Pseudoprogresión tumoral en el tratamiento inmunoterápico con nivolumab en el cáncer de pulmón / Tumor pseudoprogression during nivolumab immunotherapy for lung cancer

OBJETIVOS: La inmunoterapia es un nuevo tratamiento en estadios avanzados del cáncer de pulmón de célula no pequeña (CPCNP) que modula la respuesta inmunitaria frente a células malignas. Un reto para el radiólogo es la valoración del fenómeno de la pseudoprogresión, en la que se observa un aumento o aparición de lesiones por infiltración de células inflamatorias, con posterior disminución o desaparición de estas, hecho que traduce en realidad la respuesta al tratamiento. El objetivo fue determinar la frecuencia de pseudoprogresión en pacientes con CPCNP en estadios avanzados tratados con nivolumab. PACIENTES Y MÉTODOS: Se incluyeron 56 pacientes con CPCNP en estado avanzado tratados con nivolumab en segunda línea o posterior. Se analizaron las tomografías computarizadas (TC) realizadas durante el período de tratamiento. Se consideró pseudoprogresión tumoral al aumento o aparición de lesiones con posterior disminución o desaparición en una TC de control realizada a las 4-8 semanas. Se realizó un análisis descriptivo. RESULTADOS: No se pudo valorar la existencia de pseudoprogresión en 15 pacientes porque no se disponía de al menos dos TC (por cambio de tratamiento o fallecimiento). Se observó pseudoprogresión tumoral en un 12,2% (5/41) de los pacientes, en la mayoría de los casos antes de las 12 semanas del inicio del tratamiento (en el 4. ° ciclo). Un 40% (2/5) de los pacientes con pseudoprogresión presentó un segundo episodio, que se produjo de forma tardía, a partir de las 12 semanas del inicio del tratamiento. CONCLUSIÓN: Se observó pseudoprogresión tumoral en un 12,2% de los pacientes con CPCNP tratados con nivolumab. El aumento o aparición de lesiones debe valorarse evolutivamente para evitar diagnosticar erróneamente progresión de la enfermedad

OBJECTIVES: Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for radiologists in the evaluation of the response to immunotherapy is the phenomenon of pseudoprogression, in which the infiltration of inflammatory cells causes lesions to increase in size or new lesions to appear and then decrease in size or disappear. Pseudoprogression actually represents a response to treatment. We aimed to determine the frequency of pseudoprogression in patients with advanced stages of lung cancer treated with nivolumab. PATIENTS AND METHODS: We included 56 patients with advanced stages of lung cancer treated with nivolumab as a second-line or later treatment. We analyzed CT studies done while patients were undergoing nivolumab treatment. Tumor pseudoprogression was defined as an increase in the size of lesions or appearance of new lesions followed by a decrease in size or disappearance of these lesions on follow-up CT studies 4 to 8 weeks later. We did a descriptive analysis. RESULTS: In 15 patients, it was impossible to evaluate possible pseudoprogression because a second CT study was unavailable due to change of treatment or death. Tumor pseudoprogression was observed in 5 (12.2%) of the 41 patients, in most cases within 12 weeks of treatment initiation (in the fourth cycle). A second episode of pseudoprogression occurred in 2 (40%) of the 5 patients with an initial episode; the second episode occurred more than 12 weeks after treatment initiation. CONCLUSION: Tumor pseudoprogression occurred in 12.2% of patients with advanced stage lung cancer treated with nivolumab. An increase in lesion size or the appearance of new lesions must be assessed over time to avoid mistaking pseudoprogression for true progression of disease

Tumor pseudoprogression during nivolumab immunotherapy for lung cancer. / Pseudoprogresión tumoral en el tratamiento inmunoterápico con nivolumab en el cáncer de pulmón.

OBJECTIVES: Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for radiologists in the evaluation of the response to immunotherapy is the phenomenon of pseudoprogression, in which the infiltration of inflammatory cells causes lesions to increase in size or new lesions to appear and then decrease in size or disappear. Pseudoprogression actually represents a response to treatment. We aimed to determine the frequency of pseudoprogression in patients with advanced stages of lung cancer treated with nivolumab. PATIENTS AND METHODS: We included 56 patients with advanced stages of lung cancer treated with nivolumab as a second-line or later treatment. We analyzed CT studies done while patients were undergoing nivolumab treatment. Tumor pseudoprogression was defined as an increase in the size of lesions or appearance of new lesions followed by a decrease in size or disappearance of these lesions on follow-up CT studies 4 to 8 weeks later. We did a descriptive analysis. RESULTS: In 15 patients, it was impossible to evaluate possible pseudoprogression because a second CT study was unavailable due to change of treatment or death. Tumor pseudoprogression was observed in 5 (12.2%) of the 41 patients, in most cases within 12 weeks of treatment initiation (in the fourth cycle). A second episode of pseudoprogression occurred in 2 (40%) of the 5 patients with an initial episode; the second episode occurred more than 12 weeks after treatment initiation. CONCLUSION: Tumor pseudoprogression occurred in 12.2% of patients with advanced stage lung cancer treated with nivolumab. An increase in lesion size or the appearance of new lesions must be assessed over time to avoid mistaking pseudoprogression for true progression of disease.

SEOM clinical guidelines in early stage breast cancer (2018)

Breast cancer is the most common cancer in women in our country and it is usually diagnosed in the early and potentially curable stages. Nevertheless, around 20-30% of patients will relapse despite appropriate locoregional and systemic therapies. A better knowledge of this disease is improving our ability to select the most appropriate therapy for each patient with a recent diagnosis of an early stage breast cancer, minimizing unnecessary toxicities and improving long-term efficacy

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SEOM clinical guidelines in early stage breast cancer (2018).

Breast cancer is the most common cancer in women in our country and it is usually diagnosed in the early and potentially curable stages. Nevertheless, around 20-30% of patients will relapse despite appropriate locoregional and systemic therapies. A better knowledge of this disease is improving our ability to select the most appropriate therapy for each patient with a recent diagnosis of an early stage breast cancer, minimizing unnecessary toxicities and improving long-term efficacy.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: a new era begins.

The discovery of mutated oncogenes has opened up a new era for the development of more effective treatments for non-small cell lung cancer patients (NSCLC) harbouring EGFR mutations. However, patients with EGFR-activating mutation ultimately develop acquired resistance (AR). Several studies have identified some of the mechanisms involved in the development of AR to EGFR tyrosine kinase inhibitors (TKI) that can be potential therapeutic strategies, although in up to 30% of cases, the underlying mechanism of AR are still unexplained. In this review we aim to summarize the main mechanisms of AR to EGFR TKI and some clinical strategies that can be used in the daily clinical practice to overcome this resistance and try to prolong the outcomes in this subgroup of patients.

Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response

PURPOSE: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. METHODS: Patients with HER-negative operable stage II-III BC ≥ 2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. RESULTS: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. CONCLUSION: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials (AU)

Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response.

PURPOSE: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. METHODS: Patients with HER-negative operable stage II-III BC ≥ 2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. RESULTS: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. CONCLUSION: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.

The combined performance of UV light and chlorine during reclaimed water disinfection.

The combined effects of disinfectant agents on the microbiological quality of reclaimed water produced by two full-scale water reclamation plants in Catalonia, Spain, were examined in this work. All the disinfectant treatments tested led to the absence, or near absence, of E. coli in 100 mL samples of water, with log reductions of more than 3 log u. Hypochlorite reduced the bacterial concentrations. However, ultraviolet light was more effective than hypochlorite at reducing the concentrations of bacteriophages, viruses and pathogenic protozoa such as Cryptosporidium spp. We conclude that a combination of these two disinfectant agents is effective in protecting public health, as each agent acts to a different degree against the different groups of microorganisms studied. Further studies should investigate the combined action of disinfectant agents at water reclamation plants with ultraviolet light equipment in more favourable working conditions in order to assess their capacity to inactivate microorganisms.

[Patient satisfaction in a home enteral nutrition program]. / Evaluación del grado de satisfacción de un programa de nutrición enteral domiciliaria.

UNLABELLED: Home enteral nutrition is a treatment carried out frequently due to advantages for patients and caregivers (lower risk of nosocomial infections and better integration in socio-familiar media) but also for the health administration because of the lower economic cost and the release of hospital beds. OBJECTIVE: To investigate patients' and caregivers' satisfaction related to tube enteral nutrition administered at home by a Service controlled and followed by the Nutritional Support Unit from the reference hospital. METHODS: One questionnaire for the patients and another for the caregivers were delivered to the patients with home enteral nutrition asking for voluntary response. Similar questionnaires were sent to hospitalized patients and their relatives or possible caregivers. RESULTS: According to the results of the questionnaires, the majority of patients and relatives were satisfied with the service received. In the cases in which the service was offered at home, the preference was to continue there and not to return to the hospital. Finally, the possibility of telephone contact and home visits were the most important factors that influenced patient satisfaction. CONCLUSION: Our results let us conclude that home enteral nutrition controlled and followed up by the Nutritional Support Unit form the hospital is a treatment well accepted both by patients and relatives.

Evaluación del grado de satisfacción de un programa de nutrición enteral domiciliaria / Patient satisfaction in a home enteral nutrition program

La nutrición enteral a domicilio es un tratamiento cada vez más utilizado por las ventajas que comporta no sólo al paciente y familiares o cuidadores (menos riesgo de infecciones nosocomiales y mejor integración socio-familiar) sino también a la administración en el sentido de representar un ahorro en coste económico además de disponer de mas camas de hospitalización. Objetivo: Analizar el grado de satisfacción de los pacientes y familiares o cuidadores en relación a un servicio de Nutrición Enteral Domiciliaria (NED) controlado desde la Unidad de Nutrición del Hospital. Metodología: Un cuestionario para los pacientes y otro para los familiares/cuidadores fue remitido a los enfermos que recibiendo nutrición enteral por sonda en su domicilio quisieron voluntariamente colaborar. Cuestionarios similares se remitieron a pacientes ingresados en el hospital tratados con nutrición enteral así como a sus posibles cuidadores en el caso de que recibieran este tratamiento a domicilio. Resultados: De acuerdo con los resultados, en general los pacientes y cuidadores consideran bueno o muy bueno el servicio recibido. Si este tratamiento se ofrece en el domicilio lo habitual es que quieran seguir con esta modalidad y no volver al hospital para recibirlo. Finalmente, la posibilidad de disponer de contacto telefónico seguido de visita si es necesaria, es la preferencia de elección. Conclusiones: Los resultados de las encuestas realizadas en nuestros pacientes/familiares permiten concluir que la nutrición enteral domiciliaría dentro de un programa de atención y seguimiento a domicilio controlado desde la Unidad de Nutrición del hospital de referencia es un tratamiento muy bien aceptado tanto por pacientes como por familiares de los mismos o cuidadores

Home enteral nutrition is a treatment carried out frequently due to advantages for patients and caregivers (lower risk of nosocomial infections and better integration in socio-familiar media) but also for the health administration because of the lower economic cost and the release of hospital beds. Objetive: To investigate patients’ and caregivers’ satisfaction related to tube enteral nutrition administered at home by a Service controlled and followed by the Nutritional Support Unit from the reference hospital. Methods: One questionnaire for the patients and another for the caregivers were delivered to the patients with home enteral nutrition asking for voluntary response. Similar questionnaires were sent to hospitalized patients and their relatives or possible caregivers. Results: According to the results of the questionnaires, the majority of patients and relatives were satisfied with the service received. In the cases in which the service was offered at home, the preference was to continue there and not to return to the hospital. Finally, the possibility of telephone contact and home visits were the most important factors that influenced patient satisfaction. Conclusion: Our results let us conclude that home enteral nutrition controlled and followed up by the Nutritional Support Unit form the hospital is a treatment well accepted both by patients and relatives

Gastrointestinal stromal tumors.

BACKGROUND: We reviewed radiologic features of gastrointestinal stromal tumors (GISTs) and correlated them with clinical and pathologic findings. METHODS: We investigated a series of 39 c-Kit-positive GISTs. Clinical and radiologic findings and management of these patients were recorded. RESULTS: Twenty women and 19 men (mean age 64 years) had histologically proved GIST. Tumor locations were the small bowel (n = 20), stomach (n = 14), rectum (n = 4), and omentum (n = l). Symptoms at presentation were most frequently gastrointestinal bleeding (n = 14) and abdominal pain (n = l1). Tumors were classified as very low risk (n = 2), low risk (n = 10), intermediate risk (n = 12), and high risk (n = 11). Ultrasonography, computed tomography, magnetic resonance, digital subtraction angiography, and barium series were used in the evaluation of these tumors. Most tumors were seen as well-delineated soft tissue masses with heterogeneous contrast enhancement. Necrosis, calcification, and ulceration were most commonly seen in large tumors that presented a more aggressive behavior. CONCLUSION: GISTs can arise anywhere in the gastrointestinal tract and present a great variety of clinical and radiologic features, depending mostly on size and location.

[Use of magnetic resonance imaging to evaluate morphological disorders in the brains of patients with sickle cell anaemia]. / Evaluación de las afecciones morfológicas en el cerebro de pacientes con anemia de células falciformes con el uso de imágenes de resonancia magnética.

INTRODUCTION: Blocked blood flow in the brain of patients with sickle cell anaemia (SCA) gives rise to disorders in this organ and, occasionally, courses with no clinical symptoms. AIMS: Our objective was to determine the most common lesions in the brains of patients with SCA in the eastern region of Cuba. PATIENTS AND METHODS: We conducted a study with children and adults with SCA, who were voluntarily included in the research protocol. The 28 adult patients had no history of vaso-occlusive crises of the central nervous system, and their ages ranged from 17 to 48 years. In addition, 50 paediatric-aged patients between the ages of 2 and 17 years were evaluated. Images were obtained with the Cuban magnetic resonance imaging equipment Giroimag 01 at 0.05 T. RESULTS: Both studies showed that cortical atrophy (CA) is the most frequent brain lesion among those found in the population of patients evaluated. The study revealed 35.7% of patients with silent lesions in adults and 18% in the children. CONCLUSIONS: CA is the lesion that is most commonly seen in the population studied. The brain lesions that were found are possibly triggered by the effect of blockages in the blood flow in the brain. A population study must be conducted in order to determine the first disorders triggered by the blocked blood flow in the brains of these patients. There is also a need to evaluate the possible risk factors that favour the development of these lesions.

Evaluación de las afecciones morfológicas en el cerebro de pacientes con anemia de células falciformes con el uso de imágenes de resonancia magnética / Use of magnetic resonance imaging to evaluate morphological disorders in the brains of patients with sickle cell anaemia

Introducción. La oclusión del flujo de sangre en el cerebro de los pacientes con anemia de células falciformes (ACF) provoca afecciones en este órgano, y en ocasiones transcurren sin síntomas clínicos. Objetivo. Encontrar las lesiones más comunes en el cerebro de pacientes con ACF de la región oriental de Cuba. Pacientes y métodos. Estudio de niños y adultos con ACF, incluidos voluntariamente en el protocolo de investigación. Los 28 pacientes adultos no tenían antecedentes de crisis vasooclusivas del sistema nervioso central, y sus edades estaban comprendidas entre 17 y 48 años. Se evaluaron 50 pacientes en edad pediátrica, entre los 2 y los 17 años. Las imágenes se obtuvieron con el equipo cubano de imágenes de resonancia magnética Giroimag ® 01 a 0,05 T. Resultados. Ambos estudios mostraron que la atrofia cortical es la lesión cerebral más frecuente de las encontradas en la población de pacientes evaluados. El estudio refleja un 35,7 por ciento de pacientes con lesiones silenciosas en los adultos y un 18 por ciento en los niños. Conclusiones. La atrofia cortical es la lesión que más se manifiesta dentro de la población estudiada. Las lesiones cerebrales encontradas pueden ser provocadas por el efecto de la oclusión de la circulación sanguínea en el cerebro. Es necesario desarrollar un estudio de población para determinar las primeras afecciones provocadas por la oclusión del flujo sanguíneo en el cerebro de estos pacientes. También se deben evaluar los posibles factores de riesgo que favorecen el desarrollo de estas lesiones (AU)

Introduction. Blocked blood flow in the brain of patients with sickle cell anaemia (SCA) gives rise to disorders in this organ and, occasionally, courses with no clinical symptoms. Aims. Our objective was to determine the most common lesions in the brains of patients with SCA in the eastern region of Cuba. Patients and methods. We conducted a study with children and adults with SCA, who were voluntarily included in the research protocol. The 28 adult patients had no history of vaso-occlusive crises of the central nervous system, and their ages ranged from 17 to 48 years. In addition, 50 paediatric-aged patients between the ages of 2 and 17 years were evaluated. Images were obtained with the Cuban magnetic resonance imaging equipment Giroimag ® 01 at 0.05 T. Results. Both studies showed that cortical atrophy (CA) is the most frequent brain lesion among those found in the population of patients evaluated. The study revealed 35.7% of patients with silent lesions in adults and 18% in the children. Conclusions. CA is the lesion that is most commonly seen in the population studied. The brain lesions that were found are possibly triggered by the effect of blockages in the blood flow in the brain. A population study must be conducted in order to determine the first disorders triggered by the blocked blood flow in the brains of these patients. There is also a need to evaluate the possible risk factors that favour the development of these lesions (AU)

Medicare's DRG-weights in a European environment: the Spanish experience.

Hospital payment systems are being changed to mixed systems, composed of case-mix categories and structure indicators. The Health Care Financing Administration's Diagnosis-Related-Groups (HCFA's DRG-weights are used in Catalonia as Prospective Payment System (PPS)-instruments for hospital inpatient reimbursement. The Catalonian and Spanish health systems, however, are very different from the US health environment. The aim of this study is to determine whether the HCFA's DRG-weights fit the special characteristics of a European environment. To do this, cost-based weights, determined from information from the cost accounting system of two public hospitals in Barcelona, are compared with Medicare-weights. A total of 35 262 discharges representing 12 794 million pesetas are analyzed. Medicare-weights do not differ globally from cost-based-weights and the adjusted correlation weighted least squares regression between the two weight-scales is 95%. There are, however, systematic deviations in six DRG-groupings. The most important deviations are concentrated in Ambulatory Surgery categories, in DRGs in which prostheses are used, and in specialties excluded from several PPSs because of extreme variables in treatment intensity. In conclusion, Medicare-weights can be used to pay hospital output in European environment but they should be adjusted to avoid systematic deviations.

Effect of different carbon sources on lipase production by Candida rugosa.

Different carbon sources affecting growth and lipase production in Candida rugosa were studied by using batch cultures on defined medium. Carbohydrates and acids non-related to fats did not induce lipase production. The highest yields of enzyme were obtained with lipids or fatty acids as carbon sources. Tween 80 stimulated lipase biosynthesis and secretion outside the cell. Combinations of two types of substrates, carbohydrates and fatty acids, did not improve lipase production, and in some cases, their consumption was produced in a sequential pattern. Glucose presented a repressing effect on lipase production. Moreover, glucose was found to be effective in stimulating lipase secretion by cells with a high level of cell-bound lipase activity because of their previous growth in oleic acid.

Prunus Rootstock Evaluation to Root-knot and Lesion Nematodes in Spain.

Two screening and one resistance verification trial involving 20 Prunus rootstocks were conducted under greenhouse conditions against Meloidogyne spp. and Pratylenchus vulnus. Most of the rootstocks were experimental genotypes or new commercial peach and plums of Spanish and French origin. Nearly all are interspecific hybrid rootstocks. In the first trial, the rootstocks Bruce, Cadaman, Mirac, G x N No. 15, Cachirulo x (G x N No. 9), and P. myra x peach were immune or resistant to a mixture of seven isolates of M. incognita. In the second screening trial, the hybrid plum P 2588 was a poor host to a mixture of four isolates of P. vulnus. The remaining seven rootstocks were good hosts to the root-lesion nematode. In the resistance verification trial GF-31, G x N No. 15, Torinel, AD- l 01, Monpol, Nemaguard, and Cadaman maintained a high level of resistance when tested against a mixture of 17 isolates comprising M. incognita, M. javanica, M. arenaria, M. hapla, and M. hispanica. Barrier peach suffered a partial loss of resistance not detected in previous tests.