Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Real-world effectiveness of pembrolizumab as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma: the ARON-2 study.

BACKGROUND: The advent of immune-checkpoint inhibitors has challenged previous treatment paradigms for advanced urothelial carcinoma (UC) in the post-platinum setting as well as in the first-line setting for cisplatin-ineligible patients. In this study, we investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC. METHODS: Data from patients aged ≥ 18 years with cisplatin-ineligible UC and receiving first-line pembrolizumab from January 1st 2017 to September 1st 2022 were collected. Cisplatin ineligibility was defined according to the Galsky criteria. Thirty-three Institutions from 18 countries were involved in the ARON-2 study. RESULTS: Our analysis included 162 patients. The median follow-up time was 18.9 months (95%CI 15.3-76.9). In the overall study population, the median OS was 15.8 months (95%CI 11.3-32.4). The median OS was significantly longer in males versus females while no statistically significant differences were observed between patients aged < 65y versus ≥ 65y and between smokers and non-smokers. According to Recist 1.1 criteria, 26 patients (16%) experienced CR, 32 (20%) PR, 39 (24%) SD and 55 (34%) PD. CONCLUSIONS: Our data confirm the role of pembrolizumab as first-line therapy for cisplatin-unfit patients. Further studies investigating the biological and immunological characteristics of UC patients are warranted in order to optimize the outcome of patients receiving immunotherapy in this setting.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

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.

Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non-clear cell renal cell carcinoma: Real-world data from a Japanese multicenter retrospective study.

OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

Nomogram predicting testicular torsion in Japanese patients with acute scrotal pain using physical examination findings and environmental conditions: Development and prospective external validation.

OBJECTIVES: To develop a prediction tool based on physical findings and environmental conditions without utilizing color Doppler ultrasonography to guide non-urologists and patients' families in determining the testicular torsion possibility among patients with acute scrotal pain. METHODS: Overall, 110 consecutive patients aged ≤30 years with acute scrotal pain at Saitama Medical Center between 2012 and 2014 were retrospectively evaluated. Physical examination results, including scrotal inspection, palpation and gait observation, and environmental conditions at pain onset (time range and ambient temperature) were collected. Multivariate analysis identified significant and independent risk factors for testicular torsion, and a nomogram predicting testicular torsion was constructed. The model underwent prospective validation in an independent set of 123 consecutive patients admitted with acute scrotal pain to our institution between 2015 and 2017. RESULTS: Testicular torsion diagnosis rates were 27% (30/110) and 26% (32/123) in the training and validation cohorts, respectively. Logistic regression analysis showed four risk factors for developing testicular torsion: abnormal testicular position, walking difficulty, midnight to early morning onset and ambient temperature <15°C at pain onset. The constructed nomogram showed that the areas under the receiver operating characteristic curves were 0.92 and 0.84 for the training and validation cohorts, respectively. The calibration plot showed an acceptable fitness between the predicted probability and the observed rate of testicular torsion. CONCLUSIONS: A novel nomogram was developed solely based on physical findings and environmental conditions to predict testicular torsion in Japanese patients with acute scrotal pain.

Treatment strategies and outcomes in a long-term registry study of patients with high-risk metastatic hormone-naïve prostate cancer in Japan: An interim analysis of the J-ROCK study.

OBJECTIVE: The prognosis of high-risk metastatic hormone-naïve prostate cancer is poor, and real-world evidence of therapeutic options and sequences is lacking. The J-ROCK study aimed to evaluate the outcomes in a real-world setting in Japan. METHODS: Patients with high-risk metastatic hormone-naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). RESULTS: In this first interim analysis (cut-off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow-up period was 7.6 (range 0.1-20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate-specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate-specific antigen-progression-free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345-1.147]). CONCLUSIONS: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real-world treatment of high-risk metastatic hormone-naïve prostate cancer in Japan. Some factors including prostate-specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate-specific antigen-progression-free survival in patients with high-risk metastatic hormone-naïve prostate cancer.

[HUGE RENAL ANGIOMYOLIPOMA COMPLICATED WITH COMMON ILIAC VEIN THROMBUS BECAUSE OF THE TUMOR PRESSURE].

A 47-year-old woman was transferred to our hospital in June 2014 in hemorrhagic shock due to rupture of a huge right renal angiomyolipoma (AML). Selective right renal arterial embolization performed that same day reversed the shock immediately. Despite the huge abdominal tumor, the patient was discharged 2 weeks later after refusing any further treatment.Two weeks later she noticed the abdominal tumor growing. One month after discharge, she was readmitted due to dyspnea caused by restriction of her breathing by the growing tumor mass. A CT revealed a massive increase in tumor size with internal liquefaction, a thrombus in the left common iliac vein, and a 12 mm aneurysm in the right renal artery. The patient requested removal of the abdominal tumor since her ADL had deteriorated. We decided to perform a right nephrectomy with consideration of the left common iliac vein thrombus and right renal arterial aneurysm.As a precaution against pulmonary embolism in case the left common iliac vein thrombus dislodged, a retrievable inferior vena cava (IVC) filter was inserted before surgery. We were also concerned about possible rupture of the right renal aneurysm, so the right renal artery was embolized before surgery. After these procedures, a right nephrectomy was performed via a transperitoneal approach.The surgery was uneventful. The tumor weighed about 11 kg including 7,000 mL of bloody fluid. The IVC filter was removed the day after surgery, but the thrombus in the left common iliac vein remained, and an anticoagulant was started. Three months later, the thrombus had disappeared, and the anticoagulant was discontinued six months after surgery.According to the treatment guidelines for deep vein thrombosis, anticoagulants are the drugs of choice. IVC filters are seldom used to prevent pulmonary embolism. We initially administered an anticoagulant for the thrombus in the left iliac vein. However, an increase in abdominal tumor size suggested the drug had caused internal rebleeding and it had to be discontinued. Ultimately, we used a temporary retrievable IVC filter during the right nephrectomy with success.There is currently no consensus on when to use an IVC filter. Moreover, very little data exists on the use of an IVC filter during the perioperative period. Therefore, given the risk of potential thromboembolism, although we were able to use it successfully in our surgery, it should not be employed without a thorough benefit-risk assessment.

ASSOCIATION BETWEEN THE RISK OF TESTICULAR TORSION AMONG ACUTE SCROTUM AND AMBIENT TEMPERATURE.

(Objectives) Testicular torsion (TT) is a socially and clinically important urological emergency condition because delayed diagnosis and treatment can lead to testicular loss. Although a possible association between TT and low ambient temperature has been argued, the clinical significance of the association has not been fully elucidated. We retrospectively collected acute scrotum cases and investigated the association between the risk of TT among acute scrotums and ambient temperatures on the day of onset. (Patients and methods) We studied 105 consecutive acute scrotum patients with suspected TT who underwent urgent surgical exploration between October 2004 and October 2014. The patients' age, residential area, time and date of onset, laboratory findings, and operative findings were collected from their medical records. Climate data, including daily mean ambient temperature (DMAT), diurnal temperature change (DTC), humidity, and atmospheric pressure at the time of onset, were obtained from the Japan Meteorological Agency website. The chi-square and Wilcoxon rank sum tests were used to evaluate statistical differences. Logistic regression analysis used to identify significant predictors of TT. (Results) The median age of the patients was 13 years (range, 1-43 years). The affected side was the right/left/bilateral side in 46/58/1 of the patients. Surgical exploration revealed TT in 67 patients. The remaining 38 non-TT patients included 12 with testicular appendage torsions, 12 with epididymal appendage torsions, 9 with epididymitis, 2 with orchitis, 2 with idiopathic hematomas, and 1 with allergic purpura. The median DMATs at the day of onset were 10.8°C (1.8-29.4°C) in the TT patients and 19.4°C (1.9-29.1°C) in the non-TT patients. The incidence of TT among the patients with acute scrotum explored surgically (TT incidence) in days with DMATs <15°C (80%) was significantly higher than that in days with DMATs ≥ 15°C (45%; p<0.001). During days with DMATs ≥15°C, the TT incidence in days with DTCs ≥10°C (62%) was significantly higher than that in days with DTCs <10°C (32%; p=0.037). Multivariate analysis revealed higher age (≥14), low serum C-reactive protein level (<0.5 ng/ml) and low DMAT (<15°C) were significant risk factor for TT in patients with acute scrotum undergoing surgery. (Conclusions) It should be noted that in this study, the onset of acute scrotum during days with low ambient temperatures or large DTCs was associated with a moderate to high possibility of TT.

Diagnostic performance and safety of a three-dimensional 14-core systematic biopsy method.

OBJECTIVE: To investigate the diagnostic performance and safety of a three-dimensional 14-core biopsy (3D14PBx) method, which is a combination of the transrectal six-core and transperineal eight-core biopsy methods. PATIENTS AND METHODS: Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our institutions and were analysed prospectively. Biopsy criteria included a PSA level of 2.5-20 ng/mL or abnormal digital rectal examination (DRE) findings, or both. The primary endpoint of the study was diagnostic performance and the secondary endpoint was safety. We applied recursive partitioning to the entire study cohort to delineate the unique contribution of each sampling site to overall and clinically significant cancer detection. RESULTS: Prostate cancer was detected in 503 of the 1103 patients (45.6%). Age, family history of prostate cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with the positive biopsy results significantly and independently. Of the 503 cancers detected, 39 (7.8%) were clinically locally advanced (≥cT3a), 348 (69%) had a biopsy Gleason score (GS) of ≥7, and 463 (92%) met the definition of biopsy-based significant cancer. Recursive partitioning analysis showed that each sampling site contributed uniquely to both the overall and the biopsy-based significant cancer detection rate of the 3D14PBx method. The overall cancer-positive rate of each sampling site ranged from 14.5% in the transrectal far lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210 patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found to have pathologically non-organ-confined disease, 174 (83%) had prostatectomy GS ≥7 and 185 (88%) met the definition of prostatectomy-based significant cancer. CONCLUSIONS: This is the first prospective analysis of the diagnostic performance of an extended biopsy method, which is a simplified version of the somewhat redundant super-extended three-dimensional 26-core biopsy. As expected, each sampling site uniquely contributed not only to overall cancer detection, but also to significant cancer detection. 3D14PBx is a feasible systematic biopsy method in men with PSA <20 ng/mL.

A novel approach to patient self-monitoring of sonographic examinations using a head-mounted display.

OBJECTIVES: Patients' use of a head-mounted display during their sonographic examinations could provide them with information about their diseases in real time and might help improve "patient-centered care." We conducted this prospective study to evaluate the feasibility of a modern head-mounted display for patient self-monitoring of sonographic examinations. METHODS: In November and December 2013, 58 patients were enrolled. Patients wore a head-mounted display (HMZ-T2; Sony Corporation, Tokyo, Japan) during their sonographic examinations and watched their own images in real time. After the sonographic examinations, the patients completed a questionnaire, in which they evaluated the utility of the head-mounted display, their understanding of their diseases, their satisfaction with using the head-mounted display, and any adverse events. Until November 26, 2013, patients' names were requested on the questionnaire; after that date, the questionnaire was changed to be anonymous. RESULTS: Of the 58 patients, 56 (97%) elected to participate in this study. The head-mounted display was reported to have good image quality by 42 patients (75%) and good wearability by 39 (70%). Thirty-six patients (64%) reported they had deepened their understanding of their diseases. There were no major complications, and only 2 patients (4%) had mild eye fatigue. There was no significant association between questionnaire results and patient characteristics. None of the questionnaire results changed significantly after the questionnaire was made anonymous. CONCLUSIONS: The use of a modern head-mounted display by patients during sonographic examinations provided good image quality with acceptable wearability. It could deepen their understanding of their diseases and help develop patient-centered care.

Head-mounted display for a personal integrated image monitoring system: ureteral stent placement.

The personal head-mounted display (HMD) has emerged as a novel image monitoring system. We present here the application of a high-definition organic electroluminescent binocular HMD in ureteral stent placement. Our HMD system displayed multiple forms of information such as integrated, sharp, high-contrast images using a four-split screen or a picture-in-picture technique both seamlessly and synchronously. When both the operator and the assistant wore an HMD, they could continuously and simultaneously monitor the cystoscopic and fluoroscopic images in an ergonomically natural position. Furthermore, each participant was able to modulate the displayed images depending on the procedure. In all five cases, both the operator and the assistant successfully used this system with no unfavorable event. No participants experienced any HMD wear-related adverse effects. We therefore believe this HMD system might be potentially beneficial during ureteral stent placement procedures. Furthermore, it is compact, easily introduced and affordable.

Clinical application of a modern high-definition head-mounted display in sonography.

Because of the remarkably improved image quality and wearability of modern head-mounted displays, a monitoring system using a head-mounted display rather than a fixed-site monitor for sonographic scanning has the potential to improve the diagnostic performance and lessen the examiner's physical burden during a sonographic examination. In a preclinical setting, 2 head-mounted displays, the HMZ-T2 (Sony Corporation, Tokyo, Japan) and the Wrap1200 (Vuzix Corporation, Rochester, NY), were found to be applicable to sonography. In a clinical setting, the feasibility of the HMZ-T2 was shown by its good image quality and acceptable wearability. This modern device is appropriate for clinical use in sonography.

Bone abnormal signal incidentally found in pre-biopsy diffusion-weighted MRI for suspected prostate cancer: what does it reflect?

OBJECTIVE: To clarify the clinical significance of incidentally found diffusion-weighted MRI (DW-MRI)-positive findings on pre-biopsy MRI in patients with suspected prostate cancer. PATIENTS AND METHODS: 754 consecutive patients with suspected prostate cancer underwent pelvic MRI including DW-MRI. 43 DW-MRI-positive bone lesions were found in 27 patients. Imaging findings of these lesions were compared with the clinical diagnosis. RESULTS: Of the 43 DW-MRI-positive bone lesions, 21 (48.8%) were diagnosed as metastatic prostate cancer. The remaining 22 (51.2%) were diagnosed as red bone marrow in 17, enchondroma in 1, ganglion in 1, osteoma in 1, fibrous dysplasia in 1 and bone infarction in 1. Enchondroma, ganglion, osteoma and fibrous dysplasia all showed T1-weighted imaging (T1WI) low and T2-weighted imaging (T2WI) high signals, while others, including prostate cancer metastases, showed T1WI and T2WI low signals. Of the 40 lesions with T1WI and T2WI low signals, metastatic prostate cancer had higher apparent diffusion coefficient values (median 0.42 × 10(-3) mm(2)/s) than other lesions (0.26 × 10(-3) mm(2)/s; p < 0.0001). CONCLUSIONS: DW-MRI-positive bone lesions represent various coexisting types of bone lesions, including metastatic cancer in patients with suspected prostate cancer. T2WI findings and apparent diffusion coefficient values can be helpful in diagnosing metastatic cancer.

Renal function after radical nephrectomy: development and validation of predictive models in Japanese patients.

OBJECTIVES: To develop and validate predictive models for postoperative estimated glomerular filtration rate and risk of chronic kidney disease after radical nephrectomy in Japanese patients. METHODS: The present retrospective study included a development cohort of 209 patients without preoperative chronic kidney disease who underwent radical nephrectomy between 1994 and 2008, and were followed up for longer than 3 years, and a validation cohort of 144 similar such patients. Univariate and multivariate linear regression or logistic regression analyses were carried out to identify the independent predictors of estimated glomerular filtration rate or chronic kidney disease 3 years after radical nephrectomy. Incorporating all independent predictors, predictive models for postoperative renal function were developed and externally validated. RESULTS: Age, the presence of diabetes mellitus, and preoperative estimated glomerular filtration rate were independent predictors of both postoperative estimated glomerular filtration rate and chronic kidney disease. A formula for predicting the postoperative estimated glomerular filtration rate and a nomogram for predicting the risk of postoperative chronic kidney disease were developed. The adjusted R(2) of the formula and area under the receiver operating characteristic curves of the nomogram were 0.446 and 0.865 in the development cohort, and 0.396 and 0.787 in the validation cohort, respectively. CONCLUSIONS: We developed and validated novel predictive models for the postoperative renal function 3 years after radical nephrectomy in Japanese patients.

New head-mounted display system applied to endoscopic management of upper urinary tract carcinomas.

PURPOSE: We tested a new head-mounted display (HMD) system for surgery on the upper urinary tract. SURGICAL TECHNIQUE: Four women and one man with abnormal findings in the renal pelvis on computed tomography and magnetic resonance imaging underwent surgery using this new system. A high definition HMD (Sony, Tokyo, Japan) is connected to a flexible ureteroscope (Olympus, Tokyo, Japan) and the images from the ureteroscope are delivered simultaneously to various participants wearing HMDs. Furthermore, various information in addition to that available through the endoscope, such as the narrow band image, the fluoroscope, input from a video camera mounted on the lead surgeon's HMD and the vital monitors can be viewed on each HMD. RESULTS: Median operative duration and anesthesia time were 53 and 111 minutes, respectively. The ureteroscopic procedures were successfully performed in all cases. There were no notable negative outcomes or incidents (Clavien-Dindo grade ≥ 1). CONCLUSION: The HMD system offers simultaneous, high-quality magnified imagery in front of the eyes, regardless of head position, to those participating in the endoscopic procedures. This affordable display system also provides various forms of information related to examinations and operations while allowing direct vision and navigated vision.

Pembrolizumab in patients with advanced upper tract urothelial carcinoma: a real-world study from ARON-2 project.

Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6-12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9-6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status.

[Case of inflammatory lesion in urinary bladder showing high signal intensity on diffusion-weighted MRI: correlation with histopathological finding].

A 66-year-old woman was referred to our department for thickening bladder wall incidentally found during postoperative follow-up of transverse colon cancer. Cystoscopy showed edematous tumor with a diameter of 5 cm on the right wall. Deep portion of the tumor showed high intensity on diffusion-weighted magnetic resonance imaging (DW-MRI). Transurethral resection and transvaginal needle biopsy was performed, and pathological examination revealed granulation tissues mainly consisted of inflammatory cells and fibrosis. DW-MRI is a functional imaging constructed by quantifying the diffusion of water molecules. Recently, the feasibility of this imaging in the diagnosis of bladder cancer has been reported. However, we should keep in mind that granulation tissues consisted of inflammatory cells and fibrosis is also possible to be positive for DW-MRI.