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Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

ObjectivesSerous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality.DesignRetrospective multinational study including SCN diagnosed between 1990 and 2014.Results2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1).ConclusionsAfter a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN.Trial registration numberIRB 00006477.

Background: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC. Methods: We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive. Results: PD-1 positive (+) was significantly associated with current smoking status ( P =0.02) and with the presence of KRAS mutations ( P =0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology ( P =0.005) and with presence of EGFR mutations ( P =0.001). In patients treated with EGFR tyrosine kinase inhibitors ( N =95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P =0.01) time to progression (TTP: P <0.0001) and survival (OS: P =0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative ( P =0.01). Conclusions: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.

Background After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy. Methods In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort ( n  = 268). For both approaches, we accounted for immortal time bias. Results Of the 31 patients in the platinum cohort (R0 n  = 25, RX n  = 4, R1 n  = 2; ENSAT Stage II n  = 11, III n  = 16, IV n  = 4, median Ki67 30%, mitotane n  = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95% CI 0.09–0.42; P  < 0.001). Using propensity score matching, the HR for RFS was 0.45 (0.29–0.89, P  = 0.021) and for OS 0.25 (0.09–0.69; P  = 0.007). Conclusions Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.

BackgroundThe 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4 vessels involved) are grouped as one category, and substantial invasion as another.ObjectiveTo assess the association between lymphovascular invasion and oncologic outcomes.MethodsWe retrospectively identified patients with FIGO 2009 stage I endometrioid endometrial cancer treated surgically with total hysterectomy and lymph node assessment at two tertiary care centers between January 1, 2012, and December 31, 2019. Lymphovascular space invasion was categorized as focal (<5 vessels involved), substantial (≥5 vessels involved), and no lymphovascular invasion using WHO criteria.ResultsOf 1555 patients included, 65 (4.2%) had substantial, 119 (7.7%) had focal, and 1371 (88.2%) had no lymphovascular invasion. Median age was 64 years (range 24–92). Thirty-five patients (53.8%) with substantial, 44 (37%) with focal, and 115 (8.4%) with no lymphovascular invasion had stage IB disease (p<0.001); 21 (32.3%) with substantial, 24 (20.2%) with focal, and 91 (6.6%) with no lymphovascular invasion had grade 3 disease (p<0.001). Thirty-six patients (55.4%) with substantial, 80 (67.2%) with focal, and 207 (15.1%) with no lymphovascular invasion received adjuvant treatment (p<0.001). Median follow-up was 61.5 months (range 0.8–133.9). Five-year progression-free survival rates were 68.7% (substantial), 70.5% (focal), and 90.7% (no invasion) (p<0.001). On multivariate analysis, any lymphovascular invasion was associated with increased risk of progression/death (adjusted HR (aHR)=1.84 (95% CI 1.73 to 1.96) for focal; 2.17 (95% CI 1.96 to 2.39) for substantial). Compared with focal, substantial lymphovascular invasion was associated with an aHR for disease progression of 1.18 (95% CI 1.00 to 1.39).ConclusionsFocal and substantial lymphovascular invasion were associated with increased risk of disease progression and do not appear to be prognostically distinct. Focal versus no lymphovascular invasion have different prognostic outcomes and should not be combined into one category.

Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic. To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality. The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR. Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting). The primary outcome was early mortality; secondary outcomes were postoperative complications. Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P < .001) and early surgery (time to surgery ≥7 days, survived: 105 [57.4%]; died, 47 [35.1%]; P < .001) were associated with lower survival. At multivariate analysis, older age (odds ratio [OR], 1.05; 95% CI, 1.02-1.08; P = .001), preoperative cardiac arrest (OR, 2.71; 95% CI, 1.18-6.27; P = .02) and percutaneous revascularization (OR, 1.63; 95% CI, 1.003-2.65; P = .048), and postoperative need for intra-aortic balloon pump (OR, 2.98; 95% CI, 1.46-6.09; P = .003) and extracorporeal membrane oxygenation (OR, 3.19; 95% CI, 1.30-7.38; P = .01) were independently associated with mortality. In this study, surgical repair of postinfarction VSR was associated with a high risk of early mortality; this risk has remained unchanged during the last 2 decades. Delayed surgery seemed associated with better survival. Age, preoperative cardiac arrest and percutaneous revascularization, and postoperative need for intra-aortic balloon pump and extracorporeal membrane oxygenation were independently associated with early mortality. Further prospective studies addressing preoperative and perioperative patient management are warranted to hopefully improve the currently suboptimal outcome.

Purpose To perform a systematic review of literature specific to single-fraction stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS), maximum diameter ≥ 2.5 cm and/or classified as Koos Grade IV, and to present consensus recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). Methods The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. We considered eligible prospective and retrospective studies, written in the English language, reporting treatment outcomes for large VS; SRS for large post-operative tumors were analyzed in aggregate and separately. Results 19 of the 229 studies initially identified met the final inclusion criteria. Overall crude rate of tumor control was 89% (93.7% with no prior surgery vs 87.7% with prior surgery). Rates of salvage microsurgical resection, need for shunt, and additional SRS in all series versus those with no prior surgery were 9.6% vs 3.3%, 4.7% vs 6.4% and 1% vs 0.9%, respectively. Rates of facial palsy and hearing preservation in all series versus those with no prior surgery were 1.3% vs 3.4% and 34.2% vs 40.4%, respectively. Conclusions Upfront SRS resulted in high rates of tumor control with acceptable rates of facial palsy and hearing preservation as compared to the results in those series including patients with prior surgery (level C evidence). Therefore, although large VS are considered classic indication for microsurgical resection, upfront SRS can be considered in selected patients and we recommend a prescribed marginal dose from 11 to 13 Gy (level C evidence).

Abstract Purpose Male breast cancer (MBC) is a rare, but increasingly common disease, and lacks prospective studies. Collaborative efforts are needed to understand and address MBC, including its prognosis, in different countries. Methods We retrospectively reviewed the clinical, histopathological, and molecular-genetic characteristics, treatments, and survival outcomes of MBC diagnosed between 2007 and 2017 in the Czech Republic. Prognostic factors of overall survival (OS), recurrence-free interval (RFi), and breast cancer-specific mortality (BCSM) were analyzed and indirectly compared to international data. Results We analyzed 256 patients with MBC (median age 66 years), including 12% with de novo metastatic (M1). Of 201 non-metastatic (M0) patients, 6% were <40 years old, 29% had stage I, 55% were cN0, and 54% underwent genetic testing. Overall, 97% of tumors had estrogen receptor expression ≥10%, 61% had high Ki67 index, 40% were high-grade (G3), and 68% were luminal B-like (HER2-negative). Systemic therapies included endocrine therapy (90%) and chemotherapy (53%). Few (5%) patients discontinued adjuvant endocrine therapy for reasons other than disease relapse or death. Patients treated with aromatase inhibitors alone had significantly shorter RFi (P < .001). OS, RFi, and BCSM were associated with disease stage, T stage, N stage, progesterone receptor expression, grade, and Ki67 index. Median OS reached 122 and 42 months in M0 and de novo M1 patients, respectively. Conclusion Due to the rarity of MBC, this study highlights important findings from real clinical practice. Although the number of patients with MBC with unfavorable features was higher in this Czech dataset than in international studies, the prognosis remains consistent with real-world evidence. This study evaluated patient and disease characteristics, treatment, and prognosis of male breast cancer among patients registered with the Complex Oncological Centers in the Czech Republic, and indirectly compared these findings with international data.

In 2020, the world gained dramatic experience of the development of the 2019 coronavirus disease pandemic (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Recent researches notice an increasing prevalence of anxiety and circadian rhythm disorders during COVID-19 pandemic. The aim of the study was describing clinical features of circadian rhythm disorders and the level of anxiety in persons who have had COVID-19. We have conducted a cohort retrospective study that included 278 patients who were divided into 2 study groups according to medical history: group 1 includes patients with a history of COVID-19; group 2 consists of patients who did not have clinically confirmed COVID-19 and are therefore considered not to have had this disease. To objectify circadian rhythm disorders, they were verified in accordance with the criteria of the International Classification of Sleep Disorders-3. The level of anxiety was assessed by the State-Trait Anxiety Inventory. The most common circadian rhythm disorders were sleep phase shifts. We found that COVID-19 in the anamnesis caused a greater predisposition of patients to the development of circadian rhythm disorders, in particular delayed sleep phase disorder. In addition, it was found that after COVID-19 patients have increased levels of both trait and state anxiety. In our study, it was the first time that relationships between post-COVID-19 anxiety and circadian rhythm disorders had been indicated. Circadian rhythm disorders are associated with increased trait and state anxiety, which may indicate additional ways to correct post-COVID mental disorders and their comorbidity with sleep disorders.

ABSTRACT Background Left atrium (LA) is an integral component of left heart remodeling, reflecting hemodynamics and ventricular status. It remains uncertain whether left atrial diameter (LAD) can be utilized for predicting and evaluating the occurrence of heart failure (HF) in middle‐aged and elderly individuals. Methods The study aimed to explore the correlation between LAD and HF in middle‐aged and elderly individuals, elucidating the timing of occurrence HF in relation to LAD. The retrospective‐prospective study investigated 4025 patients who underwent echocardiography at Zhongshan Hospital's Cardiovascular Department from January 2015 to December 2017. Patients were continuously monitored for HF until January 31, 2024. Cox regression analyses related baseline LAD to HF incidence, adjusted for known risk factors. Results A total of 4025 individuals (mean age: 55 years, 45.29% male) were studied, spanning ages 45–91. Fifty‐one developed HF during a median follow‐up of 4.36 years. Cox regression model demonstrated the association between HF and LAD (HR = 5.721, 95% CI 3.768–8.687, p < 0.001) even after adjusting for covariates (age, weight, eGFR, HDL‐C, lymphocyte count, systolic blood pressure, FPG, HbA1C, waist circumference, hip circumference, valvular disease history, atrial fibrillation history). Conclusions The link between LAD and future HF occurrence risk among middle‐aged and older adults shows a dose–response pattern. This relationship persists post‐adjustment for HF‐related factors, highlighting the predictive value of LAD in forecasting HF incidence. The association between LAD and future HF risk among middle‐aged and older adults shows a dose–response pattern. This relationship persists after adjusting for HF‐related factors, highlighting the predictive value of LAD in forecasting HF incidence.