Publications by authors named "M Malvezzi"

127 Publications

European cancer mortality predictions for the year 2021 with focus on pancreatic and female lung cancer.

Ann Oncol 2021 04 21;32(4):478-487. Epub 2021 Feb 21.

Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Background: We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer.

Materials And Methods: We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardised (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021.

Results: We predicted 1 267 000 cancer deaths for 2021 in the EU, corresponding to age-standardised rates of 130.4/100 000 men (-6.6% since 2015) and 81.0/100 000 for women (-4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100 000 in 2021. The breast cancer predicted rate in the EU was 13.3/100 000 (-7.8%). The rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by >10%; trends for other cancer sites were also favourable, except for the pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100 000 in men and 5.6/100 000 in women. Rates for pancreatic cancer in EU men aged 25-49 and 50-64 years declined, respectively, by 10% and 1.8%, while for those aged 65+ years increased by 1.3%. Rates fell for young women only (-3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988.

Conclusion: Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows a sizeable decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for one-third of the total EU cancer deaths, especially in women, who showed less favourable trends.
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http://dx.doi.org/10.1016/j.annonc.2021.01.006DOI Listing
April 2021

Trends in male breast cancer mortality: a global overview.

Eur J Cancer Prev 2021 Jan 18. Epub 2021 Jan 18.

Department of Clinical Sciences and Community Health Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy Department of Epidemiology and Health Services Research, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

Objectives: Recent trends in male breast cancer have been inadequately studied. We updated mortality trends in selected countries and regions worldwide using most recent available data and we predicted figures for 2020.

Methods: We extracted official death certification data for male breast cancer and population estimates from the WHO and the Pan American Health Organization databases, from 2000 to 2017. We computed age-standardized (world population) death rates for selected countries and regions worldwide. We used joinpoint regression analysis to identify significant changes in trends and to predict death numbers and rates for 2020.

Results: In 2015-2017, Central-Eastern Europe had a rate of 2.85/1 000 000, and Russia of 2.22, ranking among the highest. North-Western and Southern Europe, the European Union as a whole and the USA showed rates ranging between 1.5 and 2.0. Lower rates were observed in most Latin American countries, with values below 1.35/1 000 000, in Australia, 1.22, and Japan, 0.58. Between 2000-2004 and 2015-2017, age-adjusted death rates decreased between 10 and 40% in North-Western Europe, Russia, and the USA, and between 1.5 and 25% in the other areas under study, except Latin America (+0.8%). Except for Central-Eastern Europe, predicted rates for 2020 were favourable.

Conclusion: Advancements in management are likely the main drivers of the favourable trends in male breast cancer death rates over the last decades. Delayed diagnosis and limited access to effective care explain the higher mortality in some areas.
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http://dx.doi.org/10.1097/CEJ.0000000000000651DOI Listing
January 2021

Colorectal Cancer Mortality in Young Adults Is Rising in the United States, Canada, United Kingdom, and Australia but Not in Europe and Asia.

Gastroenterology 2021 Apr 6;160(5):1860-1862.e2. Epub 2021 Jan 6.

Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.12.070DOI Listing
April 2021

Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation.

Hematol Transfus Cell Ther 2020 Nov 21. Epub 2020 Nov 21.

Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Introduction: The minimal residual disease (MRD) status plays a crucial role in the treatment of acute lymphoblastic leukemia (ALL) and is currently used in most therapeutic protocols to guide the appropriate therapeutic decision. Therefore, it is imperative that laboratories offer accurate and reliable results through well standardized technical processes by establishing rigorous operating procedures.

Method: Our goal is to propose a monoclonal antibody (MoAb) panel for MRD detection in ALL and provide recommendations intended for flow cytometry laboratories that work on 4-color flow cytometry platforms.

Results And Conclusion: The document includes pre-analytical and analytical procedures, quality control assurance, technical procedures, as well as the information that needs to be included in the reports for clinicians.
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http://dx.doi.org/10.1016/j.htct.2020.09.148DOI Listing
November 2020

Cancer mortality and predictions for 2020 in selected Australasian countries, Russia and Ukraine.

Eur J Cancer Prev 2021 Jan;30(1):1-14

Department of Clinical Sciences and Community Health.

Objectives: Predicted cancer mortality figures are useful for public health planning. We predicted cancer mortality rates in Israel, Hong Kong, Japan, the Philippines, Korea, Australia, Russia and Ukraine for the year 2020 using the most recent available data. We focused on breast cancer.

Methods: We obtained cancer death certification and population data from the WHO and the United Nations Population Division databases. We derived figures for 10 major cancer sites and total cancers over 1970-2017. We predicted numbers of deaths and age-standardized mortality rates for 2020 through joinpoint regression models. We calculated the number of avoided deaths from 1994-2020.

Results: Overall, total cancer mortality is predicted to decline. Russia had the highest all cancers rates in 2020, 151.9/100 000 men and 79.6 women; the Philippines had the lowest rate in men, 78.0/100 000, Korea in women, 47.5. Stomach cancer rates declined over the whole period in all countries considered, colorectal cancer since the late 1990s. Trends for pancreas were inconsistent. Predicted rates for lung and breast cancer were favourable; women from Hong Kong, Korea and Australia had lung cancer death rates higher than breast ones. Predicted rates for uterine, ovarian, prostate and bladder cancers and leukaemias were downward for most countries. Between 1994 and 2020, over 3.3 million cancer deaths were avoided in the considered countries, except for the Philippines where no reduction was observed.

Conclusion: Predicted cancer rates were lower than in the European Union and the USA, even though falls started later and were less marked.
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http://dx.doi.org/10.1097/CEJ.0000000000000639DOI Listing
January 2021

Impact of Lifestyle Variables on Oral Diseases and Oral Health-Related Quality of Life in Children of Milan (Italy).

Int J Environ Res Public Health 2020 09 11;17(18). Epub 2020 Sep 11.

Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20133 Milano, Italy.

A large part of the Italian population doesn't receive adequate information and support on how to maintain oral health. In this observational, cross-sectional, pilot study, we investigated how some lifestyle-related variables affect oral diseases and oral health-related quality of life (OHRQoL) of children attending public-school summer services in Milan. A survey that included questions on children's oral disease, OHRQoL and lifestyle-related factors (feeding habits, oral hygiene protective behaviors, dental coaching and socio-economic and educational status), was administered to the children's caregivers. Data from 296 surveys were analyzed to assess the protective/negative effect of each variable on oral disease and OHRQoL. With respect to disease, the "never" consumption of fruit juice, the use of fluoride toothpaste, higher educational qualification and ISEE (equivalent family income) of those who filled out the form, resulted protective factors. Regarding OHRQoL, the "never" assumption/use of tea bottle, sugared pacifier and fruit juice as well as the use of fluoride toothpaste, a higher educational qualification and ISEE of those who filled out the form, resulted to have protective effects. In conclusion, protective behaviors and socio-economic status affect oral disease and OHRQoL in children of Milan.
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http://dx.doi.org/10.3390/ijerph17186612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559912PMC
September 2020

Cancer mortality in the oldest old: a global overview.

Aging (Albany NY) 2020 Sep 3;12(17):16744-16758. Epub 2020 Sep 3.

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Background: As a higher proportion of adults live beyond 85 years, their cancer burden is expected to increase. While trends among the oldest old are established for major epithelial cancers (breast, prostate, lung, and colorectal cancers), they are less studied for minor cancers. This study describes age trends of cancer mortality, with emphasis on individuals aged 85+ years.

Results: Overall cancer mortality peaked at 85 years old and decreased or stabilized for all countries except the USA, France, and Japan, in which mortality continued to increase after age 85 years. For most countries, cancers of the oesophagus, stomach, liver, and larynx have a similar flat trend patterns across all ages. Bladder and kidney cancers as well as non-Hodgkin lymphoma, multiple myeloma, and leukemia showed a decreasing pattern after 85 years for UK, Germany, Italy and Poland. Lung cancer peaked at 80 years, although the age-specific peak among women did not follow the same pattern among all countries. Breast and prostate cancers increased after 85 years.

Conclusion: Mortality stabilized or decreased after age 85, particularly for non-hormonal cancers. Whether this reflects a true biological levelling of mortality rates, or lower validity of cancer registration among the oldest old, remains open to discussion.

Methods: Completed death data were obtained from the World Health Organization (WHO) for eight countries (2000 to 2014). Age-specific mortality rates were calculated for each 5-year age group above age 64. Joinpoint regression models were used to identify significant changes in mortality trends by age.
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http://dx.doi.org/10.18632/aging.103503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521488PMC
September 2020

Progress in cancer mortality, incidence, and survival: a global overview.

Eur J Cancer Prev 2020 09;29(5):367-381

Department of Clinical Sciences and Community Health.

Cancer mortality has declined over the last three decades in most high-income countries reflecting improvements in cancer prevention, diagnosis, and management. However, there are persisting and substantial differences in mortality, incidence, and survival worldwide. In order to provide an up-to-date overview of trends in mortality, incidence, and survival, we retrieved data from high-quality, population-based cancer registries for all cancers and 10 selected cancer sites in six high-income countries and the European Union. We computed age-standardized (world standard population) mortality and incidence rates, and applied joinpoint regression models. Mortality from all cancers and most common cancer sites has declined over the last 25 years, except for the pancreas and lung (in women). The patterns for incidence are less consistent between countries, except for a steady decrease in stomach cancer in both sexes and lung cancer in men. Survival for all cancers and the selected cancer sites increased in all countries, even if there is still a substantial variability. Although overall cancer death rates continue to decline, incidence rates have been levelling off among men and have been moderately increasing among women. These trends reflect changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are diagnosed early. Population-based cancer incidence and mortality data can be used to focus efforts to decrease the cancer burden and regularly monitor progress towards cancer control goals.
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http://dx.doi.org/10.1097/CEJ.0000000000000594DOI Listing
September 2020

Cohort Analysis of Epithelial Cancer Mortality Male-to-Female Sex Ratios in the European Union, USA, and Japan.

Int J Environ Res Public Health 2020 07 23;17(15). Epub 2020 Jul 23.

Department of Clinical Sciences and Community Health, Universitá degli Studi di Milano, 20133 Milan, Italy.

Objective: To illustrate trends in sex ratios in epithelial cancer mortality in the EU, USA, and Japan, with a focus on age-specific and cohort patterns.

Methods: We obtained certified deaths and resident populations from the World Health Organisation for the period of 1970-2014 for the USA, Japan, and the EU for 12 epithelial cancer sites. From these, we calculated both the age-specific and age-standardised male-to-female mortality sex ratios. We applied an age-period-cohort model to the sex ratios in order to disentangle the effects of age, period of death, and birth cohort.

Results: Age-standardised mortality sex ratios were found to be unfavourable to males, apart from thyroid cancer. The highest standardised rates were in laryngeal cancer: 7·7 in the 1970s in the USA, 17·4 in the 1980s in the EU, and 16·8 in the 2000s in Japan. Cohort patterns likely to be due to excess smoking (1890 cohort) and drinking (1940 cohort) in men were identified in the USA, and were present but less defined in the EU and Japan for the oral cavity, oesophagus, liver, pancreas, larynx, lung, bladder, and kidney.

Conclusion: Mortality sex ratio patterns are partly explained by the differences in exposure to known and avoidable risk factors. These are mostly tobacco, alcohol, and obesity/overweight, as well as other lifestyle-related factors.
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http://dx.doi.org/10.3390/ijerph17155311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432705PMC
July 2020

Childhood cancer mortality trends in Europe, 1990-2017, with focus on geographic differences.

Cancer Epidemiol 2020 08 24;67:101768. Epub 2020 Jun 24.

Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy.

Aim: To monitor trends in childhood cancer mortality in Europe.

Methods: We calculated age-standardized mortality rates per 100,000 children (age 0-14 years) from 1990 to the last available calendar year, for all neoplasms and six main cancers in childhood, in selected European countries and geographic areas, plus the European Union (EU), using data from the World Health Organization database. We carried out a joinpoint regression analysis of mortality trends for all neoplasms, leukaemia and tumours of the nervous system. Results of the joinpoint regression were summarized through annual percent change (APC) for each identified linear segment, and weighted average APC (AAPC) over the whole period.

Results: From 1990 to 2015, childhood total cancer mortality rates dropped by 2.8% per year in the EU, to reach 2.6/100,000 in the latest available calendar years. The greatest declines were in central-eastern countries (AAPCs -3% to -4%). Recent rates ranged between 1.7 and 4.3 deaths/100,000, with the highest values in central-eastern Europe. Leukaemia mortality rates in the EU decreased from 1.6 to 0.6/100,000 in the latest calendar years (AAPC -4%). The deepest declines were registered in central-eastern countries, though they still showed the highest rates (0.9). The lowest leukaemia mortality rates were in northern-western Europe (0.5/100,000), but also in the Czech Republic and Poland. Southern European countries showed comparatively high rates (0.8). Nervous system tumours showed relatively modest falls (AAPC: -1.7% in the EU).

Conclusions: Childhood cancer mortality continued to decline steady in Europe, though geographic differences persist. Further efforts are required to fill the gap, by promoting widespread and rational adoption of currently available treatment protocols.
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http://dx.doi.org/10.1016/j.canep.2020.101768DOI Listing
August 2020

European cancer mortality predictions for the year 2020 with a focus on prostate cancer.

Ann Oncol 2020 05 19;31(5):650-658. Epub 2020 Apr 19.

Department of Clinical Sciences and Community Health, Universitá degli Studi di Milano, Milan, Italy.

Background: Current cancer mortality figures are important for disease management and resource allocation. We estimated mortality counts and rates for 2020 in the European Union (EU) and for its six most populous countries.

Materials And Methods: We obtained cancer death certification and population data from the World Health Organization and Eurostat databases for 1970-2015. We estimated projections to 2020 for 10 major cancer sites plus all neoplasms and calculated the number of avoided deaths over 1989-2020.

Results: Total cancer mortality rates in the EU are predicted to decline reaching 130.1/100 000 men (-5.4% since 2015) and 82.2 in women (-4.1%) in 2020. The predicted number of deaths will increase by 4.7% reaching 1 428 800 in 2020. In women, the upward lung cancer trend is predicted to continue with a rate in 2020 of 15.1/100 000 (higher than that for breast cancer, 13.5) while in men we predicted further falls. Pancreatic cancer rates are also increasing in women (+1.2%) but decreasing in men (-1.9%). In the EU, the prostate cancer predicted rate is 10.0/100 000, declining by 7.1% since 2015; decreases for this neoplasm are ∼8% at age 45-64, 14% at 65-74 and 75-84, and 6% at 85 and over. Poland is the only country with an increasing prostate cancer trend (+18%). Mortality rates for other cancers are predicted to decline further. Over 1989-2020, we estimated over 5 million avoided total cancer deaths and over 400 000 for prostate cancer.

Conclusion: Cancer mortality predictions for 2020 in the EU are favourable with a greater decline in men. The number of deaths continue to rise due to population ageing. Due to the persistent amount of predicted lung (and other tobacco-related) cancer deaths, tobacco control remains a public health priority, especially for women. Favourable trends for prostate cancer are largely attributable to continuing therapeutic improvements along with early diagnosis.
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http://dx.doi.org/10.1016/j.annonc.2020.02.009DOI Listing
May 2020

Exploiting Robot Hand Compliance and Environmental Constraints for Edge Grasps.

Front Robot AI 2019 19;6:135. Epub 2019 Dec 19.

Department of Advanced Robotics, Istituto Italiano di Tecnologia, Genoa, Italy.

This paper presents a method to grasp objects that cannot be picked directly from a table, using a soft, underactuated hand. These grasps are achieved by dragging the object to the edge of a table, and grasping it from the protruding part, performing so-called grasps. This type of approach, which uses the environment to facilitate the grasp, is named Environmental Constraint Exploitation (ECE), and has been shown to improve the robustness of grasps while reducing the planning effort. The paper proposes two strategies, namely and , that are designed to deal with different objects. In the first strategy, the hand is positioned over the object and assumed to stick to it during the sliding until the edge, where the fingers wrap around the object and pick it up. In the second strategy, instead, the sliding motion is performed using pivoting, and thus the object is allowed to rotate with respect to the hand that drags it toward the edge. Then, as soon as the object reaches the desired position, the hand detaches from the object and moves to grasp the object from the side. In both strategies, the hand positioning for grasping the object is implemented using a recently proposed functional model for soft hands, the , whereas the sliding motion on the table is executed by using a hybrid force-velocity controller. We conducted 320 grasping trials with 16 different objects using a soft hand attached to a collaborative robot arm. Experiments showed that the Continuous Slide and Grasp is more suitable for small objects (e.g., a credit card), whereas the Pivot and Re-Grasp performs better with larger objects (e.g., a big book). The gathered data were used to train a classifier that selects the most suitable strategy to use, according to the object size and weight. Implementing ECE strategies with soft hands is a first step toward their use in real-world scenarios, where the environment should be seen more as a help than as a hindrance.
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http://dx.doi.org/10.3389/frobt.2019.00135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805883PMC
December 2019

Cancer mortality predictions for 2019 in Latin America.

Int J Cancer 2020 08 27;147(3):619-632. Epub 2019 Nov 27.

Department of Biomedical and Clinical Sciences, L. Sacco, Università degli Studi di Milano, Milan, Italy.

We estimated mortality figures for 2019 in seven Latin American countries, with focus on breast cancer. We retrieved cancer death certification and population data from the WHO and PAHO databases. We obtained mortality statistics for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela for 1970-2015. We predicted current death numbers and age-standardised (world population) mortality rates using joinpoint regression models. Total cancer mortality is predicted to decline in all countries and both sexes, except Argentinian women. Cuba had the highest all cancer rates for 2019, 136.9/100,000 men and 90.4 women, while Mexico showed the lowest ones, 63.8/100,000 men and 61.9 women. Stomach cancer showed favourable trends over the whole period, while colorectal cancer only recently. Lung cancer rates declined in men, while in women they decreased slightly over the most recent years, only. In Cuban women, lung cancer rates overtook breast cancer ones. Breast cancer showed overall favourable trends, but rates are rising in young women. Prostate and uterine cancer had favourable trends. Pancreas, ovary, bladder and leukaemias showed slightly decreasing trends. Between 1990 and 2019, mortality from all neoplasms is predicted to fall by about 18% in Argentina, 26% in Chile, 14% in Colombia, 17% in Mexico and 13% in Venezuela, corresponding to almost 0.5 million avoided cancer deaths. No decline was observed in Brazil and Cuba. Of concern, the persisting high rates of (cervix) uterus cancer, the high lung cancer rates in Cuba, the possible increases in breast cancer in young women, and the lack of overall declines in Brazil, Cuba and Venezuelan men.
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http://dx.doi.org/10.1002/ijc.32749DOI Listing
August 2020

Reply to: "Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma".

J Hepatol 2019 12 26;71(6):1262-1263. Epub 2019 Sep 26.

Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

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http://dx.doi.org/10.1016/j.jhep.2019.08.033DOI Listing
December 2019

Cancer mortality in Europe in 2015 and an overview of trends since 1990.

Ann Oncol 2019 08;30(8):1356-1369

Departments of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan.

Background: Cancer mortality in Europe has been decreasing since the late 1980s or 1990s in some countries with different patterns in many areas. In this study, we updated trends in cancer mortality in Europe.

Materials And Methods: We extracted data from the World Health Organization mortality database for 24 cancer sites, 36 European countries and the European Union (EU) as a whole over the 1990-2017 period. We computed age-standardized death rates per 100 000 person-years, and we carried out a joinpoint regression analysis of mortality trends from all cancers and selected major neoplasms. The estimated annual percent change (APC) for each identified linear segment, and the weighted average APC (AAPC) over the entire study period were provided as summary measures of the changes in rates over the time period.

Results: In 2015, the age-standardized mortality rates from all cancers in the EU were 137.5 deaths per 100 000 in men and 85.7 in women. Eastern European countries showed the highest rates with values over 150 deaths per 100 000 in men and over 100 deaths per 100 000 in women. Mortality from all cancers in the EU declined annually by 1.5% in men since 2006 and by 0.8% in women since 2007. Most cancer sites showed decreasing trends, with steady declines over the whole period for cancers of stomach, intestines, lung in men, breast and prostate. Unfavourable mortality trends persisted for cancers of liver, lung in women, pancreas, besides skin and kidney in men.

Conclusions: The downward trends in total cancer mortality in Europe still continue over the last decade. However, the trends were less favourable in most eastern European countries. Tobacco control in men (but not in women), improvements in diagnosis and therapy were the main underlying factors of these trends.
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http://dx.doi.org/10.1093/annonc/mdz179DOI Listing
August 2019

Cancer mortality in the elderly in 11 countries worldwide, 1970-2015.

Ann Oncol 2019 08;30(8):1344-1355

Departments of Clinical Sciences and Community Health, Universitá degli Studi di Milano, Milan, Italy. Electronic address:

Background: Population ageing results in an increasing cancer burden in the elderly. We aimed to evaluate time-trends in cancer mortality for adults aged 65 and over for 17 major cancer types and all cancers combined in 11 countries worldwide over the period 1970-2015.

Materials And Methods: We obtained cancer death certification and population figures from the WHO and PAHO databases. We computed age-standardised (world standard population) rates for individuals aged 65 and over, and applied joinpoint regression models.

Results: Age-standardised mortality rates for all cancers combined showed a heterogeneous, but widespread decline. Lung cancer mortality rates have been decreasing among men, and increasing among women. Pancreatic cancer had unfavourable trends in all countries for both sexes. Despite variability across countries, other tobacco-related cancers (except kidney) showed overall favourable trends, except in Poland and Russia. Age-standardised mortality rates from stomach cancer have been declining in all countries for both sexes. Colorectal mortality has been declining, except in Poland and Russia. Liver cancer mortality increased in all countries, except in Japan, France and Italy, which had the highest rates in the past. Breast cancer mortality decreased for most countries, except for Japan, Poland and Russia. Trends for age-standardised uterine cancer rates in the USA, Canada and the UK were increasing over the last decade. Ovarian cancer rates showed declines in most countries. With the exception of Russia, prostate cancer rates showed overall declines. Lymphoid neoplasms rates have been declining in both sexes, except in Poland and Russia.

Conclusion: Over the last decades, age-standardised cancer mortality in the elderly has been decreasing in major countries worldwide and for major cancer sites, with the major exception of lung and uterine cancer in women and liver, pancreatic and kidney cancers in both sexes. Cancer mortality for the elderly in central and eastern Europe remains comparatively high.
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http://dx.doi.org/10.1093/annonc/mdz178DOI Listing
August 2019

CEMP-1 Levels in Periodontal Wound Fluid during the Early Phase of Healing: Prospective Clinical Trial.

Mediators Inflamm 2019 24;2019:1737306. Epub 2019 Feb 24.

Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy.

Objectives: Cementogenesis seems to be significantly compromised during tissue inflammation. In dental practice, surgical procedures are performed with the aim to regenerate periodontium including cementum. However, inflammation that occurs during the initial healing phases after surgery may impair regeneration of this tissues. The aim of the present study was to assess if surgical procedures designed to regenerate periodontium might affect levels of cementum protein-1 (CEMP-1) in periodontal wound fluid during early phase of healing.

Materials And Methods: In 36 patients, 18 intrabony periodontal defects were treated with regenerative therapy (REG group) and 18 suprabony periodontal defects were treated with open flap debridement (OFD group). In the experimental sites, gingival crevicular fluid was collected immediately before surgery, and periodontal wound fluid was collected 4, 7, 14, and 21 days after surgery. CEMP-1 levels were detected by indirect enzyme-linked immunosorbent assay technique.

Results: At the analysis, it resulted that there was a significant average difference in CEMP-1 values between the REG and OFD groups at baseline ( = 0.041), the CEMP-1-modeled average in the OFD group was lower by 0.45 ng/ml. There was a significant trend in CEMP-1 over time, and this trend was different among the 2 groups: the REG group showed a statistically significant rising CEMP-1 trend (0.18 ng/ml a week = 0.012), while the OFD had a trend that was significantly lower (-0.22 ng/ml a week compared to the REG group trend = 0.023), the OFD group lost on average 0.05 ng/ml a week. In REG sites, GCF protein levels resulted also related to clinical parameters.

Conclusions: During the initial inflammatory phase of periodontal healing, CEMP-1 levels decrease regardless of the surgical protocol applied. The surgical procedures used to regenerate periodontal tissue are able to reverse this trend and to induce significant increase of CEMP-1 in periodontal wound fluid after the first week postop.
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http://dx.doi.org/10.1155/2019/1737306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409030PMC
July 2019

Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma.

J Hepatol 2019 07 23;71(1):104-114. Epub 2019 Mar 23.

Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Background & Aims: Intrahepatic (ICC) and extrahepatic cholangiocarcinoma (ECC) have rarely been studied individually, probably due to difficulties in their diagnosis and certification. Mortality trends from these 2 neoplasms have been inconsistent over the last decades. The aim of this study was to analyze worldwide trends in mortality from ICC and ECC in selected countries.

Methods: We extracted death certification data for ICC and ECC, and population estimates from the World Health Organization and Pan American Health Organization databases for 32 selected countries from Europe, the Americas, and Australasia from 1995 to 2016. We computed age-standardized (world population) mortality rates from ICC and ECC, and performed joinpoint regression analysis.

Results: Mortality rates from ICC increased in all countries considered, with a levelling off over recent years in Germany (women), Italy (men), Argentina (men), the USA (men), Hong Kong (men), and Japan (both sexes). The highest rates in 2010-2014 (1.5-2.5/100,000 in men and 1.2-1.7/100,000 in women) were registered in Hong Kong, France, Austria, Spain, the UK, and Australia. The lowest rates (0.2-0.6/100,000 in both sexes) were registered in Latin American and eastern European countries. Mortality from ECC decreased in most of the countries considered, with rates below 1/100,000 in both sexes between 2010 and 2014, with the only exception being Japan (2.8/100,000 in men and 1.4/100,000 in women).

Conclusions: Increasing mortality from ICC was observed globally, due to trends in risk factors and possibly, in part, due to better disease classification. Mortality from ECC levelled off or decreased, most likely following the increased use of laparoscopic cholecystectomy.

Lay Summary: Biliary tract cancers include intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), however there are some differences in their risk factors. Consequently, the distinction between ICC and ECC is important. Over the last few decades, mortality from ICC has tended to rise in several areas of the world, following the increased prevalence of its major risk factors. In contrast, mortality from ECC tended to decrease in most countries, following the increased use of laparoscopic cholecystectomy.
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http://dx.doi.org/10.1016/j.jhep.2019.03.013DOI Listing
July 2019

European cancer mortality predictions for the year 2019 with focus on breast cancer.

Ann Oncol 2019 05;30(5):781-787

Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Background: To overcome the lag with which cancer statistics become available, we predicted numbers of deaths and rates from all cancers and selected cancer sites for 2019 in the European Union (EU).

Materials And Methods: We retrieved cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2014. We obtained estimates for 2019 with a linear regression on number of deaths over the most recent trend period identified by a logarithmic Poisson joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2019.

Results: We estimated about 1 410 000 cancer deaths in the EU for 2019, corresponding to age-standardized rates of 130.9/100 000 men (-5.9% since 2014) and 82.9 women (-3.6%). Lung cancer trends in women are predicted to increase 4.4% between 2014 and 2019, reaching a rate of 14.8. The projected rate for breast cancer was 13.4. Favourable trends for major neoplasms are predicted to continue, except for pancreatic cancer. Trends in breast cancer mortality were favourable in all six countries considered, except Poland. The falls were largest in women 50-69 (-16.4%), i.e. the age group covered by screening, but also seen at age 20-49 (-13.8%), while more modest at age 70-79 (-6.1%). As compared to the peak rate in 1988, over 5 million cancer deaths have been avoided in the EU over the 1989-2019 period. Of these, 440 000 were breast cancer deaths.

Conclusion: Between 2014 and 2019, cancer mortality will continue to fall in both sexes. Breast cancer rates will fall steadily, with about 35% decline in rates over the last three decades. This is likely due to reduced hormone replacement therapy use, improvements in screening, early diagnosis and treatment. Due to population ageing, however, the number of breast cancer deaths is not declining.
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http://dx.doi.org/10.1093/annonc/mdz051DOI Listing
May 2019

European cancer mortality predictions for the year 2019 with focus on breast cancer.

Ann Oncol 2019 05;30(5):781-787

Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Background: To overcome the lag with which cancer statistics become available, we predicted numbers of deaths and rates from all cancers and selected cancer sites for 2019 in the European Union (EU).

Materials And Methods: We retrieved cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2014. We obtained estimates for 2019 with a linear regression on number of deaths over the most recent trend period identified by a logarithmic Poisson joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2019.

Results: We estimated about 1 410 000 cancer deaths in the EU for 2019, corresponding to age-standardized rates of 130.9/100 000 men (-5.9% since 2014) and 82.9 women (-3.6%). Lung cancer trends in women are predicted to increase 4.4% between 2014 and 2019, reaching a rate of 14.8. The projected rate for breast cancer was 13.4. Favourable trends for major neoplasms are predicted to continue, except for pancreatic cancer. Trends in breast cancer mortality were favourable in all six countries considered, except Poland. The falls were largest in women 50-69 (-16.4%), i.e. the age group covered by screening, but also seen at age 20-49 (-13.8%), while more modest at age 70-79 (-6.1%). As compared to the peak rate in 1988, over 5 million cancer deaths have been avoided in the EU over the 1989-2019 period. Of these, 440 000 were breast cancer deaths.

Conclusion: Between 2014 and 2019, cancer mortality will continue to fall in both sexes. Breast cancer rates will fall steadily, with about 35% decline in rates over the last three decades. This is likely due to reduced hormone replacement therapy use, improvements in screening, early diagnosis and treatment. Due to population ageing, however, the number of breast cancer deaths is not declining.
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http://dx.doi.org/10.1093/annonc/mdz051DOI Listing
May 2019

Cancer mortality and predictions for 2018 in selected Australasian countries and Russia.

Ann Oncol 2019 01;30(1):132-142

Departments of Clinical Sciences and Community Health. Electronic address:

Background: Predicted cancer mortality figures and rates are useful for public health planning.

Materials And Methods: We retrieved cancer death certification data for 10 major cancer sites and total cancers from the World Health Organization (WHO) database and population data from WHO and United Nations Population Division databases. We obtained figures for Russia, Israel, Hong Kong, Japan, the Philippines, Korea, and Australia in 1970-2015. We predicted numbers of deaths by age group and age-standardized rates (world population) for 2018 by applying a linear regression to mortality data of each age group over the most recent trend segment identified by a joinpoint regression model.

Results: Russia had the highest predicted total cancer mortality rates, 158.5/100 000 men and 84.1/100 000 women. Men in the Philippines showed the lowest rates for 2018 (84.6/100 000) and Korean males the most favourable predicted fall (21% between 2012 and 2018). Women in Korea had the lowest total cancer predicted rate (52.5/100 000). Between 1993 and 2018, i.e. by applying the 1993 rates to populations in subsequent years, a substantial number of cancer deaths was avoided in Russia (1 000 000 deaths, 821 000 in men and 179 000 in women), Israel (40 000 deaths, 21 000 in men and 19 000 in women), Hong Kong (63 000 deaths, 40 000 in men and 23 000 in women), Japan (651 000 deaths, 473 000 in men and 178 000 in women), Korea (327 000 deaths, 250 000 in men and 77 000 in women), and Australia (181 000 deaths, 125 000 in men and 56 000 in women). No appreciable reduction in cancer deaths was found in the Philippines.

Conclusion: Overall, we predicted falls in cancer mortality. However, these are less marked and later compared with the European Union and United States. Substantial numbers of deaths were avoided in all countries considered except the Philippines. Lung cancer mortality remains exceedingly high in Russian men, despite recent falls.
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http://dx.doi.org/10.1093/annonc/mdy489DOI Listing
January 2019

Low-level fluoride exposure reduces glycemia in NOD mice.

Ecotoxicol Environ Saf 2019 Jan 30;168:198-204. Epub 2018 Oct 30.

Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, 17012-901 Bauru, São Paulo, Brazil. Electronic address:

Water fluoridation is the most widespread measure to prevent dental caries but its relationship with the development of type-1 diabetes (T1D), which has been increasing by 2-5% worldwide, is not quite well understood.

Aim: This study evaluated if fluoride (F) administered in the drinking water can prevent or reduce the development of T1D in non-obese diabetic (NOD) mice, as well as to explore the underlying mechanisms.

Materials And Methods: Twenty-four weaning NOD mice received water containing 0, 10 or 50 ppm F for 21 days. Plasma glucose and insulin were analyzed. Quantitative proteomic analysis was conducted in the liver and gastrocnemius muscle.

Results: Animals treated with 10 ppm F had significantly lower glucose levels than the control group, but there was no significant difference among the groups in relation to insulin. The % of β-cell function was significantly higher in the 10 ppm F group. Changes in the proteomic profile of muscle and liver were seen among the groups. In the muscle, the 10 ppm F group presented, when compared with control, increased expression of proteins involved in energy metabolism. The 50 ppm F group, compared with control, presented increased expression of proteins related to muscle contraction, differentiation of brown adipose tissue and apoptosis. For the liver, the 10 ppm F group had increase in proteins involved in energy metabolism and protein synthesis, in respect to control. There was also an increase in isoforms of Glutathione S transferase, which was confirmed by Western blotting. In the group treated with 50 ppm F, proteins related to ROS metabolism and energetic metabolism were altered.

Conclusion: Increased expression of antioxidant proteins by treatment with low F concentration may possibly help to explain protection against the development of T1D, which should be better explored in future mechanistic studies.
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http://dx.doi.org/10.1016/j.ecoenv.2018.10.055DOI Listing
January 2019

International Analysis of Age-Specific Mortality Rates From Mesothelioma on the Basis of the International Classification of Diseases, 10th Revision.

J Glob Oncol 2018 09 11;4:1-15. Epub 2017 Aug 11.

Paolo Boffetta, Icahn School of Medicine at Mount Sinai, New York, NY; Matteo Malvezzi, Eva Negri, and Carlo La Vecchia, University of Milan, Milan; and Enrico Pira, University of Turin, Turin, Italy.

Past analyses of mortality data from mesothelioma relied on unspecific codes, such as pleural neoplasms. We calculated temporal trends in age-specific mortality rates in Canada, the United States, Japan, France, Germany, Italy, the Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th version of the International Classification of Diseases, which includes a specific code for mesothelioma. Older age groups showed an increase (in the United States, a weaker decrease) during the study period, whereas in young age groups, there was a decrease (in Poland, a weaker increase, starting, however, from low rates). Results were consistent between men and women and between pleural and peritoneal mesothelioma, although a smaller number of events in women and for peritoneal mesothelioma resulted in less precise results. The results show the heterogeneous effect of the reduction of asbestos exposure on different age groups; decreasing mortality in young people reflects reduced exposure opportunity, and increasing mortality in the elderly shows the long-term effect of early exposures.
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http://dx.doi.org/10.1200/JGO.2017.010116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180783PMC
September 2018

Projections in Breast and Lung Cancer Mortality among Women: A Bayesian Analysis of 52 Countries Worldwide.

Cancer Res 2018 08;78(15):4436-4442

Grupo de Evaluación de Determinantes de Salud y Políticas Sanitarias, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain.

Among women, lung cancer mortality rates have surpassed those for breast cancer in several countries. This reflects the breast cancer mortality declines due to access to screening and effective treatment alongside the entrance of certain countries in stages of the tobacco epidemic in which smoking becomes more prevalent in women. In this study, we project lung and breast cancer mortality until 2030 in 52 countries. Cancer mortality data were obtained from the WHO Mortality Database. Age-standardized mortality rates (ASMR), per 100,000, were calculated (direct method) for 2008 to 2014 and projected for the years 2015, 2020, 2025, and 2030 using a Bayesian log-linear Poisson model. In 52 countries studied around the world, between 2015 and 2030, the median ASMR are projected to increase for lung cancer, from 11.2 to 16.0, whereas declines are expected for breast cancer, from 16.1 to 14.7. In the same period, the ASMR will decrease in 36 countries for breast cancer and in 15 countries for lung cancer. In half of the countries analyzed, and in nearly three quarters of those classified as high-income countries, the ASMR for lung cancer has already surpassed or will surpass the breast cancer ASMR before 2030. The mortality for lung and breast cancer is higher in high-income countries than in middle-income countries; lung cancer mortality is lower in the latter because the tobacco epidemic is not yet widespread. Due to these observed characteristics of lung cancer, primary prevention should still be a key factor to decrease lung cancer mortality. The mortality for lung and breast cancer is projected to be higher in high-income countries than in middle-income countries, where lung cancer mortality is expected to surpass breast cancer mortality before 2030. .
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http://dx.doi.org/10.1158/0008-5472.CAN-18-0187DOI Listing
August 2018

Relation between mortality trends of cardiovascular diseases and selected cancers in the European Union, in 1970-2017. Focus on cohort and period effects.

Eur J Cancer 2018 11 17;103:341-355. Epub 2018 Jul 17.

Department of Clinical Sciences and Community Health, Universitá Degli Studi di Milano, Milan, Italy. Electronic address:

Aim: To characterise mortality trends from major non-communicable diseases in the European Union (EU) analysing data from the World Health Organization (WHO) Mortality Database.

Methods: We obtained EU population and death certification data for major non-communicable diseases, i.e. seven cancer sites (stomach, intestine, pancreas, lung, breast, prostate and haematopoietic), total cancers, coronary heart diseases (CHDs) and cerebrovascular diseases (CVDs) from the WHO Mortality Database over the 1970 and 2012 period. We computed age-standardised rates (world standard population) and applied joinpoint regression models to identify temporal trends and age period cohort (APC) models to disentangle the effects of age, period of death and cohort of birth on mortality.

Results: In 2012, 2.4 million deaths were recorded in the EU (1.3 million from cancers and 1.1 million from CHD and CVD combined). Over the last decade, mortality from cancer fell by 14% in men and 8% in women, resulting in age-standardised rates of 144 and 88/100,000 persons, respectively, in 2012. The only exceptions to the general downward trends were pancreatic cancer and female lung cancer. Both cardiovascular diseases mortality fell over 35% in both sexes with rates of 60 and 28/100,000 for CHD, and of 30 and 23/100,000 for CVD, in men and women, respectively, in 2012.

Conclusions: Overall trends in mortality rates from non-communicable diseases in the EU were favourable, and the joinpoint and APC models indicated these trends are likely to continue in the near future. Lack of progress in tobacco-related mortality in women underlines the importance of female-specific anti-tobacco policies.
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http://dx.doi.org/10.1016/j.ejca.2018.06.018DOI Listing
November 2018

Out-of-the-groove transport of lipids by TMEM16 and GPCR scramblases.

Proc Natl Acad Sci U S A 2018 07 20;115(30):E7033-E7042. Epub 2018 Jun 20.

Department of Anesthesiology, Weill Cornell Medical College, New York, NY 10065;

Phospholipid scramblases externalize phosphatidylserine to facilitate numerous physiological processes. Several members of the structurally unrelated TMEM16 and G protein-coupled receptor (GPCR) protein families mediate phospholipid scrambling. The structure of a TMEM16 scramblase shows a membrane-exposed hydrophilic cavity, suggesting that scrambling occurs via the ‟credit-card" mechanism where lipid headgroups permeate through the cavity while their tails remain associated with the membrane core. Here we show that afTMEM16 and opsin, representatives of the TMEM16 and GCPR scramblase families, transport phospholipids with polyethylene glycol headgroups whose globular dimensions are much larger than the width of the cavity. This suggests that transport of these large headgroups occurs outside rather than within the cavity. These large lipids are scrambled at rates comparable to those of normal phospholipids and their presence in the reconstituted vesicles promotes scrambling of normal phospholipids. This suggests that both large and small phospholipids can move outside the cavity. We propose that the conformational rearrangements underlying TMEM16- and GPCR-mediated credit-card scrambling locally deform the membrane to allow transbilayer lipid translocation outside the cavity and that both mechanisms underlie transport of normal phospholipids.
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http://dx.doi.org/10.1073/pnas.1806721115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065010PMC
July 2018

Known structures and unknown mechanisms of TMEM16 scramblases and channels.

J Gen Physiol 2018 07 18;150(7):933-947. Epub 2018 Jun 18.

Department of Biochemistry, Weill Cornell Medical School, New York, NY

The TMEM16 family of membrane proteins is composed of both Ca-gated Cl channels and Ca-dependent phospholipid scramblases. The functional diversity of TMEM16s underlies their involvement in numerous signal transduction pathways that connect changes in cytosolic Ca levels to cellular signaling networks. Indeed, defects in the function of several TMEM16s cause a variety of genetic disorders, highlighting their fundamental pathophysiological importance. Here, we review how our mechanistic understanding of TMEM16 function has been shaped by recent functional and structural work. Remarkably, the recent determination of near-atomic-resolution structures of TMEM16 proteins of both functional persuasions has revealed how relatively minimal rearrangements in the substrate translocation pathway are sufficient to precipitate the dramatic functional differences that characterize the family. These structures, when interpreted in the light of extensive functional analysis, point to an unusual mechanism for Ca-dependent activation of TMEM16 proteins in which substrate permeation is regulated by a combination of conformational rearrangements and electrostatics. These breakthroughs pave the way to elucidate the mechanistic bases of ion and lipid transport by the TMEM16 proteins and unravel the molecular links between these transport activities and their function in human pathophysiology.
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http://dx.doi.org/10.1085/jgp.201711957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028493PMC
July 2018