-
1.
Fenretinide in young women at genetic or familial risk of breast cancer: A placebo-controlled biomarker trial.
Aristarco, V, Serrano, D, Maisonneuve, P, Guerrieri-Gonzaga, A, Lazzeroni, M, Feroce, I, Macis, D, Cavadini, E, Albertazzi, E, Jemos, C, et al
Cancer prevention research (Philadelphia, Pa.). 2024
Abstract
Fenretinide, a retinoid with a low toxicity profile that accumulates in the breast, has been shown to prevent second breast cancer in young women. Fenretinide exhibits apoptotic and anti-invasive properties and it improves insulin sensitivity in overweight premenopausal women with insulin resistance. The present study aimed to further characterize its role in cancer prevention by measuring circulating biomarkers related to insulin sensitivity and breast cancer risk. Sixty-two women, aged 20 to 46 years, healthy or who had already undergone breast cancer surgery, with a known BRCA1/2 mutation or a likelihood of mutation ≥ 20% according to the BRCAPRO model, were randomly assigned to receive fenretinide (200 mg/day) or placebo for 5 years (trial registration: EudraCT Number: 2009-010260-41). Fasting blood samples were drawn at baseline, 12 and 36 months, and the following biomarkers were analyzed: retinol, leptin, adiponectin, retinol-binding protein 4, total cholesterol, HDL and LDL cholesterol, triglycerides, glucose, insulin, IGF-I, IGFBP-3, SHBG, testosterone, and VEGF. After 12 months of treatment, we observed a favorable effect of fenretinide on glucose (decrease; P=0.005), insulin (decrease; P=0.03), HOMA index (decrease; P=0.004), HDL cholesterol (increase; P=0.002), even though these effects were less prominent after 36 months. Retinol and retinol-binding protein 4 markedly decreased (P<0.0001) throughout the study. None of the other measured biomarkers changed.
-
2.
Physical activity and/or dietary intervention in overweight or obese breast cancer survivors: results of the InForma randomized trial.
Gnagnarella, P, Dragà, D, Raja, S, Baggi, F, Simoncini, MC, Sabbatini, A, Mazzocco, K, Masiero, M, Bassi, FD, Peradze, N, et al
Journal of cancer survivorship : research and practice. 2023
Abstract
PURPOSE This study aimed to test the efficacy of a 6-month intervention on weight loss in a group of overweight or obese breast cancer (BC) survivors. We promoted adherence to a healthy diet or/and to increase physical activity, making use of a step counter device. Here we present results regarding the change in anthropometric measures and blood parameters. METHODS 266 women treated for BC with a BMI ≥ 25 kg/m2 were randomized to a 6-month intervention into four arms: Dietary Intervention (DI); Physical Activity Intervention (PAI); Physical Activity and Dietary Intervention (PADI); Minimal Intervention (MI). Women were offered individualized counseling by a dietitian, a physiotherapist and a psychologist. Participants were followed up for an additional 18 months. RESULTS 231 women completed the 6-month intervention and 167 completed the additional 18-month follow-up. Respectively, 37.5% and 36.7% of women included in the DI and PADI arm reached the objective of the trial (weight reduction > 5%). Significant weight and circumferences decrease was observed at 6-month in the four arms. Weight decrease was more pronounced in the DI (-4.7% ± 5.0%) and PADI (-3.9% ± 4.5%) arms, persisted over time (at 12 and 24 months), where counseling was mainly focused on the dietic component. The intervention had an effect on the glucose level with a significant reduction in whole population (-0.9 ± 11.7 p-value 0.02) and most pronounced in the PADI arm (-2.4 ± 7.8 p-value 0.03). CONCLUSIONS Lifestyle intervention mainly focused on the dietetic component and making use of a step counter improved body weight, circumferences and glucose levels. IMPLICATIONS FOR CANCER SURVIVORS A personalized approach yields a potential clinical benefit for BC survivors.
-
3.
Clinical usefulness of scoring systems to predict severe acute pancreatitis: A systematic review and meta-analysis with pre and post-test probability assessment.
Capurso, G, Ponz de Leon Pisani, R, Lauri, G, Archibugi, L, Hegyi, P, Papachristou, GI, Pandanaboyana, S, Maisonneuve, P, Arcidiacono, PG, de-Madaria, E
United European gastroenterology journal. 2023;(9):825-836
-
-
Free full text
-
Abstract
BACKGROUND Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking. OBJECTIVE To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP. METHODS Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022. Retrospective, prospective, cross-sectional studies or clinical trials on patients with acute pancreatitis defined as Revised Atlanta Criteria, reporting rate of SAP and using at least one score among Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Examination (APACHE)-II, RANSON, and Systemic Inflammatory Response Syndrome (SIRS) with their sensitivity and specificity were included. Random effects model meta-analyses were performed. Pre-test probability and likelihood ratio (LR) were combined to estimate post-test probability on Fagan nomograms. Pooled severity rate was used as pre-test probability of SAP and pooled sensitivity and specificity to calculate LR and generate post-test probability. A priori hypotheses for heterogeneity were developed and sensitivity analyses planned. RESULTS 43 studies yielding 14,116 acute pancreatitis patients were included: 42 with BISAP, 30 with APACHE-II, 27 with Ranson, 8 with SIRS. Pooled pre-test probability of SAP ranged 16.6%-25.3%. The post-test probability of SAP with positive/negative score was 47%/6% for BISAP, 43%/5% for APACHE-II, 48%/5% for Ranson, 40%/12% for SIRS. In 18 studies comparing BISAP, APACHE-II, and Ranson in 6740 patients with pooled pre-test probability of SAP of 18.7%, post-test probability when scores were positive was 48% for BISAP, 46% for APACHE-II, 50% for Ranson. When scores were negative, post-test probability dropped to 7% for BISAP, 6% for Ranson, 5% for APACHE-II. Quality, design, and country of origin of the studies did not explain the observed high heterogeneity. CONCLUSIONS The most commonly used scoring systems to predict SAP perform poorly and do not aid in decision-making.
-
4.
Low-dose computed tomography screening for lung cancer in people with workplace exposure to asbestos.
Maisonneuve, P, Rampinelli, C, Bertolotti, R, Misotti, A, Lococo, F, Casiraghi, M, Spaggiari, L, Bellomi, M, Novellis, P, Solinas, M, et al
Lung cancer (Amsterdam, Netherlands). 2019;:23-30
Abstract
OBJECTIVES Smoking is the main risk factor for lung cancer, but environmental and occupational exposure to carcinogens also increase lung cancer risk. We assessed whether extending low-dose computed tomography (LDCT) screening to persons with occupational exposure to asbestos may be an effective way reducing lung cancer mortality. MATERIALS AND METHODS We conducted a nested case-control study within the COSMOS screening program, assessing past asbestos exposure with a questionnaire. LDCT scans of asbestos-exposed participants were reviewed to assess the presence of pulmonary, interstitial and pleural alterations in comparison to matched unexposed controls. We also performed an exhaustive review, with meta-analysis, of the literature on LDCT screening in asbestos-exposed persons. RESULTS Exposure to asbestos, initially self-reported by 9.8% of COSMOS participants, was confirmed in 216 of 544 assessable cases, corresponding to 2.6% of the screened population. LDCT of asbestos-exposed persons had significantly more pleural plaques, diaphragmatic pleural thickening and pleural calcifications, but similar frequency of parenchymal and interstitial alterations to unexposed persons. From 16 papers, including this study, overall lung cancer detection rates at baseline were 0.81% (95% CI 0.50-1.19) in asbestos-exposed persons, 0.94% (95% CI 0.47-1.53) in asbestos-exposed smokers (12 studies), and 0.11% (95% CI 0.00-0.43) in asbestos-exposed non-smokers (9 studies). CONCLUSION Persons occupationally exposed to asbestos should be monitored to gather more information about risks. Although LDCT screening is effective in the early detection lung cancer in asbestos-exposed smokers, our data suggest that screening of asbestos-exposed persons with no additional risk factors for cancer does is not viable due to the low detection rate.
-
5.
Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis.
Robinson, SM, Rasch, S, Beer, S, Valantiene, I, Mickevicius, A, Schlaipfer, E, Mann, J, Maisonneuve, P, Charnley, RM, Rosendahl, J
Scientific reports. 2019;(1):7318
Abstract
Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28). The serum inflammatory profile was assessed using an MSD 30-plex array. The relationship between clinical variables, inflammatory cytokines and quality of life was determined by a GLM-MANOVA and the individual impact of significant variables evaluated by a second ANOVA. In total, 211 patients with a median age of 53 years were recruited across 5 European centres. Gender, age, nicotine and alcohol abuse were clinical variables associated with altered quality of life. Systemic inflammation with high levels of pro-inflammatory cytokines (Eotaxin, IL-1β, IL-7, IL-8, IL-12/IL-23p40, IL-12p70, IL-13, IL-16, IP-10, MCP-1, MCP-4, MDC, MIP-1a, TARC, TNFß) was associated with diminished quality of life in general and specific domains including pain, physical and cognitive functioning. As conclusion, CP is associated with a systemic inflammatory response that has a negative impact on quality of life and accelerates aging.
-
6.
Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations.
Hadjiliadis, D, Khoruts, A, Zauber, AG, Hempstead, SE, Maisonneuve, P, Lowenfels, AB, ,
Gastroenterology. 2018;(3):736-745.e14
-
-
Free full text
-
Abstract
BACKGROUND & AIMS Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5-10 times greater compared to the general population, and 25-30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations. METHODS The 18-member task force consisted of experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3 workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February-March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159 articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modeling Network. The task force included recommendation statements in the final guideline only if they reached an 80% acceptance threshold. RESULTS The task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unless shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening at age 30 years within 2 years of the transplantation because of the additional risk for colon cancer associated with immunosuppression. CONCLUSIONS These recommendations aim to help CF adults, families, primary care physicians, gastroenterologists, and CF and transplantation centers address the issue of CRC screening. They differ from guidelines developed for the general population with respect to the recommended age of screening initiation, screening method, preparation, and the interval for repeat screening and surveillance.
-
7.
Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.
Alterio, D, Gerardi, MA, Cella, L, Spoto, R, Zurlo, V, Sabbatini, A, Fodor, C, D'Avino, V, Conson, M, Valoriani, F, et al
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2017;(11):971-981
Abstract
PURPOSE Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.
-
8.
Promoting weight loss through diet and exercise in overweight or obese breast cancer survivors (InForma): study protocol for a randomized controlled trial.
Gnagnarella, P, Dragà, D, Baggi, F, Simoncini, MC, Sabbatini, A, Mazzocco, K, Bassi, FD, Pravettoni, G, Maisonneuve, P
Trials. 2016;:363
Abstract
BACKGROUND Most women with breast cancer experience a progressive weight gain during and after treatment. Obesity is associated with an increased risk of recurrence, contralateral breast cancer, and death. Physical activity after cancer diagnosis has been reported to have positive effects on body composition and quality of life. We present the protocol of the InForma study, a trial testing the efficacy of an intervention on weight loss (≥5 % of the baseline body weight) in a group of overweight or obese breast cancer survivors. METHODS/DESIGN This is a four-arm randomized controlled trial. Patients will receive a 6-month intervention and be followed for a further 18 months. Intervention is designed to improve adherence to a healthy diet and/or to increase physical activity, taking advantage of a wrist-based activity monitor. Participants will be recruited among overweight or obese breast cancer patients treated at the European Institute of Oncology, after completion of eventual adjuvant chemotherapy and/or radiotherapy. It is envisaged that 260 patients will be randomized into four arms: Dietary Intervention; Physical Activity Intervention; Physical Activity and Dietary Intervention; and Less Intensive Intervention. Women will be offered individualized counseling consisting of face-to face discussion and phone calls in addition to group meetings. A motivational interviewing approach will be used to encourage health behavior change. All participants will be given a pedometer device to monitor their physical activity. Participants' dietary intake will be repeatedly assessed using a validated food frequency questionnaire. Participants' quality of life and anxiety will be assessed with the Functional Assessment of Cancer Therapy-Breast and the State-Trait Anxiety Inventory questionnaires. Blood samples will be collected at baseline and follow-up visits to assess lipid and hormone profiles. Body composition will be repeatedly assessed using bioelectrical impedance vector analysis for identifying changes of fat and fat-free mass. Women allocated to the less intensive intervention arm will be considered as the control group. DISCUSSION While there is a rising concern about the role of obesity in cancer recurrence and survival, this trial with its multi-arm design, motivational approach and use of a pedometer device will provide important insights regarding the most effective approach in promoting weight control in breast cancer survivors. TRIAL REGISTRATION ISRCTN53325751 (registration date: 16 October 2015); ClinicalTrials.gov NCT02622711 (registration date: 2 December 2015).
-
9.
Predictors of advanced colorectal neoplasia at initial and surveillance colonoscopy after positive screening immunochemical faecal occult blood test.
Botteri, E, Crosta, C, Bagnardi, V, Tamayo, D, Sonzogni, AM, De Roberto, G, de Leone, A, Lowenfels, A, Maisonneuve, P
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2016;(3):321-6
Abstract
BACKGROUND Characteristics such as gender and lifestyle are not taken in account in colorectal cancer screening and surveillance recommendations. AIMS To identify factors associated with advanced neoplasia at initial and surveillance colonoscopy. METHODS In this observational study, 750 individuals with positive faecal occult blood test, aged 50-74 years, underwent a first screening colonoscopy in 2007-2009. We collected anthropometric data as well as data on physical activity, smoking and drinking habits, fruit and vegetable consumption and low-dose aspirin use through a questionnaire. RESULTS At initial colonoscopy advanced neoplasia (n=399, 53.2%) was positively associated with age, male gender, smoking and alcohol drinking, and inversely associated with physical activity, fruit and vegetables consumption and long-term use of aspirin. These 7 factors were used to calculate a risk score, ranging from 0 (no unfavourable characteristics) to 7 (all unfavourable characteristics present), which was significantly associated with advanced neoplasia (odds ratio 1.55 for one point increase, P<0.01). Among the 372 adenoma patients who returned for follow-up surveillance colonoscopy, the score remained associated with advanced neoplasia (odds ratio 1.28 for one point increase, P=0.01). CONCLUSION Besides age and gender, modifiable factors such as lifestyle and aspirin use were associated with the risk of advanced neoplasia at initial and surveillance colonoscopy.
-
10.
Risk factors for pancreatic cancer: a summary review of meta-analytical studies.
Maisonneuve, P, Lowenfels, AB
International journal of epidemiology. 2015;44(1):186-98
-
-
-
Plain language summary
Pancreatic cancer (PC) is one of the four or five most common causes of cancer mortality in developed countries. The aim of this review was to summarize results from pooled analyses and meta-analyses to estimate the fraction of PCs attributable to many different risk factors. A comprehensive review of the literature was carried out by searching for meta-analytical studies on the association between specific risk factors and PC risk or multiple cancer sites. Results indicate that PC has a multifactorial aetiology. All identified factors can be combined into a specific aetiological (the philosophy or study of causation) pathway for PC. The main pathways include insulin resistance (central adiposity, diabetes, metabolic syndrome), inflammation (tobacco, alcohol, pancreatitis), DNA damage (tobacco, red meat) and haemostasis (blood group, history of thrombosis). Authors conclude that about two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.
Abstract
BACKGROUND The aetiology of pancreatic cancer (PC) has been extensively studied and is the subject of numerous meta-analyses and pooled analyses. We have summarized results from these pooled and meta-analytical studies to estimate the fraction of PCs attributable to each of the identified risk factors. METHODS Using a comprehensive strategy, we retrieved 117 meta-analytical or pooled reports dealing with the association between specific risk factors and PC risk. We combined estimates of relative risk and estimates of exposure to calculate the fraction of PCs caused or prevented by a particular exposure. RESULTS Tobacco smoking ('strong' evidence) and Helicobacter pylori infection ('moderate' evidence) are the major risk factors associated with PC, with respective estimated population attributable fractions of 11-32% and 4-25%. The major protective factors are history of allergy ('strong' evidence) and increasing fruit or folate intake ('moderate' evidence), with respective population preventable fractions of 3-7% and 0-12%. CONCLUSIONS We summarized results of 117 meta-analytical or pooled data reports dealing with 37 aetiological exposures, to obtain robust information about the suspected causes of PC. By combining these estimates with their prevalences in the population, we calculated population attributable or population preventable fractions. About two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.