Increasing Annual Cancer Incidence in Patients Age 20-49 Years: A Real-Data Study.

PURPOSE: Data from population-based studies have shown an increased incidence of certain types of neoplasms in patients younger than 50 years (early-onset cancer [EOC]); however, little information is derived from other real-world data sources. In a nonpopulation registry, we analyzed changes in the incidence of several neoplasms in successive generations. METHODS: This cross-sectional study included all patients with a cancer diagnosis registered in one university hospital in Málaga, Spain, between 1998 and 2021, and 18 neoplasms were analyzed. For each neoplasm, the proportion of patients younger than 50 years and age 50 years and older (late-onset cancer [LOC]) of the total number of patients diagnosed each year was determined. In addition, the age limit was lowered to 45-40 years. Changes in these proportions between each year and the following year were assessed by calculating the annual percentage change (APC), and a final assessment of these changes was performed by determining the average APC (AAPC). RESULTS: Of the 24,596 patients, 5,466 (22.2%) had EOC, and 19,130 (77.8%) had LOC. The incidence of all tumors increased throughout the study period in both age groups. The AAPC increase was higher in patients with EOC than in those with LOC for the following neoplasms: head and neck (6.1% v 4.6%), colon (11.0% v 8.2%), testicular (16.3% v -13.1%), non-Hodgkin lymphoma (8.4% v 5.9%), rectum (16.1% v 6.8%), kidney (27.8% v 20.1%), and sarcoma (43.4% v 28.6%). This increase was confirmed in patients younger than 45 years and 40 years. CONCLUSION: Our results are consistent with the data published for most tumor sites analyzed. This global public health problem requires the utmost attention to decrease excess cancer in young patients.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Health, economic and social burden of tobacco in Latin America and the expected gains of fully implementing taxes, plain packaging, advertising bans and smoke-free environments control measures: a modelling study.

OBJECTIVE: To investigate the tobacco-attributable burden on disease, medical costs, productivity losses and informal caregiving; and to estimate the health and economic gains that can be achieved if the main tobacco control measures (raising taxes on tobacco, plain packaging, advertising bans and smoke-free environments) are fully implemented in eight countries that encompass 80% of the Latin American population. DESIGN: Markov probabilistic microsimulation economic model of the natural history, costs and quality of life associated with the main tobacco-related diseases. Model inputs and data on labour productivity, informal caregivers' burden and interventions' effectiveness were obtained through literature review, surveys, civil registrations, vital statistics and hospital databases. Epidemiological and economic data from January to October 2020 were used to populate the model. FINDINGS: In these eight countries, smoking is responsible each year for 351 000 deaths, 2.25 million disease events, 12.2 million healthy years of life lost, US$22.8 billion in direct medical costs, US$16.2 billion in lost productivity and US$10.8 billion in caregiver costs. These economic losses represent 1.4% of countries' aggregated gross domestic products. The full implementation and enforcement of the four strategies: taxes, plain packaging, advertising bans and smoke-free environments would avert 271 000, 78 000, 71 000 and 39 000 deaths, respectively, in the next 10 years, and result in US$63.8, US$12.3, US$11.4 and US$5.7 billions in economic gains, respectively, on top of the benefits being achieved today by the current level of implementation of these measures. CONCLUSIONS: Smoking represents a substantial burden in Latin America. The full implementation of tobacco control measures could successfully avert deaths and disability, reduce healthcare spending and caregiver and productivity losses, likely resulting in large net economic benefits.

Budget impact analysis of transurethral water vapor therapy for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in the Spanish national healthcare system.

BACKGROUND: Several surgical treatments are available for managing lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Water vapor thermal therapy (WVTT) is a new minimally invasive therapy. This study estimates the budget impact of introducing WVTT for LUTS/BPH into the Spanish health care system. METHODS: A model simulated the evolution of men over 45 years of age with moderate-severe LUTS/BPH after surgical treatment, over a 4-year time horizon, from the Spanish public health care service´s perspective. The technologies in scope included those most used in Spain: WVTT, transurethral resection (TURP), photoselective laser vapourization (PVP) and holmium laser enucleation (HoLEP). Transition probabilities, adverse events and costs were identified from the scientific literature and validated by a panel of experts. Sensitivity analyses were performed by varying the most uncertain parameters. RESULTS: Per intervention, WVTT resulted in savings of €3,317, €1,933 and €2,661 compared to TURP, PVP and HoLEP. Over a 4-year time horizon, when performed in 10% of the cohort of 109,603 Spanish males with LUTS/BPH, WVTT saved €28,770,125 against the scenario without WVTT availability. CONCLUSIONS: WVTT could reduce the cost of managing LUTS/BPH, increase the quality of health care and reduce the length of procedure and hospital stay.

Transurethral water vapor therapy for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a cost-minimization and budget impact analysis from an Italian healthcare perspective.

BACKGROUND: The aim of this study was to compare the costs and budget impact of adopting water vapor thermal therapy with the Rezum™ System, for treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) to transurethral resection of the prostate (TURP), from an Italian hospital healthcare perspective. METHODS: A Markov model (4-year time horizon, 3-month cycle length), developed to support a submission to the National Institute of Health and Care Excellence (NICE) in England, was adapted to an Italian payer perspective. A cost minimization analysis was conducted, assuming equal efficacy between both therapies. Net difference in costs per patient was reported, considering procedure, adverse events and retreatment costs. Probabilistic and deterministic sensitivity analyses considered the uncertainty of the results. Population data and market share distribution assumptions were applied to a cohort of Italian patients treated in one year to report the budget and capacity impact of increased use of Rezum. RESULTS: Over 4 years, the costs per patient with Rezum were €2072 compared to €2836 with TURP, resulting in net savings of €764. Sensitivity analyses showed that this conclusion was robust. Replacing 10% of TURP procedures with Rezum generates cost-savings of € 7,139,549 over 4 years and saves 4671 theatre hours and 26,856 bed days in one year. Replacing 30% of BPH surgical procedures with Rezum generates cost-savings to € 21,418,647 over 4 years, saves 14,012 theatre hours and 80,567 bed-days in one year. CONCLUSIONS: This analysis demonstrates that Rezum is highly likely to be cost-saving compared to TURP from an Italian hospital healthcare perspective.

Impact of orange essential oil on enteric methane emissions of heifers fed bermudagrass hay.

In this study, the effects of orange essential oil (OEO) on the rumen fermentation, nutrient utilization, and methane (CH4) emissions of beef heifers fed a diet of bermudagrass (Cynodon dactylon) were examined. In addition, in vitro and in situ experiments were conducted. The in vitro experiment consisted of three treatments: control (CTL, no OEO), OEO1 (0.25% OEO), and OEO2 (0.5% OEO). The forage to concentrate ratio was 70:30 (dry matter [DM] basis) in all treatments. No changes in pH, proportions of volatile fatty acids, and the acetate:propionate ratio were observed (P > 0.05). The addition of 0.25% OEO resulted in a reduction in CH4 production (mL/g) relative to the control (P < 0.05). In the in situ experiment, 5 g of total mixed ration (CTL, OEO1, and OEO2) were incubated for 6, 12, 24, 48, and 72 h. Potential and effective degradability were not affected by OEO supplementation (P > 0.05). In the in vivo study, six crossbred beef heifers (Bos indicus × Bos taurus), fitted with rumen cannulas, were assigned to three different treatments: no additive (CTL), 0.25% OEO (OEO1), and 0.5% OEO (OEO2) in a replicated 3 × 3 Latin square (21-day periods). Heifers were fed at 2.8% body weight. In vivo CH4 production was measured in open-circuit respiration chambers. Reductions in gross energy consumption, apparent total tract digestibility, and rumen valerate concentration were observed for OEO2 compared to the control (P < 0.05). Additionally, decreases in CH4 emissions (g/day; P < 0.05) and CH4 (MJ gross energy intake/day; P < 0.05) were observed in response to supplementation of 0.5% OEO as compared to the CTL treatment. Thus, supplementation of 0.5% OEO reduced CH4 emissions (g/day) by 12% without impacting the DM intake of heifers fed bermudagrass hay as a basal ration.

Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study.

The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of -17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases; 0.5% increase) or 2017 and 2019 (2909 new cases; 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (-26.1%), colorectal neoplasms (-16.9%), and head and neck tumors (-19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.

Effect of Chitosan and Naringin on Enteric Methane Emissions in Crossbred Heifers Fed Tropical Grass.

In order to meet consumer needs, the livestock industry is increasingly seeking natural feed additives with the ability to improve the efficiency of nutrient utilization, alternatives to antibiotics, and mitigate methane emissions in ruminants. Chitosan (CHI) is a polysaccharide with antimicrobial capability against protozoa and Gram-positive and -negative bacteria, fungi, and yeasts while naringin (NA) is a flavonoid with antimicrobial and antioxidant properties. First, an in vitro gas production experiment was performed adding 0, 1.5, 3.0 g/kg of CHI and NA under a completely randomized design. The substrate containing forage and concentrate in a 70:30 ratio on a dry matter (DM) basis. Compounds increased the concentration of propionic acid, and a significant reduction in methane production was observed with the inclusion of CHI at 1.5 g/kg in in vitro experiments (p < 0.001). In a dry matter rumen degradability study for 96 h, there were no differences in potential and effective degradability. In the in vivo study, six crossbred heifers fitted with rumen cannulas were assigned to a 6 × 6 Latin square design according to the following treatments: control (CTL), no additive; chitosan (CHI1, 1.5 g/kg DMI); (CHI2, 3.0 g/kg DMI); naringin (NA1, 1.5 g/kg DMI); (NA2, 3.0 g/kg DMI) and a mixture of CHI and NA (1.5 + 1.5 g/kg DMI) given directly through the rumen cannula. Additives did not affect rumen fermentation (p > 0.05), DM intake and digestibility of (p > 0.05), and enteric methane emissions (p > 0.05). CHI at a concentration of 1.5 g/kg DM in in vitro experiments had a positive effect on fermentation pattern increasing propionate and reduced methane production. In contrast, in the in vivo studies, there was not a positive effect on rumen fermentation, nor in enteric methane production in crossbred heifers fed a basal ration of tropical grass.

Reduction in the in vitro ruminal methane production with the inclusion of Cucurbita foetidissima / Reducción en la producción ruminal de metano in vitro con la inclusión de Cucurbita foetidissima

ABSTRACT Objective. This research aimed to evaluate the inclusion of Cucurbita foetidissima (BG) leaves as a partial or total substitution of alfalfa hay (AH) in beef cattle diets on in vitro methane output, gas kinetics and volatile fatty acids production. Materials and Methods. Five experimental treatments were formulated with the inclusion of BG as alfalfa hay (AH) substitute at 0, 25, 50, 75 and 100% in experimental treatments denominated CON (control), BG25, BG50, BG75 and BG100, respectively. Results. Lignin and organic matter decreased with BG inclusion (p<0.05). However, NDF, CT and TPC increased with higher levels of BG (p<0.05). Maximum gas production diminished with BG inclusion (p<0.05); whereas, microbial protein production, specific gas production rate and latency period were not affected (p>0.05). Methane production decreased linearly with BG inclusion (p<0.05). Nevertheless, CO2 production showed no changes with inclusion of graded levels of BG in the experimental treatments (p>0.05). Additionally, acetate and butyrate were not affected by BG inclusion (p>0.05); although, propionate increased linearly among treatments (p<0.05). Furthermore, inclusion of 75% of BG reduced 31% in vitro methane production without changes in CO2 production, suggesting an inhibition of endogenous methanogenesis. Conclusions. These results promote the inclusion of BG leaves as a potential and environmentally friendly forage source for beef cattle feeding.

RESUMEN Objetivo. El objetivo de este estudio fue evaluar la inclusión de hojas de Cucurbita foetidissima (BG) como sustituto parcial o total de la alfafa (AH) en la dieta de ganado de engorda sobre la cinética de producción de gas y producción ruminal in vitro de metano y ácidos grasos volátiles. Materiales y Métodos. Se formularon cinco dietas con la inclusión de BG como sustituto de heno de alfalfa a 0, 25, 50, 75 y 100% en los tratamientos experimentales que se denominaron CON (control), BG25, BG50, BG75 y BG100, respectivamente. Resultados. La lignina y la materia orgánica disminuyeron con la inclusión de BG (p<0.05). La máxima producción de gas disminuyó con la inclusión de BG (p<0.05); mientras que la producción de proteína microbiana, la tasa específica de producción de gas y el tiempo de latencia no mostraron cambios(p>0.05). La producción de metano disminuyó linealmente con la inclusión de BG (p<0.05). No obstante, la producción de CO2 no mostró cambios con la inclusión de BG en los tratamientos (p<0.05). Adicionalmente, el acetato y el butirato no fueron afectados por la inclusión de BG (p>0.05); a pesar de que el propionato se incrementó linealmente (p<0.05). Además, la inclusión de BG en un 75% redujo la producción de metano 31% sin afectar la producción de CO2, lo que sugiere una inhibición de la metanogenesis endógena. Conclusiones. Estos resultados promueven la inclusión de hojas de BG como una fuente de forraje potencial y amigable con el ambiente en la alimentación de ganado de engorda.

Impact of Tumor LINE-1 Methylation Level and Neoadjuvant Treatment and Its Association with Colorectal Cancer Survival.

Recent studies suggest that long-interspersed nucleotide element-1 (LINE-1) hypomethylation is commonly found in colorectal cancer (CRC), and is associated with worse prognosis. However, the utility of LINE-1 methylation on the prognosis of CRC is still controversial, and may be due to the fact that some clinical and pathological features may affect LINE-1 methylation. Thus, the aim of this study was to assess the prognostic value of tumor LINE-1 methylation in CRC, through their association with the CRC clinical and pathological characteristics. Survival of sixty-seven CRC patients was evaluated according to the median of tumor LINE-1 methylation, as well as pathological and oncological variables. We also studied the association between LINE-1 methylation and pathological features, and finally, we assessed the overall and disease-free survival of LINE1 methylation, stratified by neoadjuvant treatment and further checked by multivariate Cox regression to assess the statistical interactions. LINE-1 was hypomethylated in the CRC tumor with respect to the tumor adjacent-free area (p < 0.05), without association with any other clinical and oncological features, nor with overall and disease-free survival rates for CRC. Relevantly, in neoadjuvant treatment, LINE-1 methylation was associated with survival rates. Thus, disease-free and overall survival rates of treated CRC patients were worse in the hypomethylated LINE-1 tumors than those with normal LINE-1 methylation (p = 0.004 and 0.0049, respectively). Indeed, LINE-1 was hypermethylated more in the treated patients than in the non-treated patients (p < 0.05). The present study showed that tumor LINE-1 hypomethylation was associated with worse survival rates in only treated patients. Our data suggest an interactive effect of neoadjuvant treatment and tumor LINE-1 methylation, which could be a specific-tissue biomarker to predict survival of the treated patients, and help to personalize treatment in CRC.

The health and economic burden of smoking in 12 Latin American countries and the potential effect of increasing tobacco taxes: an economic modelling study.

BACKGROUND: Worldwide, smoking tobacco causes 7 million deaths annually, and this toll is expected to increase, especially in low-income and middle-income countries. In Latin America, smoking is a leading risk factor for death and disability, contributes to poverty, and imposes an economic burden on health systems. Despite being one of the most effective measures to reduce smoking, tobacco taxation is underused and cigarettes are more affordable in Latin America than in other regions. Our aim was to estimate the tobacco-attributable burden on mortality, disease incidence, quality of life lost, and medical costs in 12 Latin American countries, and the expected health and economic effects of increasing tobacco taxes. METHODS: In this modelling study, we developed a Markov probabilistic microsimulation economic model of the natural history, medical costs, and quality-of-life losses associated with the most common tobacco-related diseases in 12 countries in Latin America. Data inputs were obtained through a literature review, vital statistics, and hospital databases from each country: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Mexico, Paraguay, Peru, and Uruguay. The main outcomes of the model are life-years, quality-adjusted life-years, disease events, hospitalisations, disease incidence, disease cost, and healthy years of life lost. We estimated direct medical costs for each tobacco-related disease included in the model using a common costing methodology for each country. The disease burden was estimated as the difference in disease events, deaths, and associated costs between the results predicted by the model for current smoking prevalence and a hypothetical cohort of people in each country who had never smoked. The model estimates the health and financial effects of a price increase of cigarettes through taxes, in terms of disease and health-care costs averted, and increased tax revenues. FINDINGS: In the 12 Latin American countries analysed, we estimated that smoking is responsible for approximately 345 000 (12%) of the total 2 860 921 adult deaths, 2·21 million disease events, 8·77 million healthy years of life lost, and $26·9 billion in direct medical costs annually. Health-care costs attributable to smoking were estimated to represent 6·9% of the health budgets of these countries, equivalent to 0·6% of their gross domestic product. Tax revenues from cigarette sales cover 36·0% of the estimated health expenditures caused by smoking. We estimated that a 50% increase in cigarette price through taxation would avert more than 300 000 deaths, 1·3 million disease events, gain 9 million healthy life-years, and save $26·7 billion in health-care costs in the next 10 years, with a total economic benefit of $43·7 billion. INTERPRETATION: Smoking represents a substantial health and economic burden in these 12 countries of Latin America. Tobacco tax increases could successfully avert deaths and disability, reduce health-care spending, and increase tax revenues, resulting in large net economic benefits. FUNDING: International Development Research Centre (IDRC), Canada.

Carga de enfermedad atribuible al uso de tabaco en Colombia y potenciales beneficios sanitarios y económicos del aumento del precio del cigarrillo mediante impuestos / Disease burden attributable to smoking in Colombia and potential economic and health benefits of price increase through taxes

Resumen Objetivo: estimar la carga de enfermedad asociada al consumo de tabaco en Colombia y evaluar el potencial efecto sanitario y económico del aumento de precio en los cigarrillos mediante impuestos. Materiales y métodos: se diseñó un modelo de simulación de Monte Cario de primer orden que incorporó la historia natural, los costos y la calidad de vida de enfermedades relacionadas con el consumo de tabaco en adultos. Se estimó el impacto en la prevalencia de tabaquismo y en la recaudación de diferentes escenarios de aumento de precio a través de impuestos. Resultados: en Colombia cada año mueren 32.088 personas como consecuencia del consumo de cigarrillo y pueden atribuírsele los siguientes porcentajes: el 16% de las muertes cardiovasculares, el 13% de las producidas por accidentes cerebrovasculares, el 77% de las muertes ocasionadas por enfermedad pulmonar obstructiva crónica y el 80% de las muertes por cáncer de pulmón. Las enfermedades relacionadas con el cigarrillo representan un costo directo anual al sistema de salud de más de 4,5 billones de pesos, mientras la recaudación impositiva por la venta de cigarrillos apenas logra cubrir un 10% de este gasto. Un aumento en el precio de los cigarrillos del 50% podría evitar, en un horizonte de 10 años, más de 45.000 muertes y generar recursos por 8 billones por ahorro en gastos sanitarios y aumento de recaudación. Conclusiones: la carga de enfermedad y el costo para el sistema de salud asociados al consumo de tabaco son muy elevados en Colombia. Un aumento del precio de los cigarrillos a través de los impuestos tendría importantes beneficios tanto sanitarios como económicos.

Abstract Objective: to estimate the burden of disease associated with tobacco consumption in Colombia and to evaluate the potential health and economic effect of the price increase in cigarettes through taxes. Materials and methods: to estimate the burden of disease, a first-order Monte Carlo simulation model was designed that incorporated the natural history, costs and quality of life of diseases related to tobacco consumption in adults. A tax model was designed to calculate the impact on the prevalence of smoking and on the collection of different price increase scenarios. Results: according to the proposed model, it can be estimated that in Colombia 26,464 people die every year as a result of cigarette smoking. 13% of cardiovascular deaths, 13% of those caused by strokes, 77% of deaths caused by chronic lung disease and 81 % of deaths from lung cancer can be attributed to their consumption. The diseases related to cigarettes in Colombia represent a direct annual cost of more than 4 billion pesos, while the tax collection from the sale of cigarettes barely covers 10% of this expense. An increase in the price of cigarettes of 50% could prevent more than 30,000 deaths in ten years and generate resources for 7.9 billion savings in health spending and increased collection. Conclusions: the burden of disease and the cost to the health system associated with tobacco use are very high in Colombia. An increase in the price of cigarettes through taxes would have important health and economic benefits for Colombia.

The Role of Chitosan as a Possible Agent for Enteric Methane Mitigation in Ruminants.

Livestock production is a main source of anthropogenic greenhouse gases (GHG). The main gases are CH4 with a global warming potential (GWP) 25 times and nitrous oxide (N2O) with a GWP 298 times, that of carbon dioxide (CO2) arising from enteric fermentation or from manure management, respectively. In fact, CH4 is the second most important GHG emitted globally. This current scenario has increased the concerns about global warming and encouraged the development of intensive research on different natural compounds to be used as feed additives in ruminant rations and modify the rumen ecosystem, fermentation pattern, and mitigate enteric CH4. The compounds most studied are the secondary metabolites of plants, which include a vast array of chemical substances like polyphenols and saponins that are present in plant tissues of different species, but the results are not consistent, and the extraction cost has constrained their utilization in practical animal feeding. Other new compounds of interest include polysaccharide biopolymers such as chitosan, mainly obtained as a marine co-product. As with other compounds, the effect of chitosan on the rumen microbial population depends on the source, purity, dose, process of extraction, and storage. In addition, it is important to identify compounds without adverse effects on rumen fermentation. The present review is aimed at providing information about chitosan for dietary manipulation to be considered for future studies to mitigate enteric methane and reduce the environmental impact of GHGs arising from livestock production systems. Chitosan is a promising agent with methane mitigating effects, but further research is required with in vivo models to establish effective daily doses without any detrimental effect to the animal and consider its addition in practical rations as well as the economic cost of methane mitigation.

Pathological Response to Neoadjuvant Chemotherapy and the Molecular Classification of Locally Advanced Breast Cancer in a Latin American Cohort.

BACKGROUND: The majority of patients with breast cancer in Colombia are admitted into oncological centers at locally advanced stages of the disease (53.9%). The aim of this study was to describe the pathological response obtained with neoadjuvant chemotherapy (NACT) according to the molecular classification of breast cancer in patients with locally advanced tumors treated within the National Cancer Institute (NCI) Functional Breast Cancer Unit (FBCU) in Bogotá, Colombia. MATERIALS AND METHODS: This was an observational, descriptive, historical cohort study of patients with locally advanced breast cancer treated within the NCI FBCU. RESULTS: We included 414 patients who received NACT and surgical management. Most patients had luminal B HER2-negative tumors (n = 134, 32.4%). The overall rate of pathological complete response (pCR) ypT0/ypN0 was 15.2% (n = 63). Tumors that presented the highest rate of pCR were pure HER2, at 40.5% (n = 15; odds ratio [OR], 6.7); however, with a follow-up of 60 months, only the triple negative tumors presented a statistically significant difference for event-free survival (EFS; median recurrence time, 18 months; range, 1-46) and overall survival (OS; median follow-up, 31 months; range 10-57). The molecular subtype that most recurrences presented was luminal B HER2 negative, at 38.3% (n = 28). The majority of recurrences (93.2 %; n = 68; OR, 5.9) occurred in patients in whom no pathological response was obtained (Chevallier 3 and 4). CONCLUSION: Pathological response in locally advanced tumors is related to the molecular subtype of breast cancer, finding higher pCR rates in pure HER2 and triple-negative tumors. A direct relationship was found between disease recurrences and the pathological response, evidencing greater tumor recurrence in patients who did not respond to NACT (Chevallier 3 and 4). EFS and OS were greater in patients with pCR, with statistical significance only in triple-negative tumors. IMPLICATIONS FOR PRACTICE: This research article is of scientific interest, because it describes the clinical and pathological features and analyzes the correlation between pathological response to neoadjuvant chemotherapy and the molecular classification of locally advanced breast cancer in patients treated in the National Cancer Institute in Bogotá, Colombia. It was found that pathological response is related to the molecular subtype of breast cancer. In addition, there is a direct relationship between disease recurrences and pathological response. The survival results were greater in patients with pathological complete response.

Novel SFRP2 DNA Methylation Profile Following Neoadjuvant Therapy in Colorectal Cancer Patients with Different Grades of BMI.

The relationship between body weight and different cancers is now well-recognized and among such cancers, colorectal cancer (CRC) is reported most frequently. Our group recently published findings, through an epigenome-wide association study, suggesting that body mass index (BMI) could act as a relevant risk factor in the CRC. In addition, aberrant SFRP2 methylation is one of the major mechanisms for Wnt signaling activation in CRC. Conversely, neoadjuvant chemo-radiotherapy appears to alter the rectal cancer epigenome. This study was aimed to evaluate the effect of obesity, measured by BMI, on the methylation of SFRP2 in tumor samples of patients with CRC. Non-treated CRC patients and CRC patients treated with pre-operative neoadjuvant therapy from 2011 to 2013 were included and classified by BMI < 25.0 kg/m2 and BMI > 25.0 kg/m2. SFRP2 DNA methylation in tumor samples was measured by pyrosequencing. Our findings suggest a possible interaction between SFRP2 methylation levels and BMI in CRC tumor samples. The correlation of SFRP2 hypomethylation with an elevated BMI was stronger within the non-treated CRC patient group than within the treated CRC patient group. We have successfully demonstrated that the beneficial association of tumor SFRP2 hypomethylation is dependent on patient BMI in non-treated CRC, suggesting a possible tumor suppressor role for SFRP2 in overweight and obese patients. Additional studies of clinical pathologies would be necessary to strengthen these preliminary results.

Association between serum 25-hydroxyvitamin D and global DNA methylation in visceral adipose tissue from colorectal cancer patients.

BACKGROUND: Visceral adipose tissue (VAT) has been identified as the essential fat depot for pathogenetic theories that associateobesity and colon cancer. LINE-1 hypomethylation has been mostly detected in tumor colon tissue, but less is known about the epigenetic pattern in surrounding tissues. The aim was to analyze for the first time the potential relationship between serum vitamin D, obesity and global methylation (LINE-1) in the visceral adipose tissue (VAT) from patients with and without colorectal cancer. METHODS: A total of 55 patients with colorectal cancer and 35 control subjects participated in the study. LINE-1 DNA methylation in VAT was measured by pyrosequencing. Serum 25(OH)D levels were determined by ELISA. RESULTS: Cancer patients had lower levels of LINE-1 methylation in VAT compared with the control group. In the subjects with colorectal cancer, LINE-1 DNA methylation levels were associated positively with vitamin D levels (r = 0,463; p < 0.001) and negatively with BMI (r = - 0.334, p = 0.01) and HOMA insulin resistance index (r = - 0.348, p = 0.01). Serum vitamin D was the main variable explaining the LINE-1% variance in the cancer group (ß = 0.460, p < 0.001). In a multivariate analysis, subjects with higher LINE-1 methylation values had lower risk of developing colorectal cancer (OR = 0.53; IC95% =0.28-0.99) compared with the control group. CONCLUSIONS: We showed for the first time an association between LINE-1 DNA methylation in VAT and vitamin D levels in subjects with colorectal cancer, highlighting the importance of VAT from cancer patients, which could be modified epigenetically compared to healthy subjects.

Identification of an episignature of human colorectal cancer associated with obesity by genome-wide DNA methylation analysis.

BACKGROUND: Obesity was established as a relevant modifiable risk factor in the onset and progression of colorectal cancer (CRC). This relationship could be mediated by an epigenetic regulation. OBJECTIVES: The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC. METHODS: Fifty-six CRC-diagnosed patients (50 years) were included in the study and categorized according to their body mass index (BMI) as non-obese (BMI ≤ 25 kg/m2) or overweight/obese (BMI > 25 kg/m2). Data from Infinium 450k array-based methylomes of 28 CRC tumor samples were coupled with information on BMI categories. Additionally, DNA methylation results were validated in 28 CRC tumor samples. RESULTS: The analysis revealed statistically significant differences at 299 CpG sites, and they were mostly characterized as changes towards CpG hypermethylation occurring in the obese group. The 152 identified genes were involved in inflammatory and metabolic functional processes. Among these genes, novel genes were identified as epigenetically regulated in CRC depending on adiposity. ZNF397OS and ZNF543 represented the top scoring associated events that were further validated in an independent cohort and exhibited strong correlation with BMI and excellent and statistically significant efficiency in the discrimination of obese from non-obese CRC patients (area under the curve >0.80; p < 0.05). CONCLUSIONS: The present study identifies a potential epigenome mark of obesity-related CRC that could be useful for precision medicine in the management of this disease taking into account adiposity as a relevant risk factor.