Half of the patients with subepithelial tumours present borderline or pathologic anxiety-distress and carcinophobia: multicentre cohort study

Background and aims: minor nonspecific gastrointestinal sub-epithelial lesions (usually defined by the term 'tumor') are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion.Methods: prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threat-ening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale).Results: forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13 % (5/40, 95 % CI: 4-27 %) and 35 % (14/40, 95 % CI: 21-52 %) of participants, respectively, whereas, cancer-relat-ed worries (moderate to very high) were observed in 48 % (19/40, 95 % CI: 32-64 %) of participants. Pathologic global distress was identified in 25 % (10/40, 95 % CI: 13-42 %) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia.Conclusions: almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion pre-sented anxiety-distress and/or carcinophobia. Specific associ-ations with anxiety-distress reaction and fears were detected

Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model

Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC50 3 nmol/L) than pancreatic tumor cells (IC50 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment

Clinical relevance of histologic subtypes in locally advanced esophageal carcinoma treated with pre-operative chemoradiotherapy: Experience of a monographic oncologic centre

Background: Locally advanced esophageal carcinoma (LAEC) represents less than 30% of all diagnosed esophageal carcinoma worldwide. The standard of care for resectable tumours consists of preoperative chemoradiotherapy (CRT) followed by surgery. Despite the curative intent, the prognosis is still poor mainly due to relapse. A multidisciplinary approach is required in order to optimize the therapeutic strategy and follow-up. Differences in outcomes between the two main histological subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SCC), have been reported. Nevertheless, the heterogeneity in trials design and data available have hampered the achievement of clear conclusions. The purpose of this study is to report the outcomes from a cohort of patients with LAEC treated with a multidisciplinary approach and to remark the differences observed between the two main histologic subtypes and their clinical implications. Methods: We retrospectively reviewed 100 patients diagnosed with LAEC that were treated with preoperative CRT at our institution and integrated centres. Histopathological characteristics and toxicities during treatment were recorded. Patterns of recurrence at the first relapse were analysed. Survival curves were plotted using the Kaplan Meier method and multivariate Cox proportional hazards models were used. Results: Among the patients who received preoperative CRT, 83% underwent surgery. The median overall survival (mOS) was 31.7 months, 26.9 months for ADC and 45.5 for SCC (p-value = 0.33). In the multivariate Cox regression analysis, ypN+ was the only factor that negatively influenced in OS (OR = 4.1, p-value = 0.022). Patterns of recurrence differed according to histologic subtype. Distant relapse was more frequent in ADC (62%), whereas locoregional relapse was higher in SCC (50%) (p-value = 0.027). Second line therapeutic strategies could be offered to 50% of those patients who relapsed. Conclusions: Differences in outcomes and recurrence pattern could be observed between the two main histologic subtypes of LAEC. A better molecular characterization, adapted therapeutic regimens and follow up strategies should be adopted in order to improve survival of these patients

ICO-ICS Praxi per al tractament mèdic i amb irradiació de càncer gàstric i d'unió esofagogàstrica

Tractament mèdic; Tractament amb irradiació; Càncer de la unió esofagogàstricaTratamiento médico; Tratamiento con irradiación; Cáncer de la unión esofagogástricaMedical treatment; Irradiation treatment; Esophagogastric union cancerEl càncer gàstric (CG) és actualment el vuitè tipus de càncer més prevalent a la Unió Europea on, segons les estimacions, el 2018 es calculen 80.211 casos diagnosticats en ambdós sexes amb una taxa estimada d'incidència estandarditzada per edat de 6,4 casos per cada 100.000 habitants. En el cas d'Espanya, segons dades d'incidència i mortalitat del projecte GLOBOCAN i de l'Observatori Europeu del Càncer, se situa en novè lloc, després del càncer de bufeta i el càncer uterí, pel que fa a freqüència. Els objectius d'aquesta guia són: Desenvolupar, difondre, implementar i avaluar resultats de l'ICO-ICSPraxi de càncer gàstric i d'unió esofagogàstrica. Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. Implementar els resultats de la terapèutica en els pacients amb càncer gàstric i d'unió esofagogàstrica tractats d'acord amb les recomanacions d'aquesta guia.El cáncer gástrico (CG) es actualmente el octavo tipo de cáncer más prevalente en la Unión Europea donde, según las estimaciones, el 2018 se calculan 80.211 casos diagnosticados en ambos sexos con una tasa estimada de incidencia estandarizada por edad de 6,4 casos por cada 100.000 habitantes. En el caso de España, según datos de incidencia y mortalidad del proyecto GLOBOCAN y del Observatorio Europeo del Cáncer, se sitúa en noveno lugar, después del cáncer de vejiga y el cáncer uterino, en cuanto a frecuencia. Los objetivos de esta guía son: Desarrollar, difundir, implementar y evaluar resultados del ICO-ICSPraxi de cáncer gástrico y de unión esofagogástrica. Disminuir la variabilidad terapéutica entre los pacientes tratados en los diferentes centros de esta institución. Implementar los resultados de la terapéutica en los pacientes con cáncer gástrico y de unión esofagogástrica tratados de acuerdo con las recomendaciones de esta guía.Gastric cancer (GC) is currently the eighth most prevalent type of cancer in the European Union where, according to estimates, 80,211 cases diagnosed in both sexes are estimated at an estimated rate of incidence standardized by age of 6.4 cases per 100,000 people. In the case of Spain, according to the incidence and mortality data of the GLOBOCAN project and the European Cancer Observatory, it is placed ninth, after bladder cancer and uterine cancer, as it happens frequently. The objectives of this guide are: Developing, disseminating, implementing and evaluating the results of the ICO-ICSPraxi of gastric cancer and esophagogastric binding. Decrease the therapeutic variability between patients treated at the different centers of this institution. Implement the results of therapeutic treatment in patients with gastric cancer and esphagogastric binding treated in accordance with the recommendations of this guide

Endoscopic band ligation without resection in selected patients for small and superficial upper gastrointestinal tract lesions

Background and aim: The aim of this study was to evaluate the efficacy of endoscopic band ligation (EBL) in carefully selected patients who would benefit from this method of resection. Methods: Patients with early upper gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette® Multi-Band Mucosectomy) were prospectively recruited and retrospectively analyzed between 2010 and 2015. All cases were discussed in a multidisciplinary cancer committee and it was concluded that, owing to patient conditions, surgery was not possible and that not conducting histology would not change the clinical management. A first endoscopic control with biopsies was planned at 4-8 weeks. If there was no persistence of the lesion, new controls were programmed at 6 and 12 months. Results: The group (n = 12) included 5 esophagus lesions (adenosquamous carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Only one minor adverse event was described. At first follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological remission, respectively. At 6-month follow-up there was 70% of both endoscopic remission and negative biopsies. And at 12 months, there was 100% and 75% of endoscopic and histological remission, respectively. Persisting lesions were T1 cancers. The median follow-up was 30.6 months. Conclusion: EBL without resection is an easy and safe technique that should be considered in patients with multiple morbidities and small superficial UGI lesions

Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model

Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC50 3 nmol/L) than pancreatic tumor cells (IC50 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment

Clinical relevance of histologic subtypes in locally advanced esophageal carcinoma treated with pre-operative chemoradiotherapy: Experience of a monographic oncologic centre

Background: Locally advanced esophageal carcinoma (LAEC) represents less than 30% of all diagnosed esophageal carcinoma worldwide. The standard of care for resectable tumours consists of preoperative chemoradiotherapy (CRT) followed by surgery. Despite the curative intent, the prognosis is still poor mainly due to relapse. A multidisciplinary approach is required in order to optimize the therapeutic strategy and follow-up. Differences in outcomes between the two main histological subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SCC), have been reported. Nevertheless, the heterogeneity in trials design and data available have hampered the achievement of clear conclusions. The purpose of this study is to report the outcomes from a cohort of patients with LAEC treated with a multidisciplinary approach and to remark the differences observed between the two main histologic subtypes and their clinical implications. Methods: We retrospectively reviewed 100 patients diagnosed with LAEC that were treated with preoperative CRT at our institution and integrated centres. Histopathological characteristics and toxicities during treatment were recorded. Patterns of recurrence at the first relapse were analysed. Survival curves were plotted using the Kaplan Meier method and multivariate Cox proportional hazards models were used. Results: Among the patients who received preoperative CRT, 83% underwent surgery. The median overall survival (mOS) was 31.7 months, 26.9 months for ADC and 45.5 for SCC (p-value = 0.33). In the multivariate Cox regression analysis, ypN+ was the only factor that negatively influenced in OS (OR = 4.1, p-value = 0.022). Patterns of recurrence differed according to histologic subtype. Distant relapse was more frequent in ADC (62%), whereas locoregional relapse was higher in SCC (50%) (p-value = 0.027). Second line therapeutic strategies could be offered to 50% of those patients who relapsed. Conclusions: Differences in outcomes and recurrence pattern could be observed between the two main histologic subtypes of LAEC. A better molecular characterization, adapted therapeutic regimens and follow up strategies should be adopted in order to improve survival of these patients

Clinical relevance of histologic subtypes in locally advanced esophageal carcinoma treated with pre-operative chemoradiotherapy: Experience of a monographic oncologic centre

Background: Locally advanced esophageal carcinoma (LAEC) represents less than 30% of all diagnosed esophageal carcinoma worldwide. The standard of care for resectable tumours consists of preoperative chemoradiotherapy (CRT) followed by surgery. Despite the curative intent, the prognosis is still poor mainly due to relapse. A multidisciplinary approach is required in order to optimize the therapeutic strategy and follow-up. Differences in outcomes between the two main histological subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SCC), have been reported. Nevertheless, the heterogeneity in trials design and data available have hampered the achievement of clear conclusions. The purpose of this study is to report the outcomes from a cohort of patients with LAEC treated with a multidisciplinary approach and to remark the differences observed between the two main histologic subtypes and their clinical implications. Methods: We retrospectively reviewed 100 patients diagnosed with LAEC that were treated with preoperative CRT at our institution and integrated centres. Histopathological characteristics and toxicities during treatment were recorded. Patterns of recurrence at the first relapse were analysed. Survival curves were plotted using the Kaplan Meier method and multivariate Cox proportional hazards models were used. Results: Among the patients who received preoperative CRT, 83% underwent surgery. The median overall survival (mOS) was 31.7 months, 26.9 months for ADC and 45.5 for SCC (p-value = 0.33). In the multivariate Cox regression analysis, ypN+ was the only factor that negatively influenced in OS (OR = 4.1, p-value = 0.022). Patterns of recurrence differed according to histologic subtype. Distant relapse was more frequent in ADC (62%), whereas locoregional relapse was higher in SCC (50%) (p-value = 0.027). Second line therapeutic strategies could be offered to 50% of those patients who relapsed. Conclusions: Differences in outcomes and recurrence pattern could be observed between the two main histologic subtypes of LAEC. A better molecular characterization, adapted therapeutic regimens and follow up strategies should be adopted in order to improve survival of these patients

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Maria de Lourdes Farré Vallve - Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil. aCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain; bCentro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto Salud Carlos III, 28029 Madrid, Spain; cEndocrine Division, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain; dDivision of RNA Biology and Cancer (B150), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; eInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany; fExperimental Dermatology and Skin Biology Group, Ramón y Cajal Institute for Biomedical Research (IRYCIS), Ramón y Cajal University Hospital, 28034 Madrid, Spain; gBionanotechnology Laboratory, Bernardo O’Higgins University, Santiago 8370854, Chile; hPathology Department, Hospital Universitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, 08907 Barcelona, Catalonia, Spain; iDepartment of Medical Oncology, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain; jUnit of Nutrition and Cancer, Cancer Epidemiology Research Program, ICO, IDIBELL, 08908 Barcelona, Catalonia, Spain; kDepartment of Molecular Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan; lProgram Against Cancer Therapeutic Resistance (ProCURE), ICO, IDIBELL, L’Hospitalet del Llobregat, 08908 Barcelona, Catalonia, Spain; mLaboratory of Experimental Pathology (LAPEX), Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPQGM/ FIOCRUZ) and National Institute of Science and Technology of Tropical Diseases (INCT/DT), 40296710 Salvador, Bahia, Brazil; nDivision of Cancer Research, Department of Thoracic Surgery, Medical Center–University of Freiburg, 79106 Freiburg, Germany; oFaculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; pGerman Cancer Consortium (DKTK), 79106 Freiburg, Germany; qDepartament de Ciències Fisiològiques II, Escola de Medicina, Universitat de Barcelona, 08907 Barcelona, Catalonia, Spain; and rInstitució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, SpainSubmitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-24T13:39:17Z No. of bitstreams: 1 Lagares AD Epigenetic inactivation....pdf: 3833209 bytes, checksum: fcc6c212b11319a6cc7ba1aa1a191854 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-24T13:57:19Z (GMT) No. of bitstreams: 1 Lagares AD Epigenetic inactivation....pdf: 3833209 bytes, checksum: fcc6c212b11319a6cc7ba1aa1a191854 (MD5)Made available in DSpace on 2017-03-24T13:57:19Z (GMT). No. of bitstreams: 1 Lagares AD Epigenetic inactivation....pdf: 3833209 bytes, checksum: fcc6c212b11319a6cc7ba1aa1a191854 (MD5) Previous issue date: 2016Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, SpainBellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain / Instituto Salud Carlos III. Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBERobn). Madrid, Spain / Complejo Hospitalario Universitario de Santiago. Endocrine Division. Santiago de Compostela, SpainBellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain. Múltipla - ver em NotasLong noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. TP53TG1 epigenetic inactivation in cancer cells releases the transcriptional repression of YBX1-targeted growth-promoting genes and creates a chemoresistant tumor. TP53TG1 hypermethylation in primary tumors is shown to be associated with poor outcome. The epigenetic loss of TP53TG1 therefore represents an altered event in an lncRNA that is linked to classical tumoral pathways, such as p53 signaling, but is also connected to regulatory networks of the cancer cell