Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort.

Introduction: Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research. Methods: The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study's prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks. Results: The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage. Discussion: This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

Identifying MicroRNAs Suitable for Detection of Breast Cancer: A Systematic Review of Discovery Phases Studies on MicroRNA Expression Profiles.

The analysis of circulating tumor cells and tumor-derived materials, such as circulating tumor DNA, circulating miRNAs (cfmiRNAs), and extracellular vehicles provides crucial information in cancer research. CfmiRNAs, a group of short noncoding regulatory RNAs, have gained attention as diagnostic and prognostic biomarkers. This review focuses on the discovery phases of cfmiRNA studies in breast cancer patients, aiming to identify altered cfmiRNA levels compared to healthy controls. A systematic literature search was conducted, resulting in 16 eligible publications. The studies included a total of 585 breast cancer cases and 496 healthy controls, with diverse sample types and different cfmiRNA assay panels. Several cfmiRNAs, including MIR16, MIR191, MIR484, MIR106a, and MIR193b, showed differential expressions between breast cancer cases and healthy controls. However, the studies had a high risk of bias and lacked standardized protocols. The findings highlight the need for robust study designs, standardized procedures, and larger sample sizes in discovery phase studies. Furthermore, the identified cfmiRNAs can serve as potential candidates for further validation studies in different populations. Improving the design and implementation of cfmiRNA research in liquid biopsies may enhance their clinical diagnostic utility in breast cancer patients.

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. MATERIALS & METHODS: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. RESULTS: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. CONCLUSION: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.

An Epidemiological Systematic Review with Meta-Analysis on Biomarker Role of Circulating MicroRNAs in Breast Cancer Incidence.

Breast cancer (BC) is a multifactorial disease caused by an interaction between genetic predisposition and environmental exposures. MicroRNAs are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and seem to be related to cancer risk factors. We conducted a systematic review and meta-analysis to identify circulating microRNAs related to BC diagnosis, paying special attention to methodological problems in this research field. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seventy-five studies were included in the systematic review. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seven studies were included in the MIR21 and MIR155 meta-analysis, while four studies were included in the MIR10b metanalysis. The pooled sensitivity and specificity of MIR21 for BC diagnosis were 0.86 (95%CI 0.76-0.93) and 0.84 (95%CI 0.71-0.92), 0.83 (95%CI 0.72-0.91) and 0.90 (95%CI 0.69-0.97) for MIR155, and 0.56 (95%CI 0.32-0.71) and 0.95 (95%CI 0.88-0.98) for MIR10b, respectively. Several other microRNAs were found to be dysregulated, distinguishing BC patients from healthy controls. However, there was little consistency between included studies, making it difficult to identify specific microRNAs useful for diagnosis.

Mediating Role of Lifestyle Behaviors in the Association between Education and Cancer: Results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. METHODS: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). RESULTS: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). CONCLUSIONS: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. IMPACT: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Sweetened beverages are associated with a higher risk of differentiated thyroid cancer in the EPIC cohort: a dietary pattern approach.

BACKGROUND: Dietary pattern analysis has gained particular interest, because it reflects the complexity of dietary intake. The aim of this study was to explore the associations between a posteriori dietary patterns, derived using a data-driven approach, and the risk of differentiated thyroid cancer (TC) in Europe. METHODS: This investigation included 450,064 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake was assessed using validated country-specific dietary questionnaires. A posteriori dietary patterns were computed using principal component analyses. Cox regression was used to calculate multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a mean follow-up time of 14 years, 712 first differentiated TCs were diagnosed. In the fully adjusted model, a dietary pattern characterized by alcohol consumption (basically beer and wine) was negatively associated with differentiated TC risk (HRQ4vs.Q1 = 0.75; 95% CI:0.60-0.94, P-trend = 0.005), while a dietary pattern rich in sweetened beverages was positively associated with differentiated TC risk (HRQ4vs.Q1 = 1.26; 95% CI:0.99-1.61; P-trend = 0.07). The remaining 8 dietary patterns were not related to differentiated TC risk. The intake of sweetened beverages was positively associated with differentiated TC risk (HR100mL/d = 1.05; 95% CI:1.00-1.11), especially with papillary TC risk (HR100mL/d = 1.07; 95% CI:1.01-1.13). Similar results were observed with sugary and artificially sweetened beverages. CONCLUSIONS: The investigation of dietary patterns detected that the consumption of sweetened beverages was associated with a higher risk of differentiated thyroid cancer. Our results are in line with the general dietary recommendations of reducing the consumption of sweetened beverages.

Investigating the Role of Circulating miRNAs as Biomarkers in Colorectal Cancer: An Epidemiological Systematic Review.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Primary and secondary preventions are key to reducing the global burden. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and to be related to cancer risk factors, such as obesity and inflammation. We conducted a systematic review and meta-analysis to identify circulating miRNAs related to CRC diagnosis that could be selected as biomarkers in a meet-in-the-middle analysis. Forty-four studies were included in the systematic review and nine studies in the meta-analysis. The pooled sensitivity and specificity of miR-21 for CRC diagnosis were 77% (95% CI: 69-84) and 82% (95% CI: 70-90), respectively, with an AUC of 0.86 (95% CI: 0.82-0.88). Several miRNAs were found to be dysregulated, distinguishing patients with CRC from healthy controls. However, little consistency was present across the included studies, making it challenging to identify specific miRNAs, which were consistently validated. Understanding the mechanisms by which miRNAs become biologically embedded in cancer initiation and promotion may help better understand cancer pathways to develop more effective prevention strategies and therapy approaches.

Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer.

Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.

Cruciferous Vegetable Intake and Bulky DNA Damage within Non-Smokers and Former Smokers in the Gen-Air Study (EPIC Cohort).

Epidemiologic studies have indicated that cruciferous vegetables can influence the cancer risk; therefore, we examined with a cross-sectional approach the correlation between the frequent consumption of the total cruciferous vegetables and the formation of bulky DNA damage, a biomarker of carcinogen exposure and cancer risk, in the Gen-Air study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. DNA damage measurements were performed in the peripheral blood of 696 of those apparently healthy without cancer controls, including 379 never-smokers and 317 former smokers from seven European countries by the 32P-postlabeling assay. In the Gen-Air controls, the median intake of cruciferous vegetables was 6.16 (IQR 1.16−13.66) g/day, ranging from 0.37 (IQR 0−6.00) g/day in Spain to 11.34 (IQR 6.02−16.07) g/day in the UK. Based on this information, participants were grouped into: (a) high consumers (>20 g/day), (b) medium consumers (3−20 g/day) and (c) low consumers (<3.0 g/day). Overall, low cruciferous vegetable intake was correlated with a greater frequency of bulky DNA lesions, including benzo(a)pyrene, lactone and quinone-adducts and bulky oxidative lesions, in the adjusted models. Conversely, a high versus low intake of cruciferous vegetables was associated with a reduction in DNA damage (up to a 23% change, p = 0.032); this was particularly evident in former smokers (up to a 40% change, p = 0.008). The Generalized Linear Regression models indicated an overall Mean Ratio between the high and the low consumers of 0.78 (95% confidence interval, 0.64−0.97). The current study suggests that a higher intake of cruciferous vegetables is associated with a lower level of bulky DNA adducts and supports the potential for cancer prevention strategies through dietary habit changes aimed at increasing the consumption of cruciferous vegetables.

Subacromial spacer implantation: an alternative to arthroscopic superior capsular reconstruction. A systematic review.

INTRODUCTION: This systematic review evaluated and compared the use of a subacromial spacer implantation (SSI) with arthroscopic superior capsular repair (ASCR) in the management of massive irreparable rotator cuff tears (MIRCTs) with an assessment of clinical and imaging outcomes. SOURCES OF DATA: This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched in PubMed, Medline and Embase database literature using the keywords 'subacromial spacer', 'subacromial balloon', 'subacromial device', 'arthroscopy', 'superior capsular reconstruction', 'irreparable rotator cuff tears', 'satisfaction' and 'quality of life'. AREAS OF AGREEMENT: We included a total of 29 articles (14 about SSI and 15 about ASCR) dealing with outcomes, satisfaction and patients' quality of life. AREAS OF CONTROVERSY: The use of a subacromial spacer showed similar results in terms of patients' satisfaction and quality of life when compared with ASCR. GROWING POINTS: SSI can be implanted quickly and has a low complication rate. It can therefore be considered a good alternative for the management of MIRCTs. AREAS TIMELY FOR DEVELOPING RESEARCH: The subacromial spacer is a biodegradable implant easily implanted at arthroscopy. It can lead good clinical and imaging outcomes in MIRCTs. Similarly, ASCR can be performed with either an autograft or synthetic allograft transplantation, with satisfactory results. Long-term prospective studies are needed to compare SSI and ASCR to verify their effectiveness.

Arthroscopic superior capsular reconstruction versus latissimus dorsi transfer for irreparable rotator cuff lesions: a systematic review.

INTRODUCTION: The present systematic review compared arthroscopic superior capsular reconstruction (ASCR) and latissimus dorsi transfer (ALDT) for the management of massive irreparable rotator cuff lesions. SOURCES OF DATA: We performed a systematic review searching the literature on Medline, Cochrane and Scopus databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. AREAS OF AGREEMENT: We included a total of 20 articles, 10 on ASCR and 10 on ALDT (12 retrospective and 8 prospective studies), all published between 2013 and 2019. AREAS OF CONTROVERSY: ASCR and ALDT are technical demanding procedures. When compared to each other, they do not produce significantly different improvements in clinical outcome. GROWING POINTS: Both ASCR and ALDT are valid options for surgical management of MIRCLs. Although ALDT has shown a greater complication rate and a less improvement in acromion-humeral distance, its clinical outcomes overlap those obtained with ASCR. AREAS TIMELY FOR DEVELOPING RESEARCH: Further comparative prospective and retrospective studies with longer follow-up could confirm which surgical procedure can lead to better outcomes with a lower complication rate.

Surgical treatment of periprosthetic femoral fractures: a retrospective study with functional and radiological outcomes from 2010 to 2016.

BACKGROUND: The treatment of periprosthetic femoral fractures is a great challenge for the orthopedic surgeon and requires a knowledge of bone fracture fixation as well as skills and experience in revision surgery. The aim of this retrospective study was to evaluate the functional and radiological outcomes of periprosthetic femoral fractures surgically treated in our department from 2010 to 2016. MATERIALS AND METHODS: This study involved 73 patients with a periprosthetic femoral fracture after total hip arthroplasty or hemiarthroplasty. Periprosthetic femoral fractures were classified using the Vancouver system. Functional outcomes were assessed using Harris hip score, Palmer Parker score, SF-36 score and ambulatory status. Radiological findings were classified using Beals and Tower's criteria. RESULTS: The mean age of patients was 79.6 years old. Local risks factors were identified in 67% of the patients, principally osteoporosis (63.0%), followed by osteolysis (26.0%) and loosening of the stem (8.2%). According to the Vancouver classification, there were 10 type A, 49 type B and 14 type C fractures. Of the type B fractures, 26 were B1, 17 were B2 and 6 were B3. Applying Beals and Tower's criteria, radiological results were excellent in 24 patients (32.9%), good in 35 (47.9%) and poor in 14 (19.2%). The mean Harris hip score post-operatively was 72.5. CONCLUSIONS: These kinds of fractures should be assessed individually and the optimal treatment plan should be made in accordance with the bone stock quality, stem stability, location of the fracture and patient expectations.