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OBJECTIVE Pheochromocytoma is a rare neuroendocrine tumour that secretes catecholamines and originates in the adrenal gland. Although surgical resection is the only curative therapy for pheochromocytoma, it is associated with a risk of haemodynamic instability (HDI), such as extremely high blood pressure and/or post tumour removal hypotension and shock. We investigated the risk factors for HDI during pheochromocytoma surgery. DESIGN AND PATIENTS Eighty-two patients who underwent laparoscopic adrenalectomy for pheochromocytoma between July 2002 and February 2020 were examined. We excluded 3 patients with bilateral disease and 11 without detailed 24 h urinary data. We defined HDI as systolic blood pressure ≥ 200 or

Despite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8+ T-cell infiltration into the tumor beds is related to a poor prognosis. To approach the inner landscape of immunobiology of RCC, we performed multiplexed seven-color immunohistochemistry (CD8, CD39, PD-1, Foxp3, PD-L1, and pan-cytokeratin AE1/AE3 with DAPI), which revealed the automated single-cell counts and calculations of individual cell-to-cell distances. In total, 186 subjects were included, in which CD39 was used as a marker for distinguishing tumor-specific (CD39+) and bystander (CD39-) T-cells. Our clear cell RCC cohort also revealed a poor prognosis if the tumor showed increased CD8+ T-cell infiltration. Intratumoral CD8+CD39+ T-cells as well as their exhausted CD8+CD39+PD-1+ T-cells in the central tumor areas enabled the subgrouping of patients according to malignancy. Analysis using specimens post-antiangiogenic treatment revealed a dramatic increase in proliferative Treg fraction Foxp3+PD-1+ cells, suggesting a potential mechanism of hyperprogressive disease after uses of anti-PD-1 antibody. Our cell-by-cell study platform provided spatial information on tumors, where bystander CD8+CD39- T-cells were dominant in the invasive margin areas. We uncovered a potential interaction between CD8+CD39+PD-1+ T-cells and Foxp3+PD-1+ Treg cells due to cell-to-cell proximity, forming a spatial niche more specialized in immunosuppression under PD-1 blockade. A paradigm shift to the immunosuppressive environment was more obvious in metastatic lesions; rather the infiltration of Foxp3+ and Foxp3+PD-1+ Treg cells was more pronounced. With this multiplexed single-cell pathology technique, we revealed further insight into the immunobiological standing of RCC.

The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC). A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed. Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1–19.8, p = 0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p = 0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14–0.99, p = 0.047). The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.

To evaluate the association between a sign and visceral pleural invasion (VPI) of peripheral non–small-cell lung cancer (NSCLC) that does not appear touching the pleural surface. A total of 221 consecutive patients with NSCLC that did not appear touching the pleural surface, ≤ 3 cm in solid tumor diameter, and was surgically resected between January 2009 and December 2015 were included. We focused on the flat distortion of the tumor caused by an arch-shaped linear tag between the tumor and the pleura on CT and named it a bridge tag sign. We evaluated the associations between the clinicopathological features of the tumor, including the bridge tag sign, and VPI. We also evaluated the associations between histopathological findings and the bridge tag sign. The utility of the bridge tag sign in the diagnosis of VPI was statistically assessed. The bridge tag sign was observed in 48 (20.8%) patients. VPI was positive in 9 (4.1%) patients; among these, the bridge tag sign was positive in 8 patients. In multivariate analysis, a bridge tag sign was significantly associated with VPI. The bridge tag sign was associated with longer contact length of the pleura with the tumor and trapezoid type pleural retraction. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of VPI were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively. A bridge tag sign on CT might improve the accuracy of the prediction of VPI. • We present the bridge tag sign which is defined as a flat distortion of an NSCLC tumor by an arch-shaped linear tag between the tumor and chest wall or interlobar fissure. • The bridge tag sign was an independent predictive factor for visceral pleural invasion. • The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of visceral pleural invasion were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively.

The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2 ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0 ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC). During the mean follow-up period of 8.5 years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan–Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group ≥ 4 and PSA-doubling time

To differentiate between infectious and non-infectious diseases occurring in immunocompromised patients without acquired immunodeficiency syndrome (AIDS) using high-resolution computed tomography (HRCT).HRCT images of 555 patients with chest complications were reviewed retrospectively. Infectious diseases (n=341) included bacterial pneumonia (n=123), fungal infection (n=80), septic emboli (n=11), tuberculosis (n=15), pneumocystis pneumonia (n=101), and cytomegalovirus pneumonia (n=11), while non-infectious diseases (n=214) included drug toxicity (n=84), infiltration of underlying diseases (n=83), idiopathic pneumonia syndrome (n=34), diffuse alveolar haemorrhage (n=8), and pulmonary oedema (n=5). Lung parenchymal abnormalities were compared between the two groups using the χThe χ2 test results showed significant differences in many HRCT findings between the two groups. Multiple logistic regression analysis results indicated the presence of nodules with a halo and the absence of interlobular septal (ILS) thickening were the significant indicators that could differentiate infectious from non-infectious diseases. ILS thickening was generally less frequent among most infectious diseases and more frequent among most non-infectious diseases, with a good odds ratio (7.887, p0.001). The sensitivity and accuracy for infectious diseases in the absence of ILS thickening were better (70% and 73%, respectively) than those of nodules with a halo (19% and 48%, respectively), while the specificity in the nodules with a halo was better (93%) than that of ILS thickening (78%).The presence of nodules with a halo or the absence of ILS thickening tends to suggest infectious disease. Specifically, ILS thickening seems to be a more reliable indicator.

Intravesical bacillus Calmette–Guerin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy. We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens. According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p = 0.116, and p

To evaluate the oncological feasibility of pure laparoscopic radical nephroureterectomy (p-LRNU) for upper tract urothelial carcinoma (UTUC) compared with conventional LRNU (c-LRNU) using a propensity-adjusted multi-institutional collaboration dataset. Among the 503 UTUC patients who underwent RNU, we identified 219 who underwent c-LRNU (laparoscopic nephrectomy with open bladder cuff resection) and 72 who underwent p-LRNU (dissecting the kidney, ureter, and bladder cuff under complete laparoscopy). We adopted a propensity score (PS) matching method to achieve homogeneity with respect to patient backgrounds. PS matching-adjusted Cox-regression analysis was performed to evaluate the risk factors that influenced oncological outcomes. Sixty-eight p-LRNU and 68 c-LRNU patients were matched. Overall, 51 (37.0%) developed intravesical recurrence (IVR), 21 (15.4%) had disease recurrence, and 20 (14.7%) died. Patients who underwent p-LRNU had a significantly shorter operation time and less blood loss than those who underwent c-LRNU. Although no significant differences in 3-year recurrence-free survival were found between the two methods, atypical recurrence sites were observed in the p-LRNU group, including the brain, sigmoid colon, vagina, and peritoneum. Regarding IVR, the 3-year IVR-free survival rate was 41.8% in the p-LRNU group, which was significantly lower than that in the c-LRNU group (66.6%, p = 0.004). Multivariate analysis demonstrated that a history of bladder cancer, ureteral cancer, and p-LRNU were independent risk factors for subsequent IVR. Although p-LRNU is less invasive, the current technique may increase the incidence of atypical disease recurrence and subsequent IVR due to extravesical and intravesical tumor dissemination.

The development of systemic therapies, including vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI) and mammalian target of rapamycin (mTOR) inhibitors, represents a major breakthrough in the treatment of patients with renal cell carcinoma (RCC). However, inherent resistance is observed in some patients and acquired resistance commonly develops in many patients within several months of the initiation of systemic therapies. Since these treatments rarely cure patients, their aim is to suppress tumor progression and prolong survival. Therefore, the establishment of dependable criteria that predict responses and resistance to systemic therapies is clinically important, and the underlying molecular mechanisms also need to be elucidated for the future development of more effective therapies. We herein review recent advances in research on the molecular mechanisms underlying resistance, with a focus on morphological characteristics, tumor angiogenesis, and the tumor immune microenvironment in RCC and their relationships with VEGF-TKI treatments. Recent therapies using immune checkpoint inhibitors (ICI) and newly developed VEGF-TKI also appear to be effective for advanced RCC, with stable and durable responses to ICI being observed in some RCC patients. These new drugs and their outcomes have been briefly described.

Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an increase in asymptomatic prostate-specific antigen (PSA). We previously reported the “optimal PSA follow-up schedule after RP”. The aim of this study was to confirm the usefulness and safety of that follow-up schedule in another cohort. We retrospectively reviewed the clinicopathological data of 798 consecutive patients who underwent radical prostatectomy between 2009 and 2017. We examined all PSA values measured during follow-up. Furthermore, we estimated the PSA value when we observed the “optimal PSA follow-up schedule” at each timing in the virtual follow-up. BCR was defined as an elevation of PSA to greater than 0.2 ng/ml, and the ideal PSA range for detection of BCR was regarded to be 0.2–0.4 ng/ml. During the mean follow-up period of 5.8 years, BCR occurred in 115 (14.9%) patients and the frequency of virtual follow-up was significantly lower than the actual frequency. However, overlooking of BCR (detecting BCR when PSA exceeded 0.4 ng/ml) was observed in 17 patients, which is higher than the actual frequency of overlooking (12 patients). Therefore, we modified the follow-up schedule, which could achieve the lower follow-up frequency and a limited number of overlooking of BCR (7 patients). This external validation study revealed that the "modified optimal PSA follow-up schedule after RP" can reduce the frequency of PSA measurement with a limited risk of overlooking BCR.

CONTEXT The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. OBJECTIVE To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. DESIGN AND PATIENTS A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). RESULTS PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0 pg/mL, P

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs., Targeting the inhibitory receptors (IRs) LAG-3, TIM-3 and TIGIT is a promising immune-oncology approach and the identification of biomarkers of response is crucial. Here, the authors apply automated single-cell count for these IRs in human renal cell carcinoma and investigate the immunogenomic landscape of the disease.

INTRODUCTION The goal of partial nephrectomy for renal tumors is complete tumor removal with the preservation of renal function and no complications. Trifecta (total ischemia time

Reduced cortical plasticity has been previously reported in older adult as compared with young adults. However, the effects of dopamine on this plasticity reduction remain unknown. Here, we assessed the effects of high-dose (200 mg) and medium-dose (100 mg) L-3,4-dihydroxyphenylalanine (L-DOPA) intake on the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS) in older adults (aged ∼65 years). The subjects were 32 (200 mg) and 20 (100 mg) healthy older adult volunteers. This study was designed as a double-blind, crossover and placebo-controlled trial on one dose of L-dopa. Two hours after taking L-DOPA or placebo-drug, QPS was applied over the motor cortex. Motor evoked potentials were recorded to evaluate the motor cortical excitability changes. We found that both doses of L-DOPA enhanced LTP after QPS in older adults as one group. We classified subjects into QPS responders and QPS nonresponders. Both L-DOPA doses produced significant LTP enhancement in QPS nonresponders, whereas either of doses did not produce significant LTP enhancement in QPS responders. Collectively, our findings suggest that the neural plasticity reductions observed in older adults could be partly improved by dopamine.

To examine the prognosis after BCR with and without salvage therapy, including radiation and/or androgen deprivation.The study population consisted of 431 patients, all of whom underwent radical prostatectomy and developed BCR (PSA 0.2 ng/mL). According to the two risk factors [Gleason score ≥ 8 and PSA-doubling time (DT) 6 months], we divided the patients into two groups. The high/intermediate-risk group consisted of patients with both or one risk factor. On the other hand, patients with neither factor were in the low-risk group. We set the starting point at the timing of BCR, and the endpoints were development to castration-resistant prostate cancer (CRPC) and cancer-specific death.During the mean follow-up period of 8.3 years after BCR, CRPC was observed in 49 patients (11.4%), and 21 patients (4.9%) died due to prostate cancer. We first divided the 191 high/intermediate-risk patients according to the PSA level (PSA 1.0 ng/mL, PSA 1.0-4.0, and PSA 4.0 or no therapy) at the initiation of salvage therapy, including radiation and/or androgen deprivation. We found that delayed (PSA 4.0 ng/mL) or no salvage therapy was significantly associated with CRPC and cancer-specific death. In the 240 low-risk patients, Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival or cancer-specific survival within 10 years from the timing of BCR.Observation after BCR without salvage therapy or delayed administration may be an option for low-risk patients with a Gleason score ≤ 7 and PSA-DT ≥ 6 months when their life expectancy is within 10 years.

Background International Metastatic Renal Cell Carcinoma Database Consortium model predicts the outcomes of metastatic renal cell carcinoma stratified into favorable, intermediate, and poor risk groups (FG, IG, and PG, respectively), with approximately 50% of patients being classified as IG. We aimed to generate better risk model based on the sub-classification of IG. Methods We analyzed records of 213 consecutive patients receiving molecular targeted therapy. Age, gender, histology, type of initial molecular targeted therapy, serum laboratory data, previous nephrectomy and immunotherapy, and metastatic sites were used for IG sub-stratification. Modified and original models were compared using a concordance correlation coefficient analysis. Results Median follow-up was 17.8 months. Serum albumin, serum C-reactive protein, and bone metastases were independent predictors of overall survival (OS) in IG. IG was sub-classified into low-, middle-, and high-risk IG according to the number of predictors. The following modified model was developed: modified FG (FG & low-risk IG), modified IG (middle-risk IG), and modified PG (PG & high-risk IG). Concordance indices for original and modified models were 0.68 and 0.73, respectively (P < 0.001). OS was significantly longer in modified PG treated with mammalian target of rapamycin inhibitors as second-line therapy than with tyrosine kinase inhibitors, whereas this was not observed in the original model. Conclusions We successfully developed modified IMDC model using a two-step process: the original IMDC plus an IG sub-stratification, and demonstrated that it predicts outcomes more accurately than original model.

The later-line treatment of metastatic renal cell carcinoma (mRCC) has been drastically changing by the development of immune-oncology drugs and molecular targeted treatment in recent years. Although the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is useful for second-line setting, this model has the problem that over 50% patients are classified as intermediate risk group. The aim of this study is to evaluate whether the serum C-reactive protein (CRP) levels prior to second-line treatment could divide intermediate risk group patients. We retrospectively reviewed 82 consequent intermediate-risk mRCC patients who received second-line molecular targeted therapy. We classified patients who had serum CRP higher than 0.5 mg/dl in elevated CRP group because the median baseline serum CRP level before second-line treatment was 0.51 mg/dl. We assessed the prognostic impact of serum CRP levels prior to second-line treatment initiation to predict overall survival (OS). Thirty-three out of 82 (40%) patients demonstrated elevated baseline CRP levels. The median OS of elevated and non-elevated CRP group was 11.5 (95% CI 5.4–17.5) and 29.4 (95% CI 25.5–33.5) months, respectively (p = 0.001). The serum CRP elevation could predict prognosis in intermediate risk patients treated with second-line treatment (HR 2.5, 95% CI 1.4–4.2, p = 0.001). The serum CRP levels after first-line treatment termination could divide intermediate risk group mRCC patients into two prognostic subgroups in second-line targeted treatment setting.

The aims of this study were to compare the high-resolution computed tomography (HRCT) findings of pulmonary infections in immunocompromised patients and to assess the usefulness of HRCT in the differential diagnosis of these infections. A total of 345 immunocompromised patients with pulmonary infections were included in this study. The diagnoses of the patients consisted of bacterial pneumonia (123 cases), pneumocystis pneumonia (PCP) (105 cases), fungal pneumonia (80 cases), tuberculosis (15 cases), cytomegalovirus pneumonia (11 cases), and septic embolism (11 cases). Two chest radiologists retrospectively evaluated the computed tomography (CT) images, which consisted of 22 findings including ground-glass attenuation, consolidation, nodules, and thickening of the bronchial wall and interlobular septum. Associations between the CT criteria and infections were investigated using χ2 test; multiple logistic regression analyses were conducted to identify the significant indicator for each infection. The area under the curve (AUC) of each model was calculated. Bronchial wall thickening was a significant indicator for bacterial pneumonia (p = 0.002; odds ratio [OR], 2.341; 95% confidence interval [CI], 1.378–3.978). The presence of a mosaic pattern and the absence of nodules were significant indicators for PCP (p

In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However, these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis.We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The end point of this study was biochemical recurrence, and median followup was 4.2 years.Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2, and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year biochemical recurrence-free survival rates were 76%, and 67%, respectively. The 5-year biochemical recurrence-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and p=0.014, respectively).Our study suggests that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

Purpose The purpose of this study was to compare the high-resolution CT (HRCT) findings of pulmonary infectious and noninfectious complications with extensive ground-glass attenuation (GGA) in immunocompromised patients. Materials and methods One hundred fifty-two immunocompromised patients with pulmonary complications that showed extensive GGA (> 50% of the whole lung on HRCT) were included in this study. The diagnoses of the 152 patients were as follows: pneumocystis pneumonia (PCP), n = 82; drug-induced pneumonia, n = 38; bacterial pneumonia, n = 9; cytomegalovirus pneumonia, n = 6; idiopathic pneumonia syndrome, n = 6; diffuse alveolar hemorrhage (DAH), n = 4; fungal infection, n = 3; tuberculosis, n = 2 and pulmonary edema, n = 2. Two chest radiologists retrospectively evaluated the CT criteria, which consisted of 12 findings. Results The nodule (p = 0.015), the bronchovascular bundle (BVB) thickening (p = 0.001), and the interlobular septum (ILS) thickening (p = 0.002) were significantly infrequent in PCP. The ILS thickening was significantly frequent in drug-induced pneumonia (p p = 0.005). The nodule was significantly frequent in DAH (p = 0.049). Conclusion Nodules, BVB thickening, and ILS thickening could be useful HRCT findings for the differential diagnosis of pulmonary complications in immunocompromised patients with extensive GGA.

Background Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the prostate size and tumor volume or to prevent tumor progression during the wait times for surgery in clinical practice. On the other hand, the impact of NHT on the pattern of biochemical recurrence (BCR) is unknown. Methods We retrospectively examined 1749 consecutive patients who underwent RP between 1996 and 2017. Among the patients who met the inclusion criteria, BCR developed in 240 of non-NHT patients and in 120 of NHT patients during the mean follow-up period of 6.9 years. We examined the impact of NHT on the PSA-doubling time (DT) following BCR at different times after RP. Results The median PSA-DTs in non-NHT patients who experienced BCR in the first year after surgery, between 1 and 2 years, between 2 and 3 years, between 3 and 4 years, between 4 and 5 years, and at > 5 years were 5.5, 8.8, 11.3, 17.7, 18.2, and 18.4 months, respectively. On the other hand, those in NHT patients were 1.4, 4.1, 9.1, 13.4, 27.2, and 19.3 months, respectively. The differences of PSA-DTs in the first year after surgery (p

Background Alzheimer’s disease (AD) is assessed by carefully examining a patient’s cognitive impairment. However, previous studies reported inadequate diagnostic accuracy for dementia in primary care settings. Many hospitals use the automated quantitative evaluation method known as the Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD), wherein brain MRI data are used to evaluate brain morphological abnormalities associated with AD. Similarly, an automated quantitative evaluation application called the easy Z-score imaging system (eZIS), which uses brain SPECT data to detect regional cerebral blood flow decreases associated with AD, is widely used. These applications have several indicators, each of which is known to correlate with the degree of AD. However, it is not completely known whether these indicators work better when used in combination in real-world clinical practice. Methods We included 112 participants with mild cognitive impairment (MCI) and 128 participants with early AD in this study. All participants underwent MRI, SPECT, and the Mini-Mental State Examination (MMSE). Demographic and clinical characteristics were assessed by univariate analysis, and logistic regression analysis with a combination of MMSE, VSRAD and eZIS indicators was performed to verify whether the diagnostic accuracy in discriminating between MCI and early AD was improved. Results The area under the receiver operating characteristic curve (AUC) for the MMSE score alone was 0.835. The AUC was significantly improved to 0.870 by combining the MMSE score with two quantitative indicators from the VSRAD and eZIS that assessed the extent of brain abnormalities. Conclusion Compared with the MMSE score alone, the combination of the MMSE score with the VSRAD and eZIS indicators significantly improves the accuracy of discrimination between patients with MCI and early AD. Implementing VSRAD and eZIS does not require professional clinical experience in the treatment of dementia. Therefore, the accuracy of dementia diagnosis by physicians may easily be improved in real-world primary care settings.

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle‐invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa‐4N0‐2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2‐4N0‐2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer‐specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non‐MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC., We conducted a multicenter cohort study describing the clinicopathological characteristics of muscle‐invasive bladder recurrence developed after surgical management of upper tract urothelial carcinoma.

The aim of this study was to validate contemporary grading systems, in particular, the Gleason grade group (GGG) 5.We retrospectively reviewed the clinicopathologic data of 176 patients who underwent radical prostatectomy and whose pathologic results were GGG 4 or 5. The endpoints were biochemical recurrence (BCR) and castration-resistant prostate cancer (CRPC).The GGG 4 group was composed of 69 patients. The GGG 5 group consisted of 78 patients with GS 4+5 and 29 patients with GS 5+4 or higher. The 5-year BCR-free survival rates for men with GGG 4, GS 4+5, and GS 5+4 or higher were 59%, 54%, and 20%, respectively, and the 5-year CRPC-free survival rates were 98%, 100%, and 88%, respectively. Both the BCR- and CRPC-free survival rates were significantly higher in GS 4+5 than in GS 5+4 or higher (P .001 and P = .002, respectively), but there were no significant differences between GGG 4 and GS 4+5 (P = .702 and P = .803, respectively). The multivariate analysis demonstrated that GS 5+4 or higher (hazard ratio, 3.4; P = .002) and lymphovascular invasion (hazard ratio, 3.4; P .001) greatly affected BCR.Our follow-up study revealed that men with GS 4+5 and those with GGG 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4+5 and GS 5+4 or higher. This suggested that GGG 4 and 5 in the contemporary prostate cancer grading system should be reviewed. Furthermore, lymphovascular invasion may be useful to subgroup these pathologically high-risk patients.

INTRODUCTION AND OBJECTIVE:Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an asymptomatic prostate specific antigen (PSA) increase. PSA monito...

INTRODUCTION AND OBJECTIVE:Robot-assisted laparoscopic radical prostatectomy (RALP) is a valuable treatment option for clinically localized prostate cancer . However, RALP for larger prostates is a...

INTRODUCTION AND OBJECTIVE:Liposarcoma is one of the most common subtypes of soft tissue sarcoma. The tumor often develops in the lower extremities and the retroperitoneal or paratesticular region....

INTRODUCTION AND OBJECTIVE:Although Vesical Imaging-Reporting and Data System (VI-RADS) has introduced for additional diagnostic modality for bladder cancer (Bca) patients, the diagnostic accuracy ...

INTRODUCTION AND OBJECTIVE:The number of chronic renal failure has been rapidly growing. Further, not only in advanced nations, the number of dialysis patients continues to increase explosively eve...

Objective The indications of neoadjuvant chemotherapy (NAC) for lymph node-positive upper tract urothelial carcinoma (UTUC) have not been investigated regarding improved survival outcomes. Our specific aim was to compare the clinical outcomes of clinically node-positive UTUC patients who were treated by NAC followed by radical nephroureterectomy (RNU) or upfront RNU followed by adjuvant chemotherapy (AC). Materials and methods Among 966 UTUC patients, we identified 89 with clinical nodal involvement who received either NAC before RNU nor AC after upfront RNU. Cox proportional hazard models were employed to evaluate the impact of chemotherapy modality on the oncological outcomes. Results Of the patient cohort, 36 (40.4%) received NAC followed by RNU, whereas 53 (59.6%) underwent RNU followed by AC. Multivariate analysis revealed that tumor size ≥3 cm, clinical T4, and gemcitabine and cisplatin regimen were independent risk factors for disease recurrence, whereas NAC followed by RNU was an independent factor for favorable RFS. Furthermore, regarding cancer-specific survival (CSS), NAC followed by RNU remained an independent factor for favorable CSS. According to Kaplan-Meier analysis, the 1-year and 2-year RFS were 67.9% and 47.0%, respectively, in the NAC+RNU group, which were significantly higher than those in the RNU+AC group (43.9% and 24.6%, respectively, P = 0.006). Moreover, the 1-year and 2-year CSS were 80.5% and 64.2%, respectively, in the NAC+RNU group, which were higher than those in the RNU+AC group (68.6% and 48.2%, respectively, P = 0.016). Conclusion For node-positive UTUC patients, NAC followed by RNU was more clinically beneficial than RNU followed by AC.

Purpose To investigate whether a history of non–muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. Patients and Methods A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n = 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n = 51). Results The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P = .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P = .039) and 76.1% versus 61.6% (P = .005), respectively. Progressive MIBC (hazard ratio, 2.170; P = .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P = .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. Conclusion MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy.

Light-sheet microscopy offers new possibilities to efficiently visualize large tissue samples in three dimensions. Volumetric 3D imaging can uncover detailed information about the inner landscape of tumors, which can improve cancer diagnosis and therapy. This Forum article highlights the advantages of using light-sheet microscopy for pathological examinations of intact tumor specimens.

Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogeneity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin-embedded (FFPE) biopsy samples. We also show that cleared FFPE samples can be re-embedded in paraffin after examination for future use, and that our tumour-phenotyping pipeline can determine tumour stage and stratify patient prognosis from clinical samples with higher accuracy than current diagnostic methods, thus facilitating the design of more efficient cancer therapies. A method that identifies patterns of tumour heterogeneity in intact biopsy samples using 3D light-sheet microscopy stratifies patients by tumour stage.

The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.

INTRODUCTION AND OBJECTIVES:We conducted a retrospective study to examine whether a history of non-muscle invasive bladder cancer (NMIBC) plays a prognostic role in radical cystectomy (RC)-treated ...

INTRODUCTION AND OBJECTIVES:Pheochromocytoma is a rare neuroendocrine tumor that secretes catecholamines and mainly originates in the adrenal grand. Surgical resection is the only curative therapy ...

Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy.We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction.The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI 0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI 0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively.The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

Background and study aims: Epidermal cell sheet (ECS) transplantation immediately after aggressive endoscopic submucosal dissection (ESD) has been shown to be safe and effective in the prevention of esophageal strictures. This study evaluated the feasibility of ECS transplantation after endoscopic balloon dilation (EBD) in a porcine model. Methods: Six pigs underwent circumferential esophageal ESD under general anesthesia. Two weeks later, two pigs underwent EBD and transplantation of an autologous ECS, two underwent EBD alone, and two underwent endoscopic observation only (control). Results: The two pigs in the transplantation group underwent six ECS transplants after EBD with five of the six (83 %) being successful, as shown by engraftment of transplanted ECSs after 7 days. No adverse events were observed. Stricture rates were lower in the two transplanted pigs (55 % and 60 %) than in the control (92.2 % and 87.7 %) and EBD-treated (71.7 % and 78.2 %) pigs. Infiltration of inflammatory cells was significantly lower in the transplanted pigs than in the control and EBD-treated pigs. Conclusion: Preliminary results indicate the stability of the ECS transplantation procedure and the engraftment of transplanted ECS in the tears after EBD. This proof-of-concept study suggests that covering tears with ECSs after EBD may avoid re-strictures.

The relationship between endogenous creatinine clearance (eCrCl) and renal function values obtained using mathematical formulas has not yet been fully elucidated, especially in patients with upper tract urothelial carcinoma that are treated with radical nephroureterectomy followed by cisplatin-based chemotherapy.Sixty patients who received cisplatin-based chemotherapy for locally advanced or metastatic upper tract urothelial carcinoma after radical nephroureterectomy between 2000 and 2012 were retrospectively identified. eCrCl was measured based on 24-hour urine specimens obtained immediately prior to each cycle of chemotherapy. Renal function was estimated with 4 different formulas: the Cockcroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Wright formulas. We evaluated the relationship between eCrCl and the renal function values obtained with each formula using the Pearson correlation coefficient and κ statistics.The median eCrCl was 53.9 mL/min. The Pearson correlation coefficients and κ statistics for the relationships between eCrCl and the renal function values obtained with each of the mathematical formulas ranged from 0.600 to 0.763 and from 0.29 to 0.67, respectively. Among the patients with eCrCl of ≥ 60 mL/min, 70%, 60%, 50%, and 20% were estimated to have the renal function values of 60 mL/min by the Cockcroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Wright formulas, respectively.All 4 of the tested formulas underestimated eCrCl. The values obtained with the Wright formula were most closely associated with eCrCl.

Idiopathic pneumonia syndrome (IPS) is an acute lung dysfunction of non-infectious aetiology and a severe complication following haematopoietic stem cell transplantation (HSCT). Recently, the American Thoracic Society (ATS) updated the concept of IPS and extended the concept to a wider range; it defined IPS as "an idiopathic syndrome of pneumopathy after HSCT, with evidence of widespread alveolar injury and in which infectious aetiologies and cardiac dysfunction, acute renal failure, or iatrogenic fluid overload have been excluded." The ATS also categorised the presumed site of primary tissue injury into three patterns (pulmonary parenchyma, vascular endothelium, and airway epithelium), each of which has several entities. Since the therapeutic strategies for IPS are clearly different from those of infectious diseases, and therapeutic delay causes a poor prognosis, radiologists should be aware of some characteristic HRCT findings of IPS, which includes a wide spectrum of entities. In this article, the characteristic HRCT findings of these entities, including acute interstitial pneumonia/acute respiratory distress syndrome, eosinophilic pneumonia, non-cardiogenic capillary leak syndrome, diffuse alveolar haemorrhage, transfusion-related acute lung injury, organising pneumonia, and bronchiolitis obliterans syndrome, are shown.

Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy.To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy.A total of 311 patients were assessed retrospectively.All patients underwent targeted therapy.Survival outcomes were assessed using Kaplan-Meier analysis. The predictive ability was evaluated using the c-index.Regarding to the first-line targeted therapy, the 3-yr overall survival (OS) rates of the MSKCC (p0.001) and IMDC models (p0.001) were 76.2% and 77.3%, respectively, in the favorable-risk group; 46.7% and 47.9%, respectively, in the intermediate-risk group; and 13.4% and 15.6%, respectively, in the poor-risk group. The c-indexes were 0.68 for the MSKCC model and 0.69 for the IMDC model in a first-line setting. Regarding the second-line targeted therapy, the 1-yr OS rates of the MSKCC (p0.001) and IMDC models (p0.001) were 80.9% and 90.5%, respectively, in the favorable-risk group; 71.4% and 70.6%, respectively, in the intermediate-risk group; and 31.7% and 24.6%, respectively, in the poor-risk group. The c-indexes were 0.66 for the MSKCC model and 0.65 for the IMDC model in the second-line setting. The study is limited by its retrospective nature.The results may assist physicians in providing more appropriate patient counseling and imply the need for a future prognostic tool in mRCC treated with targeted therapy.Both risk models were useful for the risk stratification in metastatic renal cell carcinoma (mRCC) patients treated with first-line and second-line targeted therapy; however, it might be necessary to further update or optimize the models for our Japanese cohort of mRCC patients.

Semaphorins and their receptors are abnormally expressed in various cancers, but little is known about the expression and function of semaphorin 3E (SEMA3E) and its receptor, plexin D1 (PLXND1), in gastric cancer development or metastasis. We evaluated SEMA3E and PLXND1 expression by quantitative RT-PCR in gastric tissues from 62 patients who underwent gastrectomy and analyzed the correlation between their expression and clinicopathological variables. To assess the function of SEMA3E, we generated human gastric cancer cell lines with suppressed or increased SEMA3E expression. The expression level of SEMA3E, but not PLXND1, was correlated with lymph node involvement and metastatic progression in gastric cancer. A significant association was observed between a high level of SEMA3E expression and poor differentiation or poor survival in the intestinal type of gastric cancer. SEMA3E knockdown in gastric cancer cells attenuated cell proliferation and metastatic ability in vitro and in vivo. Moreover, SEMA3E caused cell proliferation and anchorage-independent cell growth in the intestinal type of gastric cancer. These results suggested that SEMA3E is likely to be involved in the development of gastric cancer and might also be a therapeutic target for its treatment.

Background In recent years, a variety of clinical types of amyotrophic lateral sclerosis have come to be recognized. As some patients present with oculomotor abnormalities both clinically and pathologically, the progressive supranuclear palsy variant of amyotrophic lateral sclerosis has been proposed. Aim To describe atypical cases of motor neuron disease with abnormal extraocular movements mimicking progressive supranuclear palsy. Methods We present three motor neuron disease patients with slow saccades, who were aged 57, 63 and 62 years. Neurological examinations found vertical gaze palsy in two patients. The two patients who presented extrapyramidal signs were regarded as motor neuron disease with parkinsonism, whereas the other was diagnosed with amyotrophic lateral sclerosis. Their saccades were investigated by visually-guided saccade and memory-guided saccade tasks, and were compared with those of 14 age-matched normal participants (60.3 ± 1.9 years). Results In all these patients, the visually-guided saccade latencies were significantly prolonged compared with normal participants, whereas the memory-guided saccade latencies were not. The velocity and amplitude of saccades of the patients were significantly reduced in visually-guided saccade and memory-guided saccade in comparison with normal participants. Conclusion The patterns of saccadic abnormalities in the patients were similar to those of progressive supranuclear palsy patients, suggesting that some patients with motor neuron disease show saccade abnormalities similar to those of progressive supranuclear palsy patients from the clinical and physiological perspective. Motor neuron disease with slow saccades and parkinsonism, as reported here, suggest the existence of progressive supranuclear palsy-variant amyotrophic lateral sclerosis.