Clinical factors predictive for histological aggressiveness of basal cell carcinoma: A prospective study of 2274 cases.

INTRODUCTION: Since surgery is the first-line treatment for basal cell carcinomas (BCC), the histological aggressiveness of the disease must be clinically predicted in order to apply optimal safety margins that ensure a high rate of complete resection while minimising the risk of recurrence. OBJECTIVES: To evaluate clinical predictive factors of histological aggressiveness of BCC, we conducted a national prospective multi-centre study. METHODS: All consecutive patients presenting for BCC surgery were included, and standardised clinical data collected, and slides were submitted for review. Trabecular, micronodular and morpheaform BCCs were classified as aggressive. RESULTS: Of the 2710 cases included, 2274 were histologically confirmed. Clinical subtyping was correct in 49.9% of superficial BCCs, 86.2% of nodular BCCs and only 22% of aggressive BCCs. By multivariate analysis, aggressive BCCs were more frequently ulcerated (45%), indurated (70%), showed adherence (8.6%), and were associated with high-risk anatomical zones (50.3%, P<0.0001). These predictive clinical features may be helpful for decision making.

Leukocyte and platelet counts as prognostic values of testicular germ cell tumours. / Valor pronóstico del recuento de leucocitos y plaquetas, en tumores testiculares de células germinales.

INTRODUCTION: The immune system plays an essential role in the organism's response to cancer. Several haematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumours. MATERIAL AND METHODS: Retrospective cohort study on 164 patients with germ cell tumours. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analysed. RESULTS: 17.7% had NLR>4 and 14.6% ANC>8000/µL. These patients presented higher percentages of residual disease and stage II-III tumours. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet >400000/µL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumours. 28.4% showed platelet-lymphocyte values>150. This data was associated to higher percentages of residual disease, progression, stage II and III tumours and seminomatous tumours. 83.3% had an lymphocyte-monocyte >3. These patients presented: higher tumour markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumours. The mean survival time was shorter in patients with NLR>4 and absolute neutrophil >8,000/µL. The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte >3, and prediction of survival and values NLR>4. CONCLUSION: Our results indicate that the analysed haematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumours.

Combined immunotherapy encompassing intratumoral poly-ICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients.

Background: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. Patients and methods: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24 h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m2 was administered 1 week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating peripheral blood mononuclear cell (PBMCs) and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre- and post-treatment PBMC from patients achieving durable stable disease (SD) were studied by IFNγ ELISPOT-assays responding to tumor-lysate loaded DC and by TCRß sequencing. Results: Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+ immunotherapy. No objective responses were observed, while nine patients presented SD (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-ß and IFN-α mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1ß concentrations, especially in patients presenting SD. IFNγ-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD. Conclusions: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.

Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients.

BACKGROUND: Surrogate biomarkers of efficacy are needed for anti-PD1/PD-L1 therapy, given the existence of delayed responses and pseudo-progressions. We evaluated changes in serum IL-8 levels as a biomarker of response to anti-PD-1 blockade in melanoma and non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Metastatic melanoma and NSCLC patients treated with nivolumab or pembrolizumab alone or nivolumab plus ipilimumab were studied. Serum was collected at baseline; at 2-4 weeks after the first dose; and at the time-points of response evaluation. Serum IL-8 levels were determined by sandwich ELISA. Changes in serum IL-8 levels were compared with the Wilcoxon test and their strength of association with response was assessed with the Mann-Whitney test. Accuracy of changes in IL-8 levels to predict response was estimated using receiver operation characteristics curves. RESULTS: Twenty-nine melanoma patients treated with nivolumab or pembrolizumab were studied. In responding patients, serum IL-8 levels significantly decreased between baseline and best response (P <0.001), and significantly increased upon progression (P =  0.004). In non-responders, IL-8 levels significantly increased between baseline and progression (P =  0.013). Early changes in serum IL-8 levels (2-4 weeks after treatment initiation) were strongly associated with response (P <0.001). These observations were validated in 19 NSCLC patients treated with nivolumab or pembrolizumab (P =  0.001), and in 15 melanoma patients treated with nivolumab plus ipilimumab (P <0.001). Early decreases in serum IL-8 levels were associated with longer overall survival in melanoma (P =  0.001) and NSCLC (P =  0.015) patients. Serum IL-8 levels also correctly reflected true response in three cancer patients presenting pseudoprogression. CONCLUSIONS: Changes in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.

Utility of neurological smears for intrasurgical brain cancer diagnostics and tumour cell percentage by DESI-MS.

Analysis of neurological smears by desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging diagnostic strategy for intraoperative consultation in brain tumor resection. DESI-MS allows rapid sampling while providing accurate diagnostic information. We assess the chemical homogeneity of neurological smears using DESI-MS imaging and the quality of rapid DESI-MS diagnosis.

Uso de toxina botulínica tipo A en el manejo de dolor crónico refractario a tratamiento. Reporte de una serie de casos. / Use of botulinum toxin type A in the management of chronic pain refractory to treatment. Report a series cases

Botulinum toxin type A (BTA) has analgesic effect independent of its action in muscle tone, inhibiting the release of neurotransmitters (substance P-glutamate) and neuropeptides of nociceptors. Objective: To characterize infiltration procedures with Botox® in patients with chronic pain refractory to treatment. Method: Observational-cross-retrospective study. Infiltrations with botox procedures performed in Hospital Clínico Mutual de Seguridad, between 01.01.2014 and 30.04.2015 were analyzed. Medical record data were extracted. Information analyzed with Excel2013® using Chi-square test (p <0.05). Results: 31 patients treated, 83.9 percent male. Average age 51 years (SD ± 11.9yo). Diagnostics causes of pain: post-traumatic pain and myofascial syndrome (25.8 percent); complex regional pain syndrome (16.1 percent) and partial hand amputation (12.9 percent). Predominant type of pain: neuropathic pain (64.5 percent). Common procedures: median nerve blockade (21.2 percent) and infiltration of lumbar back trigger points (15.4 percent). 77.4 percent reported good pain control, crisis decreased 74.2 percent and 71 percent decreases opioid use. Return work was effective in 64.5 percent of patients. 93.6 percent satisfactorily tolerated the procedure, 9.7 percent showed fewer adverse effects. The subgroup neuropathic pain had significantly worse results regarding mixed pain subgroup (p <0.05). Discussion: In this study, the use of BTA in chronic pain proved to be a safe and effective procedure for the management of chronic musculoskeletal pain...

Testicular and epididymal ltrasonography in Santa Inês lambs raised in Brazil

The objective of this work was to study, through ultrasonographic evaluation, changes in testes and epididymides of clinically healthy, peripubertal and pubertal Santa Inês lambs raised in Brazil. Periodic e valuations of weight, biometric characteristics (scrotal circumference, width and length) and ultrasound examinatio ns of the testes and epididymides of 20 lambs were performed between 84 and 280 days old at intervals of 28 days. Scans were performed in the sagittal, transverse, frontal and oblique planes to evaluate the echotexture of the testicular parenchyma and mediastinum and the tail epididymis as well as the thickness and width of the mediastinum testis. The testicular parenchyma demonstrated a homogeneous echogenicity patter n ranging from low to moderate. The echogenicity of testicular parenchyma increased in direct proportion to animal age, being higher in pubertal lambs when compared to prepubertal at the same age. The mediastinum testis was observed in 100% of the evaluated animals, regardless of the scan plane used, and was classified as diffuse or moderately or highly echogenic. Echogenicity and the thickness of the mediastinum testis increased in direct proportion to animal age. The epididymal tail was presented in hypoechoic relation to the testicular parenchyma. Based on these results, it was concluded that ultrasound is useful tool for selection and morphophysiological evaluation of Santa Inês lambs on peripubertal and pubertal phases, when used in combination with other methods such as semen evaluation.

[Specialized dendritic cells in cross-presentation of exogenous antigens to cytotoxic T lymphocytes]. / Células dendríticas especializadas en presentación de antígenos exógenos a linfocitos T citotóxicos.

Dendritic cells (DC) are cells of hematopoietic origin, which constitutively express MHC class I and II, and are functionally the most potent inducers of T-lymphocyte activation and proliferation. CD8+ T lymphocytes proliferate and acquire cytotoxic functions upon recognition of their cognate antigen on the surface of one or various dendritic cells with which they interact. However, only some DC subsets are able to present antigen to cytotoxic T cell precursors as taken up from extracellular sources. This function is termed cross-presentation (in Spanish, presentación cruzada or presentación subrogada) and requires shuttle mechanisms from phagosomes to the cytosol for antigen processing. It has been demonstrated that the differentiation of DC with these capabilities is dependent on FLT-3L and the transcription factor BATF3. They express peculiar functions and differentiation markers. These cells are distinguished in mice by surface CD8 features, while CD141 (BDCA-3) marks these cells in the human. These subpopulations are capable of selective internalization of necrotic cell debris by means of their CLEC9A lectin which is a receptor for extracellular polymerized actin. Expression of the chemokine receptor XCR1 favours contact with CD8+ T cells. Therapeutic vaccination with tumour antigens using DC is a strategy under development for the treatment of cancer. The use of DC subsets with more prominent capabilities for cross-presentation would mimic the natural mechanisms of immunization to induce cytolitic T lymphocytes. In vivo targeting of antigens with monoclonal antibodies against DEC-205 or CLEC9A attains very robust immune responses and is a strategy undergoing clinical trials for chronic viral diseases and malignancies.

[Hyperammonemic encephalopathy: nutritional assessment and management of a case]. / Encefalopatía hiperamoniémica: valoración y manejo nutricional a propósito de un caso.

OTC deficiency is a disorder of the urea cycle X-linked. It is manifested in men as severe hyperammonemia in the first days of life. In women the disease is milder severity. Various conditions cause decompensation with hyperammonemia. It could be fatal or cause permanent neurological damage. We report a 36 years old woman admitted for surgery, she suffered a decompensation in conjunction with surgical wound infection. Hyperammonemia caused neurological deterioration with decreased level of consciousness, tetraparesis and neurogenic dysphagia. The treatment consisting of low-protein diet, ammonium chelating drugs and dialytic measures, was effective in controlling hyperammonaemia and improving neurological status. This case illustrates the importance of nutritional support of patients with disorders of the urea cycle in the hospital because the descompensations are more frecuent here.

Achados ultrassonográficos nos testículos e epidídimos de carneiros deslanados jovens e clinicamente sadios / Ultrasonographic findings in the testis and epididymis of clinically healthy young hair sheep

Objetivou-se descrever os achados ultrassonográficos nos testículos e epidídimos de carneiros jovens. Análises de desenvolvimento ponderal, mensurações das características biométricas testiculares e exames ultrassonográficos foram realizados dos 140 aos 280 dias de idade, a cada 28 dias. O parênquima testicular apresentou ecogenicidade homogênea (baixa a moderada) que aumentou com a idade. A ecogenicidade e a espessura do mediastino aumentaram com a idade, e a cauda do epidídimo apresentou aspecto hipoecoico em relação ao parênquima testicular. Foram observadas calcificações de grau leve nos testículos de cinco cordeiros. Conclui-se que o exame ultrassonográfico contribui para o monitoramento dos testículos e epidídimos de carneiros.

This study aimed to describe ultrasonographic findings in the testis and epididymis of young sheep. Evaluations of the development of weight, measurements of biometric characteristics of the tests and ultrasound examinations of the tests and epididymis were performed from 140 to 280 days of age, each 28 days. The testicular parenchyma showed homogeneous echogenicity (low to moderate) and increased with the age. The mediastinum echogenicity and thickness increased with age and the epididymis tail showed hypoechoic appearance in relation to the testicular parenchyma. Mild calcification was observed in the testis parenchyma of five lambs. In conclusion, ultrasonographic exams help to monitor testes and epididymis of young hair rams.

Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y -14 en lesiones apicales asociadas con periodontitis apical asintomática / Immunodetection of matrix metalloproteinases (MMPs)-2, -9, -13 and -14 in periapical lesions associated with asymptomatic apical periodontitis

La periodontitis apical asintomática (PAa) es una patología infecciosa caracterizada por destrucción ósea perirradicular asociada a un proceso inflamatorio crónico y producción de mediadores inflamatorios, entre los cuales se encuentran las metaloproteinasas de matriz extracelular (MMPs). Entre éstas, las MMPs-13, -14, -2 y -9, son producidas por el tejido óseo y degradan sinérgicamente el colágeno tipo I, principal componente de los tejidos periodontales, y gelatina, producto de la degradación y desnaturación del colágeno. El objetivo de este estudio fue determinar el patrón de expresión de las MMPs-2, -9, -13 y -14 en granulomas periapicales (GPAs), quistes radiculares inflamatorios (QRIs) y ligamento periodontal sano (LS). Materiales y Métodos: Se seleccionaron 12 pacientes con diagnóstico clínico de PAa e indicación de exodoncia a partir de los cuales se obtuvieron biopsias de lesiones periapicales (LPAs). Como controles, se seleccionaron 7 individuos con indicación de exodoncia de premolares por ortodoncia, obteniéndose biopsias de LS. Se efectuó el diagnóstico anátomo-patológico de los especímenes y se caracterizó la expresión de las MMPs en estudio mediante inmunohistoquímica. Resultados: Las MMPs en estudio sólo se detectaron en GPAs y QRIs, y se inmunolocalizaron principalmente en el infiltrado inflamatorio de éstos. Adicionalmente, la MMP-2 se identificó en fibroblastos del tejido conectivo. Conclusiones: MMPs-2, -9, -13 y -14 se expresan predominantemente en el infiltrado inflamatorio de las LPAs y no en LS, y por tanto se sugiere la participación de estos mediadores en la patogénesis de la PAa.

Asymptomatic apical periodontitis (aAP) is an infectious disease characterized by perirradicular bone destruction associated with chronic inflammation and release of inflammatory mediators, such as matrix metalloproteinases (MMPs). MMPs-13, -14 and -2, -9 are bone-expressed enzymes that can synergistically degrade collagen I, the main component of periodontal extracellular matrix, and gelatin, the product of degradation and denaturation of collagen. The aim of this study was to characterize the expression pattern of MMPs-2, -9, -13, and -14 in periapical granulomas (PGs), radicular cysts (RCs) and healthy periodontal ligament (PDL). Materials and Methods: Individuals with clinical diagnosis of aAP and indication of extraction were selected (N=12), and biopsies of periapical lesions (PLs) were obtained. For controls, 7 subjects with indication of premolar extraction for orthodontic reasons were selected, and PDL biopsies were obtained. Samples were diagnosed by anatomopathological examination and immunohistochemical staining was carried out to characterize MMPs expression. Results: MMPs-2, -9, -13 and -14 detection was limited to PLs and were localized mainly to inflammatory infiltrate on both, PGs and RCs. Additionally, MMP-2 was immunolocalized to fibroblasts from the connective tissue. Conclusions: Whereas MMPs-2, -9, -13 and -14 were not detected in healthy periodontal ligament, they were highly expressed on inflammatory infiltrate from PGs and RCs, suggesting a role of these mediators in aAP pathogenesis.

Propranolol en el tratamiento de los hemangiomas de la infancia / Propranolol in the treatment of infantile hemangioma

Infantile Hemangiomas (IH) are common vascular tumors in children. Only 10-15 percent) should be treated by any vital, functional or aesthetic complications. Oral corticosteroids are the treatment of choice. However, in the last two years an excellent response to treatment of hemangiomas with oral Propranolol has been reported. Objective: evaluate this new therapy in a limited number of chilean patients with IH with an indication of systemic treatment and present this experience. Patients and Methods: We present 30 cases of IH treated at our institution with oral Propranolol, using a dose of 2 mg/kg/day divided in 2 daily doses. Results: 11 percent of patients were female, 40 percent hemangiomas had segmental distribution, 90 percent were solitary, 61 percent were located in the head and neck and 23 percent were ulcerated. The treatment started at an average of 119 days of life and lasted for an average of 7 months. In all our patients the use of Propranolol accelerated the onset of involution of the hemangiomas and decreased color, brightness and growth too. 43 percent of the patients had irritability and sleep disorders. No significant adverse effects were reported in any of our patients. Conclusión: Propranolol treatment was highly effective and safe in our series of patients and we propose, taking into account published reports based on this data, it should become the treatment of choice for IH.

Los Hemangiomas de la Infancia (HI) son tumores vasculares frecuentes en la edad pediátrica. Sólo un 10-15 por cientoo debe ser tratado por eventuales consecuencias vitales, funcionales o estéticas. Los corticoides orales son el tratamiento de elección actual. Sin embargo, en los últimos 2 años se ha reportado la excelente respuesta de los hemangiomas al tratamiento con Propranolol oral. Objetivo: Evaluar esta nueva terapéutica en un número limitado de pacientes Chilenos con hemangiomas de la infancia con indicación de tratamiento sistémico y presentar esta experiencia. Pacientes y Método: Presentamos 30 casos de HI tratados en nuestra institución con Propranolol oral, usando una dosis de 2 mg/kg/día en 2 tomas diarias. Resultados: Un 77 por ciento de los pacientes eran de sexo femenino. El 40 por ciento de los hemangiomas eran segmentarios, 90 por ciento eran únicos, 67 por ciento estaban ubicados en cabeza y cuello y 23 por ciento estaban ulcerados. El tratamiento se inició en promedio a los 119 días de vida y duró en promedio 7 meses. En la totalidad de nuestros pacientes el uso de Propranolol aceleró el inicio de la involución del hemangioma y disminuyó el color, brillo y crecimiento. El 43 por ciento de los pacientes presentó irritabilidad y trastornos del sueño. No se presentaron efectos adversos importantes en ninguno de nuestros pacientes. Conclusión: El tratamiento con Propranolol fue altamente efectivo y seguro en nuestra serie de pacientes y proponemos, tomando en cuenta los reportes publicados al respecto, que debiera ser el tratamiento de elección para los hemangiomas de la infancia.

Cutis marmorata telangiectático congénito: a propósito de cuatro casos / Congenital cutis marmorata telangiectasia: four case review

Congenital Cutis Marmorata Telangiectasia (CCMT) is a skin vascular malformation of low flow compromi-sing venous and capillary vessels. Of unknown origin, it shows in an estimated 1/3 000 births. In over 90 percent of cases it can be seen since birth, although it can appear on the first few days after. Clinical manisfestation includes poorly defined reticular erythematopurpureal maculae, frequently associated to ßreas of segmental, asymetric skin atrophy, most often seen in the lower extremitie. The diagnosis is mostly clinical, important to make as it is associated in 30 percent) of cases to other congenital abnormalities. No specific treatment is required, with spontaneous resolution. Prognosis is good, depending on the associated malformations. Four patients are described in this paper, as a reminder of the clinical entity.

El Cutis Marmorata Telangiectático Congénito (CMTC) es un tipo de malformación vascular cutánea de bajo flujo que compromete vasos capilares y venosos. Su causa es desconocida y tiene una incidencia estimada de 1/3 000 recién nacidos. En más del 90 por ciento> de los casos se presenta desde el nacimiento. Sin embargo, también puede aparecer en los primeros días de vida. Clínicamente se observan máculas eritematovioláceas, de aspecto reticulado, de bordes mal definidos, asociado frecuentemente a zonas de atrofia cutánea, de distribución segmentaria, asimétricas. Se ubican de preferencia en las extremidades, siendo las inferiores las más afectadas. El diagnóstico es fundamentalmente clínico y su importancia radica en que aproximadamente el 30 por ciento> de los casos se asocia a otras anomalías congénitas, la mayoría de carácter leve. No tiene un tratamiento específico, ya que evoluciona en poco tiempo a la resolución en forma espontánea. El pronóstico es generalmente bueno, aunque depende de las anomalías asociadas. En este artículo se presentan cuatro pacientes cuya historia clínica es compatible con este diagnóstico, para dar a conocer esta entidad clínica a los pediatras.

Protocolo de farmacovigilancia a reacciones de hipersensibilidad a medicamentos: resultados de su aplicación en 5 centros de Santiago / Pharmacovigilance protocol for cutaneous drug hypersentivity reactions in Santiago, Chile

Introducción: Las Reacciones de Hipersensibilidad Medicomentosa (RHM) son un motivo de consulta muy común en Dermatología. Con el objetivo de implementar la farmacovigilancia dentro de la Sociedad Chilena de Dermatología (SOCHIDERM) se creó un Protocolo paro la notificación de RHM de tipo muco-cutáneo. Objetivo: Validar una propuesta de Protocolo de Farmacovigilancia de RHM de tipo mucocutáneo de la SOCHIDERM paro el uso de dermatólogos y médicos de nuestro país. Resultados: En nuestro estudio, la frecuencia de RHM fue 0,3% -0,5% del total de consultas ambulatorias y 5,2% 17,2% de las interconsultas a Dermatología. Los patrones más frecuentes fueron el urticarial, morbiliforme y la reacción medicamentosa fija. Los fármacos imputados con mayor frecuencia fueron los analgésicos/antiinflamatorios, los fármacos con acción en el sistema nervioso central, los antibióticos y los antihipertensivos. Discusión: Es importante tener un Protocolo de Farmacovigilancia. Esto nos permitirá obtener datos a nivel nacional. El desafío a corto plazo paro farmacovigilancia en SOCHIDERM es lograr notificar las RHM de tipo muco-cutáneo graves o con compromiso vital, que sean atendidas por dermatólogos en nuestro país, a través del Protocolo de Farmacovigilancia SOCHIDERM.

Introduction: Drug Hypersensitivity Reactions (DHR) are a common cause of consultation in dermatology. In order to implement fharmacovigilance in the Chilean Society of Dermatology (SOCHIDERM), we created a protocol for the notification of mucocutaneous DHR. Objective: To validate a SOCHIDERM mucocutaneous DHR pharmacovigilance protocol for dermatologists and physicians in our country. Results: In our study. DHR accounted for 0.3-0.5 % of all outpatient consultations, and 5,2-17,2% of interconsultations in dermatology. The most frequent patterns were urticarial, morbilliform and fixed drug reaction. The drugs most frequently involved were analgesics/anti-inflammatory drugs with action in the central nervous system, antibiotics and antihypertensives. Discussion: It is important to have a Pharmacovigilance Protocol since it will allow to obtain nationwide data. The short-term challenge for the SOCHIDERM pharmacovigilance is to notify serious or life-threatening mucocutaneous DHR that have been seen by dermatologists in our country, through this Protocol.

[Radiofrequency ablation of breast carcinomas: preliminary results of a clinical trial]. / Ablación por radiofrecuencia de carcinomas de mama: resultados preliminares de un ensayo clínico.

OBJECTIVE: Among the alternatives to breast conserving surgery in breast cancer, radiofrequency ablation is the most widespread. We aimed to determine the feasibility, safety, and efficacy of this technique in our environment. MATERIAL AND METHODS: We performed radiofrequency ablation of breast carcinomas under local anesthesia in the ultrasonography examination room. We included 35 patients (mean age=61.2+/-8.25 years) with invasive carcinomas measuring less than 2cm (mean diameter=8.9+/-2.9mm) and located far from the skin and chest wall. Prior to radiofrequency treatment, all patients underwent core biopsy to confirm that the tumors were invasive carcinomas and selective lymphadenectomy. Carcinomas were excised 2 to 4 weeks after radiofrequency treatment and analyzed histologically to evaluate the effects of radiofrequency treatment on the tumor and surrounding tissue. The degree of coagulation necrosis and involvement of the margins was evaluated using hematoxylin and eosin staining. Cellular viability or effectiveness of the radiofrequency treatment was evaluated using NADH diaphorase. RESULTS: In total, 85.7% of patients reported no discomfort; 11.4% reported mild, controllable pain. Intense pain required the procedure to be discontinued in one patient. No other complications occurred. Signs of coagulation necrosis were observed in all cases; coagulation necrosis was classified as complete in 32/35 (91.4%). NADH diaphorase was negative in 27 of the 32 cases in which it was performed; one case was slightly positive and the other four were impossible to evaluate. CONCLUSION: Radiofrequency ablation of breast carcinomas is feasible, well tolerated, safe, and efficacious in nearly 90% of invasive tumors. The efficacy of the technique should be confirmed through extended follow-up of patients without subsequent surgical intervention in carefully designed and monitored phase III trials.

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes.

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators.