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BackgroundOur aim was to characterize the motions of multiple laparoscopic surgical instruments among participants with different levels of surgical experience in a series of wet-lab training drills, in which participants need to perform a range of surgical procedures including grasping tissue, tissue traction and dissection, applying a Hem-o-lok clip, and suturing/knotting, and digitize the level of surgical competency.MethodsParticipants performed tissue dissection around the aorta, dividing encountered vessels after applying a Hem-o-lok (Task 1), and renal parenchymal closure (Task 2: suturing, Task 3: suturing and knot-tying), using swine cadaveric organs placed in a box trainer under a motion capture (Mocap) system. Motion-related metrics were compared according to participants’ level of surgical experience (experts: 50 ≤ laparoscopic surgeries, intermediates: 10–49, novices: 0–9), using the Kruskal–Wallis test, and significant metrics were subjected to principal component analysis (PCA).ResultsA total of 15 experts, 12 intermediates, and 18 novices participated in the training. In Task 1, a shorter path length and faster velocity/acceleration/jerk were observed using both scissors and a Hem-o-lok applier in the experts, and Hem-o-lok-related metrics markedly contributed to the 1st principal component on PCA analysis, followed by scissors-related metrics. Higher-level skills including a shorter path length and faster velocity were observed in both hands of the experts also in tasks 2 and 3. Sub-analysis showed that, in experts with 100 ≤  cases, scissors moved more frequently in the “close zone (0  ≤ to < 2.0 cm from aorta)” than those with 50–99 cases.ConclusionOur novel Mocap system recognized significant differences in several metrics in multiple instruments according to the level of surgical experience. “Applying a Hem-o-lok clip on a pedicle” strongly reflected the level of surgical experience, and zone-metrics may be a promising tool to assess surgical expertise. Our next challenge is to give completely objective feedback to trainees on-site in the wet-lab.

Recently, immunotherapy based on blocking immune checkpoints with programmed death‐1 (PD‐1) or PD‐ligand 1 (PD‐L1) Abs has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor‐tyrosine kinase inhibitors (VEGF‐TKIs), but the significance of their expression in the tumor microenvironment is unclear. We investigated these immune checkpoint markers in tumor cells and tumor‐infiltrating immune cells (TIIC) in the tumor microenvironment of 100 untreated and 25 VEGF‐TKI‐treated primary ccRCC tissues. Upregulated expression of PD‐1 and PD‐L1 by TIIC, and PD‐L1 by tumor cells was associated with the histological grade and unfavorable prognosis of RCC patients. High PD‐1 and PD‐L1 expression by TIIC was associated with a poorer response to VEGF‐TKI, whereas PD‐L1 expression by tumor cells did not affect the efficacy of the treatment. Furthermore, increased PD‐1‐positive TIIC and PD‐L1‐positive TIIC were observed in tumors treated with VEGF‐TKIs compared with those in untreated tumors. Our data suggest that PD‐1 and PD‐L1 expression by TIIC in the tumor microenvironment is involved in treatment resistance, and that sequential therapy with immune checkpoint inhibitors could be a promising therapeutic strategy for ccRCC resistant to VEGF‐TKI treatment. In the present study, we showed that PD‐1 and PD‐L1 expression by tumor‐infiltrating immune cells (TIIC) is associated with malignant potential and poor response to vascular endothelial growth factor‐tyrosine kinase inhibitor (VEGF‐TKI) treatment in renal cell carcinoma (RCC) patients. Moreover, RCC patients treated with VEGF‐TKI had significantly more PD‐1‐ and PD‐L1‐positive TIIC compared with untreated tumors. These results suggested that upregulated PD‐1 and PD‐L1 expression by TIIC in the tumor microenvironment is associated with resistance to VEGF‐TKI treatment, and that blocking the PD‐1/PD‐L1 pathway could be an effective sequential therapy for RCC resistant to VEGF‐TKI treatment.

The quality of transurethral resection of bladder tumor (TURBT) markedly varies among surgeons and may have a considerable impact on treatment outcomes. The importance of a surgical checklist for TURBT has been suggested in order to standardize the procedure and improve surgical and oncological outcomes. In the present study, we verified the usefulness of a checklist for managing patients with non-muscle-invasive bladder cancer (NMIBC). This retrospective study included 201 NMIBC patients diagnosed with Ta, T1, or Tis between October 2011 and February 2021. After September 2016, TURBT was performed with a checklist. We analyzed the intravesical recurrence-free survival (RFS) rate and the presence or absence of the detrusor muscle in resected specimens before and after the introduction of the checklist. Survival rates were compared using the Log-rank test. A multivariate analysis with Cox proportional hazards modeling was performed to verify risk factors for intravesical recurrence. Ninety-nine patients who underwent TURBT with the checklist (checklist group) were compared with 102 patients who underwent TURBT without the checklist (non-checklist group). When the analysis was narrowed down to 9 critical items, we observed a mean number of 9 documented items per operative report (98.0% completion) after implementation of the checklist. Two-year intravesical RFS rates in the checklist and non-checklist groups were 76.7 and 69.5%, respectively (p = 0.1059). The Cox proportional multivariate analysis showed that the rate of intravesical recurrence was slightly lower in the checklist group (hazard ratio 0.7376, 95% CI 0.4064-1.3388, P = 0.3170). The introduction of a checklist is recommended for the standardization of TURBT and increasing the quality of operative reporting, and it may also improve oncological outcomes.

Parkinson’s disease (PD) is a neurodegenerative condition caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. As activation of dopaminergic receptors is fundamentally involved in the micturition reflex in PD, the objective of this study was to determine the effect of a single dose of rotigotine ([−]2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin) on intercontraction interval (ICI) and voiding pressure (VP) in a rat model of PD. We used 27 female rats, PD was induced by injecting 6-hydroxydopamine (6-OHDA; 8 μg in 2 μL of 0.9% saline containing 0.3% ascorbic acid), and rotigotine was administrated at doses of 0.125, 0.25, or 0.5 mg/kg, either intravenous or subcutaneous injection. In rats with 6-OHDA-induced PD, intravenous injection of 0.25 or 0.5 mg/kg rotigotine led to a significantly lower ICI than after vehicle injection ( p  < 0.05). Additionally, VP was significantly lower in animals administered rotigotine compared to those injected with vehicle ( p  < 0.05). Compared to vehicle-injected animals, subcutaneous administration of rotigotine (0.125, 0.25, or 0.5 mg/kg) led to a significantly higher ICI at 2 h after injection ( p  < 0.05); however, there was no change in ICI after injection with (+)-SCH23390 hydrochloride. Dermal administration of rotigotine in a rat model of PD could suppress an overactive bladder.

BackgroundPatients with favorable-risk prostate cancer on active surveillance (AS) are strictly followed for safer execution. Repeat protocol biopsy is essential for evaluating cancer aggressiveness. However, the acceptance rate of repeat biopsy is not high enough because of the burdens of biopsy. We assessed the impact of complications after the initial biopsy on repeat protocol biopsy at 1 year using data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study.MethodsWe performed a retrospective analysis using a prospective cohort in the PRIAS-JAPAN study. Patients with favorable-risk prostate cancer (n = 856) who consented to participate in the PRIAS-JAPAN study from 2010 to 2018 were enrolled. Follow-up evaluations included regular prostate-specific antigen, digital rectal examination and biopsy. Rates of complications after biopsies and repeat protocol biopsy non-acceptance rate at 1 year were reported. Logistic regression analysis explored the association between the complications after the initial biopsy and repeat protocol biopsy non-acceptance.ResultsAltogether, 759 patients (88.7%) actually proceeded to protocol at 1 year. Repeat protocol biopsy non-acceptance rate at 1 year was 14.9%. Regarding complications after the initial biopsy, hematuria (p = 0.028) and pain (p < 0.001) rates were significantly higher in the repeat biopsy non-acceptance group, but infection (p = 0.056) and hematospermia (p = 0.337) rates were not different. On multivariate logistic regression analysis, pain was a significant predictor for repeat protocol biopsy non-acceptance (odds ratio 4.68, 95% confidence interval 1.864–11.75; p = 0.001).ConclusionsPain at the initial biopsy negatively impacts patients’ compliance with further protocol biopsies during AS.

Background Conventional chemotherapy is based on the maximum tolerated dose (MTD) and requires treatment-free intervals to restore normal host cells. MTD chemotherapy may induce angiogenesis or immunosuppressive cell infiltration during treatment-free intervals. Low-dose metronomic (LDM) chemotherapy is defined as frequent administration at lower doses and causes less inflammatory change, whereas MTD chemotherapy induces an inflammatory change. Although several LDM regimens have been applied, LDM cisplatin (CDDP) has been rarely reported. This study addressed the efficacy of LDM CDDP on tumour endothelial cell phenotypic alteration compared to MTD CDDP. Methods Tumour growth and metastasis were assessed in bladder cancer-bearing mice treated with LDM or MTD gemcitabine (GEM) and CDDP. To elucidate the therapeutic effects of LDM CDDP, the change of tumour vasculature, tumour-infiltrating immune cells and inflammatory changes were evaluated by histological analysis and mRNA expression in tumour tissues. Results Tumour growth and bone metastasis were more suppressed by LDM CDDP + MTD GEM treatment than MTD CDDP + MTD GEM. Myeloid­derived suppressor cell accumulation was reduced by LDM CDDP, whereas inflammatory change was induced in the tumour microenvironment by MTD CDDP. Conclusion LDM CDDP does not cause inflammatory change unlike MTD CDDP, suggesting that it is a promising strategy in chemotherapy.

Objective Pheochromocytomas and paragangliomas (PPGLs) are rare tumors arising from the neural crest cells that form the sympathetic and parasympathetic nervous systems. Radiotherapy with [ 131 I]metaiodobenzylguanidine (MIBG) is recommended for unresectable PPGLs. We investigated the usefulness of the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from [ 18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting the prognosis of patients with unresectable PPGL(s) before receiving [ 131 I]MIBG therapy. Patients and methods We retrospectively analyzed the cases of 25 patients with unresectable PPGLs treated with [ 131 I]MIBG at our hospital between 2001 and 2020. The MTV and TLG were measured in reference to liver accumulation. We divided the patients into two groups based on median values for the maximum standardized uptake value (SUVmax), MTV, and TLG, and evaluated between-group differences using log-rank tests. Cox proportional hazards models were used to determine whether there were significant differences in prognosis with respect to tumor type (pheochromocytoma vs. paraganglioma), site of metastasis, age, past treatment (chemotherapy, external radiation or [ 131 I]MIBG treatment before the current [ 131 I]MIBG treatment), urinary catecholamine, SUVmax, MTV, and TLG. Results The median follow-up time was 42 months (range 2–136 months). The median overall survival was 63 months. The overall survival (OS) was significantly shorter in the high-MTV group (log-rank test, p  = 0.049) and the high-TLG group ( p  = 0.049), with no significant difference between the high- and low-SUVmax groups ( p  = 0.19). Likewise, there was no significant difference in prognosis according to pheochromocytoma or paraganglioma, metastasis location, age, or prior chemotherapy. A history of external radiation before [ 131 I]MIBG treatment was associated with a significantly worse prognosis (hazard ration [HR] = 7.95, p  = 0.0018). Urinary adrenaline and noradrenaline were not significant prognostic factors ( p  = 0.70, p  = 0.25, respectively), but urinary dopamine did predict a worse outcome ( p  = 0.022). There was no increased risk of death for higher SUVmax or TLG ( p  = 0.63 and 0.057, respectively), but higher MTV did predict a worse outcome (HR = 7.27, p  = 0.029). Conclusion High MTV and high TLG were significantly associated with a poor prognosis after [ 131 I]MIBG therapy for PPGLs. Other treatment strategies for such patients may need to be explored.

Purpose It has been reported that cerebral oxygen saturation (rSO 2 ) measured by near infrared spectroscopy is low in dialysis patients. We compared the rSO 2 values of dialysis patients before living donor kidney transplantation and their donors as controls by using three spectroscopes that utilize different principals, the INVOS 5100C (spatially resolved spectroscopy), FORE-SIGHT ELITE (modified Beer–Lambert law) and tNIRS-1 (time-resolved spectroscopy). Methods Before induction of anesthesia, the sensors of one of the three spectroscopes were placed on the forehead and rSO 2 values were recorded followed by the same measurement using the other two spectroscopes. The primary objective was to compare the rSO 2 values of the dialysis patients and controls using the three spectroscopes by the unpaired t test. Then we compared the rSO 2 values among the spectroscopes in both dialysis patients and controls by one-way ANOVA. Finally, we examined the relations between the rSO 2 values and the physiological values by using the Pearson correlation coefficient. Results Fifteen pairs of dialysis patients and controls were studied. With the INVOS 5100 C, the values of the dialysis patients (59.7 ± 9.7% (mean ± standard deviation) were 13% lower than those of the controls (73.3 ± 6.9%) ( P  < 0.01). With the tNIRS-1, the values were 57.8 ± 4.8% in the dialysis patients and 63.3 ± 3.5% in the controls ( P  < 0.01). Almost no differences were observed with the FORE-SIGHT ELITE (71.6 ± 4.9% [dialysis patients] vs. 70.8 ± 4.3% [Controls]) ( P  = 0.62). Among the spectroscopes, the values were significantly different in both dialysis patients and controls. For the INVOS 5100C and tNIRS-1, correlation coefficients between rSO 2 values and blood Hb and serum Alb were more than 0.5. Conclusions The rSO 2 values for comparisons between the dialysis patients and the controls were different according to differences of the principles of the near infrared spectroscopes. In the INVOS 5100C and tNIRS-1, rSO 2 values may be related to blood Hb and serum Alb.

Introduction and hypothesisThe aim was to compare pelvic floor muscle (PFM) elasticity between interstitial cystitis/bladder pain syndrome (IC/BPS) patients and healthy women using real-time tissue elastography.MethodsThe subjects were 17 IC/BPS female patients (IC/BPS group; age 34–84 years), 10 healthy middle-aged women (middle-aged group; 50–80 years), and 17 healthy young adult women (young group; 23–37 years). The target sites of elastography were the striated urethral sphincter (SUS) and adipose tissue as the reference site; muscle elasticity was calculated as the strain ratio (SR) of the SUS to the reference site. Evaluations were performed at rest and during PFM contraction. The IC/BPS group completed lower urinary tract symptom and pain questionnaires. SUS SR was compared among the three groups. SUS SR at rest and during PFM contraction was compared among the three groups with the t-test and the Wilcoxon test. Associations between questionnaire results and SUS SR were evaluated by correlation analysis.ResultsThere was no significant difference in age between the IC/BPS and middle-aged groups, but the young group was significantly younger than the other groups (p < 0.001). SUS SR at rest was significantly higher in the IC/BPS group than in the middle-aged (p = 0.014) and young groups (p = 0.002). Furthermore, in the IC/BPS group, there was no significant difference in SUS SR between at rest and during PFM contraction. SUS SR was not significantly correlated with questionnaire results for lower urinary tract symptoms.ConclusionsSUS SR at rest was significantly higher in the IC/BPS group than in the young and middle-aged groups.

Background   Nephropathy in Denys–Drash syndrome (DDS) develops within a few months of birth, often progressing to kidney failure. Wilms tumors also develop at an early age with a high rate of incidence. When a patient does not have Wilms tumor but develops kidney failure, prophylactic bilateral nephrectomy, and kidney transplantation (KTX) is an optimal approach owing to the high risk of Wilms tumor development. In the case presented here, prophylactic bilateral nephrectomy and KTX were performed in a patient who had not developed Wilms tumor or kidney failure. However, the treatment option is controversial as it involves the removal of a tumor-free kidney and performing KTX in the absence of kidney failure. Case diagnosis/treatment We present the case of a 7-year-old boy, born at 38 weeks gestation. Examinations at the age of 1 year revealed severe proteinuria and abnormal internal and external genitalia. Genetic testing identified a missense mutation in exon 9 of the WT1 gene, leading to the diagnosis of DDS. At the age of 6 years, he had not yet developed Wilms tumor and had grown to a size that allowed him to safely undergo a KTX. His kidney function was slowly deteriorating (chronic kidney disease (CKD) stage 3), but he had not yet developed kidney failure. Two treatment options were considered for this patient: observation until the development of kidney failure or prophylactic bilateral nephrectomy with KTX to avoid Wilms tumor development. After a detailed explanation of options to the patient and family, they decided to proceed with prophylactic bilateral nephrectomy and KTX. At the latest follow-up 4 months after KTX, the patient’s kidney functioned well without proteinuria. Conclusion We performed prophylactic bilateral nephrectomy with KTX on a DDS patient who had not developed kidney failure or Wilms tumor by the age of 7 years. Although the risk of development of Wilms tumor in such a patient is unclear, this treatment may be an optimal approach for patients who are physically able to undergo KTX, considering the potentially lethal nature of Wilms tumor in CKD patients.