the variation of tumor volume in RT 2 (after first irradiation) and RT 7 (after last irradiation), various parameters were verified by the Mann-Whitney U test. Results With regard to the low maximum standardized uptake values (SUVmax) group, transient increase of tumor volume was found in RT 2, and tumor volume reduction was hardly found in RT 7. With regard to the high SUVmax group, a transient increase was not found, and a definite reduction was found in the treatment course. Conclusion Accurate prediction of tumor volume variation is required for more accurate treatment, such as adaptive radiation therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Nishimura et al.)

We report a case of dialysis kidney with multiple renal carcinomas in three locations. A 74-year-old man who had a 20-year history of dialysis, was admitted to our hospital complaining of sudden right lateral area pain. Computed tomography (CT) scan revealed hemorrhage from the right dialyzed renal subcapsule. He underwent immediate transcatheter arterial embolization (TAE), but after 6 days the CT scan showed new active bleeding. A second TAE was performed, but, the CT scan several days later showed hemorrhage from the same site. So we decided to perform a right radical nephrectomy. Pathological results revealed three different renal carcinomas at sites different from the bleeding site. The presence of triple carcinomas in the same organ of the kidney is quite rare. Because of the high incidence of renal carcinoma associated with polycystic kidney disease in long-term hemodialysis patients and the possibility of multiple carcinomas as in this case, radical nephrectomy is recommended even in the case of spontaneous rupture.

Background/aim: The most severe adverse event of radiotherapy in lung cancer is radiation pneumonitis (RP). Some indices commonly used to prevent RP are evaluated based on the anatomical lung volume. The irradiation dose may be more accurately assessed by using functional lung volume. We evaluated the usefulness of computed tomography (CT) incorporating functional ventilation images acquired by the inhalation of xenon (Xe) gas (Xe-CT functional images)., Patients and Methods: Two plans were created for twelve patients: volumetric modulated arc therapy (VMAT) planning using conventional chest CT images (anatomical plans) and VMAT planning using Xe-CT functional images (functional plans), and the dosimetric parameters were compared., Results: Compared to the anatomical plans, the functional plans had significantly reduced V 20Gy in the high-functional lungs (p=0.005), but significant differences were not seen in the moderate-functional and low-functional lungs., Conclusion: The incorporation of Xe-CT functional images into VMAT plans enables radiotherapy planning with consideration of lung function., Competing Interests: The Authors have no financial relationships to disclose., (Copyright 2021, International Institute of Anticancer Research.)

Objectives: To investigate the incidence of and risk factors for febrile complications (FCs) in patients undergoing holmium laser enucleation of the prostate (HoLEP)., Methods: This retrospective study enrolled 847 consecutive patients who underwent HoLEP in our hospital from June 2006 to December 2018. FCs were defined as a body temperature ≥38.0°C within 30 days after surgery. The incidence of FCs was determined and possible risk factors assessed using multivariate logistic regression analysis., Results: Overall, 87 (10.3%) patients presented with FCs, and 6 (0.7%) had urosepsis, with no fatal complications. Multivariate logistic regression analysis revealed that patients with preoperative positive urine culture and urethral catheterization had an increased risk of FCs compared with those with a negative culture who did not need catheterization (odds ratio [OR] 2.587, 95% confidence interval [CI] 1.307-5.121). A negative urine culture with catheterization and a positive culture without catheterization were not associated with the development of FCs (OR 0.320, 95% CI 0.040-2.553 and OR 1.370, 95% CI 0.662-2.365, respectively). Other significant risk factors included preoperative serum albumin levels (OR 0.382, 95% CI 0.173-0.846) and immediate postoperative body temperature (OR 2.559, 95% CI 1.549-4.230)., Conclusions: FCs are relatively common among patients after HoLEP despite preoperative prophylactic antibiotic administration. Surgeons may need to consider performing screening of urine cultures prior to HoLEP, especially in patients with urethral catheterization, even if asymptomatic. If the culture is positive, prophylactic antibiotics should be tailored according to bacterial susceptibility., (© 2021 John Wiley & Sons Australia, Ltd.)

Objectives: A pre-equipped metal trocar is required to use as a camera trocar due to a specification change in the da Vinci X/Xi system (Intuitive Surgical). We observed slight slippage of a trocar placed by the open method. With optical trocar access (OTA), the initial trocar is viewed directly with a laparoscope during placement. Reports regarding OTA for robotic surgery are limited, particularly for robot-assisted radical prostatectomy (RARP). We modified the OTA procedure such that it was appropriate for RARP., Patients and Methods: A total of 158 patients were enrolled in this study. The first trocar placement time (FTPT) was compared between the open and OTA groups. In the OTA group, the trocar was mainly placed through the upper abdominal quadrant. We also analyzed the differences between the conventional and modified OTA procedures using the Kii Fios First Entry trocar (Applied Medical). We examined the factors affecting the FTPT using linear regression models. A P value <.05 was considered significant., Results: The FTPT was significantly shorter in the OTA group than the open group (P < .0001). The modified method was associated with a shorter FTPT (P = .0001). None of the patient characteristics affected the FTPT in either group. No major complications were observed., Conclusions: OTA was applied successfully during RARP. Use of the Kii Fios First Entry trocar with upper abdominal quadrant placement was suitable for RARP., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Neurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) serves as a nexus to transduce signals for the establishment of apicobasal and planar cell polarity during these processes. Human SCRIB gene mutations are associated with neural tube defects and this gene is located in the minimal critical region deleted in the rare Verheij syndrome. In this study, we generated brain-specific conditional cKO mouse mutants and assessed the impact of the Scrib deletion on brain morphogenesis and behavior. We showed that embryonic deletion of Scrib in the telencephalon leads to cortical thickness reduction (microcephaly) and partial corpus callosum and hippocampal commissure agenesis. We correlated these phenotypes with a disruption in various developmental mechanisms of corticogenesis including neurogenesis, neuronal migration and axonal connectivity. Finally, we show that Scrib cKO mice have psychomotor deficits such as locomotor activity impairment and memory alterations. Altogether, our results show that Scrib is essential for early brain development due to its role in several developmental cellular mechanisms that could underlie some of the deficits observed in complex neurodevelopmental pathologies.

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., (© 2020 The Japanese Urological Association.)

The coronavirus disease 2019 (COVID-19) pandemic has changed the lives of healthcare professionals, especially vulnerable physicians such as young or female cardiologists. In Japan, they are facing the fear of not only infection but also weak and unstable employment, difficulties in medical practice and training anxiety, implications for research and studying abroad, as well as worsened mental health issues due to social isolation. Conversely, some positive aspects are seen through the holding of remote meetings and conferences. Here, we suggest a new working style for cardiologists, as well as offer solutions to the medical employment problems that have been taken place in Japan.

In addition to breast, ovarian, and pancreatic cancers, BRCA1/2 genes have been associated with prostate cancer (PC). However, the role of BRCA1/2-associated family cancer history (FCH) has remained unexplored in treating these four cancer types as a homogenous pathophysiological group. We aimed to clarify the relationship between BRCA1/2-associated FCH and PC, and to assess its relationship with cancer aggressiveness. Patient characteristics, positive family history of BRCA1/2-associated cancer, and cancer characteristics (Gleason score, prostate specific antigen level at diagnosis, and clinical tumor stage) were analyzed. Among the 1,985 eligible candidates, 473 (23.83%) patients had adequately detailed FCH, obtained via questionnaire, and were thus included in the study. BRCA1/2-associated FCH was observed in 135 (28.54%) patients with PC (68, 14.38%), breast (44, 9.30%), pancreatic (31, 6.55%), or ovarian (8, 1.69%) cancers. BRCA1/2-associated FCH was not significantly associated with high Gleason score (≥ 8). Patients with BRCA-associated FCH were less likely to present with high clinical tumor stage, and no difference was observed in prostate-specific antigen level, presence of metastatic lesions at diagnosis, or likelihood of high-risk classification between patients with and without BRCA-associated FCH. This is the first report of BRCA1/2-associated FCH in Japanese men, indicating that family history did not affect the severity or aggressiveness of PC., Competing Interests: The authors have declared that no competing interests exist.

Few reports have discussed appropriate strategies for patient referrals to advanced heart failure (HF) centers with available left ventricular assist devices (LVADs). We examined the association between the characteristics and prognoses of referred patients with advanced HF and the bed volume of the referring hospitals. This retrospective analysis evaluated 186 patients with advanced HF referred to our center for consultation about the indication of LVAD between January 1, 2015, and August 31, 2018. We divided the patients into two groups according to the bed volume of their referring hospital (high bed volume hospitals (HBHs): ≥ 500 beds in the hospital; low bed volume hospitals (LBHs): < 500 beds). We compared the primary outcome measure, a composite of LVAD implantation and all-cause death, between the patients referred from HBHs and patients referred from LBHs. The 186 patients with advanced HF referred to our hospital, who were referred from 130 hospitals (87 from LBHs and 99 from HBHs), had a mean age of 43.0 ± 12.6 years and a median left ventricular ejection fraction of 22% [15-33%]. The median follow-up duration of the patients was 583 days (119-965 days), and the primary outcome occurred during follow-up in 42 patients (43%) in the HBH group and 20 patients (23%) in the LBH group. Patients referred from HBHs tended to require catecholamine infusion on transfer more often than those referred from LBLs (36.5% (HBH), 20.2% (LBL), P = 0.021). Kaplan-Meier analysis indicates that the occurrence of the primary outcome was significantly higher in the HBH patients than in the LBH patients (log-rank P = 0.0022). Multivariate Cox proportional hazards analysis revealed that catecholamine support on transfer and long disease duration were statistically significant predictors of the primary outcome. Patients from HBHs had a greater risk of the primary outcome. However, the multivariate analysis did not indicate an association between referral from an HBH and the primary outcome. In contrast, catecholamine support on transfer, long duration of disease, and low blood pressure were independent predictors of the primary outcome. Therefore, these should be considered when determining the timing of a referral to an advanced HF center, irrespective of the bed volume of the referring hospital.

Objective: To determine the safety and efficacy of the one-surgeon basketing technique for stone extraction during flexible ureteroscopy when carried out by novice surgeons under instructor guidance., Methods: We retrospectively compared perioperative results, complications and the "stone-free" rate (defined as ≤2 mm fragments on kidney-ureter-bladder imaging 1 month after flexible ureteroscopy) between experienced (group A, n = 50) and novice (group B, n = 50) surgeons using the one-surgeon basketing technique., Results: Baseline patients' characteristics were similar between the two groups. There were no significant differences between groups A and B in operative time (mean 76 min vs 85 min, P = 0.46), stone-free rate (98% vs 92%, P = 0.36), postoperative fever events (4% vs 4%, P = 1.00) and postoperative hospital stay (24 h vs 24 h, P = 1.00). Clavien-Dindo grade IIIa complications (ureter injury) were only observed in two cases (4%) in group B., Conclusions: The one-surgeon basketing technique for the extraction of stone fragments during flexible ureteroscopy might be safely and effectively carried out by surgeons with no prior experience under proper guidance., (© 2020 The Japanese Urological Association.)

Objectives: To evaluate the effectiveness of indocyanine green-guided extended pelvic lymph node dissection during robot-assisted radical prostatectomy for intermediate- to high-risk prostate cancer., Materials and Methods: After institutional review board approval, between July 2017 and December 2018, we carried out 100 indocyanine green-guided extended pelvic lymph node dissections in patients with localized intermediate- and high-risk prostate cancer, using the Firefly (Novadaq Technologies, Mississauga, ON, Canada) and da Vinci Xi surgical system (Intuitive Surgical, Sunnyvale, CA, USA). Indocyanine green was injected transrectally using ultrasound sonography before each surgery. Then, lymphatic drainage patterns and pathological findings were recorded., Results: Lymphatic drainage routes were successfully determined in 91 right-sided and 90 left-sided cases. Five main lymphatic pathways and sites were identified: (i) an internal route (57%); (ii) a lateral route (50%); (iii) a presacral route (20%); (iv) a paravesical artery site (20%); and (v) a pre-prostatic site (5%). Lymph node metastasis was positive in 15 patients, with 44 pathologically confirmed metastatic lymph nodes. Metastatic fluorescent lymph nodes were found in 15 out of 44 lymph nodes (34.1%). For sentinel lymph node identification, the 34% sensitivity and 64.8% specificity rates were detected in regard to identification of lymph node metastasis., Conclusions: Lymphatic drainage patterns from the prostate can be identified and classified using indocyanine green-guided extended pelvic lymph node dissections. Although the direct role of fluorescent lymph nodes in sentinel lymph node identification appears to be limited, the identification of lymphatic pathways could contribute to high-quality extended pelvic lymph node dissection during robot-assisted radical prostatectomy., (© 2020 The Japanese Urological Association.)

Purpose: The cumulative sum (CUSUM) approach has been adopted to evaluate surgical competence in various contexts. The CUSUM method comprises sequential monitoring of cumulative differences from a target level in performance quality over time, allowing the detection of deviations from the target. We use the CUSUM method in this study to derive both institutional and surgeon-specific learning curves for robot-assisted radical prostatectomy (RARP). Patients and Methods: We reviewed 540 patients diagnosed with localized prostate cancer (pathologic stage T2) who underwent RARP at our institution between September 2011 and December 2017. The CUSUM method was used to construct both institutional and individual-surgeon learning curves; the outcome was assessed based on whether a positive surgical margin (PSM) was present. The target PSM rate was 20%. Of seven surgeons performing robot-assisted resections for this period, four who performed ≥60 resections were assessed separately. Results: Of 540 patients, 74 (14%) had PSMs. The institutional CUSUM chart exhibited a downward trend for the first 54 cases and an upward trend thereafter. The CUSUM chart for the earliest adopter was similar to that for the institution; that is, learning was complete at 45 cases. Two adopters did not undergo a learning curve as they consistently performed well. The last adopter required 10 cases for initial learning. However, his CUSUM chart trend became negative at 46 cases and remained so afterward. Conclusions: CUSUM charts are useful for monitoring surgical quality. Long-term monitoring of the PSM rate of a surgeon who has become independent allows an attending surgeon to intervene if necessary; thus, long-term quality control is assured.

Objective: Since most radiation treatment plans are based on computed tomography (CT) images, which makes it difficult to define the targeted tumor volume located near a metal implant, this study aims to evaluate and compare three treatment plans in order to optimally reduce geometrical uncertainty in external radiation treatment of localized prostate cancer., Methods: Experimental subjects were three prostate patients with bilateral hip prosthesis who had undergone radical radiotherapy. The treatment plans were five-field three-dimensional conformal radiation therapy (3D-CRT), fixed 5-field intensity-modulated radiation therapy (IMRT) using similar gantry angles, and single-arc volumetric modulated arc therapy (VMAT). The monitor units (MUs), dose volume histograms (DVHs), the dose indices of planning target volume (PTV), clinical target volume (CTV) and rectum were compared among the three techniques. The geometrical uncertainties were evaluated by shifting the iso-center (2- 10 mm in the anterior, posterior, left, right, superior, and inferior directions). The CTV and rectum dose indexes with and without the iso-center shifts were compared in each plan., Results: The Conformity Index of PTV were 1.35 in 3D-CRT, 1.12 in IMRT, and 1.04 in VMAT, respectively. The rectum doses in 3D-CRT are also higher than those in IMRT and VMAT. The iso-center shift little affected the CTV dose when smaller than the margin size. The rectum dose increased especially after a posterior shift. Additionally, this dose increase was larger in the VMAT plan than in the 3D- CRT plan. However, the VMAT achieved a superior rectum DVH to that of 3D- CRT, and this effect clearly exceeded the rectum-dose increase elicited by the iso-center shift., Conclusion: For radiotherapy treatment of localized prostate cancer in patients with hip prosthesis, the dose distribution was better in the VMAT and Metal Artifact Reduction (MAR)-CT image methods than the conventional methods. Because the anatomical structure of the male pelvic region is relatively constant among individuals, we consider that VMAT is a valid treatment plan despite analyzing just three cases.

Using virtual reality (VR) technology such as head-mounted displays, users can be immersed in a virtual world and perceive it as reality. In radiation therapy departments, pretreatment patients and students rarely observe treatment rooms and treatment devices, making it difficult to understand the overall flow of radiation therapy. In this study, to facilitate the understanding and teaching of radiation therapy, we suggest the implementation of VR technology and develop software compatible with VR to enable a pertinent comprehension of radiation therapy. With versatility and accessibility in mind, the software is developed as an application for Android and iOS devices.Omnidirectional movies in treatment rooms were acquired from both the patient view and a third-person view using an omnidirectional camera. The Android/iOS devices used were AQUOS R (SHARP), iPhone 7 Plus (Apple), and iPad air (Apple). The software was developed using Unity 2018.4.7f (Unity Technologies). The main components of the software were as follows: (i) a home window featuring a user interface with which people can access arbitrarily rooms by tapping on floor maps or a list of treatment rooms, (ii) a snapshot mode providing 2D images of a treatment room as a slide show, and (iii) a movie mode displaying omnidirectional movies from the patient view or a third-person view. The virtual radiation therapy experience was executed by attaching the Android/iOS devices to 3D VR goggles (SAMONIC).The main components of the application operated in good conjunction on the Android/iOS devices, and live viewing in the virtual world ran smoothly with the VR technology. However, there were resolution limitations due to the specs of the camera and the devices. It will therefore be necessary to adjust the resolution and the frame rate according to the performance of the relevant devices. The application is instructive for both patients and students because the virtual radiation therapy experience is immersive when using the VR technology. In addition, the developed software can transfer data in a single package and has the ability to substitute images and omnidirectional movies with those appropriate for diagnostic radiology and nuclear medicine departments. Therefore, the developed application is highly versatile.

Congenital external iliac vein defects are extremely rare. A 56-year-old man underwent robotic prostatectomy (RARP) without pelvic lymph node dissection (PLND) for localized low-risk prostate cancer. Intraoperative findings revealed a markedly dilated vein on the dorsal side of the pubic bone,which was difficult to preserve and was therefore clipped. Sudden swelling and pain appeared in the right leg on day 2 after successful RARP. A contrast-enhanced computed tomography (CT) scan showed a deep vein thrombus (DVT) and lack of a right external iliac vein. Immediate heparinization improved the symptoms, and no other postoperative complications occurred. In the retrospective review,a large dilated vein lying transversely on the prostate surface was observed with a robotic scope,but no manipulation of the pelvic vessels was performed because PLND was not performed. Therefore,the dilated vein was not recognized as a shunt from the right femoral vein to the left external iliac vein. A preoperative staging CT scan,which faintly revealed the right external iliac vein,could be useful to identify this extremely rare deformity in advance of surgery. Although preoperative imaging examinations are often difficult to diagnose preoperatively,as in this case,we consider it important to use appropriate approaches and treatment when dealing with symptoms that arise during pelvic surgery in patients with many anatomical variations.

Automated treatment planning may decrease the effort required in planning and promote increased routine clinical use of intensity-modulated radiation therapy (IMRT) for many breast cancer patients. The aim of this study was to evaluate a new commercial automated planning software for tangential breast IMRT by comparing it with clinical plans from whole-breast irradiation. We prospectively enrolled 150 patients with Stage 0-1 breast cancer who underwent breast-conserving surgery at our institution between September 2016 and August 2017. Total doses of 42.56 Gy in 16 fractions (n = 98) or 50 Gy in 25 fractions (n = 44) were used. All treatment plans were retrospectively re-planned using the automated breast planning (ABP) software. All automated plans generated clinically deliverable beam parameters with no patient body collision and no contralateral breast pass through. The mean homogeneity index of the automatically generated clinical target volume, percentage volume of lungs receiving dose more than 20 Gy, mean heart dose, and dose to the highest irradiated 2-cc volumes of the irradiated volume were 0.077 ± 0.019, 4.2% ± 1.2%, 142 ± 69 cGy, and 105.8% ± 1.7% (prescribed dose: 100%), respectively. The mean planning time was 4.8 ± 1.4 min. The ABP software demonstrated high clinical acceptability and treatment planning cost efficiency for tangential breast IMRT. The ABP software may be useful for delivering high-quality treatment to a majority of patients with early-stage breast cancer.

Secondary lymphoid organs are critical for regulating acquired immune responses. The aim of this study was to characterize the impact of spaceflight on secondary lymphoid organs at the molecular level. We analysed the spleens and lymph nodes from mice flown aboard the International Space Station (ISS) in orbit for 35 days, as part of a Japan Aerospace Exploration Agency mission. During flight, half of the mice were exposed to 1 g by centrifuging in the ISS, to provide information regarding the effect of microgravity and 1 g exposure during spaceflight. Whole-transcript cDNA sequencing (RNA-Seq) analysis of the spleen suggested that erythrocyte-related genes regulated by the transcription factor GATA1 were significantly down-regulated in ISS-flown vs. ground control mice. GATA1 and Tal1 (regulators of erythropoiesis) mRNA expression was consistently reduced by approximately half. These reductions were not completely alleviated by 1 g exposure in the ISS, suggesting that the combined effect of space environments aside from microgravity could down-regulate gene expression in the spleen. Additionally, plasma immunoglobulin concentrations were slightly altered in ISS-flown mice. Overall, our data suggest that spaceflight might disturb the homeostatic gene expression of the spleen through a combination of microgravity and other environmental changes.

In radiation therapy, a secondary independent dose verification is an important component of a quality control system. Mobius3D calculates three-dimensional (3D) patient dose using reference beam data and a collapsed cone convolution algorithm and analyzes dose-volume histogram automatically. There are currently no published data on commissioning and determining tolerance levels of Mobius3D for TomoTherapy. To verify the calculation accuracy and adjust the parameters of this system, we compared the measured dose using an ion chamber and film in a phantom with the dose calculated using Mobius3D for nine helical intensity-modulated radiation therapy plans, each with three nominal field widths. We also compared 126 treatment plans used in our institution to treat prostate, head-and-neck, and esophagus tumors based on dose calculations by treatment planning system for given dose indices and 3D gamma passing rates with those produced by Mobius3D. On the basis of these results, we showed that the action and tolerance levels at the average dose for the planning target volume (PTV) at each treatment site are at μ ± 2σ and μ ± 3σ, respectively. After adjusting parameters, the dose difference ratio on average was -0.2 ± 0.6% using ion chamber and gamma passing rate with the criteria of 3% and 3 mm on average was 98.8 ± 1.4% using film. We also established action and tolerance levels for the PTV at the prostate, head-and-neck, esophagus, and for the organ at risk at all treatment sites. Mobius3D calculations thus provide an accurate secondary dose verification system that can be commissioned easily and immediately after installation. Before clinical use, the Mobius3D system needs to be commissioned using the treatment plans for patients treated in each institution to determine the calculational accuracy and establish tolerances for each treatment site and dose index., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objective: To evaluate the relationship between the lengths of 2 regions of the intraprostatic urethral sphincter, the distal region (from the apex to the adenoma [AA]) and the proximal region (from the adenoma to the verumontanum [AV]) and prostate volume (PV) in patients with clinical benign prostate hyperplasia., Materials and Methods: A total of 110 patients who underwent magnetic resonance imaging before holmium laser enucleation of the prostate were enrolled. The lengths of 2 distinct intraprostatic urethral regions were measured on magnetic resonance imaging, and we used multiple regression analysis to explore the association between these lengths and PV., Results: The median age was 69 years. The median AV and AA lengths were 6.0 and 5.7 mm, respectively. Multiple regression analysis to predict PV revealed that the interaction between age and AV length was significant (P = .012), whereas that between age and AA length was not (P = .819). In patients aged ≥69 years, the AV length was significantly positively associated with the PV (P = .005); in patients aged ≤69 years, a nonsignificant positive association was observed (P = .130). The AA length was not associated with the PV in either subgroup (P = .621 in those aged <69 years and P = .189 in those aged ≥69 years)., Conclusion: Our results may indicate that the proximal length, which is covered by the adenoma, becomes longer as prostate hyperplasia progresses, whereas the distal length does not. It may be important to preserve the intraprostatic length of the striated sphincter when the urethra is dissected at the apex during radical prostatectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hindlimb unloading (HU) of rodents has been used as a ground-based model of spaceflight. In this study, we investigated the detailed impact of 14-day HU on the murine thymus. Thymic mass and cell number were significantly reduced after 14 days of hindlimb unloading, which was accompanied by an increment of plasma corticosterone. Although corticosterone reportedly causes selective apoptosis of CD4 + CD8 + thymocytes (CD4 + CD8 + DPs) in mice treated with short-term HU, the reduction of thymocyte cellularity after the 14-day HU was not selective for CD4 + CD8 + DPs. In addition to the thymocyte reduction, the cellularity of thymic epithelial cells (TECs) was also reduced by the 14-day HU. Flow cytometric and RNA-sequencing analysis suggested that medullary TECs (mTECs) were preferentially reduced after HU. Moreover, immunohistochemical staining suggested that the 14-day HU caused a reduction of the mTECs expressing autoimmune regulator (Aire). Our data suggested that HU impacts both thymocytes and TECs. Consequently, these data imply that thymic T cell repertoire formation could be disturbed during spaceflight-like stress., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: We conducted a retrospective study to compare the perioperative course and lymph node (LN) counts of patients undergoing limited pelvic lymphadenectomy (lPLND) or extended pelvic lymphadenectomy (ePLND) during robot-assisted radical prostatectomy in an initial Japanese series., Methods: The cohort included 1333 patients who underwent either lPLND (n = 902) or ePLND (n = 431) during robot-assisted radical prostatectomy at five institutions in Japan. All complications within 28 days of surgery were recorded, and clinical data were collected retrospectively. The outcomes and complications were compared relative to the extent of lymphadenectomy, and we conducted univariate and multivariate logistic regression analyses to assess the predictors of the major complications., Results: On multivariate analysis for evaluating the associations between major complications and perioperative characteristics, console time (p = 0.001) was significantly associated with major complications, although the extent of lymphadenectomy (p = 0.272) was not significantly associated with major complications. In the distribution of positive LNs removed in the extended pelvic lymphadenectomy cohort, 60.4% of patients had positive LNs only in the obturator/internal iliac region. However, 22.6% of the patients with positive LNs had no positive LNs in the obturator/internal iliac region, but only in the external/common iliac region., Conclusions: ePLND, which significantly increased the console time and blood loss but nearly quadrupled the lymph node yield, is considered a relatively safe and acceptable procedure. Moreover, the results of this study suggest that ePLND improves staging and removes a greater number of metastatic nodes.

The morphological determinants of left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM) are not completely understood. We aimed to identify the anatomical risks of the obstruction using echocardiography.Fifty patients with untreated HCM were classified into two groups: those with LVOT pressure gradient (LVOTPG) ≥ 30 mmHg (obstructive HCM [HOCM] group) and those with LVOTPG < 30 mmHg (HNCM group). The echocardiographic morphological variables were analyzed to determine whether they were predictive of LVOT obstruction. Systolic anterior motions of the mitral valve were observed in 100% of patients in the HOCM group but only in 58% in the HNCM group. There were no significant differences in wall thickness, end-systolic LV dimension (LVDs), or LVOT diameter between the two groups. However, HOCM subjects had a shorter distance from papillary muscles to the inter-ventricular septum (5.97 ± 2.3 versus 9.20 ± 1.9 mm, respectively, P < 0.0001) and a longer anterior mitral leaflet (AML) length (24.7 ± 5.8 versus 20.1 ± 5.4 mm, respectively, P < 0.01) compared to the HNCM group. The AML length/LVDs ratio was significantly higher in the HOCM group compared to the HNCM group (1.02 ± 0.34 versus 0.78 ± 0.26, P < 0.01), and an LVOT obstruction was predicted with an area under the curve of 0.71 (P < 0.05). Multiple linear regression revealed that only the AML length/LVDs ratio was independently associated with LVOTPG (P < 0.01).The AML length/LVDs ratio has a significant predictive value for LVOT obstruction and a strong relationship with LVOTPGs. The AML length/LVDs ratio determines the anatomical risk of LVOT obstruction in HCM.

The MafB transcription factor is expressed in pancreatic α and β cells during development but becomes exclusive to α cells in adult rodents. Mafb -null ( Mafb -/- ) mice were reported to have reduced α- and β-cell numbers throughout embryonic development. To further analyze the postnatal function of MafB in the pancreas, we generated endocrine cell-specific ( Mafb Δ Endo ) and tamoxifen-dependent ( Mafb Δ TAM ) Mafb knockout mice. Mafb Δ Endo mice exhibited reduced populations of insulin-positive (insulin + ) and glucagon + cells at postnatal day 0, but the insulin + cell population recovered by 8 weeks of age. In contrast, the Arx + glucagon + cell fraction and glucagon expression remained decreased even in adulthood. Mafb Δ TAM mice, with Mafb deleted after pancreas maturation, also demonstrated diminished glucagon + cells and glucagon content without affecting β cells. A decreased Arx + glucagon + cell population in Mafb Δ Endo mice was compensated for by an increased Arx + pancreatic polypeptide + cell population. Furthermore, gene expression analyses from both Mafb Δ Endo and Mafb Δ TAM islets revealed that MafB is a key regulator of glucagon expression in α cells. Finally, both mutants failed to respond to arginine, likely due to impaired arginine transporter gene expression and glucagon production ability. Taken together, our findings reveal that MafB is critical for the functional maintenance of mouse α cells in vivo , including glucagon production and secretion, as well as in development., (Copyright © 2018 American Society for Microbiology.)

The core 1 β1,3-galactosyltransferase-specific molecular chaperon (Cosmc) is essential for the synthesis of the core 1 structure of mucin-type O-glycans. To clarify the physiological role of core 1-derived O-glycans in macrophages, we exploited the LysM-Cre transgene to generate a conditional Cosmc mutant allele (conditional Cosmc knockout; cKO) in myeloid cells. cKO mice developed normally with no gross phenotypic abnormalities or abnormal peripheral blood counts. Resident peritoneal macrophages (rpMacs) of cKO mice exhibited impaired engulfment of apoptotic cells but showed normal macrophage differentiation and counts. T-cell immunoglobulin and mucin domain-containing molecule 4 (Tim4) is a phosphatidylserine (PS) receptor expressed on rpMacs and possesses a heavily O-glycosylated domain. Tim4 tethers apoptotic cells through PS binding. Expression of the Tim4 transcript was unchanged in cKO rpMacs, whereas flow cytometric, Western and dot blot analyses revealed that Tim4 protein expression in cKO rpMacs was significantly lower than that in wild-type (WT) rpMacs. Moreover, the expression levels of other efferocytosis-related molecules, Mertk, Itgav and Itgb3, were normal in rpMacs. In addition, hypoglycosylated Tim4-FLAG fusion protein sufficiently recognized PS. These results demonstrated that core 1-derived O-glycan is required for Tim4-dependent normal efferocytosis and may contribute to the stable expression of the Tim4 glycoprotein., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Based on a retrospective analysis, this study aims to develop a simple index for validity of the evaluation point for the dosimetric verification of intensity-modulated radiation therapy (IMRT)., Methods: The results for the dosimetric verifications of a total of 69 IMRT plans were analyzed in this study. A Farmer-type ion chamber was used as a dose detector, and a solid water-equivalent phantom was used. Index values were obtained by dividing the difference between the maximum and minimum dosages by the mean dosage of the 69 plans, and the values were classified into five groups with index value <4, 4-8, 8-12, 12-16, and >16. A t-test was used to assess the statistical significance of the mean differences of the absolute values of the relative errors among these groups., Results: We found that there was no significant difference between the groups with index value <4 and 4-8 (p = 0.152); however, there were significant differences between the other groups (p < 0.01). In addition, when the index values were smaller than 8, the pass ratio of 3% tolerance was 96.2% and the pass ratio of 5% tolerance was 99.9%. We observed that the smaller the index value, the smaller the uncertainty of the dose measurement., Conclusions: The results obtained in this study may prove to be useful for accurate dosimetric verifications of IMRTs when ion chambers are used.

Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) chain. In cartilage, CS plays important roles as the main component of the extracellular matrix (ECM), existing as side chains of the major cartilage proteoglycan, aggrecan. Six glycosyltransferases are known to coordinately synthesize the backbone structure of CS; however, their in vivo synthetic mechanism remains unknown. Previous studies have suggested that two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. Indeed, t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in CS content in cartilage compared with wild-type (WT) mice. To reveal the synergetic roles of t1 and t2 in CS synthesis in vivo, we generated systemic single and double knockout (DKO) mice and cartilage-specific t1 and t2 double knockout (Col2-DKO) mice. DKO mice exhibited postnatal lethality, whereas t2 KO mice showed normal size and skeletal development. Col2-DKO mice survived to adulthood and showed severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice revealed disrupted endochondral ossification, characterized by drastic GAG reduction in the ECM. Moreover, DKO cartilage had reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with WT cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage had the same proliferation rate as WT chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves had an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage showed that the expression levels of Col2a1 and Ptch1 transcripts tended to decrease in DKO compared with those in WT mice. The CS content in DKO cartilage was decreased compared with that in t1 KO cartilage but was not completely absent. These results suggest that aberrant ECM caused by CS reduction disrupted endochondral ossification. Overall, we propose that both t1 and t2 are necessary for CS synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage.

Prostate cancer can be diagnosed as an incidental finding during the pathological examination of benign prostatic hyperplasia (BPH) specimens by Holmium laser enucleation of the prostate (HoLEP). BPH and comorbidities such as hypertension, diabetes, and dyslipidemia often coexist in elderly people. We identified which comorbidities can be used to predict the presence of incidental prostate cancer, particularly high-risk cancer, in men who had undergone HoLEP. On the basis of pathological findings of HoLEP specimens, patients with incidental cancer were categorized as low-risk (Gleason ≤6 and T1a) or high-risk (all others). Of the 654 patients who underwent HoLEP, 41 patients (6.3%) were identified as having incidental cancer (25 low-risk and 16 high-risk). There were no significant factors for overall prostate cancers. However, a significantly higher frequency of diabetes was observed in patients with high-risk cancer compared to those with BPH (31% vs. 13%; p = .033). Logistic regression analysis using prostate-specific antigen (PSA) and prostate volume (PV), and smoking showed that diabetes was an independent predictor of high-risk cancer (odds ratio, 3.15; 95% confidence interval, 1.06-9.43). Diabetes may be an important predictor of the presence of high-risk prostate cancer in men with BPH who have undergone HoLEP.

This Japan Aerospace Exploration Agency project focused on elucidating the impacts of partial gravity (partial g) and microgravity (μg) on mice using newly developed mouse habitat cage units (HCU) that can be installed in the Centrifuge-equipped Biological Experiment Facility in the International Space Station. In the first mission, 12 C57BL/6 J male mice were housed under μg or artificial earth-gravity (1 g). Mouse activity was monitored daily via downlinked videos; μg mice floated inside the HCU, whereas artificial 1 g mice were on their feet on the floor. After 35 days of habitation, all mice were returned to the Earth and processed. Significant decreases were evident in femur bone density and the soleus/gastrocnemius muscle weights of μg mice, whereas artificial 1 g mice maintained the same bone density and muscle weight as mice in the ground control experiment, in which housing conditions in the flight experiment were replicated. These data indicate that these changes were particularly because of gravity. They also present the first evidence that the addition of gravity can prevent decreases in bone density and muscle mass, and that the new platform 'MARS' may provide novel insights on the molecular-mechanisms regulating biological processes controlled by partial g/μg.