Cryoablation and Immunotherapy: An Enthralling Synergy for Cancer Treatment.

As less invasive options for surgical tumor removal, minimally invasive ablative techniques have gained popularity. Several solid tumors are being treated with cryoablation, a non-heat-based ablation technique. Cryoablation data in comparison over time demonstrates better tumor response and faster recovery. Combining cryosurgery with other cancer therapies has been explored to improve the cancer-killing process. Cryoablation with the combination of immunotherapy, results in a robust and efficient attack on the cancer cells. This article focuses on investigating the ability of cryosurgery to create a strong antitumor response when combined with immunologic agents resulting in a synergetic effect. To achieve this objective, we combined cryosurgery with immunotherapy using Nivolumab and lpilimumab. Five clinical cases of lymph node, lung cancer, bone, and lung metastasis were followed and analyzed. In this series of patients, percutaneous cryoablation and addressing immunity agents were technically feasible. In the follow-ups, there appeared to be no radiological evidence of new tumor development.

Factores de riesgo para el desarrollo de complicaciones tras tratamiento quirúrgico del carcinoma broncopulmonar / Risk factors for the development of complications after surgical treatment for bronchopulmonary carcinoma

INTRODUCCIÓN: El tratamiento más adecuado en la mayoría de los pacientes con cáncer de pulmón en estadio inicial es la resección quirúrgica. A pesar de evaluar anteriormente que el estado de cada paciente sea el adecuado para detectar posibles complicaciones inherentes a la intervención quirúrgica, no se ha alcanzado ningún consenso sobre los factores que son de «alto riesgo» en esos pacientes. Nuestro estudio tuvo como objetivo analizar la morbilidad y la incidencia de mortalidad asociada con esta intervención quirúrgica en nuestro entorno con un estudio multicéntrico y descubrir los parámetros de riesgo. MÉTODOS: Se trata de un estudio de análisis prospectivo con 3.307 pacientes operados de carcinoma broncopulmonar en 24 hospitales. Las variables de estudio fueron edad, sistema TNM, sexo, estadio, tabaquismo, abordaje quirúrgico, resección quirúrgica, escala ECOG, tratamiento neoadyuvante, comorbilidad, valores espirométricos y morbimortalidad intra- y postoperatoria. Se realizó un análisis de regresión logística multivariante de los factores pronósticos de morbilidad y mortalidad. RESULTADOS: Registramos el 34,2% de morbilidad postoperatoria y el 2,1% de mortalidad postoperatoria. Sexo, infarto de miocardio, angina, ECOG ≥ 1, EPOC, DLCO < 60%, estado clínico patológico, resección quirúrgica y abordaje quirúrgico aparecieron como factores pronósticos de morbilidad y mortalidad en cirugía de cáncer de pulmón en nuestra serie. CONCLUSIONES: Las principales variables que deben tenerse en cuenta al evaluar a pacientes con cáncer de pulmón para realizarles una intervención quirúrgica son sexo, infarto de miocardio, angina, ECOG, EPOC, DLCO, estado clínico patológico, resección quirúrgica y abordaje quirúrgico

INTRODUCTION: The most suitable treatment in most early-stage lung cancer patients is surgical resection. Despite previously assessing each patient's status being relevant to detect possible complications inherent to surgery, no consensus has been reached on which factors are "high risk" in such patients. Our study aimed to analyse the morbidity and the mortality incidence associated with this surgery in our setting with a multicentre study and to detect risk parameters. METHODS: A prospective analysis study with 3,307 patients operated for bronchopulmonary carcinoma in 24 hospitals. Study variables were age, TNM, gender, stage, smoking habit, surgery approach, surgical resection, ECOG, neoadjuvant therapy, comorbidity, spirometric values, and intraoperative and postoperative morbidity and mortality. A multivariate logistic regression analysis of the morbidity and mortality predictor factors was done. RESULTS: We recorded 34.2% postoperative morbidity and 2.1% postoperative mortality. Gender, myocardial infarction, angina, ECOG ≥1, COPD, DLCO <60%, clinical pathological status, surgical resection and surgery approach were shown as morbidity and mortality predictor factors in lung cancer surgery in our series. CONCLUSIONS: The main variables to consider when assessing the lung cancer patients to undergo surgery are gender, myocardial infarction, angina, ECOG, COPD, DLCO, clinical pathological status, surgical resection and surgery approach

Risk factors for the development of complications after surgical treatment for bronchopulmonary carcinoma. / Factores de riesgo para el desarrollo de complicaciones tras tratamiento quirúrgico del carcinoma broncopulmonar.

INTRODUCTION: The most suitable treatment in most early-stage lung cancer patients is surgical resection. Despite previously assessing each patient's status being relevant to detect possible complications inherent to surgery, no consensus has been reached on which factors are "high risk" in such patients. Our study aimed to analyse the morbidity and the mortality incidence associated with this surgery in our setting with a multicentre study and to detect risk parameters. METHODS: A prospective analysis study with 3,307 patients operated for bronchopulmonary carcinoma in 24 hospitals. Study variables were age, TNM, gender, stage, smoking habit, surgery approach, surgical resection, ECOG, neoadjuvant therapy, comorbidity, spirometric values, and intraoperative and postoperative morbidity and mortality. A multivariate logistic regression analysis of the morbidity and mortality predictor factors was done. RESULTS: We recorded 34.2% postoperative morbidity and 2.1% postoperative mortality. Gender, myocardial infarction, angina, ECOG ≥1, COPD, DLCO <60%, clinical pathological status, surgical resection and surgery approach were shown as morbidity and mortality predictor factors in lung cancer surgery in our series. CONCLUSIONS: The main variables to consider when assessing the lung cancer patients to undergo surgery are gender, myocardial infarction, angina, ECOG, COPD, DLCO, clinical pathological status, surgical resection and surgery approach.

Perioperative outcome of lung cancer surgery in women: results from a Spanish nationwide prospective cohort study.

BACKGROUND: To assess possible differences in the perioperative profile between men and women in lung cancer surgery. METHODS: A prospective cohort multicenter study was design, in which consecutive patients undergoing curative intent surgery for lung cancer in 24 Thoracic Services throughout Spain were included. Clinical features, tumor- and surgery-related data, postoperative complications, and mortality were recorded. RESULTS: There were 2,566 men and 741 women. Women were younger than men [mean (SD) age, 61.8 (10.8) vs. 66.5 (9.1) years, P<0.0001] and showed a more favorable preoperative characteristics, with significantly higher percentages of ECOG grade 0 and lower percentages of active smokers (28.4% vs. 33.9%; pack-years 18.8 vs. 26.9) and comorbidities [chronic obstructive pulmonary disease (COPD), diabetes, hypertension, cardiac disorders]. There were significant differences (P<0.001) in histological types and TNM stages with adenocarcinoma (70.1% vs. 46.4%) and IA stage (41.5% vs. 33.6%) more frequent in women. The use of VATS or thoracotomy was similar. The rate of pneumonectomy was higher in men (10.9%) than in women (5.1%) (P<0.001) but the distributions of other procedures were similar. Postoperative complications (pneumonitis, atelectasis, air leak, hemorrhage, fistula, empyema, wound dehiscence, and need of reintubation) were lower in women. Significant differences (P<0.0001) in the severity of postoperative complications (Clavien-Dindo classification) were also found, with higher percentages of grades I (51.6% vs. 43%) and II (37.5% vs. 33%) and lower percentages of grades III and IV among women. The mean length of hospital stay was 7.8 (7.1) days in men versus 6.3 (5.0) days in women, and the 30-day mortality rate 0.3% in women versus 2.9% in men (P<0.0001). The percentage of readmissions within 30 days after surgery was also higher in men (8.6% vs. 2.8%). CONCLUSIONS: This multicenter nationwide study of lung cancer surgery with curative intent shows that the perioperative profile is better in women than in men.

Surgical adhesive may cause false positives in integrated positron emission tomography and computed tomography after lung cancer resection.

Surgical adhesives are frequently used after pulmonary resection to prevent or reduce pulmonary air leakages, since leakages may cause complications delaying the removal of chest drainage tubes and prolonging in-hospital stay. In this paper, we present 2 patients who underwent curative-intent pulmonary resection for non-small-cell lung carcinoma, in which the biological adhesive BioGlue(®) was used. Follow-up fluoro-2-deoxy-D-glucose positron emission tomography/computed tomographic (FDG-PET/CT) imaging revealed hypermetabolic pulmonary nodular lesions. Subsequent surgical exploration showed that the lesions were foreign body reactions to the bioadhesive. To our knowledge, this is the first study to examine false-positive follow-up FDG-PET/CT scans caused by the use of BioGlue(®) in pulmonary resection procedures.

Psychosocial factors associated with the prescription of generic drugs.

OBJECTIVE: To evaluate factors associated with "Generic drug prescription" (GDP) behaviour in Spain using the ASE (Attitude, Social Influence, Self-Efficacy) Model. METHODS: General Practitioners were sent a validated and anonymous questionnaire measuring the ASE and Motivation variables for GDP and their generic drug prescription percentage. Most (n=486; 61.98%) responded to this cross-sectional survey. The mean scores and the 95% confidence intervals (95% CI) were calculated. A binary logistic regression was used to identify the variables that best predict GDP behaviour. RESULTS: The main advantages and motivations for GDP were "saving money" and "protecting professional ethics". The greatest social influences were "doctors' personal preferences" and "authorities' pressure". GDP accounted for a scarce 15% of the total prescription. ASE and Motivation items were the best predictors: they explain 25% of being a 'high prescriber'. The highest prescribers were paediatricians (OR=5.07), workers in rural settings (OR=3.68) and professionals with high Motivation (OR=1.17) and Attitude (OR=1.11) scores. CONCLUSIONS: GDP percentage is very low compared with other countries. Interventions to modify the Attitudes of Primary Care doctors towards generic drugs should be implemented. Better informed patients, longer doctor appointment times and more varied dosage forms of generic drugs would also facilitate improvements in GDP.

Risk factors for second primary tumours in breast cancer survivors.

Breast cancer (BC) survivors have an increased risk of developing second primary cancer (SPC). The aim of this study was to detect and compare SPC predictors linked to the host, the first BC and its treatment. Two hundred and seventeen patients with a nonbreast SPC and 465 matched controls, nested in the cohort of BC patients diagnosed in a Spanish region between 1975 and 2003, were involved in a case-control study. The Tumour Registry database provided information about the host, BC and its treatment factors. Their contribution to the risk of developing SPC was measured by means of a conditional logistic regression. After controlling for differences between cases and controls at baseline, obesity [odds ratio (OR): 7.48; 95% confidence interval (CI): 1.25-44.88], smoking (OR: 3.16; 95% CI: 1.23-8.15), high blood pressure (OR: 1.68; 95% CI: 1.04-2.71) and having first-degree relatives suffering from cancer (OR: 1.69; 95% CI: 1.05-2.72) were the best SPC predictors. The risk of SPC increases by 1% per month of survival from BC (OR: 1.01; 95% CI: 1.007-1.012), while having metastases (OR: 0.23; 95% CI: 0.14-0.37) and being premenopausal at diagnosis of the BC (OR: 0.44; 95% CI: 0.247-0.792) diminish the risk, probably decreasing survival. The treatments were the regression model's worst predictors. Controlling modifiable factors linked to lifestyle such as obesity and smoking is essential to prevent SPC in survivors of BC. Health education to remove persistent risk factors should be included in the treatment protocol of BC patients, because they are important predictors of SPC.

Impact of a primary care intervention on smoking, drinking, diet, weight, sun exposure, and work risk in families with cancer experience.

BACKGROUND: Modifying multiple behavior risks is a promising approach to reduce cancer risk. Primary prevention advices of the European Code against Cancer were included in an educational intervention (EI) using social cognitive theories for motivating families with cancer experiences to adopt six cancer prevention behaviors. METHODS: A randomized clinical controlled trial recruited 3,031 patients from Primary Care among cancer patients' relatives. The experimental group (EG) received four EI, one EI every six months, focused on tobacco, alcohol, diet, weight, sun and work, and based on social cognitive models. The impact of the first three EI was calculated measuring at baseline and 18 months later: (a) The percentage of people with each risk behavior; (b) The score reached in a Total Cancer Behavioral Risk (TCBR) indicator; (c) The Odds Ratios at the post-test. RESULTS: Five risk behaviors decreased significantly more (p<0.01) in the EG than in the CG: Smoking (OR=0.662), drinking (OR=0.504), diet (OR=0.542), weight (OR=0.698), and sun (OR=0.389). The TCBR indicator also decreased an average of nearly 5 points (28.42 vs. 23.82), significantly more (p<0.001) in the EG. CONCLUSION: Families with cancer experiences changed five cancer risk behaviors when approached in Primary Care with interventions based on social cognitive models.

Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung.

BACKGROUND: This study examines the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung with patients treated surgically for typical and atypical carcinoid tumours. METHODS: From 1980 to 2002, 661 patients were treated surgically for 569 typical carcinoid tumours and 92 atypical carcinoid tumours. Three hundred and four cases were studied retrospectively from 1980 to 1997 (261 typical carcinoid and 43 atypical carcinoid tumours); the other 357 new cases (308 typical carcinoid and 49 atypical carcinoid tumours) were collected prospectively from 1998 to 2002. Tumours were classified according the 1999 classification from the WHO and the International Association for the Study of Lung Cancer (IASLC). Several variables were reviewed in all patients. Univariate and multivariate statistical analyses were performed in order to determine whether clinical characteristics were associated with significant differences in survival. RESULTS: In the total of the patients, 5-year survival for different tumours was as follows: typical carcinoid: overall survival 97%; with nodal involvement 100%; atypical carcinoid: overall 78%; with nodal involvement 60%. A significant difference in survival was found between patients in the retrospective and prospective groups with atypical carcinoid and nodal involvement. The comparative analysis of several factors in typical and atypical carcinoid tumours showed a significant difference for mean age, tumour size, nodal involvement and distant metastases. CONCLUSION: Nodal involvement and histological sub-type appear as the most important factors influencing the prognosis. Adequate lung resection and systematic radical mediastinal lymphadenectomy should always be performed. Sleeve resection could be performed in central typical and atypical carcinoid tumours, avoiding pneumonectomy.

Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin.

BACKGROUND: It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. METHODS: One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12-24 h and 36-48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. RESULTS: The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12-24 h and 36-48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12-24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36-48 h of birth (sensitivity 86.5%, specificity 72.7%). CONCLUSION: Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation.

Attitude to primary prevention advice of the European Code against cancer in relatives of cancer patients: implications for the development of preventive programmes.

Achieving a preventive attitude is the first step in eliminating cancer risk behaviours. This cross-sectional study evaluated the attitude towards the European Code against Cancer, in 3,031 relatives of cancer patients. The study looked for keys to improve attitude by means of educational interventions. Attitude was evaluated using a questionnaire with 63 items and a Likert's scale. Measured from -2 to +2 , the mean score was 0.905 [0.894 - 0.971]. Five per cent had a mean score under 0.38 and another 5% over 1.46. A multivariate analysis found that age, sex and level of education were significantly associated with attitude: young men with a low cultural level were those with the lowest preventive attitude. The family history of cancer was not associated with attitude. Educational interventions should modify the perceived advantages of smoking and drinking, and the disadvantages related to preventive diet and sun and workplace protection.

Impact of cigarette advertising on smoking behaviour in Spanish adolescents as measured using recognition of billboard advertising.

BACKGROUND: Cross-sectional studies provide empirical support for associations between advertising and adolescent smoking. The aim of this study was to investigate the relationship between Spanish adolescent smoking behaviour and prior awareness of cigarette advertisements on billboards, using a prospective design. METHODS: 3,664 Spanish children aged 13 and 14 years filled in self-completion questionnaires at baseline, and 6, 12, and 18 months later (cohort study). Slides of three advertisements were projected at baseline. A multivariate logistic regression analysis was carried out to detect possible association between number of identified tobacco advertisements brands at baseline and smoking status along time, controlling ASE Model smoking determinants, smoking prevention interventions, age, gender and socio-economic status. RESULTS: The more advertisements identified at baseline, the greater was the risk of being a smoker (p<0.0001). Final percentages of smokers were 15.8%, 16.3%, 19.3%, and 32.6%, respectively, for zero, one, two and three advertisements recognized. When confounders were controlled, the probability of being a smoker increased with the number of advertisements identified [OR 1.26 (95% CI: 1.09-1.46) after 6 months, OR 1.18 (95% CI: 1.03-1.35) after 12 months and 1.15 (95% CI: 1.02-1.30)] after 18 months. It is possible the association would have been even greater if there had not been a differential loss of smokers from the sample. CONCLUSION: Increased awareness of cigarette advertising was associated with a higher smoking incidence and an increased risk of Spanish children becoming smokers. It is, therefore, imperative that cigarette advertising should be banned as a matter of urgency.

Epidemiología básica para dermatólogos / Basic epidemiology for dermatologists

La epidemiología es la ciencia que estudia la frecuencia de las enfermedades. Los estudios epidemiológicos se dividen en dos grupos, el primero de ellos engloba los dirigidos a determinar la frecuencia de enfermedad y los segundos las asociaciones entre frecuencia y exposición. Se revisan los conceptos básicos del primer grupo de estudios y se describe el segundo tipo con los errores que se presentan más frecuentemente. Se hace especial hincapié en la calidad y validez de los estudios epidemiológicos y en la evaluación y aplicación de los resultados de los estudios de tests diagnósticos (AU)

Nódulo pulmonar solitario producido por Brucella melitensis / Solitary lung nodules produced by Bruccella melitensis

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