A case of dedifferentiated liposarcoma discovered due to an intrascrotal calcified ossification.

Dedifferentiated liposarcoma is a rare cancer with a poor prognosis. A 52-year-old man presented with a chief complaint of a mass in his left scrotum. He came with suspected testicular tumor, but all the measured tumor markers were negative. Imaging test showed approximately 2 cm diameter mass accompanied by calcification with some substantial components between the testis and epididymis. Left high testicular resection was performed. The tumor had no continuity between the testis and epididymis, and the spermatic cord transection was negative. Pathological findings showed well differentiated fatty component and a dedifferentiated component around the trabecular bone-like tissue. We observed dedifferentiated dysmorphic cells mixed with fatty droplets of unequal size. Immunostaining led to the diagnosis of dedifferentiated liposarcoma. No additional postoperative therapy was performed. The possibility of dedifferentiated liposarcoma should be kept in mind even if mass is confined to the scrotum and consisted of calcification. In the case of an intrascrotal calcified mass with malignant perspective, radical surgery is highly recommended.

Recurrent episodes of atrioventricular nodal reentrant tachycardia: Sites of ablation success, ablation endpoint, and primary culprits for recurrence.

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) sometimes recurs even after anatomical slow pathway (SP) ablation targeting the rightward inferior extension (RIE). This multicenter study aimed to determine the reasons for AVNRT recurrence. Methods and Results: Forty-six patients were treated successfully for recurrent AVNRT. Initial treatment was for 38 slow-fast AVNRTs, 3 fast-slow AVNRTs, 2 slow-slow AVNRTs, 2 slow-fast and fast-slow AVNRTs, and 1 noninducible AVNRT. All initial treatments were of RF application to the RIE; SP elimination was achieved in 11, dual AVN physiology was seen in 29, and AVNRT remained inducible in 5. The recurrent AVNRTs included 34 slow-fast AVNRTs, 6 fast-slow AVNRTs, 3 slow-slow AVNRTs, 2 slow-fast and fast-slow AVNRTs, and 1 slow-fast and slow-slow AVNRTs. Successful ablation site was within the RIE in 39 and left inferior extension in 7. In 30 of 39, the successful RIE site was in the same area or higher than that of the initial procedure. Conclusion: For a high majority (around 85%) of patients in whom AVNRT recurs after initial ablation success, the site of a second successful procedure will be within the RIE even though the RIE was originally targeted. Furthermore, a high majority (around 86%) of sites of successful ablation will be higher than those originally targeted.

Beyond the lens: Unveiling the invisible atrioventricular node in the era of high-density mapping.

Numerous studies have clarified the histological characteristics of the area surrounding the atrioventricular (AV) node, commonly referred to as the triangle of Koch (ToK). Although it is suggested that the conduction of electric impulses from the atria to the ventricles via the AV node involves myocytes possessing distinct conduction properties and gap junction proteins, a comprehensive understanding of this complex conduction has not been fully established. Moreover, although various pathways have been proposed for both anterograde and retrograde conduction during atrioventricular nodal reentrant tachycardia (AVNRT), the reentrant circuits of AVNRT are not fully elucidated. Therefore, the slow pathway ablation for AVNRT has been conventionally performed, targeting both its anatomical location and slow pathway potential obtained during sinus rhythm. Recently, advancements in high-density three-dimensional (3D) mapping systems have facilitated the acquisition of more detailed electrophysiological potentials within the ToK. Several studies have indicated that the activation pattern, the low-voltage area within the ToK obtained during sinus rhythm, and the fractionated potentials acquired during tachycardia may be optimal targets for slow pathway ablation. This review provides an overview of the tissue surrounding the AV node as reported to date and summarizes the current understanding of AV conduction and AVNRT circuits. Furthermore, we discuss recent findings on slow pathway ablation utilizing high-density 3D mapping systems, exploring strategies for optimal slow pathway ablation.

Unveiling the Genomic Landscape of Intraductal Carcinoma of the Prostate Using Spatial Gene Expression Analysis.

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Optimal timing of electrical cardioversion for acute decompensated heart failure caused by atrial arrhythmias: The earlier, the better?

The optimal timing for electrical cardioversion (ECV) in acute decompensated heart failure (ADHF) with atrial arrhythmias (AAs) is unknown. Here, we retrospectively evaluated the impact of ECV timing on SR maintenance, hospitalization duration, and cardiac function in patients with ADHF and AAs. Between October 2017 and December 2022, ECV was attempted in 73 patients (62 with atrial fibrillation and 11 with atrial flutter). Patients were classified into two groups based on the median number of days from hospitalization to ECV, as follows: early ECV (within 8 days, n = 38) and delayed ECV (9 days or more, n = 35). The primary endpoint was very short-term and short-term ECV failure (unsuccessful cardioversion and AA recurrence during hospitalization and within one month after ECV). Secondary endpoints included (1) acute ECV success, (2) ECVs attempted, (3) periprocedural complications, (4) transthoracic echocardiographic parameter changes within two months following successful ECV, and (5) hospitalization duration. ECV successfully restored SR in 62 of 73 patients (85%), with 10 (14%) requiring multiple ECV attempts (≥ 3), and periprocedural complications occurring in six (8%). Very short-term and short-term ECV failure occurred without between-group differences (51% vs. 63%, P = 0.87 and 61% vs. 72%, P = 0.43, respectively). Among 37 patients who underwent echocardiography before and after ECV success, the left ventricular ejection fraction (LVEF) significantly increased (38% [31-52] to 51% [39-63], P = 0.008) between admission and follow-up. Additionally, hospital stay length was shorter in the early ECV group than in the delayed ECV group (14 days [12-21] vs. 17 days [15-26], P < 0.001). Hospital stay duration was also correlated with days from admission to ECV (Spearman's ρ = 0.47, P < 0.001). In clinical practice, early ECV was associated with a shortened hospitalization duration and significantly increased LVEF in patients with ADHF and AAs.

Where is the gap after a 90 W/4 s very-high-power short-duration ablation of atrial fibrillation?: Association with the left atrial-pulmonary vein voltage and wall thickness.

Background: Although pulmonary vein isolation (PVI) for atrial fibrillation (AF) utilizing radiofrequency (RF) applications with a very high-power and short-duration (vHPSD) has shortened the procedure time, the determinants of pulmonary vein (PV) gaps in the first-pass PVI and acute PV reconnections are unclear. Methods: An extensive encircling PVI was performed with the QDOT MICRO catheter with a vHPSD (90 W-4 s) in 30 patients with AF (19 men, 64 ± 10 years). The association of the PV gap sites (first-pass PVI failure, acute PV reconnections [spontaneous reconnections or dormant conduction provoked by adenosine triphosphate] or both) with the left atrial (LA) wall thickness and LA bipolar voltage on the PVI line and ablation-related parameters were assessed. Results: PV gaps were observed in 29 (6%) of 480 segments (16 segments per patient) in 17 patients (56%). The PV gaps were associated with the LA wall thickness, bipolar voltage, and the number of RF points (LA wall thickness, 2.5 ± 0.5 vs. 1.9 ± 0.4 mm, p < .001; bipolar voltage, 2.59 ± 1.62 vs. 1.34 ± 1.14 mV, p < .001; RF points, 6 ± 2 vs. 4 ± 2, p = .008) but were not with the other ablation-related parameters. Receiver operating characteristic curves yielded that an LA wall thickness ≥2.3 mm and bipolar voltage ≥2.40 mV were determinants of PV gaps with an area under the curve of 0.82 and 0.73, respectively. Conclusions: The LA voltage and wall thickness on the PV-encircling ablation line were highly associated with PV gaps using the 90 W/4 s-vHPSD ablation.

Clinical implication of the patient's disease awareness and adherence to medications in patients undergoing atrial fibrillation ablation.

Background: The effects of the patient's disease awareness on the management of postablation of atrial fibrillation (AF) are unknown. Methods: One hundred thirty-three AF patients undergoing an initial ablation were given a disease awareness questionnaire with a score of 16 points (8 points about AF in general and 8 points about oral anticoagulants) for the Jessa Atrial Fibrillation Knowledge Questionnaire (JAKQ) before and 1-year-after ablation. We divided them into the poor disease awareness group and good disease awareness group according to the median value (75%) of the total JAKQ score about AF in general, and compared the baseline patient characteristics and the 1-year changes in the JAKQ score, medication adherence, blood pressure, laboratory data, echocardiographic parameters, and AF/atrial tachycardia (AT) recurrence rate between the two groups. Results: Forty-two (31.6%) patients were classified as having poor disease awareness (<75% of the total JAKQ score), which was closely associated with poor medication adherence, hypertension, diabetes, dyslipidemia, and greater left atrial volume (LAV). These trends in the poor disease awareness group remained unchanged 1 year after the ablation. During the 25.3-month follow-up, the AF/AT recurrence rate was significantly higher in the poor disease awareness than the good disease awareness group (23.8% vs. 7.7%; p = .003 by the log-rank test). Conclusions: Poor disease awareness was linked to poor medication adherence, lifestyle-related diseases, and greater LAV before and even 1 year after the ablation, making it a potential surrogate marker for AF/AT recurrence. These findings highlight the clinical significance of disease awareness in AF management.

Pseudo-slow-fast atrioventricular nodal reentrant tachycardia: Is the fast pathway a criminal or innocent bystander?

The intracardiac electrograms are shown during scanned single premature ventricular extrastimuli with a decreasing coupling interval in a very short RP tachycardia. What is the diagnosis and is the fast pathway essential for sustaining the tachycardia?

Systematic observation-based diagnosis of atrioventricular nodal reentrant tachycardia with a bystander concealed nodoventricular pathway.

Background: This study aimed to establish a systematic method for diagnosing atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed nodoventricular pathway (cNVP). Methods: We analyzed 13 cases of AVNRT with a bystander cNVP, 11 connected to the slow pathway (cNVP-SP) and two to the fast pathway (cNVP-FP), along with two cases of cNVP-related orthodromic reciprocating tachycardia (ORT). Results: The diagnostic process was summarized in three steps. Step 1 was identification of the presence of an accessory pathway by resetting the tachycardia with delay (n = 9) and termination without atrial capture (n = 4) immediately after delivery of a His-refractory premature ventricular contraction (PVC). Step 2 was exclusion of ORT by atrio-His block during the tachycardia (n = 4), disappearance of the reset phenomenon after the early PVC (n = 7), or dissociation of His from the tachycardia during ventricular overdrive pacing (n = 1). Moreover, tachycardia reset/termination without the atrial capture (n = 2/2) 1 cycle after the His-refractory PVC was specifically diagnostic. Exceptionally, the disappearance of the reset phenomenon was also observed in the two cNVP-ORTs. Step 3 was verification of the AVN as the cNVP insertion site, evidenced by an atrial reset/block preceding the His reset/block in fast-slow AVNRT with a cNVP-SP and slow-fast AVNRT with a cNVP-FP or His reset preceding the atrial reset in slow-fast AVNRT with a cNVP-SP. Conclusion: AVNRT with a bystander cNVP can be diagnosed in the three steps with few exceptions. Notably, tachycardia reset/termination without atrial capture one cycle after delivery of a His-refractory PVC is specifically diagnostic.

Termination of slow-fast atrioventricular reentrant tachycardia by a single cryoablation of the slow pathway guided by a fractionation map.

This is a slow-fast atrioventricular nodal reentrant tachycardia (AVNRT) case wherein the fractionation map-guided cryoablation of the slow pathway (SP) successfully terminated the tachycardia. In this case, the Advisor™ HD Grid catheter and fractionation map in the EnSite™ X EP system with relatively high-sensitive settings were useful for detecting the target SP area. Direct AVNRT termination by cryomapping at the fractionated potential area might be a quick and safe ablation strategy, which may provide a new workflow for SP ablation.

External Validation of the HELT-E2S2 Score in Japanese Patients With Nonvalvular Atrial Fibrillation　- A Pooled Analysis of the RAFFINE and SAKURA Registries.

BACKGROUND: The HELT-E2S2score, which assigns 1 point to Hypertension, Elderly aged 75-84 years, Low body mass index <18.5 kg/m2, and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.Methods and Results: We evaluated the prognostic performance of the HELT-E2S2score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E2S2score was 0.661 (95% confidence interval [CI], 0.629-0.692), which was numerically higher than with the CHADS2score (0.644, 95% CI 0.613-0.675; P=0.15 vs. HELT-E2S2) or CHA2DS2-VASc score (0.650, 95% CI, 0.619-0.680; P=0.37 vs. HELT-E2S2). In the SAKURA AF Registry, the C-statistic of the HELT-E2S2score was consistently higher than the CHADS2and CHA2DS2-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals. CONCLUSIONS: The HELT-E2S2score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS2or CHA2DS2-VASc scores may vary across different hospital settings.

Trends over the recent 6 years in ablation modalities and strategies, post-ablation medication, and clinical outcomes of atrial fibrillation ablation.

Background: Ablation strategies and modalities for atrial fibrillation (AF) have transitioned over the past decade, but their impact on post-ablation medication and clinical outcomes remains to be fully investigated. Methods: We divided 682 patients who had undergone AF ablation in 2014-2019 (420 paroxysmal AFs [PAF], 262 persistent AFs [PerAF]) into three groups according to the period, that is, the 2014-2015 (n = 139), 2016-2017 (n = 244), and 2018-2019 groups (n = 299), respectively. Results: Persistent AF became more prevalent and the left atrial (LA) diameter larger over the 6 years. Extra-pulmonary vein (PV)-LA ablation was more frequently performed in the 2014-2015 group than in the 2016-2017 and 2018-2019 groups (41.1% vs. 9.1% and 8.1%; p < .001). The 2-year freedom rate from AF/atrial tachycardias for PAF was similar among the three groups (84.0% vs. 83.1% vs. 86.7%; p = .98) but lowest in the 2014-2015 group for PerAF (63.9% vs. 82.7% and 86.3%; p = .025) despite the highest post-ablation antiarrhythmic drug use. Cardiac tamponade was significantly decreased in the 2018-2019 group (3.6% vs. 2.0% vs. 0.33%; p = 0.021). There was no difference in the 2-year clinically relevant events among the three groups. Conclusion: Although ablation was performed in a more diseased LA and extra-PV-LA ablation was less frequent in recent years, the complication rate decreased, and AF recurrences for PAF remained unchanged, but that for PerAF decreased. Clinically relevant events remained unchanged over the recent 6 years, suggesting that the impact of the recent ablation modalities and strategies on remote clinically relevant events may be small during this study period.

Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer.

Neuroendocrine prostate carcinoma (NEPC) accounts for less than 1% of prostate neoplasms and has extremely poorer prognosis than the typical androgen receptor pathway-positive adenocarcinoma of the prostate (ARPC). However, very few cases in which de novo NEPC and APRC are diagnosed simultaneously in the same tissue have been reported. We report herein a 78-year-old man of de novo metastatic NEPC coexisting with ARPC treated at Ehime University Hospital. Visium CytAssist Spatial Gene Expression analysis (10× genetics) was performed using formalin-fixed, paraffin-embedded (FFPE) samples. The neuroendocrine signatures were upregulated in NEPC sites, and androgen receptor signatures were upregulated in ARPC sites. TP53, RB1, or PTEN and upregulation of the homologous recombination repair genes at NEPC sites were not downregulated. Urothelial carcinoma markers were not elevated. Meanwhile, Rbfox3 and SFRTM2 levels were downregulated while the levels of the fibrosis markers HGF, HMOX1, ELN, and GREM1 were upregulated in the tumor microenvironment of NEPC. In conclusion, the findings of spatial gene expression analysis in a patient with coexisting ARPC and de novo NEPC are reported. The accumulation of cases and basic data will help with the development of novel treatments for NEPC and improve the prognosis of patients with castration-resistant prostate cancer.

Registry for Evaluating Healthy Life Expectancy and Long-Term Outcomes after Catheter Ablation of Atrial Fibrillation in the Very Elderly (REHEALTH AF) study: rationale and design of a prospective, multicentre, observational, comparative study.

INTRODUCTION: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes. METHODS AND ANALYSIS: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results. ETHICS AND DISSEMINATION: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000047023.

Chronic Ablation Lesions after Cryoballoon and Hot Balloon Ablation of Atrial Fibrillation.

BACKGROUND: Chronological changes in ablation lesions after cryoballoon ablation (CBA) and hot balloon ablation (HBA) of atrial fibrillation (AF) remain unclear. METHODS: Of 90 patients who underwent initial balloon-based catheter ablation of AF and cardiac magnetic resonance imaging (cMRI) 3 months after ablation, data from 48 propensity score-matched patients (24 per group; 34 males; age 62±10 years) were analyzed. High-density pulmonary vein-left antrum (PV-LA) voltage mapping was performed after PV isolation, and low voltage areas around the PV ostia were defined as the total acute ablation lesion area (cm2). cMRI-derived dense fibrotic tissue localized around PVs was defined as the total chronic ablation lesion area (cm2). The percentage of total ablation lesion areas to total PV-LA surface area (%ablation lesion) was calculated during each phase, and %acute ablation lesion and %chronic ablation lesion areas were compared in patients who had undergone CBA and HBA. RESULTS: The %acute ablation lesion area was larger for the CBA group than for the HBA group (30.8±5.8% vs. 23.0±5.5%, p < 0.001). There was no difference in %chronic cMRI-derived ablation lesion area (24.8±10.8% vs. 21.1±11.6%, p = 0.26) between groups. The rates of chronic AF recurrence were 12.5% and 8.3%, respectively (p = 0.45; log-rank test). LA volume and LA surface area were strongly associated with AF recurrence, but %chronic ablation lesion area was not (27±8% vs. 23±12%, p = 0.39). CONCLUSION: Large acute ablation lesions after CBA were smaller during the chronic phase. The size of chronic ablation lesions and the rate of AF recurrence were both similar for CBA and HBA.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Novel "red-bull sign" during cavotricuspid isthmus ablation: Indication of an ablation catheter stuck in the subeustachian pouch.

Background: A subeustachian pouch (SEP) often hinders the completion of a cavotricuspid isthmus (CTI) ablation of typical atrial flutter (AFL) and sometimes causes steam-pops during a power-controlled ablation. We hypothesized that real-time bull's-eye monitoring of the catheter surface temperature might be useful to locate the SEP where the temperature can rise rapidly, and a temperature-controlled ablation might avoid steam pops. This study aimed to demonstrate this hypothesis. Methods: A temperature-controlled CTI ablation with a QDOT MICRO™ catheter (n = 10) and a conventional power-controlled CTI ablation (n = 10) were performed with an output power of 35 W. During the RF application, the bull's eye monitor for monitoring the catheter surface temperatures was assessed. A "red-bull sign" was defined as an entire red-colored bull's-eye monitor, indicating that the catheter-tip temperature of all 6 thermocouples rose rapidly over 47°C. Results: In a total of 115 lesions (12 ± 3 per patient), a "red-bull sign" was observed in 39 (33.9%) lesions where the RF output was reduced to 26 ± 8 W. All 39 "red-bull sign" lesions corresponded to the location of the SEP as delineated by ICE before the ablation. The red-bull sign accurately indicated the presence of a SEP with a sensitivity of 84.7% and specificity of 100%. Bidirectional block of the CTI was completed in all patients in either catheter group without any steam-pops. Conclusion: Real-time surface temperature monitoring and a red-bull sign might be useful to detect the SEP. A temperature-controlled CTI ablation with the QDOT MICRO catheter might be safe for avoiding steam pops.

CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma.

Immune checkpoint inhibitor (ICI) therapy increases the risk of immune-related adverse events (irAEs). In particular, combination checkpoint blockade (CCB) targeting inhibitory CTLA-4 and PD-1 receptors could lead to irAEs at a higher rate than ICI monotherapy. Management of irAEs is important while using ICIs. However, there are no reliable biomarkers for predicting irAEs. The aim of this study was to elucidate early B cell changes after CCB therapy in patients with renal cell carcinoma (RCC) and verify whether B cells can be a predictor of irAEs. This prospective cohort study was conducted with 23 Japanese patients with metastatic RCC. An increase in the proportion of CD21lo B cells and CD21lo memory B cells was confirmed following CCB therapy. Although there were no differences in clinical outcomes between irAE and no-irAE groups, the proportion of CD21lo B cells at baseline was lower in the irAE group, with a significant increase after the first cycle of CCB therapy. Further analysis revealed a moderate correlation between irAEs and CD21lo B cell levels at baseline (area under the curve: 0.83, cut-off: 3.13%, sensitivity: 92.3, specificity: 70.0). This finding indicates that patients with low baseline CD21lo B cell levels warrant closer monitoring for irAEs. The clinical registration number by the Certified Review Board of Ehime University is No. 1902011.