OBJECTIVE: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain.
METHODS: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization.
RESULTS: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)].
CONCLUSIONS: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.

Flat epithelial atypia (FEA), lobular neoplasia (LN), papillary lesions (PL), radial scar (RS) and atypical ductal hyperplasia (ADH) are lesions of uncertain malignant potential and classified as B3 lesions by the European guidelines for quality assurance in breast cancer screening and diagnosis. Current management is usually wide local excision (WE), surveillance may be sufficient for some. We investigated the upgrade rate of B3 lesions to breast malignancy in a subsequent resection specimen after diagnosis on core needle-or vacuum assisted biopsy (CNB-VAB) in a national population-based series.
Using data from the Belgian Cancer Registry (BCR) between January 1, 2013 and December 31, 2016, inclusion criteria were new diagnosis of a B3 lesion on CNB or VAB with subsequent histological assessment on a wider excision specimen. Histological agreement between first- and follow-up investigation was analyzed to determine the upgrade risk to ductal adenocarcinoma in situ (DCIS) or invasive breast cancer (IC) according to the type of B3 lesion.
Of 1855 diagnosed B3 lesions, 812 were included in this study: 551 after CNB-261 after VAB. After diagnosis on CNB and VAB, we found 19.0% and 14.9% upgrade to malignancy respectively. Upgrade risks after CNB and VAB were: FEA 39.5% and 17.6%; LN 40.5% and 4.3%; PL 10.4% and 12.5%; RS 25.7%and 0.0%; ADH 29.5% and 20.0%.
Based on the observed upgrade rate we propose three recommendations: first, resection of ADH, and FEA with WE; second, resection of RS and classical LN with therapeutic VAB and further surveillance when radio-pathological correlation is concordant; third, surveillance of PL.

Background The rate of upgrading ductal carcinoma in situ (DCIS) to invasive cancer varies widely in the literature with no consensus regarding sentinel lymph node biopsy (SLNB) for DCIS; however, some guidelines do recommend it in the event of a mastectomy. The primary aim of this study was to determine the upgrade rate of DCIS to invasive carcinoma (IC) in patients undergoing mastectomy for DCIS and identify the clinicopathological predicting factors for the upgrade. The secondary aim was to determine the SLNB positivity rate. Methodology We retrospectively analysed consecutive patients with DCIS diagnosed through a biopsy who then underwent mastectomy over a 10-year period (2010 to 2020). Clinical, radiological, and histological variables were collected from medical records. Results We studied 143 women (mean age = 57.4 years, range = 26-85 years) who underwent mastectomy for DCIS identified on biopsy. Almost two-thirds (62.9%, 90/143) of the patients were detected on screening mammography, while 35.6% (51/143) were diagnosed following presentation with either an area of palpable concern or nipple discharge. The most common mammographic presentation of DCIS was calcification (83.9%, 120/143), and, in 85.9% of the patients, the mammographic lesion was more than 20 mm. High-grade DCIS was noted in 76.9% of preoperative biopsy results, while the rest was either low or intermediate-grade DCIS. Overall, 24.5% (35/143) were upgraded to IC (upgraded group) on postoperative histology, whereas 108/143 remained DCIS postoperatively (pure DCIS group). The positivity rate of SLNB was 4.8%. Multifocality was the only significant predictor of IC on multivariate analyses of clinicopathological predictors (odds ratio = 3.0, 95% confidence interval = 1.0-8.7). The presence of comedonecrosis was higher in the upgraded group compared to the pure DCIS group (42.9% vs. 27.8%), but this was not statistically significant. Conclusions In our study cohort, nearly one in four (24.5%) patients were upgraded from DCIS to IC on postoperative histology, with an SLNB positivity rate of 4.8%. This is important when counselling patients regarding the risk of coincident occult IC and the importance of SLNB at the time of mastectomy. Multifocality on preoperative imaging was the only significant predictive factor. Based on this result, we recommend that SLNB should also be considered if patients have multifocal DCIS and planned for oncoplastic breast-conserving surgery. However, further studies are required to investigate the association between multifocal DCIS and the risk of upgrading to IC.

The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies.
This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%).
When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events.
ClinicalTrials.gov NCT02270840.

UNASSIGNED: This study aimed to evaluate the pathological concordance from combined systematic and MRI-targeted prostate biopsy to final pathology and to verify the effectiveness of a machine learning-based model with targeted biopsy (TB) features in predicting pathological upgrade.
UNASSIGNED: All patients in this study underwent prostate multiparametric MRI (mpMRI), transperineal systematic plus transperineal targeted prostate biopsy under local anesthesia, and robot-assisted laparoscopic radical prostatectomy (RARP) for prostate cancer (PCa) sequentially from October 2016 to February 2020 in two referral centers. For cores with cancer, grade group (GG) and Gleason score were determined by using the 2014 International Society of Urological Pathology (ISUP) guidelines. Four supervised machine learning methods were employed, including two base classifiers and two ensemble learning-based classifiers. In all classifiers, the training set was 395 of 565 (70%) patients, and the test set was the remaining 170 patients. The prediction performance of each model was evaluated by area under the receiver operating characteristic curve (AUC). The Gini index was used to evaluate the importance of all features and to figure out the most contributed features. A nomogram was established to visually predict the risk of upgrading. Predicted probability was a prevalence rate calculated by a proposed nomogram.
UNASSIGNED: A total of 515 patients were included in our cohort. The combined biopsy had a better concordance of postoperative histopathology than a systematic biopsy (SB) only (48.15% vs. 40.19%, p = 0.012). The combined biopsy could significantly reduce the upgrading rate of postoperative pathology, in comparison to SB only (23.30% vs. 39.61%, p < 0.0001) or TB only (23.30% vs. 40.19%, p < 0.0001). The most common pathological upgrade occurred in ISUP GG1 and GG2, accounting for 53.28% and 20.42%, respectively. All machine learning methods had satisfactory predictive efficacy. The overall accuracy was 0.703, 0.768, 0.794, and 0.761 for logistic regression, random forest, eXtreme Gradient Boosting, and support vector machine, respectively. TB-related features were among the most contributed features of a prediction model for upgrade prediction.
UNASSIGNED: The combined effect of SB plus TB led to a better pathological concordance rate and less upgrading from biopsy to RP. Machine learning models with features of TB to predict PCa GG upgrading have a satisfactory predictive efficacy.

OBJECTIVE: This study aims to investigate the consequences of comedonecrosis omission as an exclusion criterion of the Comparison of Operative vs Monitoring and Endocrine Therapy (COMET) trial.
METHODS: The clinical inclusion criteria of the COMET trial were applied on women who were mammographically screened between 2007 and 2017 and had a diagnosis of low- or intermediate-grade ductal carcinoma in situ (DCIS). The percentage of ductal diameter occupied by necrosis was calculated.
RESULTS: Twenty-six of 129 (20.2%) cases were upgraded. Larger calcification span correlated with upgrade (P = .02), with the best cutoff of 1.1 cm, and negative predictive value of 86%. When solely analyzing cases with no comedonecrosis (n = 76), none of the variables correlated with upgrade. Comedonecrosis was significantly correlated with upgrade to invasive carcinoma (P = .041), with the best cutoff of 53% of ductal diameter occupied by necrosis.
CONCLUSIONS: Results indicate that comedonecrosis and span of mammographic calcifications could be risk factors in women managed with active surveillance.

Management of classic lobular neoplasia (cLN) diagnosed on core needle biopsy (CNB) is controversial. Our aim in this study was to review cases of cLN diagnosed on CNB to determine the rate and risk factors of an upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma on excision. All breast CNBs with a diagnosis of atypical lobular hyperplasia (ALH) or classic lobular carcinoma in situ (cLCIS) from three different institutions within a single health care system between 2013 and 2018 were retrieved. Cases with any additional high-risk lesions in the same CNB or discordant radiological-pathological correlation were excluded. Information about age, personal history of prior or concurrent breast cancer (P/CBC), and radiological and histological findings were recorded. A total of 287 cLN cases underwent surgical excision. Analysis of these 287 cLN cases showed 11 (3.8%) upgrade lesions on excision. Among the 172 ALH cases, there were 3 (1.7%) upgrades, which were all invasive lobular carcinomas (ILCs). On the other hand, 8 of 115 (7%) cLCIS cases revealed upgrade on excision (2 ILC, 5 DCIS. and 1 ILC + DCIS). Statistical analysis revealed that cLN cases with P/CBC, radiological asymmetry, or architectural distortion had a statistically significant higher upgrade rate on excision. Our findings revealed a low upgrade rate (3.8%) on the excision of classic lobular neoplasia diagnosed on breast core needle biopsy. Clinicoradiological surveillance can be appropriate when lobular neoplasia is identified on core biopsy with pathological radiological concordance in patients without a history of breast cancer, with the caveat that radiological asymmetry and architectural distortion are associated with a significant increase in an upgrade on excision.

Management recommendations for lobular neoplasia (LN) including lobular carcinoma-in-situ (LCIS) and atypical lobular hyperplasia (ALH) diagnosed in core biopsies (CB) are controversial. Our aim was to prospectively identify a subset of patients who do not require subsequent surgical excision (SE).
All patients diagnosed with LN on CB were enrolled and referred for SE. Cases with coexistent ductal carcinoma-in-situ or invasive carcinoma were excluded. Cases with coexistent ductal atypia (LN-DA) and LCIS variants (LN-V) were separated from pure classic LN (LN-C). Dedicated breast pathologists and radiologists reviewed cases with careful imaging/pathology correlation.
Of 13,772 total percutaneous breast CB procedures, 302 of 370 patients diagnosed with LN underwent SE. Upgrade to carcinoma was present in 3.5% (8/228) LN-C, 26.7% LN-V (4/15), and 28.3% LN-DA (15/53). Calcifications were the imaging target for 180 (79%) of 228 LN-C cases; 7 were associated with upgrade (3.9%). Upgrades were rare for mass lesions (1/32) and magnetic resonance imaging-targeted lesions (0/14). Upgrades were similar for ALH and LCIS (3.4% vs. 4.5%). During postsurgical follow-up (mean, 34.5 months), 6.5% LN-C patients developed carcinoma in either breast.
Although LN with nonclassic morphology or with associated ductal atypia requires SE, this can be avoided in LN-C diagnosed on CB targeting calcifications when careful imaging/pathology correlation is applied. Until larger numbers are studied, excising LN-C diagnosed as masses or magnetic resonance imaging-detected lesions may be prudent. Regardless of their selection for surgical management, LN patients need close surveillance in view of their long-term risk of breast cancer.

BACKGROUND: The BLOCK HF trial showed that heart failure patients with atrioventricular block (AVB) and left ventricular systolic dysfunction (LVSD) are considered good candidates for cardiac resynchronization therapy (CRT), even though they have a narrow QRS duration. We aimed to compare the clinical response to CRT between patients with AVB combined with LVSD and patients with pre-existing CRT indications.
METHODS: We compared the clinical data on CRT across the following 3 groups in 3 cardiovascular centers; heart failure patients with an LV ejection fraction (LVEF) of ≤35% who had a QRS duration of ≥120ms (standard indication, n=125), those needing an upgrade to CRT (upgrade, n=49), and patients with an LVEF of ≤50% who had advanced AVB (AVB with LVSD, n=27).
RESULTS: The prevalence of left bundle branch block differed significantly across the groups (87.2%, 98.0% and 40.7%; P<0.001). No inter-group difference was found in the percentage of patients in whom clinical composite score (CCS) assessed 6months after the CRT was improved (60.8%, 57.1% and 70.4%; P=0.67). Whereas, even among the patients with an improved CCS, a significantly smaller LV end-systolic volume reduction after the CRT was seen in the ABV with LVSD group (-35.3±34.7, -21.4±28.5 and -5.2±23.9%; P=0.001). The incidence of cardiovascular death or hospitalization from heart failure within 5years occurred with a similar frequency (44%, 55.1% and 44.4%; P=0.9).
CONCLUSIONS: As compared to patients with preexisting CRT indications, CRT may be similarly effective for patients with AVB and LVSD, however, LV reverse remodeling may be uncommon among them.

OBJECTIVE: To identify variables that can predict upgrade for magnetic resonance imaging (MRI)-detected atypical ductal hyperplasia (ADH).
RESULTS: We reviewed 1655 MRI-guided core biopsies between 2005 and 2013, yielding 100 (6%) cases with ADH. The pathological features of ADH and MRI findings were recorded. An upgrade was considered when the subsequent surgical excision yielded invasive carcinoma (IC) or ductal carcinoma in situ (DCIS). The rate of ADH between institutions was 3.3-7.1%, with an average of 6%. A total of 15 (15%) cases had upgrade, 12 DCIS and three IC. When all cases were included, only increased number of involved cores was statistically significant (P = 0.02). When cases with concurrent lobular neoplasia (LN) were excluded (n = 14), increased number of ADH foci and increased number of involved cores were statistically significant (P = 0.002, P = 0.009). We analysed the data separately from a single institution (n = 61). Increased number of foci, increased number of total cores and involved cores and larger ADH size predicted upgrade with statistical significance.
CONCLUSIONS: The incidence of ADH in MRI-guided core biopsy is rare. The rate of upgrade is comparable to mammographically detected ADH, warranting surgical excision. Similar to mammographically detected lesions, the volume of the ADH predicts the upgrade.