Erythromycin: an alternative for the management of oral mucositis?

Background: Oral mucositis (OM) is an important acute adverse effect of anticancer therapy. This condition presents high morbidity and may lead to the suspension of anticancer therapy.Material and Methods: We reviewed the literature on the pathobiology of OM and the properties of erythromycin(EM), to consider the possibility of its use for the prevention and treatment of OM. We searched the PubMed,Scopus and Web of Science databases and selected complete articles published in English or Spanish that met theinclusion criteria. The search terms “erythromycin”, “inflammation”, “immunomodulation” and “oral mucositis”were used.Results: The control of free radicals, transcription factors and pro-inflammatory cytokines has been consideredas the key to the management of OM. EM has the ability to modulate oxidative stress, acts on the transcriptionalsystem and inhibits the production of several cytokines that have been directly implicated in OM pathobiology.Conclusions: The present review suggests that EM could be effective in the treatment of OM. Experimental studies investigating the use of EM in OM should be encouraged. (AU)

Risk factors for oral mucositis during chemotherapy treatmentfor solid tumors: a retrospective STROBE-guided study

Background: This study retrospectively analyzed the risk factors for transchemotherapy oral mucositis (OM).Material and Methods: Before each chemotherapy cycle, patients were routinely evaluated for the presence/severity of OM based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effectsand graded as follows: However, specific conditions such as mucositis are graded on a five-point scale: 0, absenceof mucositis, grade 1 (Asymptomatic or mild), 2 (Presence of pain and moderate ulceration, without interferencewith food intake), 3 (severe pain with interference with food intake) or 4 (Life-threatening with the need for urgentintervention). Information from 2 years of evaluations was collected and patient medical records were reviewed toobtain data on chemotherapy cycle, sex, age, body mass index, body surface area, primary tumor, chemotherapyprotocol, and history of head and neck radiotherapy. The X² test and multinomial logistic regression were used forstatistical analysis (SPSS 20.0, p<0.05).Results: Among 19,000 total evaluations of 3,529 patients during 5.32±4.7 chemotherapy cycles (CT) the prevalence of OM was 6.3% (n=1,195). Chemotherapy duration (p<0.001), female sex (p=0.001), adjuvant intention(p=0.008) and the use of carboplatin (p=0.001), cisplatin (p=0.029), docetaxel (p<0.001) and bevacizumab(p=0.026) independently increased the risk of mucositis. In head and neck tumors, 2018 year (p=0.017), chemotherapy duration (p=0.018), BMI>30 (p=0.008), radiotherapy (p=0.037) and use of carboplatin (p=0.046) andcyclophosphamide (p=0.010) increased this prevalence.Conclusions: Cycles of chemotherapy, sex, cytotoxicity drugs, bevacizumab and head and neck radiotherapy increase the risk of OM in solid tumors. (AU)

Erythritol-enriched powder and oral biofilm regrowth on dental implants: an in vitro study / Polvo enriquecido con eritritol y crecimiento de biopelículas orales sobre implantes dentales: un estudio in vitro

Backgroud: Peri-implant mucositis and peri-implantitis are the main biological complications associated withdental implants. Since most authors agree that bacteria play a major etiological role, the main aims of this studywere to determine if a formulation of erythritol and chlorhexidine applied with an air polishing system inhibitsbiofilm re-growth over dental implants and to compare the decontamination capacity of this therapy with that ofmechanical removal by saline and gauze.Material and Methods: A multispecies biofilm (P. gingivalis, A. actinomycetemcomitans, F. nucleatum, A. naes-lundii, V. parvula and S. oralis) was grown for 14 days on 52 dental implants in an artificial mouth. These implantswere divided into three groups according to the applied treatment: 14 negative control (CON), 19 erythritol-chlorhexidine (ERY) and 19 gauze with saline (GAU) samples. Twelve dental implants from the ERY and GAUgroups and 8 implants from the CON group were re-incubated for 7 additional days after treatment. The bacterialcount was performed by quantitative polymerase chain reaction (qPCR) using propidium monoazide (PMA). Adescriptive and bivariate analysis of the data was performed.Results: The erythritol and chlorhexidine formulation significantly inhibited biofilm regrowth in comparison withthe mechanical treatment (GAU), since a significant decrease in all the species was observed in the ERY group(except for Aggregatibacter actinomycetemcomitans). The antibiofilm and antibacterial capacity of the two activetreatment groups (ERY and GAU) was similar for a 14 days multispecies in vitro biofilm, except for the lowercount of A. naeslundii in the GAU group. Conclusions: The use of erythritol powder with chlorhexidine applied with an air polishing system reduces biofilmregrowth over dental implants when compared with mechanical removal by saline and gauze. This effect might bebeneficial for patients included in peri-implant maintenance programs.(AU)

La mucositis por metotrexato como marcador de toxicidad medular. Estudio retrospectivo de las características clínicas y epidemiológicas / Methotrexate-Induced Mucositis as a Sign of Bone Marrow Toxicity: A Retrospective Study of Clinical and Epidemiological Characteristics

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Interacción mortal entre 5-fluorouracilo y brivudina / Lethal interaction between 5-fluorouracil and brivudine

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Prevention of oral mucositis secondary to antineoplastic treatments in head and neck cancer by supplementation with oral glutamine / Prevención de la mucositis oral secundaria a los tratamientos antineoplásicos en el cáncer de cabeza y cuello mediante suplemento con glutamina oral

Objectives: to evaluate the efficacy of glutamine in the prevention of the incidence of oral mucositis secondary to cancer therapies in patients with head and neck cancer (HNC). Secondary objectives were to know the incidence of odynophagia, interruptions of treatment and the requirements of analgesia and nasogastric tube. Material and methods: prospective cohort study of patients with squamous cell carcinoma of HNC treated with radiotherapy ± concomitant chemotherapy. We compared 131 patients receiving glutamine orally at a dose of 10 g/8 hours with 131 patients who did not receive it. Results: patients not taking glutamine had a hazard ratio 1.78 times higher of mucositis (95% CI [1.01-3.16], p = 0.047). Regarding odynophagia, patients not taking glutamine had a hazard ratio 2.87 times higher (95% CI [1.62-5.18], p = 0.0003). The 19.8% of patients who did not take glutamine discontinued treatment versus 6.9% of patients who took (p = 0.002). Regarding support requirements, 87.8% of patients without glutamine required analgesia versus 77.9% of patients with glutamine (p = 0.03) and nasogastric tube was indicated in 9.9% and 3.1% respectively (p = 0.02). Conclusion: oral glutamine in patients receiving cancer treatments for HNC prevents the incidence of oral mucositis and odynophagia, and decreases treatment interruptions and the use of analgesia and nasogastric tube

Objetivos: evaluar la eficacia de la glutamina en la prevención de la incidencia de mucositis secundaria a las terapias oncológicas en pacientes con carcinoma de cabeza y cuello. Los objetivos secundarios fueron conocer la incidencia de odinofagia e interrupciones de los tratamientos y los requerimientos de analgesia y sonda nasogástrica. Material y métodos: estudio prospectivo de cohortes de pacientes con carcinoma epidermoide de cabeza y cuello tratados con radioterapia ± quimioterapia concomitante. Se compararon 131 pacientes que recibieron glutamina oral a una dosis de 10 g/8 horas con 131 pacientes que no la recibieron. Resultados: los pacientes que no tomaron glutamina tuvieron una hazard ratio 1,78 veces mayor de mucositis (IC 95% [1,01-3,16], p = 0,047). Respecto a la odinofagia, los pacientes que no tomaron glutamina tuvieron una hazard ratio 2,87 veces mayor (IC 95% [1,62-5,18], p = 0,0003]. El 19,8% de los pacientes que no tomaron glutamina interrumpieron el tratamiento versus 6,9% de los pacientes que la tomaron (p = 0,002). En cuanto a los tratamientos de soporte, el 87,8% de los pacientes sin glutamina requirieron analgesia versus 77,9% de los pacientes con glutamina (p = 0,03) y la sonda nasogástrica fue indicada en un 9,9% y 3,1% respectivamente (p = 0,02). Conclusión: la glutamina oral en pacientes que reciben tratamiento por carcinoma de cabeza y cuello, previene la incidencia de mucositis oral y odinofagia y disminuye las interrupciones de tratamientos y el uso de analgesia y sonda nasogástrica

Bacteriemia por Leptotrichia trevesanii. Descripción de un caso / Bacteremia by Leptotrichia trevesanii. Case report

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Chewing gum is more effective than saline-solution gargling for reducing oral mucositis

Objective: This quasi-experimental study compared the effectiveness of chewing gum and gargling with a saline solution as two types of intervention to reduce oral mucositis scores. Method: The sample consisted of 44 children who were divided into two groups, one of which chewed gum, and the other gargled with a saline solution. The Mann-Whitney U test was used to analyze the data. Results: There was a significant difference (p = 0.001) in post-intervention oral-mucositis scores. The significant mean difference between the groups indicated that the decreased oral mucositis scores for the chewing gum group was more substantial than for the group gargling with a saline solution (p = 0.001). Conclusions: The data showed that chewing gum is more effective than gargling with a saline solution, and it can be incorporated into the nursing protocol for treating pediatric cancer patients

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Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells

Purpose. Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model. Methods. Syrian hamsters, 8–9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression. Results. TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05). Conclusions. TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients (AU)

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Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy

Purpose. The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent. Methods. A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT. Results. Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use. Conclusions. FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use (AU)

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Exantema mucocutáneo inducido por Mycoplasma pneumoniae: ¿un nuevo síndrome separado del eritema multiforme? Un nuevo caso y revisión de la literatura / Mycoplasma pneumoniae-Induced Mucocutaneous Rash: A New Syndrome Distinct from Erythema Multiforme? Report of a New Case and Review of the Literature

La infección respiratoria por Mycoplasma pneumoniae (MP) puede producir erupciones cutáneo-mucosas que se han considerado parte del espectro eritema multiforme o del síndrome de Stevens-Johnson. La clasificación de estas reacciones cutáneas, que tiene importancia pronóstica y terapéutica, ha generado mucha controversia en la literatura. Recientemente, una revisión sistemática de 202 casos de erupciones mucocutáneas asociadas a infección por MP concluye que pueden constituir una entidad distinta para la que se propone la expresión Mycoplasma-induced rash and mucositis. Presentamos un caso de infección respiratoria aguda por MP con lesiones mucosas y cutáneas difíciles de clasificar como eritema multiforme o síndrome de Stevens-Johnson, y cuyas características son compatibles con la nueva enfermedad propuesta

Respiratory tract infection due to Mycoplasma pneumoniae can provoke cutaneous and mucosal rashes, which have been classified within the spectrum of erythema multiforme or Stevens-Johnson syndrome. This classification is of therapeutic and prognostic importance and has generated intense debate in the literature. A recent systematic review of 202 cases of mucocutaneous rashes associated with M. pneumoniae infection concluded that these rashes might constitute a distinct entity, for which the term Mycoplasma-induced rash and mucositis was proposed. We describe a patient with acute M pneumoniae respiratory tract infection who presented mucosal and cutaneous lesions that were difficult to classify as erythema multiforme or Stevens-Johnson syndrome; the lesions were compatible with the proposed new disease

Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients

Introduction: Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged C70 years. Materials and methods Clinical: records of patients aged C70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11-70 Gy) for curative purposes and 54 Gy (range 40-56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI). Results: Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70–90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade C1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade C1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed. Conclusion: Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity (AU)

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Jaw mobility changes in patients with upper aerodigestive tract cancer undergoing radiation therapy

BACKGROUND: Radiation therapy is a therapeutic modality widely used for treatment of upper aerodigestive tract (UADT) neoplasms. However, its action is not restricted to tumor cells, and it may cause a variety of adverse reactions, including reduced jaw mobility. MATERIAL AND METHODS: A prospective cohort study was conducted to assess changes in jaw mobility in patients with UADT cancer undergoing radiation therapy. RESULTS: Fifty-six patients completed the study. The results showed a significant reduction in mouth opening (p < 0.001), right lateral excursion (p = 0.038) and left lateral excursion (p = 0.035) of the jaw, a significant increase in the presence (p < 0.001) and severity of oral mucositis (p < 0.001), and a significant decrease in performance status (p < 0.001) after radiation therapy. Thirty-six patients (64.3%) exhibited reduction in mouth opening after treatment. The variables significantly associated with mouth opening reduction on bivariate analysis were: modification of diet (p = 0.037), radiation field (p = 0.024), presence of mucositis (p = 0.003), and reduction in performance status (p = 0.007). After adjustment by the multivariate model, the only variables that remained significantly associated with reduction in mouth opening were presence of mucositis (p = 0.018) and reduction in performance status (p = 0.47). CONCLUSIONS: These findings indicate that patients with upper aerodigestive tract cancer experience reduced jaw mobility after radiation therapy, which is strongly correlated with mucositis and reduced functional ability

Casos clínicos de eficacia y seguridad del fentanilo intranasal con pectina en Oncología Radioterápica / Efficacy and safety of fentanyl pectin nasal spray in Radiation Oncology: clinical cases

Aproximadamente un 60% de los pacientes diagnosticados de cáncer requiere, en algún momento de su enfermedad, radioterapia. Aunque suelen ser tratamientos bien tolerados, en ocasiones los pacientes presentan dolor de intensidad moderada-severa en relación con la irradiación de determinadas localizaciones o al realizar dolorosos procedimientos necesarios para administrar el tratamiento. Este trabajo describe 2 situaciones clínicas con dolor irruptivo frecuentes en la asistencia diaria de los servicios de radioterapia: en primer lugar, el dolor secundario a la mucositis, que conlleva pérdida de peso y detrimento de la calidad de vida del paciente y, en segundo lugar, el dolor incidental producido por los posicionamientos y maniobras necesarias para administrar el tratamiento. Para ambas situaciones, en la Fundación Jiménez Díaz se diseñaron 2 estudios prospectivos introduciendo el fentanilo intranasal con pectina, con eficacia y resultados satisfactorios para pacientes y profesionales sanitarios. Estos 2 estudios continúan abiertos y se sigue reclutando pacientes para confirmar estos resultados

Approximately 60% of patients with a cancer diagnosis require radiotherapy. Although usually well tolerated, this treatment can sometimes produce radiation-related moderate-to-severe pain in certain locations or during painful procedures required for radiotherapy administration. This article describes two clinical situations of breakthrough pain in routine practice in radiotherapy departments: firstly, pain secondary to mucositis, which leads to weight loss and impaired quality of life; secondly, incidental pain caused by positioning and the maneuvers required for treatment administration. In both situations, we designed two prospective studies of fentanyl pectin nasal spray in the Fundación Jiménez Días. The results were satisfactory for both patients and healthcare professionals. These two studies remain open and are recruiting patients to confirm these results

Uso de la glutamina en la nutricion parenteral total de pacientes sometidos a trasplante de médula ósea / Use of glutamine in total parenteral nutrition of bone marrow transplant patients

La glutamina es un amioácido esencial para la síntesis de nucleótidos y una fuente de energía para la replicación celular, existe evidencia contradictoria respecto a los beneficios de su administración como parte de la nutrición parenteral en pacientes sometidos a trasplante de médula ósea (TMO). Más del 75% de los pacientes sometidos a trasplante de precursores hematopoyéticos, presentan durante su evolución complicaciones que comprometen el tracto digestivo, principalmente mucositis, limitando la ingesta oral, de allí la necesidad del uso de nutrición parenteral total (NPT) en estos casos. Objetivo: Analizar la relación entre uso de glutamina en la NPT de TMO y la evolución de complicaciones agudas como mucositis, EICH e infecciones, así como la estancia hospitalaria y los días de nutrición parenteral total. Material y métodos: Estudio observacional retrospectivo. Se incluyeron la totalidad de TMO con NPT entre 2007 y 2013 en nuestro hospital. Se analizaron días de hospitalización, días de soporte nutricional, uso de glutamina y complicaciones agudas. Los resultados se analizaron con el programa SPSS 15.0. Resultados: Se incluyeron 73 pacientes trasplantados, se dividieron en dos grupos según el aporte de glutamina siendo ambos grupos comparables entre sí. La edad media fue de 36,96±12,89 años. El 47,9% de los pacientes estudiados recibió suplemento de glutamina en la NPT. Los pacientes que recibieron glutamina tuvieron una estancia media de 31,49±7,41 días con 14,11±5,87 días de NPT en comparación a los que no recibieron glutamina con 32,16±7,99 y 15,50±7,71 días respectivamente (p=0,71 y 0,39). La duración de la mucositis en los pacientes que recibieron glutamina fue de 12,23±5,66 días comparado con 15,50±7,71 días en los que no recibieron glutamina (p=0,042).Se observaron grados severos de EICH (II, III) en un 20,6% de los pacientes sin glutamina en comparación al 13,7% en los que la recibieron (p=0,636). Del total de los de los pacientes estudiados, el 13,7% sufrieron complicaciones infecciosas mientras recibían NPT con glutamina, comparado con 16,4% en pacientes que no recibieron (p=0,700). Conclusiones: En nuestra serie, se observó una reducción estadísticamente significativa en la duración de la mucositis en pacientes que recibieron NPT con glutamina

Glutamine is an essential amino acid for nucleotide synthesis and an important energy resource for cellular division. There is contradictory evidence about its benefits as part of parenteral nutrition. More than 75% of bone marrow transplant patients (BMTP) have, during their evolution, digestive tract complications limiting enteral nutrition, for this reason, sometimes total parenteral nutrition (TPN) is required. Objective: Our aim was to analyze the relation between the use of glutamine in TPN of BMTP, and the evolution of clinical acute complications as mucositis, graft versus host disease (GVHD) and infections days of stay and days of TPN. Materials and Methods: observational retrospective study. All BMTP with total parenteral nutrition during the period 2007-2013 were included. We analyzed days of stay, days of nutrition, glutamine use and acute complications. Results were analyzed in SPSS 15.0. Results: 73 BMTP were divided in two comparable groups depending on glutamine use. The mean age was 36,96 ± 12,89 years. 47,9% of patients received glutamine in TPN. Patients who received glutamine had a mean stay of 31,49±7,41 days with 14,11±5,87 days of TPN compared with the non-glutamine group with 32,16±7,99 and 15,50±7,71 days respectively (p=0,71 y 0,39). Mucositis lasted 12,23±5,66 days in the glutamine group, and 15,50±7,71 days in the non-glutamine group (p=0,042). Severe grades of GVHD (II,III) was observed in 20,6% of the non glutamine group compared with the 13,7% of the other group (p=0,636). In patients with glutamine suplementation, mucositis last 12,23±5,66 days compared with 15,50±7,71 days in the non-glutamine group (p=0,042).13,7% of all patients suffered infections while receiving TPN with glutamine compared with 16,4% in patients who did not receive glutamine (p=0,700). Conclusion: In our group, a statistically significant reduction in the duration of mucositis was observed in patients who received parenteral glutamine

Eficacia de los opioides tópicos como analgésicos en enfermedades dolorosas cutáneas. Revisión de la literatura científica y propuesta metodológica para su evaluación clínica / Analgesic efficacy of topical opioids in painful cutaneous conditions. Literature review and methodological proposal for clinical evaluation

Introducción: aunque se trata de una práctica frecuente en algunos centros, es aún poca la evidencia que justifica el uso de formulaciones tópicas a base de opioides en el tratamiento analgésico de enfermedades dolorosas cutáneas y en mucosas. Objetivos: realizar una revisión actualizada sobre la literatura científica disponible de la evidencia que justifica el uso de opioides tópicos en el tratamiento de enfermedades cutáneas y orales dolorosas. Evaluar la eficacia analgésica reportada y los efectos adversos de los opioides tópicos en el tratamiento de enfermedades cutáneas y orales dolorosas. Métodos: se realizó una búsqueda electrónica utilizando las siguientes bases de datos y motores de búsqueda: EMBASE, Medline, SCIELO, LATINDEX, Current Controlled-Trials y Google académico, para identificar la literatura sobre opioides tópicos en el tratamiento de enfermedades dolorosas de la piel y la mucosa oral. El método propuesto para la selección de la muestra de trabajos está basado en la combinación de diferentes perfiles de búsqueda electrónica compuestos por descriptores referentes a opioides tópicos y tratamiento del dolor. Se construyeron diferentes sintaxis de búsqueda, considerándose ortodoxo utilizar términos obtenidos del vocabulario MeSH. Los términos de búsqueda utilizados fueron: 'opioides', 'tópico, 'analgésico', 'úlcera', 'mucositis', 'periférico' y combinaciones de estas palabras. Se identificaron los artículos adicionales a partir de las listas de referencias de los documentos recuperados, los artículos de revisión pertinentes y de revistas seleccionadas. La búsqueda final tuvo lugar en julio de 2013. Los criterios de inclusión para la revisión fueron: estudios en humanos, publicados en los idiomas español, francés, inglés o alemán, que contuvieran los datos principales sobre la eficacia de la aplicación tópica de opioides. Se excluyeron del análisis aquellos estudios que evaluaran la eficacia de opioides administrados por métodos invasivos (como vía intrapleural, intravesical, o intraarticular) o en administración oftálmica. Resultados y conclusiones: se incluyeron 28 publicaciones a partir de la búsqueda, 11 correspondieron a estudios prospectivos, aleatorizados, controlados. La duración de los estudios aleatorizados fue corta, con un seguimiento inferior a una semana. No existe sin embargo suficiente información para comparar los estudios por la heterogeneidad de las poblaciones y de los tratamientos instaurados. Los estudios que controlaron niveles de opioides sistémicos comentan resultados contradictorios respecto a la absorción sistémica de los opioides a través de piel ulcerada, posiblemente asociado a variables como fármaco, preparación, dosis, extensión de la aplicación y duración del tratamiento. Respecto a los efectos adversos, estos son en apariencia mínimos y limitados a reacciones locales, y aquellos estudios que los reportan no determinan una relación de causalidad definitiva (AU)

Introduction: Even though it is a common practice in some centers, there is still little evidence that justifies the use of topical opioid-based analgesics in skin and mucosal diseases. Objectives: To review the available scientific literature that justifies the use of topical opioids in the treatment of painful skin and mucosal diseases. Evaluate the analgesic efficacy and adverse effects of topical opioids in the treatment of oral diseases and painful skin diseases. Methods: An electronic search was performed using the following databases and search engines: EMBASE, Medline, SCIELO, LATINDEX, Current Controlled-Trials and academic Google to identify the literature on topical opioids in the treatment of painful skin and oral mucosa diseases. The selection method was based on the combination of different descriptors concerning topical opioids and pain using MeSH vocabulary. The search terms used were 'opioid' 'topic', 'analgesic', 'ulcer', 'mucositis', 'peripheral' and combinations of these words. Additional articles were retrieved from the reference lists of papers identified. The final search took place in July 2013. The inclusion criteria for the review were: Human studies, published in Spanish, French, English or German, containing main data on the efficacy of topical opioids as analgesics. We excluded from analysis studies that evaluated the effectiveness of opioids administered by invasive methods (such intrapleural, intravesical, or intraarticular) or ophthalmic administration. Results and conclusions: 28 publications were included from the search, 11 corresponded to prospective, randomized, controlled trials. The duration of randomized studies was short, with a following period of one week or less. There isn’t however enough information to compare studies because of the heterogeneity of populations and treatments. The studies that controlled systemic levels of opioids comment conflicting results regarding the absorption of topical opioids through ulcerated skin, possibly associated with variables such as drug preparation, dosage, application extension and duration of treatment. Regarding adverse effects, these are minimal in appearance and limited to local reactions, and those studies that report these do not determine a definitive causal relationship (AU)

Safety and efficacy of metronomic non-pegylated liposomal encapsulated doxorubicin in heavily pretreated advanced breast cancer patients

PURPOSE: Metronomic administration of the same chemotherapy agents (lower doses with closer intervals) may optimize their antiangiogenic properties. The aim of our study was to determine the efficacy and safety of a metronomic regimen based in non-pegylated liposomal doxorubicin (NPLD) in advanced breast cancer patients. METHODS: Clinical records of patients with pretreated advanced breast cancer and who were treated with the Metronomic-Cooper-type regimen consisting of weekly fixed doses of NPLD (30 mg IV) plus 5-Fluorouracil (5-FU) (500 mg IV) plus vincristine (0.25 mg IV) and daily oral cyclophosphamide (50 mg) plus prednisone (20 mg) were reviewed. RESULTS: In 84 pretreated patients, a tumor response was observed in 38 patients (45 %); stable disease was observed in 23 patients (27 %). Median progression-free survival (PFS) time to progression was 8.4 months and median overall survival (OS) was 21 months. The most common grade 2-3 hematologic adverse event was neutropenia, which was observed in 47 patients (56 %). Febrile neutropenia was observed in 10 patients (12 %). The most common non-hematologic adverse events were asthenia and mucositis which were observed in 60 patients (71 %) and 26 patients (31 %), respectively. Three patients (4 %) experienced an asymptomatic decline of the left ventricular ejection fraction. CONCLUSIONS: NPLD-based metronomic regimen was effective and safe in pretreated advanced breast cancer patients. It could be considered as an appealing option to treat patients previously exposed to anthracyclines (AU)

Eficacia de la glutamina parenteral en pacientes sometidos a trasplante autólogo de médula ósea / Efficacy of parenteral glutamine in patients undergoing bone marrow transplantation

Introducción: El Trasplante Autólogo de Médula Ósea(TASPE) conlleva un alto estrés metabólico. La glutamina es considerada se ha mostrado eficaz en estados catabólicos severos, aunque hay estudios contradictorios. Objetivos: Valorar el efecto del tratamiento con nutrición parenteral (NP) suplementada con glutamina en el desarrollo de mucositis y en la estancia media hospitalaria en pacientes sometidos a TASPE. Metodología: Estudio retrospectivo de pacientes con TASPE efectuados entre 2006 y 2009. En 2008 se introdujo de forma protocolizada la adición de 1 vial de L-alanil-L-glutamina (20 g) en las fórmulas de NP de dichos pacientes. Se seleccionaron aleatoriamente 13 historias apartir de dicha fecha (grupo glutamina) y 13 historias anteriores (grupo control) (n = 26). Se comparó el grado de mucositis y la estancia hospitalaria en los dos grupos. En el subgrupo de pacientes tratados con glutamina, se comparó la dosis de glutamina que recibieron los pacientes que desarrollaron algún grado mucositis con aquellos que no presentaron dicha complicación. Resultados: Estancia media: 27,8 ± 7,4 días (grupo control) vs 20,3 ± 5,3 días (grupo glutamina) (p = 0,01). La gravedad de la mucositis fue menor en el grupo glutamina (p = 0,02). La dosis de L-alanail-L-glutamina ajustada por peso en los pacientes que no desarrollaron mucositis fue mayor que en los que la desarrollaron (0,32 vs 0,24g/kg/día; p = 0,02).Conclusiones: La suplementación con glutamina reduce el grado de mucositis y la estancia hospitalaria en pacientes sometidos a transplante autólogo de médula ósea. El grado de mucositis es menor en el subgrupo de pacientes que reciben dosis más elevadas de glutamina (AU)

Introduction: Autologous bone marrow transplant(ABMT) represents a high metabolic stress. Glutamine has proven to be effective in severe catabolic states, although there are controversial studies. Objectives: To assess the effect of parenteral nutrition(PN) therapy supplemented with glutamine on the occurrence of mucositis and mean hospital stay in patients submitted to ABMT. Methods: Retrospective study of patients submitted to ABMT between 2006 and 2009. In 2008, one vial of Lalanyl-L-glutamine (20 g) was added by protocol to the PN formulations of these patients. Thirteen clinical charts since that date (glutamine group) and 13 previous charts (control group) were randomly selected (n = 26).We compared the degree of mucositis and hospital stay in both groups. In the subgroup of glutamine-treated patients, we compare the glutamine dose in the patients developing some degree of mucositis with that of those not having this complication. Results: Mean hospital stay: 27.8 ± 7.4 days (control group) vs. 20.3 ± 5.3 days (glutamine group) (p = 0.01).The severity of mucositis was lower in the glutamine treated group (p = 0.02). The weight-adjusted dose of Lalanyl-L-glutamine in the patients not developing mucositis was higher than in the other ones (0.32 vs. 0.24g/kg/day; p = 0.02). Conclusions: Glutamine supplementation reduces the degree of mucositis and hospital stay in patients submitted to autologous bone marrow transplantation. The degree of mucositis is lower in the subgroup of patients receiving higher doses of glutamine (AU)

Influence of an immuno-enhanced formula in postsurgical ambulatory patients with head and neck cancer / Influencia de una formula inmunoenriquecida en pacientes ambulatorios postquirurgicos con cancer de cabeza y cuello

Background: Patients with head and neck cancer undergoing surgery have a high incidence of ambulatory postoperative complications. Objective: The aim of our study was to investigate the influence of an oral immunoenhanced supplement (arginine and glutamine) on nutritional and biochemical parameters in postsurgical ambulatory patients with head and neck tumor. Design: A population of 39 ambulatory postsurgical patients with oral and laryngeal cancer was enrolled. At Hospital discharge postsurgical head and neck cancer patients were asked to consume two units per day of a specially designed enhanced supplement for a twelve week period. Results: The mean age was 60.2+/-13.1 years (9 female/30 males). Duration of supplementation was 90.8 + 20days. A significant increase of album in (3.1±0.6 g/dl vs 4.12+0.7g /dl;p<0.05), prealbumin (21.4±6.3 mg/dl vs22.4+5.9 mg/dl;p<0.05) and transferr in (198.8±45.2mg/dl vs 253.8+60.7 mg/dl; p<0.05) levels were observed. No differences were detected in weight and other anthropometric parameters. Ten patients (41.3%) received radiotherapy along the enhanced supplementation period and only 5 (20% of patients with radiotherapy) developed a clinical oral mucositis. Conclusions: At dose used, arginine and glutamine enhanced formula improved seric protein levels in ambulatory postoperative head and neck cancer patients with a low rate of oral mucositis in the subgroup with radiotherapy (AU)

Antecedentes: Los pacientes con tumores de cabeza y cuello sometidos a cirugía presentan una alta incidencia de complicaciones ambulatorias. Objetivo: El principal objetivo de nuestro trabajo fue evaluar la influencia de un suplemento oral inmunoenriquecido con arginina y glutamina en pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello. Diseño: Una muestra de 39 pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello fue evaluada. Tras el alta hospitalaria, los pacientes recibieron dos bricks al día de un suplemento inmuno enriquecido durante 12 semanas. Resultados: La edad media fue de 60,2+/-13,1 años (9mujeres/30 varones). La duración media de la suplementación fue de 90,8+20 días. Se detectó un aumento significativo en los niveles de albúmina (3,1±0,6 g/dl vs4,12+0,7 mg/dl; p<0,05), prealbúmina (21,4±6,3 mg/dl vs22,4+5,9 mg/dl;p<0,05) y transferrina (198,8±45,2 mg/dlvs 253,8+60,7 mg/dl; p<0,05). No se detectaron diferencias en el peso ni en otras variables antropométricas. Un total de 10 pacientes (41,3%) recibieron radioterapia durante la suplementación, de los cuales solo 2 (20% de los pacientes con radioterapia) desarrollaron mucositis oral con significación clínica. Conclusiones: A la dosis usada, la formula enriquecida con arginina y glutamina mejoró lo niveles de proteínas séricas. Por otra parte los pacientes suplementados presentaron una baja tasa de mucositis asociada a la radioterapia (AU)