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Prebiotics may influence the risk of hormone-related female cancers by modulating the gut microbiota involved in estrogens metabolism. We evaluated the association of fiber-type prebiotic intake with breast, endometrial, and ovarian cancers. Data derived from a network of Italian hospital-based case-control studies (1991-2006), including 2560 cases of cancer of the breast (2588 controls), 454 of the endometrium (908 controls) and 1031 of the ovary (2411 controls). Inulin-type fructans (ITFs), and selected fructo-oligosaccharides (FOSs, nystose, kestose and 1F-ß-fructofuranosylnystose) and galacto-oligosaccharides (GOSs, raffinose and stachyose) were quantified in food products. Prebiotic intake was estimated by multiplying food frequency questionnaire intake by the foods' prebiotic content. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were derived by multiple logistic regression models. Nystose intake was marginally directly associated with breast (OR for the 4th versus the 1st quartile 1.20, 95% CI: 1.00-1.45), ovarian (OR 1.39, 95% CI: 1.04-1.84) and endometrial cancer risk (OR 1.32, 95% CI: 0.85-2.03). High 1F-ß-fructofuranosylnystose intake was inversely associated with ovarian cancer (OR 0.67, 95% CI: 0.52-0.85). ITFs, kestose, raffinose and stachyose were not associated with the three cancers. The intake of most fiber-type prebiotics was not appreciably and consistently associated with breast, endometrial and ovarian cancer risks.
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BACKGROUND: Tailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients. METHODS: A multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis. RESULTS: The study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables. CONCLUSIONS: The reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1.
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Dolor en Cáncer , Dimensión del Dolor , Humanos , Masculino , Femenino , Dolor en Cáncer/diagnóstico , Persona de Mediana Edad , Dimensión del Dolor/métodos , Anciano , Adulto , Respuesta Galvánica de la Piel/fisiología , Electrocardiografía/métodos , Anciano de 80 o más Años , Manejo del Dolor/métodos , Manejo del Dolor/normas , Estudios de CohortesRESUMEN
BACKGROUND: Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as "oligo-metastatic disease" (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. METHODS: The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. DISCUSSION: Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05806151.
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Neoplasias Gastrointestinales , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gastrointestinales/genética , Microambiente TumoralRESUMEN
Canned fish is a widely consumed and affordable food whose effect on cancer risk has been little investigated. We studied its effect on risk of upper digestive tract cancers using data from a network of hospital-based case-control studies from Northern Italy providing information about canned fish consumption as a separate item and including a total of 946 patients with oral cavity and pharynx cancer, 304 patients with esophageal cancer, 230 patients with gastric cancer and 3273 controls. Twenty-three percent of patients with cancer of the oral cavity or pharynx and 26% of those with cancer of the stomach consumed ≥1 serving per week of canned fish, compared to 40% and 49% of the respective control group. Among cases of esophageal cancer and controls 22% consumed ≥1 serving per week of canned fish. Odds ratios for ≥1 vs <1 portion per week were 0.79 (95% Confidence Interval, CI: 0.64-0.97) for cancer of the oral cavity and pharynx, and 0.59 (95% CI: 0.41-0.86) for stomach cancer, whereas there was no inverse association with esophageal cancer. These findings suggest a favorable role of canned fish for selected upper digestive tract cancers.
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Neoplasias Esofágicas , Neoplasias Gastrointestinales , Neoplasias Gástricas , Animales , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Estudios de Casos y ControlesRESUMEN
PURPOSE: To evaluate the association between the intake of specific fibers with prebiotic activity, namely inulin-type fructans (ITFs), fructooligosaccharides (FOSs) and galactooligosaccharides (GOSs), and colorectal cancer risk. METHODS: Within the PrebiotiCa study, we used data from a multicentric case-control study conducted in Italy and including 1953 incident, histologically confirmed, colorectal cancer patients and 4154 hospital controls. The amount of six prebiotic molecules [ITFs, nystose (FOS), kestose (FOS), 1F-ß-fructofuranosylnystose (FOS), raffinose (GOS) and stachyose (GOS)] in a variety of foods was quantified via laboratory analyses. Subjects' prebiotic fiber intake was estimated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. The odds ratios (OR) of colorectal cancer for quintiles of intakes were derived from logistic regression models including terms for major confounders and total energy intake. RESULTS: GOSs intake was inversely associated with colorectal cancer risk. The OR for the highest versus the lowest quintile of intake were 0.73 (95% confidence interval, CI 0.58-0.92) for raffinose and 0.64 (95% CI 0.53-0.77) for stachyose, with significant inverse trends across quintiles. No association was found with total ITFs and FOSs. The association with stachyose was stronger for colon (continuous OR = 0.74, 95% CI 0.66-0.83) than rectal cancer (OR = 0.89, 95% CI 0.79-1.02). CONCLUSION: Colorectal cancer risk was inversely associated with the intake of dietary GOSs, but not ITFs and FOSs.
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Neoplasias Colorrectales , Humanos , Estudios de Casos y Controles , Rafinosa , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Modelos Logísticos , Fibras de la Dieta , Fructanos , Inulina , Factores de RiesgoRESUMEN
BACKGROUND: Prostate cancer (PCa) is the second most common cancer in men worldwide. The standard non-surgical approach for localized PCa is radiotherapy (RT), but one of the limitations of high-dose RT is the potential increase in gastrointestinal and genitourinary toxicities. We present the protocol of the Microstyle study, a multicentre randomized two-arm crossover clinical trial. The primary outcome will be assessed at the end of 6-month intervention, by measuring the change in adherence to a healthy lifestyle score. The hypothesis is that modifying lifestyle we change microbiome and improve quality of life and decrease side effects of RT. METHODS: Study participants will be recruited among men undergoing RT in two Italian centers (Milan and Naples). We foresee to randomize 300 patients in two intervention arms: Intervention Group (IG) and Control Group (CG). Participants allocated to the IG will meet a dietitian and a physiotherapist before RT to receive personalized diet and exercise recommendations, according to their health status, to improve overall lifestyle and reduce side effects (bowel and/or urinary problems). Dietitian and physiotherapist will work together to set individualized goals to reduce or eliminate side effects and pain according to their health status. All participants (IG) will be given a pedometer device (steps counter) in order to monitor and to spur participants to increase physical activity and reduce sedentary behavior. Participants included in the CG will receive baseline general advice and materials available for patients undergoing RT. According to the cross-over design, the CG will cross to the intervention approach after 6-month, to actively enhance compliance towards suggested lifestyle recommendations for all patients. DISCUSSION: This trial is innovative in its design because we propose a lifestyle intervention during RT, that includes both dietary and physical activity counselling, as well as monitoring changes in microbiome and serum biomarkers. The promotion of healthy behaviour will be initiated before initiation of standard care, to achieve long lasting effects, controlling side effects, coping with feelings of anxiety and depression and improve efficacy of RT. TRIAL REGISTRATION: ClincalTrial.gov registration number: NCT05155618 . Retrospectively registered on December 13, 2021. The first patient was enrolled on October 22, 2021.
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Estilo de Vida , Microbiota , Neoplasias de la Próstata , Estudios Cruzados , Humanos , Masculino , Estudios Multicéntricos como Asunto , Neoplasias de la Próstata/microbiología , Neoplasias de la Próstata/radioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta SedentariaRESUMEN
The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published evidence-based recommendations for cancer prevention focusing on body weight, physical activity, and diet. Our aim is to evaluate whether adherence to the WCRF/AICR recommendations could reduce endometrial cancer risk. We used data from a multicentric, Italian hospital-based case-control study (1992-2006) including 454 endometrial cancer cases and 908 age-matched controls. Adherence to the WCRF/AICR recommendations was measured using a score (range: 0-7) based on seven components: body mass index (BMI), physical activity and five dietary items; higher scores indicated higher adherence. Odds ratios (OR) were estimated by multiple (adjusted) conditional logistic regression models including terms for major confounders and energy intake. Adherence to the WCRF/AICR recommendations was inversely related to endometrial cancer risk (OR = 0·42, 95 % confidence interval (CI) 0·30, 0·61 for the highest compared with the lowest score quartile), with a significant trend of decreasing risk with increasing adherence. An inverse association was also observed for a score including only dietary recommendations (OR = 0·67, 95 % CI 0·46, 0·96 for the highest compared with the lowest score tertile). In stratified analyses, the association was stronger among women with a normal weight, those who were older, and consequently those in post-menopause, and those with ≥ 2 children. In conclusion, high adherence to the WCRF/AICR recommendations has a favourable role in endometrial cancer risk, which is not fully explained by body weight.
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OBJECTIVE: The primary goal of the Campania Oncology Network (ROC) was to reduce cancer delay and care fragmentation through the establishment of cancer-specific multidisciplinary oncologic groups (GOMs) and diagnostic and therapeutic assistance paths (PDTAs). METHODS: Five cancer centres of the ROC, with their own cancer specific GOM, were selected. In our analysis, we have focused on four neoplasms: lung, colon, ovarian and prostate cancers. The median time for pre-GOM and GOM Times was calculated for each tumour site. Univariate and multivariate logistic regressions were performed to individuate risk factors for pre-GOM and GOM Time. RESULTS: Significant differences were observed for prostate cancer compared to other patients either for pre-GOM or GOM Times. Significant risks were found for ovarian and prostate cancers in pre-GOM time and for prostate cancer in GOM-Time. CONCLUSIONS: This experience will produce knowledge and data to guide decision-making and to manage more effectively the challenges of fighting cancer in Campania region. The Valutazione Percorso Rete Oncologica Campana (ValPeROC) study evaluates, for the first time, the ROC activity, through the analysis of key performance indices. Pre-GOM and GOM Time represent the quality of the entire regional health system and are useful to define models, which can evaluate the performance of the ROC over time.
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Oncología Médica , Neoplasias de la Próstata , Masculino , Humanos , Italia , Atención al Paciente , Factores de RiesgoRESUMEN
An adequate intake of branched-chain amino acids (BCAA) is required for protein synthesis and metabolic functions, including insulin metabolism. Emerging studies found positive associations between BCAA and the risk of various diseases sharing aetiological aspects with colorectal cancer (CRC), including type 2 diabetes, obesity and pancreatic cancer. We investigated the relation between dietary BCAA and CRC using data from a multicentric Italian case-control study, including 1953 cases of CRC (of these, 442 of sigmoid colon) and 4154 hospital controls with acute, non-neoplastic diseases. A validated FFQ was used to estimate the participants' usual diet and to assess dietary intakes of various nutrients, including energy, BCAA and Ca. OR and corresponding CI were computed by multiple logistic regression models adjusted for age, sex and other confounding factors, including total energy intake. BCAA intake was inversely related to CRC risk (OR for the highest v. the lowest quintile 0·73; 95 % CI 0·55, 0·97), but the association was attenuated after adjustment for Ca intake (OR 0·90; 95 % CI 0·65, 1·25). An inverse association with sigmoid colon cancer risk also remained after adjustment for other dietary factors, including Ca intake (OR 0·49; 95 % CI 0·27, 0·87). This study provides supporting evidence that higher levels of dietary BCAA intake are not associated with an increase of CRC risk, but confirms that they may be related to a reduced risk of sigmoid colon cancer.
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Aminoácidos de Cadena Ramificada/administración & dosificación , Neoplasias Colorrectales , Dieta , Neoplasias del Colon Sigmoide , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Humanos , Italia , Factores de Riesgo , Neoplasias del Colon Sigmoide/epidemiologíaRESUMEN
BACKGROUND: Physical inactivity is a major risk factor for non-communicable diseases. However, recent and systematically obtained national-level data to guide policy responses are often lacking, especially in countries in Eastern Europe and Central Asia. This article describes physical inactivity patterns among adults in Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkey and Uzbekistan. METHODS: Data were collected using the Global Physical Activity Questionnaire drawing nationally representative samples of adults in each country. The national prevalence of physical inactivity was calculated as well as the proportional contribution to total physical activity (PA) during work, transport and leisure-time. An adjusted logistic regression model was applied to analyze the association of age, gender, education, household status and income with physical inactivity. RESULTS: National prevalence of physical inactivity ranged from 10.1% to 43.6%. The highest proportion of PA was registered during work or in the household in most countries, whereas the lowest was during leisure-time in all countries. Physical inactivity was more likely with older age in eight countries, with female gender in three countries, and with living alone in three countries. There was no clear pattern of association with education and income. CONCLUSION: Prevalence of physical inactivity is heterogeneous across the region. PA during leisure-time contributes minimally to total PA in all countries. Policies and programs that increase opportunities for active travel and leisure-time PA, especially for older adults, women and people living alone will be an essential part of strategies to increase overall population PA.
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Actividades Recreativas , Conducta Sedentaria , Anciano , Asia , Europa Oriental , Femenino , Humanos , PrevalenciaRESUMEN
PURPOSE: Obesity and insulin resistance have been associated with poor prognosis in breast cancer (BC). The present prospective study aimed to investigate the impact of metabolic syndrome (MetS) and its components on early BC (eBC) patients' outcome. METHODS: MetS was defined by the presence of 3 to 5 of the following components: waist circumference > 88 cm, blood pressure ≥ 130/≥ 85 mmHg, serum levels of triglycerides ≥ 150 mg/dL, high density lipoprotein < 50 mg/dL and fasting glucose ≥ 110 mg/dL. Seven hundred and seventeen patients with data on ≥ 4 MetS components at BC diagnosis were enrolled. Study population was divided into two groups: patients with < 3 (non-MetS) vs. ≥ 3 components (MetS). Categorical variables were analyzed by Chi-square test and survival data by log-rank test and Cox proportional hazards regression model. RESULTS: Overall, 544 (75.9%) and 173 (24.1%) women were categorized as non-MetS and MetS, respectively. MetS patients were more likely to be older, postmenopausal, and insulin-resistant compared to non-MetS patients (p < 0.05). In multivariate analysis, MetS patients had a numerically higher risk of relapse [disease-free survival (DFS), hazard ratio (HR) 1.51, p = 0.07] and a significantly higher risk of death compared to non-MetS patients [overall survival (OS), HR 3.01, p < 0.0001; breast cancer-specific survival (BCSS), HR 3.16, p = 0.001]. Additionally, patients with 1 to 2 components of MetS had an increased risk of dying compared to patients with 0 components (OS, HR 4.90, p = 0.01; BCSS, HR 6.07, p = 0.02). CONCLUSIONS: MetS correlated with poor outcome in eBC patients. Among patients without full criteria for MetS diagnosis, the presence of 1 or 2 components of the syndrome may predict for worse survival.
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Neoplasias de la Mama/mortalidad , Síndrome Metabólico/epidemiología , Factores de Edad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Comorbilidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
Chemotherapy-induced peripheral neuropathy (CIPN) is the most frequently reported adverse effect of oxaliplatin. In this study, we set out to evaluate the role of the panaceo-micro-activation (PMA) zeolite in the reduction of the incidence of CIPN and hematological and liver toxicity. The possible impact of the PMA-zeolite as an adjuvant therapeutic agent is based on its detoxification properties toward agents promoting the development of neuropathy (e.g., ammonium - recognized as a neurotoxic agent produced by tumors), as well as its positive impact on immunity and oxidative stress through its effects in the gastrointestinal tract. From April 2015 to October 2018, a total of 120 patients (pts) diagnosed with predominantly colorectal cancer requiring oxaliplatin-based chemotherapy were randomized to receive either the PMA-zeolite (Multizeo Med) or placebo while undergoing oxaliplatin-based chemotherapy. A nerve-conduction study (NCS) was planned at the baseline, after three and six months of chemotherapy, to evaluate CIPN. Furthermore, the evaluation of hematological and liver toxicity was performed during every cycle of chemotherapy. 70.6% and 64.3% of patients developed CIPN in the placebo and the PMA-zeolite group, respectively. Patients treated with the PMA-zeolite were able to undergo more cycles of chemotherapy (p = 0.03), which also indicates a significant improvement in tolerance to the therapy. The group treated with the PMA-zeolite showed a lower CIPN (although not statistically significant within the whole group of subjects) compared to patients receiving placebo. This advantage was, however, statistically significant in men (p = 0.047). In addition, supplementation with the PMA-zeolite resulted in a lower incidence of severe-grade hematological toxicity (trend toward statistical significance of p = 0.09 was observed). Cancer patients may benefit from the therapy with the appropriate certified zeolite-products (e.g., the PMA-zeolite) for human use in CIPN. The lower CIPN (statistically significant results in the male subgroup) was accompanied by a trend of lower incidence of severe-grade hematological toxicity. Furthermore, these benefits led to a better tolerance toward chemotherapy (increase in cycles) and allow an improved compliance with the oncological treatment protocol.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Enfermedades del Sistema Nervioso Periférico , Zeolitas/administración & dosificación , Administración Oral , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & controlRESUMEN
Treatment of acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS) represents a clinical challenge, requiring often invasive mechanical ventilation (IMV). Since the pathogenesis of CARDS it probably involves a direct viral attack to pulmonary and endothelium cells, and immune-mediated inflammation with dysfunctional coagulation, it was suggested to interfere with interleukin-6 (IL-6) activity by using the IL-6 receptor monoclonal antibody tocilizumab (TCZ). We reported the case of a 54-year-old 100 kg male COVID-19 patient (BMI 29) with severe respiratory insufficiency featuring dyspnea and hypoxia (SpO2 89% on room; PaO2 53 mmHg). Despite treatment with antiviral and non-invasive ventilation (NIV), after 24 h there was a progressive worsening of clinical conditions with higher fever (40 °C), increased dyspnea, and hypoxia (PaO2/FiO2 or P/F ratio of 150). The patient was at the limit to be sedated and intubated for IMV. He was treated with tocilizumab (8 mg/Kg i.v., single shot 800 mg) and NIV in the prone positioning. After only 96 h, the clinical, laboratory, and imaging findings showed incredible improvement. There was an important gain in oxygenation (P/F 300), a decrease of C-reactive protein values, and a decrease of the fever. Both the neutrophil-to-lymphocyte ratio (NLR) and the derived NLR ratio dropped down to 44%. Chest imaging confirmed the favorable response. This case suggested that for CARDS management efforts are needed for reducing its underlying inflammatory processes. Through a multiprofessional approach, the combination of IL-6-targeting therapies with calibrated ventilatory strategies may represent a winning strategy for improving outcomes.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Administración Intravenosa , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antivirales/uso terapéutico , Betacoronavirus/aislamiento & purificación , COVID-19 , Terapia Combinada , Disnea/diagnóstico , Humanos , Hipoxia/diagnóstico , Masculino , Persona de Mediana Edad , Ventilación no Invasiva/métodos , Pandemias , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/terapia , SARS-CoV-2 , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. METHODS: 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. RESULTS: PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. CONCLUSIONS: Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT - Napoli - 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it.
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Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Sunitinib/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Axitinib/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: Narrow Band Imaging is a noninvasive optical diagnostic tool. It allows the visualization of sub-mucosal vasculature; four patterns of shapes of submucosal capillaries can be recognized, increasingly associated with neoplastic transformation. With such characteristics, it has showed high effectiveness for detection of Oral Squamous Cell Carcinoma. Still, scientific literature highlights several bias/confounding factors, such as Oral Lichen Planus. We performed a retrospective observational study on patients routinely examined with Narrow Band Imaging, investigating for bias, confounding factors and conditions that may limit its applicability. METHODS: Age, sex, smoking, use of dentures, history of head & neck radiotherapy, history of Oral Squamous Cell Carcinoma, site of the lesion and thickness of the epithelium of origin were statistically evaluated as possible bias/confounding factors. Pearson's Chi-squared test, multivariate logistic regression, Positive Predictive Value, Negative Predictive Value, Sensitivity, Specificity, Positive Likelihood Ratio, Negative Likelihood Ratio and accuracy were calculated, normalizing the cohort with/without patients affected by Oral Lichen Planus, to acknowledge its role as bias/confounding factor. RESULTS: Five hundred fifty-six inspections were performed on 106 oral cavity lesions from 98 patients. Age, sex, smoking, use of dentures and anamnesis of Oral Squamous Cell Carcinoma were not found to influence Narrow Band Imaging. History of head & neck radiotherapy was not assessed due to insufficient sample. Epithelium thickness does not seem to interfere with feasibility. Presence of Oral Lichen Planus patients in the cohort led to false positives but not to false negatives. Among capillary patterns, number IV was the most significantly associated to Oral Squamous Cell Carcinoma (p < 0.001), not impaired by the presence of Oral Lichen Planus patients in the cohort (accuracy: 94.3, 95% confidence interval: 88.1-97.9%; odds ratio: 261.7, 95% confidence interval: 37.7-1815.5). CONCLUSION: Narrow Band Imaging showed high reliability in detection of Oral Squamous Cell Carcinoma in a cohort of patients with oral cavity lesions not normalized for bias/confounding factors. Still, Oral Lichen Planus may lead to false positives. Narrow Band Imaging could help in the follow-up of patients with multiple lesions through detection of capillary pattern IV, which seems to be the most significantly associated to neoplastic epithelium.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Liquen Plano Oral/diagnóstico por imagen , Mucosa Bucal/diagnóstico por imagen , Neoplasias de la Boca/diagnóstico por imagen , Imagen de Banda Estrecha/métodos , Carcinoma de Células Escamosas/patología , Humanos , Liquen Plano Oral/patología , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Proyectos Piloto , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: we have recently shown that Tel-eVax, a genetic vaccine targeting dog telomerase (dTERT) and based on Adenovirus (Ad)/DNA Electro-Gene-Transfer (DNA-EGT) technology can induce strong immune response and increase overall survival (OS) of dogs affected by multicentric Diffuse Large B cell Lymphoma (DLBCL) when combined to COP therapy in a double-arm study. Here, we have utilized a clinically validated device for veterinary electroporation called Vet-ePorator™, based on Cliniporator™ technology currently utilized and approved in Europe for electrochemotherapy applications and adapted to electrogenetransfer (EGT). METHODS: 17 dogs affected by DLBCL were vaccinated using two Ad vector injections (Prime phase) followed by DNA-EGT (Boost phase) by means of a Vet-ePorator™ device and treated in the same time with a 27-week Madison Wisconsin CHOP protocol. The immune response was measured by ELISA assays using pool of peptides. RESULTS: No significant adverse effects were observed. The OS of vaccine/CHOP animals was 64.5 weeks, in line with the previous study. Dogs developed antibodies against the immunizing antigen. CONCLUSIONS: Tel-eVax in combination with CHOP is safe and immunogenic in lymphoma canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and hold promise for the treatment of dogs affected by other cancer types. More importantly, our findings may translate to human clinical trials and represent new strategies for cancer treatment.
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Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/veterinaria , Telomerasa/metabolismo , Animales , Formación de Anticuerpos/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Perros , Doxorrubicina , Femenino , Estimación de Kaplan-Meier , Cinética , Linfoma de Células B Grandes Difuso/inmunología , Masculino , Prednisona , Análisis de Supervivencia , Vacunación , VincristinaRESUMEN
In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock's genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types.
Asunto(s)
Relojes Biológicos/efectos de la radiación , Carcinogénesis/efectos de la radiación , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Neoplasias/etiología , Núcleo Supraquiasmático/efectos de la radiación , Animales , Relojes Biológicos/genética , Relojes Biológicos/inmunología , Proteínas CLOCK/genética , Proteínas CLOCK/inmunología , Proteínas CLOCK/metabolismo , Carcinogénesis/genética , Carcinogénesis/inmunología , Carcinogénesis/metabolismo , Metabolismo Energético/genética , Metabolismo Energético/inmunología , Metabolismo Energético/efectos de la radiación , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/inmunología , Inestabilidad Genómica/inmunología , Inestabilidad Genómica/efectos de la radiación , Humanos , Inmunidad Innata/efectos de la radiación , Luz/efectos adversos , Melatonina/antagonistas & inhibidores , Melatonina/biosíntesis , Melatonina/inmunología , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/prevención & control , Glándula Pineal/inmunología , Glándula Pineal/metabolismo , Glándula Pineal/efectos de la radiación , Retina/inmunología , Retina/metabolismo , Retina/efectos de la radiación , Núcleo Supraquiasmático/inmunología , Núcleo Supraquiasmático/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/efectos de la radiaciónRESUMEN
BACKGROUND: While dietary factors have been shown to play an important etiologic role in non-Hodgkin lymphoma (NHL), little is known about the association between inflammatory properties of diet and NHL risk. METHODS: We explored the association between the dietary inflammatory index (DII) and NHL risk in a multicenter Italian case-control study conducted between 1999 and 2014. Cases were 536 subjects with incident, histologically confirmed NHL from three areas in Italy. Controls were 984 subjects admitted to the same network of hospitals as the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were computed based on 30 nutrients and food items assessed using a reproducible and validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake, and other recognized confounding factors. RESULTS: Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of NHL compared with subjects in the lowest quartile (i.e., with the most anti-inflammatory diets) (ORQuartile4vs1 1.61, 95% confidence interval CI 1.07-2.43; p-trend = 0.01). Stratified analyses produced stronger associations between DII and NHL among males (ORQuartile4vs1 2.14; 95% CI 1.25-3.67) with significant heterogeneity (p value = 0.02); when analyzed by histologic subtype, a significant association was observed with diffuse large B-cell lymphoma (ORQuartile4vs1 1.84; 95% CI 1.09-3.10). CONCLUSION: A pro-inflammatory diet, as indicated by higher DII scores, is associated with elevated odds of NHL, especially among males.
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Dieta , Linfoma no Hodgkin/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Ingestión de Energía , Femenino , Humanos , Inflamación/complicaciones , Italia/epidemiología , Modelos Logísticos , Linfoma no Hodgkin/etiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. The diagnosis is often missed at birth, the median age at diagnosis being 9 years. In the attempt to shed light on BBS and improve its diagnosis and treatment, we evaluated the genotype-phenotype relationship in patients with a molecular diagnosis of BBS. METHODS: We analyzed three common BBS genes, BBS1, BBS10 and BBS2, in 25 Italian patients fulfilling the clinical criteria of BBS. In 12 patients, we identified gene-specific biallelic variants and thus correlated genotype to the ophthalmic, renal and audio-vestibular phenotypes. RESULTS: At least one sequence variant was found in 60% of patients. The most common mutated gene was BBS1 followed by BBS10. Of the 17 sequence variants we found, 11 have not previously been associated with BBS. In 12 patients, we identified biallelic pathogenic variants; they had retinitis pigmentosa with early onset of visual impairment. However, retinal dystrophy was less severe in patients with BBS1 than in those with BBS10 variants. Overall, we found a high prevalence of renal dysmorphism and dysfunction. Notably, patients with BBS10 variants had the most severe renal impairment, which resulted in a critical decline in renal function. All the patients who underwent audio-vestibular evaluation had dysfunction of the cochlear outer hair cells, thus confirming the presence of hearing defects. CONCLUSION: BBS1, BBS2 and BBS10 are major causative genes in Italian BBS patients. BBS10 was associated with the worse outcome in terms of the renal, ocular and audiovestibular phenotypes. Cochlear dysfunction should be included among the hallmarks of BBS.
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Síndrome de Bardet-Biedl/genética , Ojo/fisiopatología , Riñón/fisiopatología , Población Blanca/genética , Adolescente , Adulto , Anciano , Umbral Auditivo , Síndrome de Bardet-Biedl/patología , Chaperoninas , Niño , ADN/química , ADN/aislamiento & purificación , ADN/metabolismo , Análisis Mutacional de ADN , Ojo/diagnóstico por imagen , Femenino , Estudios de Asociación Genética , Genotipo , Chaperoninas del Grupo II/genética , Humanos , Italia , Masculino , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético , Proteínas/genética , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
BACKGROUND: Previous studies have provided limited support to the association between tobacco smoking and lymphomas with weak evidence of a dose-response relationship. METHODS: We investigated the relationship between tobacco smoking and risk of non-Hodgkin lymphomas (NHL) and Hodgkin lymphomas (HL) through logistic regression spline models. Data were derived from an Italian hospital-based case-control study (1999-2014), which enrolled 571 NHLs, 188 HLs, and 1004 cancer-free controls. Smoking habits and other lifestyle factors were assessed through a validated questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression, adjusting for potential confounders. RESULTS: Compared to never smokers, people smoking ≥15 cigarettes/day showed increased risks of both NHL (OR = 1.42, 95% CI: 1.02, 1.97) and HL (OR = 2.47, 95% CI: 1.25, 4.87); the risk was particularly elevated for follicular NHL (OR = 2.43; 95% CI:1.31-4.51) and mixed cellularity HL (OR = 5.60, 95% CI: 1.31, 23.97). No excess risk emerged for former smokers or people smoking <15 cigarettes/day. Spline analyses showed a positive dose-response relationship with significant increases in NHL and HL risks starting from 15 and 21 cigarettes/day, respectively, with the most evident effects for follicular NHL and mixed cellularity HL. Smoking duration was significantly associated with the HL risk only (OR = 2.15, 95% CI: 1.16, 3.99). CONCLUSIONS: These findings support a role of tobacco smoking in the etiology of both NHL and HL, providing evidence of a direct association of risk with smoking intensity.