Role of clinicopathological variables in predicting recurrence and survival outcomes after surgery for non-metastatic renal cell carcinoma: Systematic review and meta-analysis.

Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.

Clinical and molecular predictors of very late recurrence in oestrogen receptor-positive breast cancer patients.

BACKGROUND: Risk of recurrence from primary ER+ breast cancer continues for at least 20 years. We aimed to identify clinical and molecular features associated with risk of recurrence after 10 years. METHODS: ER+ breast cancers from patients with and without recurrence were analysed with the BC360 NanoString Panel and an 87 gene targeted-exome panel. Frequency of clinical, pathologic and molecular characteristics was compared between cases (recurred between 10 and 20 years) and controls (no recurrence by 20 years) in the Very Late Recurrence (VLR) cohort. Analogous data from METABRIC were examined to confirm or refute findings. RESULTS: VLR cases had larger tumours and higher node positivity. Both VLR and METABRIC cases had higher clinical treatment score at 5 years (CTS5). There was a trend for fewer GATA3 mutations in cases in both VLR and METABRIC but no statistically significant differences in mutation frequency. Cell cycle and proliferation genes were strongly expressed in VLR cases. Immune-related genes and cell cycle inhibitors were highly expressed in controls. Neither of these changes were significant after correction for multiple testing. CONCLUSIONS: Clinicopathologic features are prognostic beyond 10 years. Conversely, molecular features, such as copy number alterations, TP53 mutations and intrinsic subtype which have early prognostic significance, have little prognostic value after 10 years.

Repeat catheter ablation after very late recurrence of atrial fibrillation after pulmonary vein isolation.

AIMS: Atrial fibrillation (AF) recurs in about one-third of patients after catheter ablation (CA), mostly in the first year. Little is known about the electrophysiological findings and the effect of re-ablation in very late AF recurrences (VLR) after more than 1 year. The aim of this study was to determine the characteristics and outcomes of the first repeat CA after VLR of AF after index CA. METHODS AND RESULTS: We analysed patients from a prospective Swiss registry that underwent a first repeat ablation procedure. Patients were stratified depending on the time to recurrence after index procedure: early recurrence (ER) for recurrences within the first year and late recurrence (LR) if the recurrence was later. The primary endpoint was freedom from AF in the first year after repeat ablation. Out of 1864 patients included in the registry, 426 patients undergoing a repeat ablation were included in the analysis (28% female, age 63 ± 9.8 years, 46% persistent AF). Two hundred and ninety-one patients (68%) were stratified in the ER group and 135 patients (32%) in the LR group. Pulmonary vein reconnections were a common finding in both groups, with 93% in the ER group compared to 86% in the LR group (P = 0.052). In the LR group, 40 of 135 patients (30%) had a recurrence of AF compared to 90 of 291 patients (31%) in the ER group (log-rank P = 0.72). CONCLUSION: There was no association between the time to recurrence of AF after initial CA and the characteristics and outcomes of the repeat procedure.

Clinical relevance of the blanking period on late recurrence after catheter ablation of atrial fibrillation.

INTRODUCTION: Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER. METHODS AND RESULTS: Retrospective single-centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49-66] and 77% had paroxysmal AF. Median follow-up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p < .001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99-7.35; p < .001 and HR 2.73; 95% CI, 1.47-5.10; p = .002, respectively). CONCLUSION: The risk of LR after an index procedure of CA was significantly higher in patients with ER (five-fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period.

Predictors and outcomes of tricuspid regurgitation improvement after radiofrequency catheter ablation for persistent atrial fibrillation.

INTRODUCTION: Little has been reported on the predictors and outcomes of improvement of tricuspid regurgitation (TR) after radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (AF). METHODS: We enrolled 141 patients with persistent AF and moderate or severe TR assessed by transthoracic echocardiography (TTE) who underwent an initial RFCA between February 2015 and August 2021. These patients underwent follow-up TTE at 12 months after the RFCA, and were categorized into two groups based on the improvement (defined as at least one-grade improvement of TR) and non-improvement of TR: IM group and Non-IM group, respectively. We compared the patient characteristics, ablation procedures, and recurrences after the RFCA between the two groups. In addition, we examined the major event (defined as admission for heart failure or all-cause death) more than 12 months after the RFCA. RESULTS: IM group consisted of 90 patients (64%). A multivariate analysis revealed that age <71 years old and absence of late recurrence (LR, defined as recurrence of atrial tachyarrhythmia between 3 and 12 months after the RFCA) were independently associated with the improvement of TR after the RFCA. Furthermore, IM group had the higher incidence of major event-free survival than Non-IM group. CONCLUSIONS: Relatively young age and absence of LR were good predictors of improvement of TR after the RFCA for persistent AF. In addition, the improvement of TR was related to better clinical outcomes.

Utility of short-time electrocardiogram to assess risk for atrial arrhythmia recurrence: Impact of atrial premature beat occurrence 1 day after pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Atrial premature beats (APBs) are the trigger for atrial fibrillation (AF). We sought to investigate the clinical significance of APB occurrence 1 day after pulmonary vein isolation (PVI) for AF using a short-time electrocardiogram. METHODS: A total of 206 patients undergoing PVI for paroxysmal AF were included. Electrocardiogram recording for 100 consecutive beats was performed 1 day after PVI. The patients were divided into two groups: those with reproducible APBs (≥1 beat) during reassessment (APB group, n = 49) or those without (non-APB group, n = 157). Late recurrence was defined as atrial tachyarrhythmia recurrence 3-12 months after PVI. The impact of APB occurrence on outcomes was investigated. RESULTS: Late recurrence occurred in 19 patients (9.2%). The presence of low-voltage areas, left atrial volume, and recurrence rate were higher in the APB group than in the non-APB group. In the APB group, the patients with recurrence had lower prematurity index (PI, coupling interval of APB/previous cycle length) compared to those without. Receiver-operating characteristic analysis revealed PI (<59.3) to be a predictive factor of recurrence (area under the curve: 0.733). The study subjects were then reclassified into three groups according to the absence of APB occurrence (n = 157), presence thereof with PI ≥ 59.3 (n = 33), and presence with PI < 59.3 (n = 16). The multivariate Cox models revealed that APB with PI < 59.3 was an independent predictor for recurrence (hazard ratio, 8.735; p < 0.001). CONCLUSION: A short-time electrocardiogram enables risk assessment for arrhythmia recurrence, and APB with low PI 1 day after PVI is a powerful predictor.

Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome.

AIMS: Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings. METHODS AND RESULTS: Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0-67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1-2 years (n = 339), 2-5 years (n = 308), and after 5 years (CR>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P < 0.001), and use of post-procedure anti-arrhythmic drugs (P < 0.001) were lower. A CR>5 yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98-1.00), P = 0.035], low LA voltage [OR 0.61 (0.38-0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23-0.67), P < 0.001]. Extra-pulmonary vein triggers during repeat procedures were significantly greater in patients with a CR>5 yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330). CONCLUSIONS: Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.

Premature atrial contraction immediately after catheter ablation was associated with late recurrence of atrial fibrillation.

BACKGROUND: Although premature atrial contractions (PACs) just after catheter ablation (CA) for atrial fibrillation (AF) are common, their clinical significance is uncertain. This study aimed to evaluate whether the PAC burden after an initial CA for AF was associated with late recurrence. METHODS: We enrolled 346 patients with AF (median age, 65 years; 30% female; 57% with paroxysmal AF) who underwent an initial radiofrequency CA and a 24-h Holter monitoring the day after the procedure. PAC was defined as supraventricular complexes occurring ≥30% earlier than expected compared with a previous RR interval, and the number of PAC/24 h during post-procedural Holter monitoring was analyzed. RESULTS: AF recurred in 106 patients (31%) during a median follow-up of 19 months. These patients had significantly more PAC/24 h than those without (median [interquartile range], 891 [316-4351] beats vs. 409 [162-1,303] beats; p < 0.01). The number of PACs was independently associated with AF recurrence after adjustment for clinical parameters and left atrial (LA) enlargement. Receiver operating characteristic (ROC) curve analysis revealed that 1431 PAC/24 h was the optimal cut-off value for predicting AF recurrence. Adding the PAC/24 h to the prediction model with LA diameter appeared to correctly reclassify patients who were thought to be at high risk for AF recurrence into the low-risk group and vice versa. CONCLUSIONS: The number of PACs was an independent risk factor for AF recurrence. A 24-h Holter recording the day after an initial CA is a simple and beneficial tool for the risk stratification of AF recurrence.

Age, creatinine, and ejection fraction (ACEF) score as predictive values for late non-valvular atrial fibrillation recurrence after radiofrequency ablation.

The clinical risk factors associated with late recurrence in patients with non-valvular atrial fibrillation (AF) (NVAF) undergoing radiofrequency catheter ablation (RFCA) remain unknown. Furthermore, the current prognostic risk score system is commonly used in such patients as a noninvasive method to assess late AF recurrence. According to recent research, the Age, creatinine, and ejection fraction (ACEF) score is a useful risk score for cardiovascular morbidity and mortality. As a result, we hypothesized that pre-ablation ACEF score could be used to assess late recurrence in patients with NVAF. We included 325 NVAF patients undergoing RFCA. During a median follow-up period of 12 months, patients with late AF recurrence had higher ACEF scores (P < .001). The pre-ablation ACEF score was a risk factor for late AF recurrence after RFCA (P = .027). The ACEF score was a predictor of late AF recurrence after RFCA, with an AUC of 0.624 (P = .001). Moreover, the AUC of left atrial diameter (LAD) was 0.7 (P < .001), which was higher than the ACEF score, but no significant difference was found (P = .104). The ACEF score was positively correlated with LAD, advanced age, and B-type natriuretic peptide. In patients with NVAF, the pre-ablation ACEF score is a valuable risk score for assessing late AF recurrence after RFCA, as with LAD.

The ELEANOR noncoding RNA expression contributes to cancer dormancy and predicts late recurrence of estrogen receptor-positive breast cancer.

The recurrence risk of estrogen receptor (ER)-positive breast cancer remains high for a long period of time, unlike other types of cancer. Late recurrence reflects the ability of cancer cells to remain dormant through various events, including cancer stemness acquisition, but the detailed mechanism is unknown. ESR1 locus enhancing and activating noncoding RNAs (ELEANORS) are a cluster of nuclear noncoding RNAs originally identified in a recurrent breast cancer cell model. Although their functions as chromatin regulators in vitro are well characterized, their roles in vivo remain elusive. In this study, we evaluated the clinicopathologic features of ELEANORS, using primary and corresponding metastatic breast cancer tissues. The ELEANOR expression was restricted to ER-positive cases and well-correlated with the ER and progesterone receptor expression levels, especially at the metastatic sites. ELEANORS were detected in both primary and metastatic tumors (32% and 29%, respectively), and frequently in postmenopausal cases. Interestingly, after surgery, patients with ELEANOR-positive primary tumors showed increased relapse rates after, but not within, 5 years. Multivariate analysis showed that ELEANORS are an independent recurrence risk factor. Consistently, analyses with cell lines, mouse xenografts, and patient tissues revealed that ELEANORS upregulate a breast cancer stemness gene, CD44, and maintain the cancer stem cell population, which could facilitate tumor dormancy. Our findings highlight a new role of nuclear long noncoding RNAs and their clinical potential as predictive biomarkers and therapeutic targets for late recurrence of ER-positive breast cancer.

Impact of left atrial low-voltage areas during initial ablation procedures on very late recurrence of atrial fibrillation.

BACKGROUND: Very late recurrence of atrial fibrillation (VLRAF) occurring >1 year after catheter ablation may influence long-term follow-up strategies, including oral anticoagulant therapy. However, little is known about the predictors of this condition. Given that the prevalence of left atrial low-voltage areas (LVAs) is strongly associated with the recurrence of atrial tachyarrhythmias following catheter ablation, we hypothesized that VLRAF might occur more frequently in patients with LVAs at the time of initial ablation. The purpose of this study was to investigate the impact of LVAs on VLRAF. METHODS: This study included 1001 consecutive patients undergoing initial ablation procedures for AF. LVAs were defined as regions with bipolar peak-to-peak voltages of <0.50 mV on the voltage map obtained during sinus rhythm after pulmonary vein isolation. During a 1-year follow-up period, 248 patients had a late recurrence of AF (LRAF), defined as recurrence within 3-12 months after ablation. The occurrence of VLRAF was examined in 711 patients without LRAF who were followed for more than 1 year. RESULTS: A total of 711 patients who did not develop AF recurrence within 1 year and for whom clinical data were available after 1 year were analyzed. During a median follow-up of 25 (19, 37) months, VLRAF more than 1 year after the initial ablation was detected in 123 patients. On multivariate analysis, independent predictors of VLRAF were the existence of LVAs, female, left atrial diameter and early recurrence of AF. A Kaplan-Meier analysis showed that the AF-free survival rate was significantly lower in patients with LVAs than in those without LVAs within 1 year and on more than 1-year follow-up (p < .001). An additional Kaplan-Meier analysis of the incidence of VLRAF in propensity score-matched patients with and without LVAs showed that VLRAF occurred significantly more frequently in patients with LVAs (p = .003). CONCLUSIONS: LVAs during the initial AF ablation procedures have an impact on VLRAF occurrence.

Early Atrial Tachyarrhythmia Recurrence Predicts Late Atrial Tachyarrhythmia Recurrence After the Cryo-Maze Procedure　- An Observational Study.

BACKGROUND: It is unknown whether early atrial tachyarrhythmia (ATA) recurrence occurring within 3 months after the Maze procedure predicts late ATA recurrence.Methods and Results: This study involved 610 patients who underwent the modified Cryo-Maze procedure in conjunction with other cardiac surgery. The primary outcomes were late ATA recurrence, defined as occurring ≥3 months after surgery. The effects of early ATA recurrence on late ATA recurrence were analyzed using a Cox proportional hazards model. The following 11 covariates were considered explanatory variables: early ATA recurrence, age, sex, body surface area, preoperative duration of atrial fibrillation, preoperative left atrial diameter, and concomitant surgery (mitral valve replacement, mitral valve repair, aortic valve replacement, tricuspid annuloplasty, and left atrial appendage closure). Statistical analyses were performed with a 2-sided 5% significance level. Early ATA recurrence occurred in 174 patients (28.5%). Late ATA recurrence occurred in 167 patients (27.5%), with 595 events identified in these patients. The Cox proportional hazards model showed that early ATA recurrence was an independent predictor of late ATA recurrence (hazard ratio, 4.14; 95% confidence interval, 3.00-5.70; P<0.001)Conclusions: Early ATA recurrence was an independent predictor of late ATA recurrence among patients undergoing the modified Cryo-Maze procedure. The blanking period might not be applied to patients undergoing the modified Cryo-Maze procedure.

Impact of very early recurrence of atrial fibrillation after cryoballoon ablation.

BACKGROUND: Although much has been discussed about the early recurrence of atrial fibrillation (ERAF) after cryoballoon ablation (CBA), the clinical impact of very early recurrence of atrial fibrillation (VERAF) after CBA remains unclear. This study aimed to investigate the impact of VERAF after CBA. METHODS: We enrolled 236 consecutive patients who underwent an initial CBA for paroxysmal atrial fibrillation between February 2017 and December 2020 in our hospital. These patients were categorized into three groups: VERAF group who experienced an initial recurrence of atrial tachyarrhythmia within 48 h after CBA, late-ERAF (LERAF) group who experienced an initial recurrence of atrial tachyarrhythmia between 48 h and 3 months after CBA, and non-ERAF (NERAF) group who did not experience a recurrence of atrial tachyarrhythmia within 3 months after CBA. We investigated the late recurrence of AF (LRAF, defined as recurrence of atrial tachyarrhythmia more than 3 months after CBA), and the incidence of non-pulmonary vein (PV) triggers in the patients who experienced a repeat ablation procedure due to LRAF. RESULTS: VERAF group had a higher incidence of freedom from LRAF than LERAF group (p = 0.032) and a lower incidence of freedom from LRAF than NERAF group (p = 0.002). Moreover, VERAF group had the highest incidence of non-PV triggers at repeat ablation procedure among the three groups (p = 0.003). CONCLUSIONS: While ERAF was a predictor of LRAF, VERAF was less related to LRAF among the patients with ERAF after CBA. Furthermore, VERAF might be associated with non-PV triggers.

Aspartate aminotransferase-to-platelet ratio index for predicting late recurrence of hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND: Our study aimed to explore the prognostic value of the aspartate aminotransferase-platelet ratio index (APRI) and to develop a new nomogram for patients with hepatocellular carcinoma (HCC) who experience late recurrence after radiofrequency ablation (RFA). To date, no study has explored the value of APRI for assessing the late recurrence of HCC after RFA. MATERIALS AND METHODS: The prognostic value of APRI was evaluated and validated in our multicenter retrospective analysis. A total of 466 HCC patients undergoing RFA were reviewed as a training cohort, and 234 HCC patients were included in the external validation cohort. The nomogram was built based on significant prognostic factors in a multivariate analysis and validated in the external validation cohort. RESULTS: The cutoff APRI score was 0.78, and it appropriately discriminated between low- and high-risk groups for late recurrence in HCC patients. The cumulative recurrence-free survival rates of the low-risk group were significantly higher than those of the high-risk group (p < 0.001), according to the Kaplan-Meier curves. Late recurrence in HCC patients after RFA was associated with APRI, sex and multiple tumors. The nomogram based on potential risk factors (APRI score, sex and multiple tumors) as indicated by multivariate Cox regression analysis showed good discrimination and calibration in the training and external verification groups. CONCLUSIONS: The APRI score is a feasible independent prognostic factor for the late recurrence of HCC after RFA. The proposed nomogram could aid clinicians in following disease progression and providing tailored therapy for patients.

Impact of radiofrequency catheter ablation for atrial fibrillation in patients with left atrial enlargement.

Little has been reported on the impact of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in patients with left atrial enlargement (LAE). A total of 706 patients underwent an initial RFCA for AF between September 2014 and September 2019 in our hospital. These patients were categorized into two groups according to the pre-procedural left atrial diameter (LAD) measured by transthoracic echocardiography (TTE): LAE group with LAD ≥ 50 mm and non-LAE group with LAD < 50 mm. We compared the patient characteristics, ablation procedures, and late recurrence of AF (LRAF, defined as a recurrence of atrial tachyarrhythmia between 3 and 12 months after the RFCA) between the two groups. In addition, we performed follow-up TTE at 12 months after RFCA and investigated the factors associated with left atrium (LA) reverse remodeling in each group. LAE group and non-LAE group consisted of 155 and 551 patients, respectively. There were no significant differences in ablation procedures, procedure-related complications, and the incidence of LRAF between the two groups. Furthermore, non-PAF was identified as an independent predictor of LA reverse remodeling in LAE group by multiple regression analysis (P = 0.020). RFCA might be an effective and safe procedure even in patients with LAD ≥ 50 mm, using the contemporary 3D-guided mapping and ablation technologies. Moreover, RFCA can lead to LA reverse remodeling in 1 year if they have non-PAF before ablation.

Machine learning-based prediction model for late recurrence after surgery in patients with renal cell carcinoma.

BACKGROUND: Renal cell carcinoma is characterized by a late recurrence that occurs 5 years after surgery; hence, continuous monitoring and follow-up is necessary. Prognosis of late recurrence of renal cell carcinoma can only be improved if it is detected early and treated appropriately. Therefore, tools for rapid and accurate renal cell carcinoma prediction are essential. METHODS: This study aimed to develop a prediction model for late recurrence after surgery in patients with renal cell carcinoma that can be used as a clinical decision support system for the early detection of late recurrence. We used the KOrean Renal Cell Carcinoma database that contains large-scale cohort data of patients with renal cell carcinoma in Korea. From the collected data, we constructed a dataset of 2956 patients for the analysis. Late recurrence and non-recurrence were classified by applying eight machine learning models, and model performance was evaluated using the area under the receiver operating characteristic curve. RESULTS: Of the eight models, the AdaBoost model showed the highest performance. The developed algorithm showed a sensitivity of 0.673, specificity of 0.807, accuracy of 0.799, area under the receiver operating characteristic curve of 0.740, and F1-score of 0.609. CONCLUSIONS: To the best of our knowledge, we developed the first algorithm to predict the probability of a late recurrence 5 years after surgery. This algorithm may be used by clinicians to identify patients at high risk of late recurrence that require long-term follow-up and to establish patient-specific treatment strategies.

Late recurrence in patients with non-muscle-invasive bladder cancer after 5-year cancer-free periods.

OBJECTIVES: There is no consensus about the follow-up schedule after 5-year cancer-free periods. In this study, we aimed to elucidate the risk factors for the recurrence in patients with non-muscle-invasive bladder cancer who remained cancer free for more than 5 years. METHODS: Data from six Japanese institutions were retrospectively reviewed. Among the patients with non-muscle-invasive bladder cancer who were treated with transurethral resection of bladder tumor between 1990 and 2013, those who had no recurrence for more than 5 years were included in this study. The Kaplan-Meier method and Cox hazards model were used to estimate recurrence-free survival and to determine the pathologic and clinical factors affecting late recurrence. RESULTS: In total, 434 patients were enrolled in this study. Of these patients, 55 patients (12.7%) experienced late recurrence. The median follow-up time was 8.9 years (interquartile range 6.9-11.3 years). Prior history of bladder cancer before the most recent transurethral resection was a significant predictor for late recurrence (hazard ratio 1.99 [95% confidence interval 1.13-3.47], P = 0.019), although other clinical factors including tumor grade, pathologic stage, tumor multiplicity, and current risk classification systems were not associated with late recurrence. CONCLUSIONS: Late recurrence after a long tumor-free period is not rare and it was not predicted by current risk classification systems. Only prior history of bladder cancer was a significant predictor for late recurrence in this study.

Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests.

In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice.

Angiographic findings in cases with a history of severe retinopathy of prematurity treated with anti-VEGFs: Follow-up to age 6 years.

PURPOSE: To report the effects of anti-vascular endothelial growth factor (VEGF) treatment in vascular development for cases of acute retinopathy of prematurity (ROP) using fluorescent angiography (FA) and to present the results of our observational approach to retinal sequelae. METHODS: A total of 31 eyes in 19 patients with a history of treatment with anti-VEGF agents for classic type 1 ROP and aggressive posterior ROP who underwent FA between March 2014 to February 2020 were reviewed. Angiograms of retinal developmental features of patients aged 4 months to 6 years were examined. RESULTS: The patients mean gestational age were 26.06 ± 1.90 weeks and the mean birth weight were 837.68 ± 236.79 g. All cases showed various abnormalities at the vascular and avascular retina, and the posterior pole. All but one case showed a peripheral avascular area on FA evaluation during the follow-up period. We did not apply prophylactic laser treatment to these avascular retina. On the final examination, except one case, we did not observe any late reactivation in any patients. CONCLUSION: FA is an important tool for assessing vascular maturation in infants. Every leakage should not be assumed to be evidence of late activation, as some leaks may be related to vascular immaturity. Retinal vascularization may not be completed in all patients, however this does not mean that all these patients need prophylactic laser application. Our observational approach may be more daring than the reports frequently encountered in the literature, but it should be noted that unnecessary laser treatment will also eliminate all the advantages of anti-VEGF treatment.

Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.

Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.