Opioid-Induced Constipation in Oncological Patients: New Strategies of Management

Opinion statement Cancer-associated pain has traditionally been treated with opioid analgesics, often in escalating doses. Opioid-induced constipation (OIC) is a common problem associated with chronic use of opioid analgesics. Typical treatment strategies to alleviate constipation are based on dietary changes, exercise, and laxatives. However, laxatives have a nonspecific action and do not target underlying mechanisms of OIC. This article will review prevalent, clinical presentation and recommendations for the treatment of OIC. An independent literature search was carried out by the authors. We reviewed the literature for randomized controlled trials that studied the efficacy of laxatives, naloxone, and naloxegol in treating OIC. Newer strategies addressing the causal pathophysiology of OIC are needed for a more effective assessment and management of OIC. Finally, traditional recommended therapies are appraised and compared with the latest pharmacological developments. Future research should address whether naloxegol is more efficacious by its comparison directly with first-line treatments, including laxatives

Expression of P-glycoprotein and metallothionein in gastrointestinal stromal tumor and leiomyosarcomas. Clinical implications

We investigated the expression of P-glycoprotein (P-GP) and metallothionein (MT) in a series of 92 GIST and 14 gastrointestinal leiomyosarcomas (GILMS) with the purpose to expand our knowledge on the biological bases of GIST chemo-resistance and to ascertain their significance in patients’ prognosis. P-GP expression was more frequent in GIST than in GI-LMS (83.7% vs. 21.4%, p<0.001), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=0.538). P-GP expression was unrelated to anatomic location (gastric vs. intestinal) in GIST (39/45 vs. 35/43, p=0.770) and in GI-LMS (0/2 vs. 2/6, p=1.000). MT expression was non-significantly higher in GI-LMS than in GIST (35.7% vs. 14.1%, p=0.060), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=1.000). MT expression was unrelated to the anatomic location (gastric vs. intestinal) in GIST (7/45 vs. 6/43) and GI-LMS (0/2 vs. 1/6) (p=1.000 and p=0.1000, respectively). Overall tumor-specific survival (p< 0.001) and disease-free survival (p<0.001) were different in GIST as compared with GI-LMS, and the number of events was higher in GI-LMS. When the survival analysis took into consideration P-GP or MT expression, the overall survival in GIST was influenced by the expression of MT (p=0.021) but not by that of P-GP (p=0.638). However, in GI-LMS, P-GP expression influenced disease-free survival (p=0.050); in addition, it is important to recognize the limited value of these results because of the low number of cases involved in the study. Differential expression of P-GP and MT might explain the known variability in response to systemic chemotherapy in these tumors. Detection of P-GP and MT seems to add certain prognostic value in GIST (MT) or GI-LMS (P-GP)

Estudio de los criterios clínico - evolutivos diferenciadores de los carcinomas “no habituales” de la mama y su influencia en el pronóstico

Cuando nos referimos al comportamiento del Carcinoma de mama, es decir a la clínica, evolución y al pronóstico que este tipo de tumor tiene, generalmente lo hacemos valorando el comportamiento del Carcinoma Ductal Infiltrare, ya que esto supone aproximadamente un 80% del total del Carcinoma de mama. No obstante sabemos que existen tipos de tumores de mama que podríamos denominar como “no habituales” que tienen características clínico-patológicas y evolutivas diferenciadoras. En este estudio nos hemos propuesto observar la incidencia de los distintos tipos histopatológicos del Carcinoma de mama; las manifestaciones clínico-evolutivas de estos subtipos y la valoración de la supervivencia actuarial de las neoplasias cuyo número de casos lo hicieron posible. Revisamos 1.000 Carcinomas de mama con confirmación anatomopatológica vistos en el quinquenio 1981-86. De todos estos pacientes recogimos en un protocolo los siguientes aspectos de cada paciente;: datos personales, datos clínicos, tratamiento inicial, tipificación anatomopatológica definitiva y la evolución posterapéutica. Los datos obtenidos fueron tratados estadísticamente, separándolos por variedades anatomopatológicas, al igual que la tasa de metástasis, el intervalo libre de enfermedad y el patrón metastásico inicial. La supervivencia actuarial fue hallada en aquellos tipos de tumores en los que la muestra fue suficiente. La proporción encontrada en nuestra muestra de Carcinomas “no habituales” de mama es de aproximadamente un 20% y en ella hemos podido distinguir: 48 Carcinomas Lobulillares Infiltrantes; 33 Carcinomas Medulares; 30 Comedocarcinomas; 27 Carcinomas Inflamatorios; 17 Carcinomas Coloides; 13 Carcinomas Papilares; 10 Enfermedad de Paget; 6 Carcinomas Lobulillares “in situ”; 6 Carcinomas Papilares Intraquísticos; 3 Carcinomas Tubulares; 3 Carcinomas de Células en anillo de sello; 2 Carcinomas Apocrinos y 1 Carcinoma Adenoide Quístico. De este grupo de enfermos podemos significar que el Carcinoma Lobulillar Infiltrante tiene unas características clínico-evolutivas muy similares al Carcinoma global de mama, si bien parece observarse una mayor tasa de metástasis con un intervalo libre de enfermedad alto y una supervivencia superponible a la del global del Carcinoma de mama. En las pacientes con Carcinoma Medular, observamos que existe una gran rapidez en la evolución de los síntomas con un retraso en la consulta sensiblemente más corta que el del global para todos los Carcinomas, así como una baja tasa de metástasis y una supervivencia más alta que la de los demás tipos histológicos. En las pacientes con Comedocarcinomas, salvo la tasa de metástasis que parece ser menor -aunque es corto el seguimiento efectuado-, la clínica y la evolución es muy similar a la del global de Carcinoma de mama. Los pacientes revisados con Carcinoma Inflamatorio tiene una clínica muy florida, con una tasa de metástasis muy alta y un pronóstico nefasto. Observamos que la edad media de los tipos histológicos “no habituales” coincide prácticamente con la global de los Carcinomas de mama, si bien esta edad es superior en los Carcinomas Coloides, en la Enfermedad de Paget y en el Carcinoma Papilar Intraquístico. Todos los tumores debutaron a nivel de T., salvo una pequeña proporción cuyo debut fue a nivel ganglionar en región axilar y ninguno con enfermedad metastásica. Cuando valoramos el tiempo de retraso a la consulta por parte del paciente para los subtipos histopatológicos y lo comparamos con el global, observamos que no existe diferencias significativas, salvo en el Carcinoma Papilar y en la Enfermedad de Paget, donde este retraso es mayor y en el Carcinoma Medular que es inferior. La valoración de la tasa de metástasis, el intervalo libre de enfermedad y el patrón metastásico, aunque el seguimiento es corto, observamos que no existe diferencias significativas con el global del Carcinoma de mama, si bien el Carcinoma Inflamatorio y la Enfermedad de Paget, tienen un alto índice de metástasis. Por último en la valoración de la supervivencia, observamos que las tasas de supervivencia a los 5 años para los estadíos II del Carcinoma Medular es más alta que para el Comedocarcinoma y para el Carcinoma Lobulillar Infiltrante, aunque no existen diferencias estadísticas significativas entre ellos. A su vez la supervivencia del global de Carcinoma de mama, aunque es algo menor, en la práctica es superponible con la de los tumores estudiados

Leptin, Both Bad and Good Actor in Cancer.

Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the "obesity paradox", and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology

Circulating regulatory T cells from breast cancer patients in response to neoadjuvant chemotherapy

Background: Immune escape of tumor cells is a new hallmark of cancer in general, and breast cancer, in particular. Previous studies have demonstrated that the immunological profile in peripheral blood may be a prognostic and/or predictive biomarker in breast cancer. Thus, higher number of regulatory T cells (Tregs) in blood from patients with breast cancer has been reported in relation to normal donors. In the present study, we planned to evaluate the changes in different cell populations in peripheral blood: neutrophils, monocytes and lymphocytes, as well as lymphocyte subpopulations [natural killer (NK), B lymphocytes, T lymphocytes, both CD4(+) and CD8(+), and Tregs] from patients with local breast cancer (both Her2(+) and Her2(-)), before, during and after neoadjuvant chemotherapy.Methods: We have employed flow cytometry for the cell analysis of fresh samples obtained before and whilst the neoadjuvant treatment was accomplished. We have studied 50 successive patients from the Breast Cancer Unit of the Virgen Macarena University Hospital during 2 years.Results: Neoadjuvant chemotherapy induced a significant reduction in B cells, especially in Her2(-) patients, and a reduction in NK cells. CD4(+) T cells decreased, whereas CD8(+) cells only decreased in Her2(-) patients. Tregs were also diminished, especially in Her2(+) patients, in response to treatment. Thus, higher CD8/Treg ratio was observed in Her2(+) patients. A higher percentage of Her2(+) patients (66.6%) achieved complete response than Her2(-) patients (27.5%). Monocytes and neutrophils were not changed in peripheral blood.Conclusions: Even though the decrease in B cells and NK cells in response to chemotherapy may be deleterious in the neoadjuvant treatment of breast cancer, the decrease in Tregs and CD4 T cells, but not CD8 T cells, increasing the CD8/Treg ratio, especially in Her2(+) patients, may reveal a new tool to monitor the immune response in breast cancer treated with chemotherapy in the neoadjuvant setting

Cáncer de mama: proceso asistencial integrado 3ª ed

YesEn el documento se aborda el cáncer de mama desde la gestión por procesos, analizando y ordenando los flujos de trabajo y con la necesidad de actualización del conocimiento científico, planes de cuidados y todos los aspectos de la enfermedad. Por ello, en esta tercera edición, se realiza una revisión y actualización de la anterior, incorporando nuevos aspectos relacionados con dimensiones específicas de calidad, tales como la persona, la evidencia científica, el uso adecuado del medicamento, los cuidados enfermeros y la seguridad del paciente