Overview of virus and cancer relationships. Position paper.

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status.

BACKGROUND: There are conflicting data regarding the role of KRAS mutation on the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients. Moreover, the role of other biomarkers such as NRAS or BRAF has not been studied. PURPOSE: To analyze the incidence of VTE in a cohort of patients with CRC based on KRAS, NRAS, and BRAF status. METHODS: We performed a retrospective review of patients with unresectable locally advanced and metastatic CRC (mCRC) and known KRAS/NRAS/BRAF status, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain). The primary outcome was VTE defined as any venous thromboembolic event that occurred either 6 months before or at any time after the diagnosis of CRC. The biomarker status (KRAS, NRAS, and BRAF) and other predictors of thrombosis were collected. RESULTS: One hundred and ninety-four patients were identified and included in the analysis. Forty-one patients (21.1%) experienced VTE. The incidence was 19.1% in RAS-mutated patients, 28.6% in BRAF-mutated patients and 21% in triple wild-type patients (p = NS). In multivariate analysis, ECOG ≥ 2 was the only independent predictor of VTE (OR 8.73; CI 95% 1.32-57.82; p = 0.025). CONCLUSIONS: In our study, biomarkers have not been associated with an increased risk of VTE in CRC patients. A high incidence of VTE in BRAF-mutated patients has been observed and should be explored in further studies.

Dental students' knowledge regarding the indications for antibiotics in the management of endodontic infections.

AIM: To determine the knowledge of undergraduate Spanish dental students regarding the indications of systemic antibiotics in the management of endodontic infections. METHODOLOGY: The final year dental students from four Spanish dental schools were requested to answer a one-page questionnaire on the indications for systemic antibiotics in the treatment of endodontic infections. One hundred and seventy-five students were asked to participate in this research. Data were analysed using descriptive statistics and chi-square test. RESULTS: One hundred and four students (93.7%) completed satisfactorily the survey and were included in the study. The average duration of antibiotic therapy was 7.0 ± 2.0 days. All respondents chose amoxicillin as the first-choice antibiotic in patients with no medical allergies, alone (47%) or associated with clavulanic acid (53%). The first drug of choice for patients with an allergy to penicillin was clindamycin 300 mg (99%). For cases of irreversible pulpitis, up to 63% of students would prescribe antibiotics. For the scenario of a necrotic pulp, symptomatic apical periodontitis and no swelling, 44% would prescribe antibiotics. Almost 40% of students would prescribe antibiotics for necrotic pulps with asymptomatic apical periodontitis and a sinus tract. CONCLUSIONS: It is necessary for the Spanish schools of dentistry to improve students' knowledge about antibiotics and their indications in endodontics. Interactive education analysing real endodontic cases using problem-based learning would help students acquire better skills in prescribing antibiotics in pulp-periapical pathosis.

New clinical trials regulation in Spain: analysis of royal decree 1090/2015

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient’s safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as «low-intervention clinical trial». The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects’ safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research (AU)

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New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Clinical guide SEOM on venous thromboembolism in cancer patients

Venous thromboembolism (VTE) is a common event in cancer patients and one of the major causes of cancer-associated mortality and a leading cause of morbidity. In recent years, the incidence rates of VTE have notably increased; however, VTE is still commonly underestimated by oncologists. VTE is considered an adverse prognostic factor in cancer patients in all settings. In 2011 the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of prophylaxis and treatment of VTE in cancer patients. In an effort to incorporate evidence obtained since the original publication, SEOM presents an update of the guideline for thrombosis and cancer in order to improve the prevention and management of VTE (AU)

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Clinical guide SEOM on venous thromboembolism in cancer patients.

Venous thromboembolism (VTE) is a common event in cancer patients and one of the major causes of cancer-associated mortality and a leading cause of morbidity. In recent years, the incidence rates of VTE have notably increased; however, VTE is still commonly underestimated by oncologists. VTE is considered an adverse prognostic factor in cancer patients in all settings. In 2011 the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of prophylaxis and treatment of VTE in cancer patients. In an effort to incorporate evidence obtained since the original publication, SEOM presents an update of the guideline for thrombosis and cancer in order to improve the prevention and management of VTE.

Incidence of venous thromboembolism (VTE) in ambulatory pancreatic cancer patients receiving chemotherapy and analysis of Khorana's predictive model

PURPOSE: To evaluate the incidence of venous thromboembolism (VTE) in ambulatory pancreas cancer patients receiving chemotherapy and analyze Khorana's predictive model of chemotherapy-associated thrombosis. METHODS/PATIENTS: We performed a retrospective review to determine the incidence of VTE in the gastrointestinal cancer unit of our center. Between 2008 and 2011, 84 consecutives patients diagnosed with pancreas adenocarcinoma were identified and included in the analysis. Pancreatic neuroendocrine tumors were excluded. RESULTS: Thirty patients experienced VTE (35.7 %) and 66 % of the events were diagnosed during the first 6 months after diagnosis. Khorana's score: 33.3 % of the intermediate category patients developed a venous thromboembolic event and 37.5 % in the high-risk category. CONCLUSIONS: The high incidence of VTE observed in this study is consistent with prior reports. Specific predictive model for chemotherapy-associated thrombosis in pancreatic cancer must be investigated (AU)

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Chemobrain: ¿podemos hablar de un daño cerebral adquirido por quimioterapia? / Chemobrain: can we consider an acquired brain injury from chemotherapy?

Objetivo: Conocer el deterioro cognitivo producido por la quimioterapia en una muestra de pacientes con cáncer de mama frente a los controles y frente a sí mismas, antes y después del tratamiento. Pacientes y método: Estudio de corte longitudinal prospectivo. Se administró la Mini International Neuropsychiatric Interview, se evaluó depresión, ansiedad, función sexual, calidad de vida y sueño. Se midió memoria, atención, velocidad de procesamiento, memoria de trabajo, función ejecutiva y fluidez. Tanto la muestra inicial como la final fue de 19 pacientes y 19 controles. Resultados: Las pacientes presentaron diferencias en depresión, ansiedad, calidad de vida, función sexual y calidad de sueño frente al grupo control en el momento basal y a los seis meses. Se encontraron diferencias neurocognitivas entre pacientes y controles antes del tratamiento en memoria y en función ejecutiva y después del tratamiento en memoria, función ejecutiva e índice de función prefrontal. Conclusiones: Encontramos diferencias entre pacientes y controles antes de comenzar el tratamiento, síntomas de ansiedad, depresión, calidad de vida y sueño, en función sexual y en las variables neurocognitivas de memoria y función ejecutiva. Tras la quimioterapia, se observó declive en las pacientes respecto a los controles en: ansiedad, depresión, calidad de vida, calidad de sueño y función sexual y los dominios cognitivo de atención, memoria, función ejecutiva e índice de función prefrontal (AU)

Objective: To meet the cognitive impairment caused by chemotherapy in a sample of patients with breast cancer versus controls and themselves, before and after treatment. Patients and methods: Prospective longitudinal study. The Mini International Neuropsychiatric Interview was administered and other emotional symptoms like depression, anxiety, sexual function, quality of life and sleep was assessed. Memory, attention, processing speed, working memory, executive function and flow were measured. Both the initial and the final sample were 19 patients and 19 controls. Results: Patients differ in depression, anxiety, quality of life, sexual function, and quality of sleep versus controls at baseline and 6-month. Neurocognitive differences between patients and control group were found in memory before treatment and executive function. After treatment the differences were in memory, executive function and index of prefrontal function. Conclusion: There are significant differences between patients and control group before starting treatment, symptoms of anxiety, depression, quality of life and sleep, sexual function and neurocognitive variables in memory and executive function. After chemotherapy, decline was seen in patients respect control group in: anxiety, depression, and quality of life, quality of sleep and sexual function and cognitive domains of attention, memory, executive function and index of prefrontal function (AU)

Sistemas ultrasónicos para la irrigación del sistema de conductos radiculares / Ultrasonic devices for root canal system irrigation

La eliminación de los restos de tejido pulpar vital y necrótico y de los microorganismos del sistema de conductos radiculares, es esencial para el éxito en endodoncia. La desinfección del canal radicular mediante la irrigación e instrumentación es el factor más importante en la prevención y tratamiento de la periodontitis apical. Al ser imposible con la instrumentación llegar a todas las áreas del sistema de conductos, la irrigación cobra especial importancia. Por este motivo, en la última década se han desarrollado una serie de sistemas de dispensación y agitación de irrigantes, tales como los ultrasonidos. En concreto, en este artículo de revisión se evalúa la información disponible de los diez últimos años sobre la efectividad de los sistemas ultrasónicos para eliminar bacterias, tejido pulpar, restos de dentina y barrillo dentinario, la capacidad de estos dispositivos para hacer que el irrigante penetre en el sistema de conductos radiculares y la seguridad en su uso. Los resultados de la revisión muestran que los sistemas ultrasónicos son más eficaces en el desbridamiento químico, biológico y físico del sistema de conductos radiculares que los sistemas de irrigación convencional, a la vez que son seguros (AU)

Removal of vital and necrotic remnants of pulp tissues and microorganisms from the root canal system is essential for endodontic success. Disinfection of the root canal by irrigation and instrumentation are the most important factors in the prevention and treatment of apical periodontitis. As it is impossible for the instruments to reach all the areas of the root canal system, the irrigation has gained special importance. Due to this fact, technological advances during the last decade have brought new delivery and agitation devices, such as ultrasonic devices. Particularly, this review article assesses the available information from the last ten years about the effectiveness of ultrasonic devices to remove bacteria, pulp tissue, dentin debris and smear layer, and the ability of these devices to make the irrigant solution penetrate into the root canal system and the safety of its use. Nowadays scientific literature reveals that ultrasonic devices are more effective on chemical, biological and physical debridement of the root canal system than conventional technique and being safety devices at the same time (AU)

Incidence of venous thromboembolism (VTE) in ambulatory pancreatic cancer patients receiving chemotherapy and analysis of Khorana's predictive model.

PURPOSE: To evaluate the incidence of venous thromboembolism (VTE) in ambulatory pancreas cancer patients receiving chemotherapy and analyze Khorana's predictive model of chemotherapy-associated thrombosis. METHODS/PATIENTS: We performed a retrospective review to determine the incidence of VTE in the gastrointestinal cancer unit of our center. Between 2008 and 2011, 84 consecutives patients diagnosed with pancreas adenocarcinoma were identified and included in the analysis. Pancreatic neuroendocrine tumors were excluded. RESULTS: Thirty patients experienced VTE (35.7 %) and 66 % of the events were diagnosed during the first 6 months after diagnosis. Khorana's score: 33.3 % of the intermediate category patients developed a venous thromboembolic event and 37.5 % in the high-risk category. CONCLUSIONS: The high incidence of VTE observed in this study is consistent with prior reports. Specific predictive model for chemotherapy-associated thrombosis in pancreatic cancer must be investigated.

Spanish Society of Medical Oncology consensus on the use of erythropoietic stimulating agents in anaemic cancer patients

Treatment of anaemia is a very important aspect in the management of cancer patients. In order to carry out a consensus process about the use of erythropoietic stimulating agents (ESAs) in cancer patients, the Spanish Society of Medical Oncology (SEOM) elaborated a working group which coordinated a panel of medical oncology specialists. This working group has reviewed the main issues about the use of ESAs. In addition a consensus meeting was held in Madrid on 25 April 2007. The following conclusions were made: Since ESA treatment increases the haemoglobin (Hb) level and decreases the red blood cell (RBC) transfusion requirements, ESAs should be used within the approved indications in patients undergoing chemotherapy treatment, beginning at a Hb level below 11 g/dl and maintaining it around 12 g/dl, with iron supplements if necessary. Neither increasing the ESA dose in nonresponders nor the use of ESAs in the treatment of chronic cancer-related anaemia is recommended (AU)

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Spanish Society of Medical Oncology consensus for the use of haematopoietic colony-stimulating factors in cancer patients

Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating factors (CSF) may be used to avoid neutropenia-associated complications. The Spanish Society of Medical Oncology (SEOM) recently constituted a working group to review the main issues concerning the use of CSF and carried out a consensus process about the use of CSF in cancer patients, held in Madrid on 26 May 2006. The group concluded the following recommendations: prophylactic use of CSF is recommended when a rate of febrile neutropenia (FN) higher than 20% is expected without the use of CSF or when additional risk factors for neutropenia exist; therapeutic use of CSF is recommended in order to treat FN episodes but not to treat afebrile neutropenic episodes. In addition, the use of CSF is considered effective when used to mobilise stem cells before high-dose chemotherapy and when used for chemotherapy schedule optimisation in dose-dense and in dose-intense regimens (AU)

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer.

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered.

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered (AU)

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Endocrine therapy of metastatic breast cancer

Breast cancer growth and dissemination is regulated by estrogen and different growth factor receptor signalling pathways. The increasing knowledge of the biology of breast cancer regarding the interaction of these signalling pathways provides a tool to understand endocrine therapies response and resistance mechanisms. In patients with slowly progressive disease, no visceral involvement, and minimal symptoms, endocrine therapy could be the strategy of choice, even if the tumor has low estrogen receptor expression. Ovarian suppression and tamoxifen are recommended for premenopausal patients whether aromatase inhibitors are the option for postmenopausal ones. Chemotherapy still remains as the right alternative for hormone unresponsive or resistant patients. This is a review focused on the different strategies and combinations of endocrine therapies for metastatic breast cancer patients considering the potential strategies clinically tested to overcome resistance and the different treatments of choice available for each scenario of disseminated disease (AU)

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[Cardiotoxicity induced by 5-fluorouracil. Review of the literature]. / Cardiotoxicidad inducida por 5-fluorouracilo. Revisión de la literatura.

5-fluorouracil is potentially cardiotoxic to man. To date, 47 patients have been reported with undesired heart disorders after the administration of this cytotoxic drug. The incidence of cardiotoxicity due to 5-FU is 1.6%. Angina-type precordial pain with electrocardiographic changes suggesting myocardial ischemia is the common clinical feature. Generally it disappears spontaneously or after the use of coronary vasodilators. Acute left ventricular failure, pericarditis and rythm disorders are not often found. The pathogenesis is unknown however, cardiac spasm as well as the direct or indirect effect of the drug on myocardium, are possible responsible mechanisms.

Treatment of advanced ovarian cancer with cisplatin, adriamycin and cyclophosphamide (PAC).

Forty two ovarian cancer patients with residual disease after the first laparotomy were treated with the combination of cisplatin (80 mg/m2 day 1), adriamycin (50 mg/m2 i.v. day 2) and cyclophosphamide (500 mg/m2 i.v. day 2) (PAC). Forty women were considered evaluable for analysis, with an overall response rate (partial, plus complete responses) of 62.5%. Twelve patients (30%) obtained a complete response (histologically confirmed after second look surgery in 6 cases, surgical complete response, residual tumor completely resected in the second look-in 5 cases and maintained complete clinical remission without second look confirmation in 1 case). Main side effects were nausea and vomiting (90%), leukopenia (70%), mucositis (45%), and anemia (37%). Seventeen percent of the patients were free of disease at 60 months, after a median follow-up of 48 months. The prognostic factors that showed significant influence on survival were the Karnofski index (90-100 vs 80 or less), stage of the disease (II + III vs IV) and the volume of residual tumor after the first surgical procedure (less than or equal to 2 cms vs greater than 2 cms). Patients who achieved a complete remission have not reached the median 5 years survival, which was 10 months for the remaining patients. These results confirm the activity of PAC in ovarian cancer, mainly in those patients with residual tumor of less than 2 cms and good performance status.