Nurse-Supervised Exercise for People with Stage IV Cancer: The EFICANCER Randomized Clinical Trial.

OBJECTIVES: To assess the effectiveness of the EFICANCER individualized and supervised exercise program for people with gastrointestinal, breast, or non-small cell lung stage IV cancer, in terms of quality of life and functional capacity. DATA SOURCES: Randomized controlled clinical trial with two parallel groups: EFICANCER (n = 47) and control (n = 43). Both groups received standard oncological care. In addition, the EFICANCER group participated in a nurse-supervised exercise program. Primary outcome was cancer-specific (EORTC QLQ-C30 questionnaire) and general quality of life (SF-36) at baseline and after 2, 6, and 12 months. Secondary outcomes were functional capacity (6-minute walking test), strength, and fatigue. The evolution in both groups was compared over 12 months using mixed-effect longitudinal models; 74.47% of patients completed at least one session of the program. At 12 months, EFICANCER group had better scores in cancer-related quality of life, with a difference between groups of 15.7 points (95% confidence interval 4.4 to 25.9) and in functional capacity, with a difference of 4.5 points (95% confidence interval -0.5 to 9.5). No significant differences in any other secondary variables were observed. CONCLUSION: The EFICANCER primary care nurse supervised exercise program is safe and feasible and improves cancer patient's outcomes. IMPLICATIONS FOR NURSING PRACTICE: Providing the best care and trying to improve the quality of life of cancer patients are essential parts of nursing practice. Eficancer adds a new dimension to nursing practice by providing greater attention and care to patients during treatment through the supervision of physical exercise, thereby contributing to improve the quality of life of this population.

Barreras y facilitadores del programa de ejercicio EfiKroniK para pacientes con enfermedad crónica en atención primaria / Barriers and facilitators of the EfiKroniK exercise program for people with chronic diseases in Primary Care

Objetivo: Explorar las percepciones de los pacientes durante el programa de ejercicio y detectar las barreras y los facilitadores que influyen en la adherencia al ejercicio al término de la supervisión. Diseño: Estudio observacional cualitativo con grupos de discusión como principal técnica de recogida de datos. Lugar: Centros de atención primaria de Vizcaya. Participantes: De los 175 pacientes aleatorizados del ensayo híbrido de efectividad-implementación se incluyeron 19 pacientes del grupo intervención (12 pacientes oncohematológicos en estadios avanzados y 7 con trastorno mental grave). Métodos: Se ha realizado un análisis de contenido de las transcripciones generadas, combinando un enfoque deductivo, basado en los dominios del marco teórico PRACTIS y uno inductivo, basado en los postulados de la teoría fundamentada. Resultados: Los participantes se mostraron satisfechos con el programa EfiKroniK y los beneficios fueron: descubrimiento de los beneficios del ejercicio físico, la gestión psicológica y emocional de la enfermedad, los beneficios de la comunicación entre iguales y del apoyo emocional y romper con la rutina de la enfermedad. Los participantes disminuyeron los niveles de ejercicio físico al término de la supervisión por la confluencia de diferentes barreras. Conclusión:Un programa de ejercicio supervisado realizado en atención primaria contribuyó a mejorar la calidad de vida, el bienestar emocional y social de pacientes en estadios avanzados de su enfermedad. Nuestro estudio ha identificado barreras potenciales y facilitadores asociados con la participación en el ejercicio y su continuidad; sin embargo, es necesario promover la coordinación intersectorial en el espacio sociosanitario para fomentar una atención integrada y continuada a los pacientes crónicos.(AU)

Objective: Explore patients’ perceptions during a supervised exercise program and detect the barriers and facilitators that influence exercise adherence after the supervision period. Design: A qualitative observational study with three focus groups as the main data collection technique was conducted. Site: Primary Health centers of Bizkaia. Participants: Out of the 175 randomized patients in the hybrid effectiveness-implementation trial, a sample of 19 patients from the intervention group were included in the qualitative study (12 advanced-stage onco-haematological patients and seven with severe mental disorders). Methods: Content analysis of the generated transcripts was performed by combining a deductive approach, based on the domains of the PRACTIS theoretical framework, and an inductive one, based on the postulates of the Grounded Theory. Results: The data analysis showed that participants were satisfied with the EfiKroniK program and that the main identified benefits were discovery of the benefits of physical exercise, the psychological and emotional management of the disease, the benefits from peer communication and emotional support, and the break from routine of their illness. Participants decreased the levels of physical exercise at the end of the supervision6 due to the confluence of several barriers. Conclusion: A supervised exercise program carried out in Primary Care contributed to the improvement of the quality of life as well as the emotional and social well-being of patients with advanced-stage diseases. Our study identified potential barriers and facilitators associated with exercise participation and its continuity, however, it is necessary to encourage inter-sectoral coordination within the socio-health system to promote integrated and continuous care for chronic patients.(AU)

[Barriers and facilitators of the EfiKroniK exercise program for people with chronic diseases in Primary Care]. / Barreras y facilitadores del programa de ejercicio EfiKroniK para pacientes con enfermedad crónica en atención primaria.

OBJECTIVE: Explore patients' perceptions during a supervised exercise program and detect the barriers and facilitators that influence exercise adherence after the supervision period. DESIGN: A qualitative observational study with three focus groups as the main data collection technique was conducted. SITE: Primary Health centers of Bizkaia. PARTICIPANTS: Out of the 175 randomized patients in the hybrid effectiveness-implementation trial, a sample of 19 patients from the intervention group were included in the qualitative study (12 advanced-stage onco-haematological patients and seven with severe mental disorders). METHODS: Content analysis of the generated transcripts was performed by combining a deductive approach, based on the domains of the PRACTIS theoretical framework, and an inductive one, based on the postulates of the Grounded Theory. RESULTS: The data analysis showed that participants were satisfied with the EfiKroniK program and that the main identified benefits were discovery of the benefits of physical exercise, the psychological and emotional management of the disease, the benefits from peer communication and emotional support, and the break from routine of their illness. Participants decreased the levels of physical exercise at the end of the supervision6 due to the confluence of several barriers. CONCLUSION: A supervised exercise program carried out in Primary Care contributed to the improvement of the quality of life as well as the emotional and social well-being of patients with advanced-stage diseases. Our study identified potential barriers and facilitators associated with exercise participation and its continuity, however, it is necessary to encourage inter-sectoral coordination within the socio-health system to promote integrated and continuous care for chronic patients.

Just an Acute Pulmonary Edema? Paraneoplastic Thyroid Storm Due to Invasive Mole.

Hydatidiform mole is a malignant entity included in the gestational trophoblastic diseases. It usually produces pregnancy hormones such as beta-human chorionic gonadotropin (ß-hCG), which in turn stimulates endogenous thyroid hormone production. We report the case of a high-risk complete invasive hydatidiform mole with pulmonary metastasis and associated paraneoplastic syndrome. The patient is a 30-year-old woman who presented symptoms of pregnancy and metrorrhagia. A uterine mass was detected. Urine ß-hCG was found negative. In serum, 2,662,000 mIU/mL (normal range: <5) was found, together with parameters of severe hyperthyroidism. The patient underwent uterine curettage with diagnostic and therapeutic means. At that precise moment, her pregnancy-like symptoms worsened and she developed restlessness, tachycardia, diaphoresis, dyspnea at rest, and peripheral edema. A scan showed bilateral pulmonary nodules suggestive of metastasis, acute pulmonary edema, and bilateral pleural effusion without signs of pulmonary thromboembolism. At that time, she presented a free T4 of 2.34 ng/dL (normal range: 0.8-1.8 ng/dL), causing a thyroid storm with secondary cardiac dysfunction. The patient was treated with corticosteroid therapy to decrease peripheral conversion of thyroid hormone T4 to active T3. Her symptoms remitted within 8 h. After 48 h, T4 level was 1.2 ng/dL while serum ß-hCG was 80,000 mIU/mL, with a positive urine result. The change in the urine analysis is due to the "hook effect" of the reactive test. An effective chemotherapy treatment was started according to the EMA-CO scheme, remaining free of disease at present. Knowing paraneoplastic syndromes is necessary to achieve the best clinical management and to start treatment early.

Effectiveness of physical exercise for people with chronic diseases: the EFIKRONIK study protocol for a hybrid, clinical and implementation randomized trial.

BACKGROUND: Chronic illnesses are the leading cause of morbidity and mortality and threaten the sustainability of healthcare systems worldwide. There is limited evidence in terms of the best modality and intensity of physical activity for improving cardiorespiratory capacity and quality of life in patients with chronic conditions. The objective of the EfiKroniK study is to estimate the common effect of innovative, individualized and supervised physical exercise, on cardiorespiratory functional capacity and quality of life across people with different chronic conditions. METHODS/DESIGN: This is a multicentre clinical trial with a type I hybrid effectiveness-implementation design, including 370 patients each with one of four different chronic illnesses: solid cancer, blood cancer, chronic obstructive pulmonary disease or schizophrenia. Patients will be randomly divided into two parallel groups, stratified by illness type. Patients in both groups will receive a standard healthy life prescription (PVS, from the Spanish "Prescribe Vida Saludable") and additionally, the EfiKroniK group will be prescribed a physical exercise programme tailored to each patient in terms of intensity in each session. The primary outcome variables will be cardiorespiratory functional capacity and quality of life. The secondary outcome variables will be signs and symptoms, psychological and social factors and specific laboratory parameters. We will also analyse the dose-response effect of the physical exercise programme. Qualitative variables will describe patients' perception of the utility and suitability of the EfiKroniK programme, as well as their expectations and satisfaction, identifying barriers to and facilitators of the EfiKroniK implementation process through discussion groups. The study will be carried out on an intention-to-treat basis, comparing changes throughout the 1-year follow-up between groups, adjusting for baseline, by performing mixed-effect analysis of covariance. We will estimate the effect of time on repeated measures in each subject and changes in the EfiKroniK and PVS groups over time. DISCUSSION: The study will provide the data necessary to allow us to prescribe physical exercise in a similar way to a drug and as a key part of the treatment of chronic illnesses within our healthcare system. TRIAL REGISTRATION: NCT03810755 . Date and version identifier: October 9, 2020. Version2.0.

Germline c.1A>C heterozygous pathogenic variant in SDHA reported for the first time in a young adult with a gastric gastrointestinal stromal tumour (GIST): a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) represent the most frequent mesenchymal tumor of the gastrointestinal tract. Less than 5% of them seem to be hereditary, being succinate dehydrogenase complex (SDHx) deficient disorders and neurofibromatosis type 1 the more related inherited conditions. Wild type (WT) KIT and PDGFRα GISTs constitute a clue for a hypothetical underlying germline condition. CASE PRESENTATION: We present a case of a 20 years old female diagnosed of a gastric WT GIST who developed hepatic metastases during her clinical course. No significant or typical phenotypic features suggestive of a specific syndrome were detected by physical examination. Also, her family history seemed to be irrelevant, since no other cases of GISTs, paragangliomas or pheochromocytomas were reported. Her paternal grandfather died as a consequence of a pituitary adenoma. In light of the age of tumor presentation and somatic features of gastric GIST, we performed genetic testing of SDHx genes. Analysis obtained from peripheral blood sample revealed the presence, in heterozygous state, of the c.1A > C; p.(Met1?) pathogenic variant in the SDHA. CONCLUSIONS: To the best of our knowledge, this is the first published report in which the c.1A > C; p.(Met1?) pathogenic variant in the SDHA is associated with a GIST. SDHA pathogenic variants increase the risk of paraganglioma, pheochromocytoma, GIST, pituitary adenoma and renal cancer in an autosomal dominant inherited condition named paraganglioma syndrome type 5. The absence of family history of tumors in SDHA pathogenic variants carriers could be related to its low penetrance. All patients diagnosed with WT GISTs should be referred to a hereditary cancer genetic counseling unit regardless of the age at presentation or the absence of a suspicious family history.

Hereditary pancreatic cancer: related syndromes and clinical perspective.

Pancreatic cancer is a very aggressive disease with a poor prognosis. The majority of them are attributed to sporadic causes, especially to many modifiable risk factors such as tobacco or alcohol abuse. The principal histologic subtype of pancreatic cancer is ductal adenocarcinoma. Pancreatic neuroendocrine tumors, which constitute a more indolent entity, represent second type of pancreatic cancer in terms of incidence. Individuals with a family history of pancreatic cancer carry an increased risk of developing the disease, which may be related to an underlying hereditary component. Unfortunately, in the majority of these families the suspected germline genetic cause responsible of the disease will not be identified, but approximately in a 20% of the cases a hereditary cancer predisposition syndrome with increased risk of pancreatic cancer development can be recognized. This review will be focused on the leading hereditary cancer syndromes related to pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors. Additionally, we will try to explain clinical aspects related to the identification of germline mutations in pancreatic cancer patients and their potential implications in oncologic treatment decisions.

Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis.

PURPOSE: The objective of this study was to determine the incremental staging information provided by positron emission tomography/computed tomography (PET/CT) and its impact on management plans in patients with untreated stage III-IV head and neck squamous cell carcinoma (HNSCC). METHODS: We prospectively studied, between September 2011 and February 2013, 84 consecutive patients [median age 63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on a conventional work-up (physical examination, CT imaging of the head, neck and chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage and a management plan for each patient, outlining the modalities to be used, including surgery, radiation therapy (RT), chemotherapy or a combination. After release of the PET/CT results, new TNM staging and management plans were agreed on by the multidisciplinary Tumour Board. Any changes in stage or intended management due to the PET/CT findings were then analysed. The impact on patient management was classified as: low (treatment modality, delivery and intent unchanged), moderate (change within the same treatment modality: type of surgery, radiation technique/dose) or high (change in treatment intent and/or treatment modality → curative to palliative, or surgery to chemoradiation or detection of unknown primary tumour or a synchronous second primary tumour). TNM stage was validated by histopathological analysis, additional imaging or follow-up. Accuracy of the conventional and PET/CT-based staging was compared using McNemar's test. RESULTS: Conventional and PET/CT stages were discordant in 32/84 (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients, with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %) patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7 %) than conventional staging with a p value < 0.001 (McNemar's test). CONCLUSION: PET/CT should be implemented in the routine imaging work-up of stage III-IV HNSCC.

Supervised physical exercise to improve the quality of life of cancer patients: the EFICANCER randomised controlled trial.

BACKGROUND: The optimal form of exercise for individuals with cancer has yet to be identified, but there is evidence that exercise improves their quality of life. The aim of this study is to assess the efficacy and efficiency of an innovative physical exercise programme, for individuals undergoing chemotherapy for breast, gastrointestinal or non-small cell lung tumours, for improving quality of life, reducing level of fatigue, and enhancing functional capacity over time. DESIGN/METHODS: We will conduct a clinical trial in 66 patients with stage IV breast, gastrointestinal or non-small cell lung cancer, recruited by the Department of Oncology of the referral hospital from 4 primary care health centres of the Basque Health Service (Osakidetza). These patients will be randomised to one of two groups. The treatment common to both groups will be the usual care for cancer: optimized usual drug therapies and strengthening of self-care; in addition, patients in the intervention group will participate in a 2-month exercise programme, including both aerobic and strength exercises, supervised by nurses in their health centre. The principal outcome variable is health-related quality of life, measured blindly with the 30-item European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire and Short Form-36 four times: at baseline, and 2, 6 and 12 months later. The secondary outcome variables are fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire), functional capacity (6-Minute Walk Test and cardiorespiratory test), muscle strength (hand-held dynamometry and sit-to-stand test), radiological response to treatment (Response Evaluation Criteria In Solid Tumors) and progression-free and overall survival. Age, sex, diagnosis, chemotherapy regimen, Eastern Cooperative Oncology Group performance status and smoking status will be considered as predictive variables. Data will be analysed on an intention-to-treat basis, comparing changes at each time point between groups, adjusting for baseline values by analysis of covariance. DISCUSSION: As well as achieving the objectives set, this study will provide us with information on patient perception of the care received and an opportunity to develop a project based on collaborative action between the primary care and oncology professionals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01786122 Registration date: 02/05/2013.

Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells.

BACKGROUND: Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA) is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC), and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. RESULTS: In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and -independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS) and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC) to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. CONCLUSIONS: We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and -independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.

Fixed-dose-rate gemcitabine infusion in patients with advanced pancreatic or biliary tree adenocarcinoma.

AIMS AND BACKGROUND: Gemcitabine is an effective agent in pancreatic adenocarcinoma. Fixed-dose-rate gemcitabine has an interesting biological and clinical rationale, with successful results in previous studies. We conducted a trial to confirm efficacy and toxicity of fixed-dose-rate gemcitabine in patients with pancreatic or biliary tree adenocarcinoma. METHODS: Eligible patients with locally advanced or metastatic pancreatic or biliary tree adenocarcinoma received fixed-dose-rate gemcitabine at a dose of 1500 mg/m(2) at a rate of 10 mg/m(2)/min weekly for 3 weeks every 28 days. Efficacy measures were overall survival, response rate and progression-free survival. RESULTS: Sixty-two patients were enrolled, and 59 were assessable for response. Seven patients (11.3%) had a partial response, 26 stable disease (41.9%) and 26 progressive disease (41.9%). Median time to progression was 21 weeks and median overall survival, 37.71 weeks. Main toxicities were grade 3-4 neutropenia (45.2%) and grade 2-3 asthenia (54.8%). No toxic deaths were documented. CONCLUSIONS: Fixed-dose-rate gemcitabine has a relevant antitumor activity but with significant toxicity. It represents an interesting schedule and could be combined with other biological or chemotherapeutic agents.