Utility of positive core number on MRI-ultrasound fusion targeted biopsy in combination with PI-RADS scores for predicting unexpected extracapsular extension of clinically localized prostate cancer.

OBJECTIVES: To evaluate the utility of magnetic resonance imaging (MRI) and MRI-ultrasound fusion targeted biopsy (TB) for predicting unexpected extracapsular extension (ECE) in clinically localized prostate cancer (CLPC). METHODS: This study enrolled 89 prostate cancer patients with one or more lesions showing a Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 but without morphological abnormality in the prostatic capsule on pre-biopsy MRI. All patients underwent TB and systematic biopsy followed by radical prostatectomy (RP). Each lesion was examined by 3-core TB, taking cores from each third of the lesion. The preoperative variables predictive of ECE were explored by referring to RP specimens in the lesion-based analysis. RESULTS: Overall, 186 lesions, including 81 (43.5%), 73 (39.2%), and 32 (17.2%) with PI-RADS 3, 4, and 5, respectively, were analyzed. One hundred and twenty-two lesions (65.6%) were diagnosed as cancer on TB, and ECE was identified in 33 (17.7%) on the RP specimens. The positive TB core number was ≤2 in 129 lesions (69.4%) and three in 57 lesions (30.6%). On the multivariate analysis, PI-RADS ≥4 (p = 0.049, odds ratio [OR] = 2.39) and three positive cores on TB (p = 0.005, OR = 3.07) were independent predictors of ECE. Lesions with PI-RADS ≥4 and a positive TB core number of 3 had a significantly higher rate of ECE than those with PI-RADS 3 and a positive TB core number ≤2 (37.5% vs. 7.8%, p < 0.001). CONCLUSIONS: Positive TB core number in combination with PI-RADS scores is helpful to predict unexpected ECE in CLPC.

Positive regulatory loop of platelet-derived growth factor DD-induced STAT3 activation is associated with poor prognosis in advanced urothelial carcinoma.

Immune checkpoint inhibitor (ICI) therapy has been established for patients with advanced urothelial cancer (UC). The necessity of overcoming resistance to ICIs and identifying a predictive factor for the same has been highlighted, such as the assessment of combination therapy with other targeted drugs and the characterization of molecular signatures in the tumor microenvironment. Recently, we reported that low hemoglobin (Hb) levels and a high platelet-to-lymphocyte ratio (PLR) were significantly associated with overall survival in patients with UC who did not benefit from pembrolizumab treatment. In the present study, we identified a possible link between these unfavorable prognostic indicators and PDGF-DD-induced STAT3 activation in UC. Overlapping patients between the high STAT3- or phosphorylated STAT3-positive score group (as assessed by immunohistochemistry) and low Hb levels or high PLR group (as assessed by blood tests) showed significantly worse outcomes after pembrolizumab treatment. Additionally, using the bladder cancer JMSU1 cell line, we demonstrated a possible positive regulatory loop between autocrine/paracrine PDGF-DD and STAT3 signaling. Therefore, we suggest that STAT3 inhibition and PDGF-DD detection in the tumor microenvironment might represent a potential therapeutic strategy to overcome resistance to pembrolizumab. Moreover, this can help identify patients with UC who could benefit from combination treatment.

The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma.

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.

Renal function outcome after selective bladder-preserving tetramodality therapy consisting of maximal transurethral resection, induction chemoradiotherapy and consolidative partial cystectomy in comparison with radical cystectomy for patients with muscle-invasive bladder cancer: a two-centre retrospective study.

OBJECTIVE: To compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC). METHODS: This 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. RESULTS: The 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. CONCLUSIONS: RF 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.

A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL).

BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.

Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis.

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 at six centres, institutions, or hospitals between September 2018 and February 2022. 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.

Deep-learning prostate cancer detection and segmentation on biparametric versus multiparametric magnetic resonance imaging: Added value of dynamic contrast-enhanced imaging.

OBJECTIVES: To develop diagnostic algorithms of multisequence prostate magnetic resonance imaging for cancer detection and segmentation using deep learning and explore values of dynamic contrast-enhanced imaging in multiparametric imaging, compared with biparametric imaging. METHODS: We collected 3227 multiparametric imaging sets from 332 patients, including 218 cancer patients (291 biopsy-proven foci) and 114 noncancer patients. Diagnostic algorithms of T2-weighted, T2-weighted plus dynamic contrast-enhanced, biparametric, and multiparametric imaging were built using 2578 sets, and their performance for clinically significant cancer was evaluated using 649 sets. RESULTS: Biparametric and multiparametric imaging had following region-based performance: sensitivity of 71.9% and 74.8% (p = 0.394) and positive predictive value of 61.3% and 74.8% (p = 0.013), respectively. In side-specific analyses of cancer images, the specificity was 72.6% and 89.5% (p < 0.001) and the negative predictive value was 78.9% and 83.5% (p = 0.364), respectively. False-negative cancer on multiparametric imaging was smaller (p = 0.002) and more dominant with grade group ≤2 (p = 0.028) than true positive foci. In the peripheral zone, false-positive regions on biparametric imaging turned out to be true negative on multiparametric imaging more frequently compared with the transition zone (78.3% vs. 47.2%, p = 0.018). In contrast, T2-weighted plus dynamic contrast-enhanced imaging had lower specificity than T2-weighted imaging (41.1% vs. 51.6%, p = 0.042). CONCLUSIONS: When using deep learning, multiparametric imaging provides superior performance to biparametric imaging in the specificity and positive predictive value, especially in the peripheral zone. Dynamic contrast-enhanced imaging helps reduce overdiagnosis in multiparametric imaging.

Patterns of recurrence in genuine and induced oligometastatic castration-resistant prostate cancer treated with progressive site-directed therapy.

OBJECTIVES: To describe oncological outcomes after progressive site-directed therapy (PSDT) in genuine and induced oligometasatic (OM)-castration-resistant prostate cancer (CRPC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Peritoneal closure and the processus vaginalis transection method to prevent inguinal hernia after robot-assisted radical prostatectomy.

OBJECTIVES: Postoperative inguinal hernia (IH) is one of the most common complications of radical prostatectomy (RP) including robot-assisted RP (RARP). However, a procedure to prevent IH after RARP has not been established. We investigated the impact of processus vaginalis transection (PVT) and PVT with peritoneal closure on IH after RARP. METHODS: A retrospective analysis was performed on data from patients who underwent RARP at two tertiary hospitals in Japan, where PVT with subsequent peritoneal closure was introduced after 2014. The incidence of IH for 2 years after RARP was compared among 79 patients without PVT or peritoneal closure, 232 patients with only PVT, and 325 patients with PVT and peritoneal closure. Multivariable Cox proportional hazard models that adjusted for hospital, age, history of abdominal operation, body mass index, operation time, and prostate weight were used. RESULTS: Postoperative IH was observed in seven (8.9%) patients without PVT or peritoneal closure, 34 (15%) patients with only PVT, and nine (2.8%) patients with PVT and peritoneal closure. Compared with patients without PVT or peritoneal closure, the incidence of IH was not different in patients with only PVT (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.34, 2.38) and significantly lower in patients with PVT and peritoneal closure (HR 0.22, 95% CI 0.07, 0.70). CONCLUSION: PVT with peritoneal closure may reduce the risk of postoperative IH after RARP. Future randomized controlled trials are required to confirm these findings.

A Case of Immune Thrombocytopenia Occurring after Radiotherapy plus Atezolizumab Treatment for Bladder Cancer.

An 84-year-old female developed gross hematuria. She was diagnosed as urinary bladder carcinoma. She was initiated on concurrent atezolizumab plus radiation(a phase Ⅱ clinical trial)(jRCT2031180060). After 8 cycles of atezolizumab, complete response was confirmed. Maintenance atezolizumab treatment was started. Platelet(Plt)count decreased, there was no rechallenge with atezolizumab. Bone marrow examination revealed normal. Plt count recovered. Plt count decreased again. The serum levels of interleukin-6(IL-6)were elevated. She was diagnosed as having immune thrombocytopenia. She was started on treatment with prednisolone(PSL)at dose of 20 mg/day. Plt count was increased.

Predictive ability of prebiopsy magnetic resonance imaging and biopsy for side-specific negative lymph node metastasis at radical prostatectomy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Unilateral LND may be indicated based on side-specific LNM risk as assessed by prebiopsy multiparametric magnetic resonance imaging and biopsy.

Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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 < 0.05 for both). The AUCs of the RF and SVM models incorporating the selected TFs were 0.82 (95% confidence interval [CI]: 0.67-0.97) and 0.96 (95% CI: 0.91-1.00), respectively, and the AUC of the SVM model was better than that of the mean ADC value (0.76, 95% CI: 0.61-0.90; p = 0.0037). CONCLUSION: TFs can serve as imaging biomarkers in MIBC patients for predicting CRT sensitivity. TAs of ADC maps can potentially optimize patient selection for CRT. KEY POINTS: • Texture analysis of ADC maps and feature selection identified important texture features for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The machine learning model incorporating the texture features set, which included first quartile ADC, GLCM correlation, and GLCM homogeneity, showed high performance in predicting chemoradiotherapy response. • Texture features could serve as imaging biomarkers that optimize eligible patient selection for chemoradiotherapy in muscle-invasive bladder cancer.

Early C-reactive protein kinetics predict survival of patients with advanced urothelial cancer treated with pembrolizumab.

OBJECTIVE: 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. PATIENTS AND METHODS: 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 < 5 mg/L), responder (baseline CRP ≥ 5 mg/L and CRP decreased below baseline at least once within 30 days), and non-responder (baseline CRP ≥ 5 mg/L and CRP never decreased to baseline within 30 days). Association between early CRP kinetics and pembrolizumab efficacy including objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated. RESULTS: Based on early CRP kinetics, 40, 27, and 30 patients were classified as non-elevated, responder, and non-responder, respectively. ORR and DCR were 33% and 60% in non-elevated, 30% and 48% in responder, and 17% and 40% in non-responder; without a statistically significant difference. OS was significantly different among the non-elevated, responder, and non-responder groups (p < 0.01), with 1-year survival rates of 69%, 61%, and 31%, respectively. Early CRP kinetics could discriminate the OS of patients without objective response. Non-responder was an independent predictor for OS (HR 3.65, p < 0.01), as well as liver metastasis and ECOG PS ≥ 2. CONCLUSION: Early CRP kinetics is associated with survival of advanced urothelial cancer patients treated with pembrolizumab and could be a potential biomarker for clinical benefit from immune checkpoint inhibitors.

Metastatic Diffusion Volume Based on Apparent Diffusion Coefficient as a Prognostic Factor in Castration-Resistant Prostate Cancer.

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 < 0.05 for both). mDV showed a statistically significant association with CSS (hazard ratio [HR]: 1.01, P < 0.05). When the mDVs calculated based on the ADC values were included, mDV0.4-0.9 (HR: 1.02, P < 0.05) and the number of therapeutic lines (HR: 1.35, P < 0.05) were significant independent indicators of CSS shortening. CONCLUSION: Assessment of metastatic tumor volume based on ADC values can be used in the prognostic evaluation of patients with CRPC. WB-DWI might be a potential prognostic imaging biomarker for CRPC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Computer-aided diagnosis with a convolutional neural network algorithm for automated detection of urinary tract stones on plain X-ray.

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.

Outcomes of gasless laparoendoscopic single-port partial nephrectomy in 356 consecutive patients: Feasibility of a clampless and sutureless technique.

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.

Trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval in Japan: A nationwide database study from 2016 to 2018.

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.

Nonuse of antimicrobial prophylaxis in clean surgeries for adrenal and renal tumors: Results of the risk-based strategy in 1362 consecutive patients.

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.

Infiltrative tumor interface with normal renal parenchyma in locally advanced renal cell carcinoma: Clinical relevance and pathological implications.

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 < 0.001 and P = 0.02, respectively). CONCLUSIONS: Locally advanced renal cell carcinoma can show radiological infiltrative features preoperatively, which are significantly associated with unfavorable prognosis. Radiological infiltrative features on preoperative imaging correspond with a high specificity to pathological renal parenchymal infiltration.

Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti-PD-1 Treatment Efficacy in Urothelial Carcinoma.

The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiation, could improve the efficacy of postirradiation anti-programmed cell death 1 (PD-1) treatment in UC. In our advanced UC patient cohort, patients with CRT showed a significantly better objective response rate (75%/22%) and overall survival (88%/30% at 12 months) following later pembrolizumab therapy compared to those without. Then, we created syngeneic UC mouse models by inoculating MB49 cells s.c. in C57BL/6J mice to examine the potential of CRT to enhance antitumor immunity in conjunction with postirradiation anti-PD-1 treatment. Nonirradiated tumors of the mice treated with CRT/postirradiation anti-PD-1 treatment had a significantly slower growth rate and a significantly higher expression of cytotoxic T cells compared to those of the mice treated with anti-PD-1 treatment alone. The mice treated with CRT/postirradiation anti-PD-1 treatment showed the best survival. Mechanistically, CRT provoked strong direct cytotoxicity and increased expressions of immunogenic cell death markers in MB49 cells. Therefore, the combination of cisplatin and irradiation induces immunogenic cell death and potentiates postirradiation anti-PD-1 treatment efficacy in UC.