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Background Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery. Methods We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan–Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery). Results Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0–12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22–258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery. Conclusions Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.

To describe oncological outcomes after progressive site-directed therapy (PSDT) in genuine and induced oligometasatic (OM)-castration-resistant prostate cancer (CRPC).Thirty-seven patients with OM-CRPC treated with PSDT were retrospectively analyzed, and oncological outcomes and recurrence patterns on whole-body diffusion-weighted MRI (WB-DWI) were evaluated.Twenty-two (59%) were classified as genuine OM-CRPC and 15 (41%) as induced OM-CRPC. A 50% decline in PSA after PSDT was observed in 21 (95%) genuine OM-CRPCs and 7 (47%) induced OM-CRPCs (p = 0.0005). At a median observation period of 7.3 months, median PSA progression-free survival were 10.9 months in the genuine OM-CRPCs and 4.8 months in the induced OM-CRPCs (p = 0.015). Among the patients who developed PSA progression after PSDT, 11 of 15 in the genuine OM-CRPCs (73%) and 11 of 14 in the induced OM-CRPCs (79%) underwent WB-DWI at PSA progression. The median numbers of newly detected metastases were 2 (range: 1-5) in the genuine OM-CRPCs and 4 (range: 1-40) in the induced OM-CRPCs (p = 0.049). Only one new metastasis appeared in 5 patients from the genuine OM-CRPCs (46%) and 1 from the induced OM-CRPCs (9.1%, p = 0.048). In 7 of 9 patients from the genuine OM-CRPCs (78%) and 7 of 8 patients from the induced OM-CRPCs (88%) who had bone metastases alone, the newly detected metastasis limited to the bone.Genuine OM-CRPC had better oncological outcomes after PSDT than induced OM-CRPC, and the number of lesions detected at recurrence was limited. Induced OM-CRPC might be a disseminated condition with micrometastases at OM diagnosis.

Background: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. Materials and methods: This retrospective study included patients who received nivolumab plus ipilimumab between September 2018 and February 2022 at six centres. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. Results: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165–0.648, p = 0.001; HR 0.334, 95% CI 0.151–0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235–1.097, p = 0.085 or HR 0.245, 95% CI 0.110–0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316–1.036, p = 0.085 or HR 0.267, 95% CI 0.113–0.628, p = 0.002) compared with those who experienced single or zero irAE. Conclusions: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Prostate cancer localization is reportedly associated with the laterality of lymph node metastasis. Thus, it may be feasible to predict side-specific lymph node metastasis (LNM) at radical prostatectomy (RP). To investigate whether multiparametric magnetic resonance imaging and biopsy findings can predict side-specific negative LNM and to explore the feasibility of unilateral lymph node dissection (LND) at RP.A total of 500 patients who were diagnosed with prostate cancer with prebiopsy multiparametric magnetic resonance imaging of the prostate and subsequent prostate biopsy and who underwent RP and extended LND without neoadjuvant treatment were enrolled. Multiparametric magnetic resonance imaging, biopsy findings, and LNM were assessed for each side. The negative predictive value (NPV) of multiparametric magnetic resonance imaging or biopsy or both for ipsilateral LNM was examined.LNM was found in 9.2% (46/500) and 15.6% (28/180) of patients in the overall and high-risk cohorts, respectively. Magnetic resonance imaging and biopsy findings were negative in 408 and 262 sides, respectively, in the overall cohort and 144 and 100 sides, respectively, in the high-risk cohort. The NPVs of magnetic resonance imaging, biopsy, and both for ipsilateral LNM were 98.3%, 98.5%, and 99.1%, respectively, in the overall cohort, and 95.8%, 97.1%, and 97.6%, respectively, in the high-risk cohort.Unilateral LND may be indicated based on side-specific LNM risk as assessed by prebiopsy multiparametric magnetic resonance imaging and biopsy.

To examine the usefulness of the texture analysis (TA) of apparent diffusion coefficient (ADC) maps in predicting the chemoradiotherapy (CRT) response of muscle-invasive bladder cancer (MIBC). We reviewed 45 MIBC patients who underwent cystectomy after CRT. CRT response was assessed through histologic evaluation of cystectomy specimens. Two radiologists determined the volume of interest for the index lesions on ADC maps of pretherapeutic 1.5-T MRI and performed TA using the LIFEx software. Forty-six texture features (TFs) were selected based on their contribution to the prediction of CRT sensitivity. To evaluate diagnostic performance, diagnostic models from the selected TFs were created using random forest (RF) and support vector machine (SVM), respectively. Twenty-three patients achieved pathologic complete response (pCR) to CRT. The feature selection identified first quartile ADC (Q1 ADC), gray-level co-occurrence matrix (GLCM) correlation, and GLCM homogeneity as important in predicting CRT response. Patients who achieved pCR showed significantly lower Q1 ADC and GLCM correlation values (0.66 × 10−3 mm2/s and 0.53, respectively) than those who did not (0.81 × 10−3 mm2/s and 0.70, respectively; p

ObjectiveTo compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC).MethodsThis study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed.ResultsThe number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of −0.7 and −1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC.ConclusionsRF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.

BACKGROUND Whole-body diffusion-weighted MRI (WB-DWI) is useful for assessing disease activity in castration-resistant prostate cancer (CRPC). MET-RADS-P is a subjective assessment-based reporting system proposed to standardize the interpretation of WB-DWI. However, a quantitative evaluation of WB-DWI has not been fully investigated. PURPOSE To investigate the validity, and analyze the prognostic value, of quantitative evaluation of WB-DWI based on apparent diffusion coefficient (ADC) values for CRPC. STUDY TYPE Retrospective. POPULATION Sixty-six patients with CRPC. The median age was 75 years. During the median follow-up period of 25.2 months, 23 of 66 patients (34.8%) died of prostate cancer. FIELD STRENGTH/SEQUENCE A 1.5 T WB-DWI was used with two b-values (0 s/mm2 -1000 s/mm2 ). A single-shot echo-planar imaging sequence was used. ASSESSMENT WB-DWI were evaluated by three readers according to MET-RADS-P scoring system. Using imaging software, Attractive BDScore, tumor diffusion volume (mDV) and ADC value of metastatic lesion (mADC) was calculated by two readers. The mDV was calculated with ADC values (×10-3 mm2 /sec) of 0.4-0.9 (mDV0.4-0.9 ), 0.9-1.4 (mDV0.9-1.4 ), and 1.4-1.8 (mDV1.4-1.8 ), respectively. STATISTICAL TESTS Spearman's rank correlation coefficient was used to assess the correlation. The relationships between the variables with cancer-specific survival (CSS) were evaluated. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS mDVs showed a strong positive correlation with MET-RADS-P scores (r = 0.90/0.87, P

Objectives To investigate the outcomes and feasibilities of gasless laparoendoscopic single-port clampless sutureless partial nephrectomy. Methods We reviewed 356 consecutive patients with primary unilateral non-metastatic renal masses who underwent gasless laparoendoscopic single-port partial nephrectomy (2011-2018), which was performed retroperitoneally using a three-dimensional flexible endoscope, without vascular clamping or renorrhaphy in principle. Results The median tumor size was 2.5 cm, and 213 (60%), 105 (29%), and 38 (11%) patients had peripheral, central, and hilar tumors, respectively. Clampless and sutureless partial nephrectomy was accomplished in 337 patients (95%), while eight (2%) and 16 (4%) patients required vascular clamping and renorrhaphy, respectively. The median operative time and blood loss were 220 min and 266 mL, respectively; eight patients (2%) received blood transfusion. Clavien-Dindo grade 3a complications occurred in 27 patients (8%); all these patients had urinary leakage treated with ureteral stent placement, one of whom also developed a postoperative pseudoaneurysm. Among 324 patients diagnosed with renal cell carcinoma, six (2%) had positive surgical margins, and one (0.3%) and seven (2%) developed metastatic and local recurrences, respectively. During a median follow-up of 54 months, no patient died from kidney cancer. The median percent decrease in estimated glomerular filtration rate at 3 months after surgery was 5.7%. No patient experienced postoperative acute renal failure, while one patient with preexisting renal impairment started dialysis at 70 months after surgery. Conclusions Clampless and sutureless partial nephrectomy can be safely accomplished in most patients undergoing gasless laparoendoscopic single-port surgery, yielding favorable oncological and functional outcomes.

To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab. We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP

Background METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) has been proposed as a standard of data acquisition and interpretation for whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) performed in men with advanced prostate cancer. The aim of this study is to demonstrate the clinical significance of the scores in castration-resistant prostate cancer (CRPC). Materials and Methods We retrospectively evaluated WB-DWI obtained from 72 patients with CRPC between 2014 and 2017, when disease progression was suspected at the time of starting a new line of anticancer therapy. Twenty-five (35%) and 30 (42%) patients had a treatment history that included taxane-based chemotherapy and new hormonal drugs, respectively. Results Active bone metastases were identified in 60 patients (83%; number of bone metastasis = 0, 1-2, 3-5, 6-10, and > 10: n = 12 [17%], 20 [28%], 11 [15%], 1 [1%], and 28 [39%], respectively). Progressive lymph node and visceral metastases were identified in 10 (14%) and 4 (6%), respectively. During the median follow-up period of 24 months, 36 (50%) died of prostate cancer. Cancer-specific survival (CSS) was significantly stratified according to the MET-RADS-P scores of osseous metastatic burden and the presence of visceral metastasis (P 10) and the presence of visceral metastasis were significant indicators of shorter CSS (P = .0036 and P = .0017, respectively). Conclusions The extent of bone metastasis and the presence of visceral metastasis on WB-DWI were associated with a shorter CSS in CRPC. MET-RADS-P score can be a prognostic imaging biomarker for CRPC.

OBJECTIVE To evaluate the time course of lower urinary tract symptoms (LUTS) after artificial urinary sphincter (AUS) implantation based on individual longitudinal changes of patient-reported outcomes. METHODS This retrospective study included 66 male patients with severe urinary incontinence who were treated with primary AUS implantation between 2009 and 2019. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and International Prostate Symptom Score (IPSS) questionnaires were used to evaluate continence status and LUTS preoperatively, 1, 3, and 12 months after activation, and then annually. The annual changes in scores were calculated with a linear mixed model. RESULTS Of the 66 patients, 63 (95%) achieved complete or social continence (number of pads used ≤1/d) at 1 month after activation. Mean preoperative ICIQ-SF, IPSS, and IPSS-quality of life (QOL) score were 18.9, 14.9, and 5.4, respectively; the corresponding scores at 1 month after activation were 4.5, 9.0, and 1.7 (all P

The purpose of this study was to evaluate the impact of progressive site-directed therapy (PSDT) for oligometastatic castration-resistant prostate cancer (OM-CRPC) on the efficacy of subsequent androgen receptor axis-targeted (ARAT) drugs, and to demonstrate the possibility of prolonging overall survival (OS). We performed a retrospective analysis of 15 OM-CRPC patients who underwent PSDT and subsequently received first-line ARAT drugs (PSDT group) and 13 OM-CRPC patients who were treated with first-line ARAT drugs without PSDT (non-PSDT group). PSDT was performed with the intention of treating all progressing sites detected by whole-body diffusion-weighted MRI with radiotherapy. Thirteen patients (86.7%) treated with PSDT had a decrease in PSA levels, which was at least 50% in 10 (66.7%) patients. The median PSA progression-free survival (PFS) for PSDT was 7.4 months. The median PSA-PFS for ARAT was 27.2 months in patients in the PSDT group and 11.7 months in the non-PSDT group, with a significant difference between the two groups (hazard ratio [HR], 0.28; p = 0.010). The median OS was not reached in the PSDT group and was significantly longer than 44.5 months in the non-PSDT group (HR, 0.11; p = 0.014). In OM-CRPC, PSDT may improve the efficacy of subsequent ARAT and OS.

OBJECTIVE To assess the feasibility and functional/oncological outcomes of selective tetramodal bladder-preservation therapy in elderly patients with muscle-invasive bladder cancer. METHODS This study analyzed 154 patients with non-metastatic muscle-invasive bladder cancer who were enrolled into the protocol. After maximal transurethral resection and induction chemoradiotherapy, patients with clinical complete response were offered consolidative partial cystectomy to achieve bladder preservation; otherwise, radical cystectomy was recommended. Postoperative complications, preserved bladder function, and oncological outcomes were compared between elderly (aged ≥75 years) and younger patients (aged

Objectives To evaluate the oncological and functional outcomes associated with selective tetramodal bladder-sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND). Materials and methods In the present study, 154 patients with non-metastatic muscle-invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder-preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC-recurrence-free survival (RFS); cancer-specific survival (CSS); overall survival (OS), and cross-sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36-item Short-Form Health Survey (SF-36) score. Results The median follow-up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder-preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5-year MIBC-RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post-void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF-36, patients had favourable scores, equivalent to the age-matched references in all the QoL scales. Conclusion Selective tetramodal bladder-preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

INTRODUCTION AND OBJECTIVE:Functional outcomes after partial nephrectomy (PN) depend on the ipsilateral (ipsi-) renal parenchymal volume (RPV) preserved. New-baseline RPV early after PN has been wi...

INTRODUCTION AND OBJECTIVE:The IMDC risk model is widely used to predict survival of patients with metastatic renal cell carcinoma (mRCC). Recent studies suggested that radiologic infiltrative feat...

AIM We aimed to explore the association between cancer cachexia phenotypes in the early phase of treatment induction and the prognosis of advanced urothelial cancer (aUC) patients receiving pembrolizumab. METHODS This retrospective study included 31 aUC patients treated with pembrolizumab as a second- or later-line therapy. Patients were categorized into three early cancer cachexia phenotypes by changes in skeletal muscle and total adipose indices calculated using computed tomography images taken immediately before and within 3 months after the initiation of pembrolizumab: No Wasting (NW, 11 patients), Fat-Only Wasting (FW, 13), and Muscle and Fat Wasting (MFW, seven). Its association with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS The median follow-up period was 5.7 months. The median number of cycles of pembrolizumab was five. The ORR in NW/FW/MFW was 86%/38%/0%, respectively (p = 0.001). The PFS and OS rates were the best in NW, followed in order by FW and MFW (PFS, 69%/45%/0% at 12 months, p = 0.008; OS, 100%/65%/0% at 12 months, p

OBJECTIVES Locally advanced renal cell carcinoma is considered clinically aggressive, despite heterogeneity in survival outcomes. We investigated the clinical relevance and pathological implications of infiltrative tumor interface with normal renal parenchyma on preoperative imaging in locally advanced renal cell carcinoma. METHODS A total of 77 patients with locally advanced renal cell carcinoma (≥pT3a Nany M0) who underwent radical or partial nephrectomy (2008-2018) were analyzed. Preoperative dynamic computed tomography images were reviewed to assess radiological infiltrative features. A radiological infiltrative feature was defined as an ill-defined tumor interface with normal renal parenchyma. The tumor interfaces were analyzed histologically and compared with radiological findings. RESULTS The median tumor size was 6.4 cm. Lymphadenopathy was observed in four patients (5.2%). Clear cell renal cell carcinoma was diagnosed in 66 patients (86%) and Fuhrman grade was 3-4 in 38 patients (49%). A total of 30 patients (39%) showed radiological infiltrative features, which were significantly associated with larger tumor size and higher clinical T stage. The specificity and sensitivity of radiological infiltrative features in predicting pathological renal parenchymal infiltration were 90 and 64%, respectively. During a median follow-up period of 3.8 years, 27 patients (35%) developed cancer recurrences, and six patients (7.8%) died of renal cell carcinoma. Multivariable analysis showed that the presence of radiological infiltrative features was an independent risk factor for cancer recurrence. Cancer recurrence and cancer-specific mortality were significantly stratified by the presence or absence of radiological infiltrative features (P

Objectives To evaluate the trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval for this type of procedure in April 2016. Methods This nationwide retrospective study included 3722 received robot-assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 participating institutions. The institutions were divided into lower- and higher-volume institutions according to the median of 19 robot-assisted partial nephrectomy cases during the study period. Surgical outcomes between 616 cases from lower-volume institutions and 3106 cases from higher-volume institutions were compared using propensity score matching. Results During the study period, both the number of robot-assisted partial nephrectomy surgeries and the number of institutions in which the surgery was carried out steadily increased. Overall, the median anesthesia time was 217 min, the median postoperative length of stay was 9 days, and the proportion of blood transfusions, complications and readmissions were 0.8%, 5.1% and 1.0%, respectively. There were no significant differences in anesthesia time, incidence of blood transfusions, and complication rates between the lower-volume and higher-volume institutions. However, a slightly, but significantly, longer postoperative length of stay and a lower incidence of readmission were observed in lower-volume institutions both before and after propensity score matching. Conclusions Robot-assisted partial nephrectomy has become widespread during the initial 2-year period after government approval with an acceptable safety profile, regardless of the institutional caseloads. This technique has become a standard of care for stage 1 renal cancer patients in Japan.

Background Recent increased use of medical images induces further burden of their interpretation for physicians. A plain X-ray is a low-cost examination that has low-dose radiation exposure and high availability, although diagnosing urolithiasis using this method is not always easy. Since the advent of a convolutional neural network via deep learning in the 2000s, computer-aided diagnosis (CAD) has had a great impact on automatic image analysis in the urological field. The objective of our study was to develop a CAD system with deep learning architecture to detect urinary tract stones on a plain X-ray and to evaluate the model’s accuracy. Methods We collected plain X-ray images of 1017 patients with a radio-opaque upper urinary tract stone. X-ray images (n = 827 and 190) were used as the training and test data, respectively. We used a 17-layer Residual Network as a convolutional neural network architecture for patch-wise training. The training data were repeatedly used until the best model accuracy was achieved within 300 runs. The F score, which is a harmonic mean of the sensitivity and positive predictive value (PPV) and represents the balance of the accuracy, was measured to evaluate the model’s accuracy. Results Using deep learning, we developed a CAD model that needed 110 ms to provide an answer for each X-ray image. The best F score was 0.752, and the sensitivity and PPV were 0.872 and 0.662, respectively. When limited to a proximal ureter stone, the sensitivity and PPV were 0.925 and 0.876, respectively, and they were the lowest at mid-ureter. Conclusion CAD of a plain X-ray may be a promising method to detect radio-opaque urinary tract stones with satisfactory sensitivity although the PPV could still be improved. The CAD model detects urinary tract stones quickly and automatically and has the potential to become a helpful screening modality especially for primary care physicians for diagnosing urolithiasis. Further study using a higher volume of data would improve the diagnostic performance of CAD models to detect urinary tract stones on a plain X-ray.

OBJECTIVES To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors. METHODS We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560) using the gasless laparoendoscopic single-port surgery technique between 2005 and 2019. In 1059 patients, antimicrobial prophylaxis was not administered. The remaining 303 patients were considered at high risk for infection and received single-dose antimicrobial prophylaxis. The endpoint was the incidence of perioperative infections within 1 month from the surgery date. Perioperative infections were classified into surgical site infections, urinary tract infections, and remote infections. RESULTS Seventy-four patients whose collecting systems were opened during partial nephrectomy were excluded, and the remaining 1013 patients with nonuse of antimicrobial prophylaxis and 275 patients with single-dose antimicrobial prophylaxis were retrospectively analyzed. The incidence of superficial surgical site infections, deep/organ-space surgical site infections, urinary tract infections, and remote infections was 1.6%, 0.7%, 2.8%, and 1.3%, respectively, in patients with nonuse of antimicrobial prophylaxis and 0.4%, 1.8%, 1.5%, and 1.5%, respectively, in patients with single-dose antimicrobial prophylaxis. All patients who developed perioperative infections were successfully treated. No clinical or surgical variables were significantly associated with the incidence of surgical site infections. One limitation of the present study was its nonrandomized and noncontrolled design. CONCLUSIONS In minimally invasive clean surgeries for adrenal and renal tumors, antimicrobial prophylaxis is not necessary when individual risk of infection is considered low.

PURPOSE To examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer. METHODS We recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2–3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)-free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated. RESULTS Median follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease. CONCLUSIONS Hemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer.

To evaluate the clinical characteristics of genuine- and induced-oligometastatic castration-resistant prostate cancer (OM-CRPC) and assess the therapeutic effect of progressive-site directed therapy (PSDT). We performed a retrospective analysis of 45 patients with OM-CRPC. Whole-body diffusion-weighted MRI (WB-DWI) was used to diagnose oligo-progressive disease. Based on the clinical and radiological findings, the OM-CRPCs were classified as genuine or induced. PSDT was performed with the intent to ablate all the progressive sites detected on WB-DWI with radiotherapy. Systemic therapy remained unchanged during and after PSDT. A total of 31 (69%) and 14 (31%) patients were diagnosed with genuine- and induced-OM-CRPC, respectively. The genuine-OM-CRPC group had significantly fewer patients treated with taxane-based chemotherapy and new hormonal drugs than the induced-OM-CRPC group. Of these, 26 OM-CRPC patients were treated with PSDT, and a 50% PSA decline was observed in 14 (93%) of 15 patients with genuine-OM-CRPC and 4 (36%) of 11 patients with induced-OM-CRPC (P = 0.033). Further, the duration of PSA-progression-free survival was significantly longer in the genuine-OM-CRPC group than in the induced-OM-CRPC group (8.7 vs. 5.8 months, P = 0.040). PSDT can be a promising treatment option for genuine-OM-CRPC. The procedure might also be considered effective for induced-OM-CRPC, although there was less therapeutic benefit of PSDT in patients with induced-OM-CRPC than in patients with genuine-OM-CRPC.

Somatic stem cells have been isolated from multiple human tissues for their potential usefulness in cell therapy. Currently, mesenchymal stromal cells (MSCs) are prepared after several passages requiring a few months of cell culture. In this study, we used a prospective isolation method of somatic stem cells from gestational or fat tissues, which were identified using CD73 antibody. CD73-positive population from various tissues existed individually in flowcytometric pattern, especially subcutaneous fat- and amniotic-derived cells showed the highest enrichment of CD73-positive cells. Moreover, the cell populations isolated with the prospective method showed higher proliferative capacity and stem cell marker expression, compared to the cell populations which isolated through several passages of culturing whole living cells: which we named “conventional method” in this paper. Furthermore, the therapeutic potential of CD73-positive cells was evaluated in vivo using a mouse model of pulmonary fibrosis. After intranasal administration, murine CD73-positive cells reduced macrophage infiltration and inhibited fibrosis development. These results suggest that further testing using CD73-positive cells may be beneficial to help establish the place in regenerative medicine use.

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, is a multifactorial syndrome reflecting frailty, poor general health status, and the possible presence of cancer cachexia. Here, we aimed to investigate the effect of sarcopenia on the efficacy of pembrolizumab in patients with advanced urothelial carcinoma (aUC). This retrospective study included 28 patients with aUC treated with pembrolizumab as a second or later-line therapy. Sarcopenia was determined based on computed tomography images. Associations of sarcopenia with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. In total, 19 (68%) patients had sarcopenia. ORR was 21% in the patients with sarcopenia, while those without sarcopenia showed significantly higher ORR (67%, P = 0.019). PFS was significantly shorter in patients with sarcopenia than in those without (median, 3 vs. 15 months, P = 0.038). Although the statistical significance was not reached, OS was shorter in patients with sarcopenia than in those without (median, 7 months vs. not reached; P = 0.086). Our preliminary results demonstrated that more than half of patients with aUC who received pembrolizumab had sarcopenia, which was significantly associated with poor therapeutic efficacy. This indicates the clinical relevance of sarcopenia in pembrolizumab therapy for patients with aUC.

Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second‐ or later‐line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non‐radiotherapy group (65% vs 19%; P, Radiotherapy to the primary tumor was significantly associated with favourable therapeutic response and prognosis following pembrolizumab therapy in advanced urothelial cancer patients. Thus, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab, indicating the possibility that radiotherapy to the primary tumor in combination with pembrolizumab may be a promising therapeutic strategy for urothelial cancer.

To evaluate the significance of the presence or absence of an “inchworm sign” on DWI for the recurrence and progression of T1 bladder cancer. We retrospectively analyzed 91 patients with pT1 urothelial carcinoma who underwent DWI prior to transurethral resection between 2007 and 2016. DWI of the dominant tumors was scrutinized for inchworm signs at b = 1000 s/mm2. The association of the presence of the inchworm sign with progression and recurrence was analyzed; progression was defined as recurrence to stage T2 or higher and/or N+, and/or M1. An inchworm sign was seen in 65 cases (71%), while it was absent in 26 cases. Among the 65, 25 (38%) had confirmed tumor recurrence, while in the remaining 26, 14 (54%) had confirmed recurrence (median time post TURB = 7.9 and 10.1 months for each). At the time of recurrence, the tumor had progressed in one (2%) inchworm-sign-positive and seven (27%) inchworm-sign-negative cases. The progression rate of inchworm-sign-negative cases was significantly higher than that of inchworm-sign-positive cases (hazard ratio = 17.2, p = 0.0017), whereas there was no significant difference in the recurrence rate between two groups. The absence of an inchworm sign and histological grade 3 were independent risk factors for progression (p

Surgical resection is commonly performed for augmented bladder cancer, yet an optimal treatment strategy for augmented bladder cancer with lymph node metastasis has not been established. Here, we report a case that achieved 7 years of survival after radical cystectomy and mesenteric lymph node dissection for squamous cell carcinoma arising from augmented bladder with lymph node metastasis. Extended surgery could be a useful treatment option for locally advanced augmented bladder cancer including mesenteric lymph node metastasis.

An association between the development of overall or specific immune-related adverse events (irAEs) and outcomes of immune checkpoint inhibitors has recently been suggested. To address this emerging association in patients with urothelial cancer receiving pembrolizumab, we conducted a multicenter retrospective analysis, which is the first and largest in an Asian cohort as well as a systematic literature review. We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab as second- or later-line treatment between January 2018 and March 2019. irAEs were categorized by the involved organs and graded using Common Terminology Criteria for Adverse Events version 5.0. Associations between irAEs and pembrolizumab efficacy, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. In our review of the literature, 28 studies, including 9 studies involving patients with urothelial cancer and 19 studies reporting the association between outcomes and spectrum of irAEs, were analyzed. Patients with irAEs had significantly higher ORR (52% vs. 16%, P .01), longer PFS (11.0 months vs. 3.6 months, P .01) and OS (median not reached vs. 13.1 months, P = .12) than in patients without irAEs. Endocrine (P = .02), pneumological (P = .06), and other (gastrointestinal, hematological, hepatic) (P = .04) irAEs were associated with increased ORR, whereas skin irAEs were not. Endocrine irAEs (P = .04) was associated with improved OS, whereas pneumological and skin irAEs were not. The association between the occurrence of irAEs and clinical efficacy of immune checkpoint inhibitors was consistently supported by the multiple studies we reviewed. The association between clinical outcomes and the spectrum of organs/systems affected by irAEs seems to be inconsistent and could be dependent on tumor type. irAEs were associated with a higher ORR and better survival of patients with advanced urothelial cancer treated with pembrolizumab.

INTRODUCTION AND OBJECTIVE:Mixed reality (MR) is a novel tool that is expected to assist medical imaging. A wearable MR device allows its wearer to view holographic 3-dimensional (3D) images projec...

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