Morphine promotes migration and lung metastasis of mouse melanoma cells

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

Carcinoma epidermoide metastásico asociado a epidermólisis ampollosa distrófica / Metastasic squamous cell carcinoma in dystrophic epidermolysis bullosa

Caso clínico: femenino de 18 años con diagnóstico de epidermolisis ampollosa distrófica (EAD) quién desarrolló una neoformación nodular sobre una úlcera crónica. Se diagnosticó carcinoma epidermoide (CE) invasor al que se realizó resección. Sin embargo, 5 meses después del tratamiento quirúrgico presentó metástasis a ganglios, pulmón e hígado con desenlace fatal. Comentarios: el CE es la causa más importante de muerte en pacientes con EAD. Suele ser agresivo y metastásico. Se recomienda una vigilancia cada 3 a 6 meses para realizar diagnóstico y tratamiento oportunos (AU)

Case report: 18-year-old female patient with dystrophic epidermolysis bullosa (DEB) who developed a tumor over a chronic ulcer. She was diagnosed with invasive squamous cell carcinoma (SCC) and underwent surgical resection. However, 5 months later she presented metastases to the lymph nodes, lung and liver with a fatal outcome. Comments: SCC is the most important cause of death in patients with DEB. It is usually aggressive and metastatic. Surveillance every 3 to 6 months is recommended for prompt diagnosis and treatment (AU)

Lung metastases at the initial diagnosis of high-grade osteosarcoma: prevalence, risk factors and prognostic factors. A large population-based cohort study

ABSTRACT BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents. Lung metastases are associated with poor prognosis. OBJECTIVE: The aim here was to explore the prevalence of and risk and prognostic factors for lung metastases in high-grade osteosarcoma patients. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: Data on 1,408 high-grade osteosarcoma patients registered in the SEER database between 2010 and 2015 were extracted. From these, all patients with high-grade osteosarcoma and initial lung metastasis were selected for analysis on risk and prognostic factors for lung metastases. Overall survival was estimated. RESULTS: There were 238 patients (16.90%) with lung metastases at diagnosis. Axial location, tumor size > 10 cm (odds ratio, OR 3.19; 95% confidence interval, CI: 1.58-6.45), higher N stage (OR 4.84; 95% CI: 1.94-12.13) and presence of bone metastases (OR 8.73; 95% CI: 4.37-17.48) or brain metastases (OR 25.63; 95% CI: 1.55-422.86) were significantly associated with lung metastases. Younger age and surgical treatment (hazard ratio, HR 0.46; 95% CI: 0.30-0.71) favored survival. Median survival was prolonged through primary tumor surgery. CONCLUSIONS: The factors revealed here may guide lung metastasis screening and prophylactic treatment for osteosarcoma patients. A primary tumor in an axial location, greater primary tumor size, higher lymph node stage and presence of bone or brain metastases were significantly correlated with lung metastases. The elderly group (≥ 60 years) showed significant correlation with poor overall survival. For improved survival among high-grade osteosarcoma patients with lung metastases, aggressive surgery on the primary tumor site should be encouraged.

Metastasis from glioblastoma multiforme: a meta-analysis

SUMMARY OBJECTIVE: Extracranial metastases of glioblastoma multiforme (GBM) are rare due to the short survival experienced by the patients. Therefore, the natural history of GBM metastases remains elusive. The identification of clinical factors promoting GBM metastases may help elucidate the mechanisms of tumor cell invasion in the brain. The aims of this study were to perform a meta-analysis evaluating the survival, characteristics, prognostic factors, and predictors of treatment outcome in patients with metastatic GBM and describe a case of metastatic extracranial GBM. METHODS: We report the case of a patient diagnosed with GBM metastatic to the lungs and the results of a meta-analysis of 114 other cases of metastatic GBM identified through a MEDLINE and BIREME search. RESULTS: The mean age of the patients was 38.2±16.1 years and 70.4% were male. The time elapsed between the identification of the metastasis and death was significantly increased in patients undergoing surgery (p=0.019), whereas the time from the diagnosis of the primary tumor to death was significantly increased in patients receiving radiation therapy (p=0.050). The time elapsed from metastasis to death and diagnosis to death was significantly longer in patients receiving chemotherapy (p<0.001 and p=0.027, respectively). The liver was the metastatic site associated with the shortest time elapsed from diagnosis to death (p=0.024). CONCLUSIONS: In GBM, surgical resection is important in reducing the risk of metastasis, and chemotherapy and radiation therapy help to prolong survival in metastatic GBM. Metastases to the liver are associated with shorter survival compared with metastases to other sites.

RESUMO OBJETIVO: Metástases extracranianas do glioblastoma multiforme (GBM) são raras devido à baixa sobrevida dos pacientes. Portanto, a história natural das metástases do GBM permanece incerta. A identificação de fatores clínicos que promovem metástases no GBM pode ajudar a elucidar os mecanismos de invasão das células tumorais no cérebro. O objetivo deste estudo foi realizar uma meta-análise avaliando a sobrevida, características, fatores prognósticos e preditores de desfechos do tratamento em pacientes com GBM metastático e descrever um caso de GBM extracraniano metastático. MÉTODOS: Relatamos o caso de uma paciente diagnosticada com GBM metastático para os pulmões e os resultados de uma meta-análise de 114 outros casos de GBM metastático identificados por meio de uma pesquisa no Medline e Bireme. RESULTADOS: A média de idade dos pacientes foi de 38,2±16,1 anos e 70,4% eram do sexo masculino. O tempo decorrido entre a identificação da metástase e o óbito foi significativamente maior em pacientes submetidos à cirurgia (p = 0,019), enquanto que o tempo do diagnóstico do tumor primário até o óbito aumentou significativamente em pacientes submetidos à radioterapia (p = 0,050). O tempo decorrido da metástase até o óbito e do diagnóstico até o óbito foi significativamente maior nos pacientes que receberam quimioterapia (p < 0,001 e p = 0,027, respectivamente). O fígado foi o local metastático associado ao menor tempo decorrido do diagnóstico até a morte (p = 0,024). CONCLUSÕES: No GBM, a ressecção cirúrgica é importante para redução do risco de metástase, e a quimioterapia e a radioterapia ajudam a prolongar a sobrevida no GBM metastático. Metástases para o fígado estão associadas a uma sobrevida mais curta quando comparadas a metástases para outros locais.

Sequencing of RAS/RAF pathway genes in primary colorectal cancer and matched liver and lung metastases

Background: Mutations in the RAS/RAF pathway predict resistance to anti-epidermal growth factor receptor antibodies in colorectal cancer (CRC), and may be targets for future therapies. This study investigates concordance of BRAF, HRAS, KRAS, NRAS and PIK3CA mutation status in primary CRC with matched liver (n = 274), lung (n = 114) or combined liver and lung metastases (n = 14). Methods: Next generation sequencing was performed on DNA from formalin-fixed paraffin embedded CRC and matched liver and/or lung metastases, for recurrent mutations in BRAF, HRAS, KRAS, NRAS and PIK3CA and using the single-molecule molecular inversion probe method. Results: Paired sequencing results on all five genes were reached in 249 of the 402 cases (62%). The obtained number of unique reads was not always sufficient to confidently call the absence or presence of mutations for all regions of interest. The mutational status of matched pairs was highly concordant; 91.1% concordance for all five genes, 95.5% for KRAS, 99.1% for NRAS. Lung metastases more often harboured RAS mutations compared to liver metastases (71% vs. 48%, p < 0.001). Conclusions: In this large series of CRC we show that both primary tumors and corresponding metastases can be used to determine the mutational status for targeted therapy, given the high concordance rates. Next generation sequencing including a single molecule tags is feasible, however in combination with archival formalin-fixed paraffin embedded material is limited by coverage depth.

Carcinoma Embrionário de Mediastino Posterior com Metástase Pulmonar: Relato de Caso / Carcinoma Embrionario de Mediastino Posterior con Metástasis Pulmonar: Relato de Caso / Posterior Mediastinum Embryonal Carcinoma with Pulmonary Metastasis: Case Report

Introdução: Os carcinomas embrionários são os mais raros e, geralmente, se apresentam quando já estão associados com outros componentes de células germinativas. Possuem características clínicas e radiológicas similares aos tumores de saco vitelino. Relato do caso: Paciente G.A.S.L, sexo masculino, 30 anos, ex-tabagista e etilista. Iniciou com quadro de dores no hemitórax esquerdo em fevereiro de 2018 com extensão dos sintomas para a região da coluna torácica e lombar. Realizou tomografia de abdômen total e tórax, com resultado sugestivo de tumor de mediastino, nódulos pulmonares, material tecidual com densidade de partes moles no mediastino posterior e numerosas linfonodomegalias retroperitoneais, evoluiu com paraplegia de membros inferiores por compressão nervosa e com hipoestesia. Realizou biópsia de tumor de mediastino posterior à esquerda com resultado de neoplasia maligna epitelial e diagnóstico de carcinoma embrionário extragonodal pouco diferenciado. O paciente apresentou metástase pulmonar, confirmando que esses tumores frequentemente se infiltram nos órgãos adjacentes. A quimioterapia baseada em cisplatina é o tratamento padrão, levando à melhora da sobrevida em pacientes com esse tipo de tumor. Após a quimioterapia, houve diminuição do volume tumoral, porém, seguiu com a paraplegia de membros inferiores em razão da compressão nervosa. Conclusão: Este estudo relata o caso de um paciente jovem, com tumor raro de células germinativas e metástase pulmonar, que evoluiu clinicamente estável após tratamento específico com quimioterápicos. Por ainda haver uma escassa literatura acerca do tema, este estudo traz novas evidências e achados.

Introduction: Embryonal carcinomas are the rarest, and usually present when they are already associated with other components of germ cells. They have clinical and radiological features similar to yolk sac tumors. Case report: Patient G.A.S.L, male, 30 years old, former smoker and alcoholic. Initially, the patient reported pain in the left hemithorax in February 2018 with extension of the symptoms to the region of the thoracic and lumbar spine. A tomography of the total abdomen and chest was performed, with result suggestive of mediastinal tumor, pulmonary nodules, tissue material with soft tissue density in the posterior mediastinum and numerous retroperitoneal lymph node enlargement, which evolved with paraplegia of the lower limbs by nerve compression and hypoesthesia. It was conducted a biopsy of a mediastinal tumor posterior to the left with result of malignant epithelial neoplasia and diagnosis of extragonadal embryonic carcinoma very little differentiated. The patient presented pulmonary metastasis confirming that these tumors frequently infiltrate into the adjacent organs. Cisplatin-based chemotherapy is the standard treatment, leading to improved survival in patients with this type of tumor. After chemotherapy, the tumor volume decreased, but the patient continued with paraplegia of lower limbs due to nerve compression. Conclusion: This study reports the case of a young patient with a rare germ cell tumor and pulmonary metastasis who evolved clinically stable after specific chemotherapy treatment. Because there is still scarce literature on the subject, this study brings new evidences and findings.

Introducción: Los carcinomas embrionarios son los más raros y generalmente se presentan cuando ya están asociados con otros componentes de células germinativas. Se presentan características clínicas y radiológicas similares a los tumores de saco vitelino. Relato del caso: Paciente G.A.S.L, sexo masculino, 30 años, ex tabaquista y etilista. Se inició con cuadro de dolores en el hemitórax izquierdo en febrero de 2018 con extensión de los síntomas para la región de la columna torácica y lumbar. Se realizó una tomografía de abdomen total y tórax, con resultado sugestivo de tumor de mediastino, nódulos pulmonares, material tisular con densidad de partes blandas en el mediastino posterior y numerosas linfonodomegalias retroperitoneales, evolucionó con paraplejia de miembros inferiores por compresión nerviosa y con hipoestesia. Se realizó biopsia de tumor de mediastino posterior a la izquierda con resultado de neoplasia maligna epitelial y diagnóstico de carcinoma embrionario extra gonodal poco diferenciado. El paciente presentó metástasis pulmonar confirmando que estos tumores frecuentemente se infiltran en los órganos adyacentes. La quimioterapia basada en cisplatino es el tratamiento estándar, llevando a la mejora de la supervivencia en pacientes con este tipo de tumor. Después de la quimioterapia hubo la disminución del volumen tumoral, sin embargo, siguió con la paraplejia de miembros inferiores debido a la compresión nerviosa. Conclusión: Este estudio informa el caso de un paciente joven con un tumor raro de células germinales y metástasis pulmonar que evolucionó clínicamente estable después de un tratamiento de quimioterapia específico. Debido a que todavía hay poca literatura sobre el tema, este estudio aporta nuevas pruebas y hallazgos.

Selective lobar blockade with a Coopdech blocker combined with a double-lumen endotracheal tube for lung metastases resection by laser / Bloqueio lobar seletivo com um bloqueador Coopdech combinado com um tubo endotraqueal de duplo lúmen para ressecção de metástases pulmonares com laser

Abstract In recent years, laser resection of lung metastases has been established as the standard procedure worldwide. To avoid airway fire, it is necessary to collapse the surgical lung. The selective lobar bronchial blockade is a technique that allows one-lung ventilation while the operated lobe is collapsed in patients with previous pulmonary resection requiring subsequent resection or with limited pulmonary reserve. We report a clinical case about our experience of a selective lobar bronchial blockade technique with a bronchial blocker (Coopdech endobronchial blocker) that was employed successfully with a double-lumen endotracheal tube in a patient with previous contralateral pulmonary resection who was scheduled for atypical resections of pulmonary metastases by laser. We selectively blocked the right intermediate bronchus for management of hypoxemia during one-lung ventilation. This technique provided adequate ventilation and oxygenation during surgery, avoiding the need of two-lung ventilation during lung metastases resection by laser. Conclusion: This case shows that if a properly positioned double-lumen tube was already in place and the patient does not tolerate one-lung ventilation because of hypoxemia, it would be possible to provide selective lobar blockade by placing a bronchial blocker through the lumen of the double-lumen tube, avoiding the use of continuous positive airway pressure during laser surgery. This technique does not disturb the operative field or interrupt the operative procedure during resection by laser, which would occur during two-lung ventilation or used of continuous positive airway pressure.

Resumo Nos últimos anos, a ressecção de metástases pulmonares com o uso de laser foi estabelecida como o procedimento padrão em todo o mundo. Para evitar queimadura das vias aéreas, o colapso cirúrgico do pulmão é necessário. O bloqueio brônquico seletivo é uma técnica que permite a ventilação de um lobo, enquanto o lobo operado é colapsado nos pacientes com ressecção pulmonar anterior que requerem ressecção subsequente ou que possuem reserva pulmonar limitada. Relatamos um caso clínico de nossa experiência com a técnica de bloqueio brônquico seletivo com bloqueador brônquico (bloqueador endobrônquico Coopdech), usado com sucesso com um tubo endotraqueal de duplo lúmen em um paciente com ressecção pulmonar contralateral prévia, agendado para ressecção atípica de metástases pulmonares com o uso de laser. Seletivamente bloqueamos o brônquio intermediário direito para o controle de hipoxemia durante a ventilação monopulmonar. Essa técnica proporcionou ventilação e oxigenação adequadas durante a cirurgia, evitando a necessidade de ventilar os dois pulmões durante a ressecção de metástases pulmonares com o uso de laser. Conclusão: Este caso mostra que, se um tubo de duplo lume estiver corretamente posicionado e o paciente não tolerar a ventilação monopulmonar devido à hipoxemia, seria possível fornecer bloqueio lobar seletivo com a colocação de um bloqueador brônquico através do lume do tubo de duplo lume, evitando o uso de pressão positiva contínua de vias aéreas (PPCVA) durante a cirurgia a laser. Essa técnica não interfere no campo operatório ou interrompe o procedimento durante a ressecção por laser, que poderia ocorrer durante a ventilação dos dois pulmões ou uso de PPCVA.

Metástases pulmonares em crianças: estamos operando desnecessariamente? / Pulmonary metastases in children: are we operating unnecessarily?

RESUMO Objetivo: determinar, em pacientes pediátricos portadores de neoplasias malignas, as características de nódulos pulmonares identificados à tomografia computadorizada, capazes de diferenciar nódulos benignos de metástases. Métodos: estudo retrospectivo de pacientes submetidos a ressecções pulmonares de nódulos diagnosticados como metástases em um período de sete anos. Achados de tomografia e da cirurgia, assim como resultados dos exames anatomopatológicos foram comparados. Resultados: nove pacientes, submetidos a 11 intervenções cirúrgicas, foram estudados. Entre as variáveis estudadas, apenas o tamanho do nódulo, maior do que 12,5mm provou ser estatisticamente significante para predizer malignidade. Conclusão: esse estudo sugere que, entre as características tomográficas de nódulos pulmonares de crianças portadoras de neoplasias malignas, apenas o tamanho da lesão foi preditor de malignidade.

ABSTRACT Objective: to determine, in pediatric patients with malignant neoplasms, the characteristics of pulmonary nodules identified on computed tomography, as well as the possibility of differentiating benign lesions from metastases. Methods: we conducted a retrospective study of patients submitted to pulmonary resections of nodules diagnosed as metastases in a period of seven years. We compared computed tomography and surgery findings, as well as results of anatomopathological examinations. Results: we studied nine patients submitted to 11 surgical interventions. Among the studied variables, only nodule size greater than 12.5mm proved to be statistically significant to predict malignancy. Conclusion: among the tomographic characteristics of pulmonary nodules in children with malignant neoplasms, only the size of the lesion was a predictor of malignancy.

Metastasis pulmonares tardías de carcinoma adenoideo quístico de la glandula de bartolino / Late lung metastases of cystic adenoid carcinoma of the bartolino gland

El carcinoma adenoideo quístico de la glándula de Bartolino (GB) es una entidad infrecuente, de crecimiento lento y comportamiento agresivo con alta recurrencia local y metástasis. Presentamos el caso de una paciente de 48 años, con antecedente de tratamiento quirúrgico de un absceso Bartolino derecho. La biopsia demostró un carcinoma adenoideo quístico (CAQ) de la GB, por lo que se realizó hemivulvectomía radical derecha y linfadenectomía inguinofemoral. El resultado de la biopsia mostró 4 ganglios positivos de 12 y margen lateral positivo a menos de 2 mm. Por lo que se realizó adyuvancia con radioterapia. La paciente no se presenta a su control y acude luego de tres años por dolor urente desde cadera izquierda hacia rodilla y cara lateral de la pierna y pie. Se realiza cintigrama óseo que muestra lesión osteoblástica sacroilíaca izquierda de 2 cm, por lo que se completó estudio de diseminación con tomografía computada de tórax, abdomen y pelvis con contraste que evidenció múltiples lesiones nodulares pulmonares bilaterales de distribución generalizada en parénquima central, periférico y subpleurales. Se deriva al Instituto Nacional del Tórax, completando estudio preoperatorio y se realizó una biopsia quirúrgica por video toracoscopía resecando un nódulo subpleural, el informe histológico señaló una metástasis de CAQ concordante con primario en GB. La paciente fue presentada en el comité oncológico y se indicó radioterapia paliativa a lesión sacroilíaca y control clínico ambulatorio. Ha evolucionado estable desde el punto de vista funcional pulmonar.

Adenoid cystic carcinoma of Bartholin glands (BG) is a rare, slow-growing but a highly aggressive tumor with remarkable capacity for local recurrence and distant metastasis. We present the case of a 48 year-old female patient with a history of surgical treatment for right Bartholin abscess. The biopsy showed a cystic adenoid carcinoma of the BG, which led to radical hemivulvectomy and inguinofemoral lymphadenectomy. The biopsy show inguinal lymph node metastasis on 4 of 12 lymph nodes and positive surgical resection margin. Adjuvant radiotherapy was applied. The patient doesnt present to her clinical follow up, and consult three years later with radiological evidence of sacroiliac metástasis on bone scintigraphy. Study was completed with thorax, abdomen and pelvis tomography scan, and showed multiple bilateral lung nodules. The patient was transfered to National Thoracic Institute, and preoperative study was performed. We decide to obtain histologycal confirmation by a video thoracoscopy, it was performed without incidents. Histology show metastasis of adenoid cystic carcinoma pattern, concordant with primary tumor. The patient was submitted to the oncology committee and palliative radiotherapy was indicated for sacroiliac lesion. The patient evolve stable and asintomatic at ambulatory clinical control.

Deaths related to differentiated thyroid cancer: a rare but real event

ABSTRACT Objective The present study describes the clinical and tumor characteristics of patients that died from differentiated thyroid cancer and reports on the cause and circumstances of death in these cases. Subjects and methods Retrospective analysis of all the differentiated thyroid cancer (DTC) related deaths at a single institution over a 5-year period, with a total of 33 patients. Results Most of the patients were female (63.6%), with a mean age at diagnosis of 58.2 years. The most common histologic type was papillary (66.7%) and 30.3% were follicular. The distribution according to the TNM classification was: 15.4% of T1; 7.7% T2; 38.4% T3; 19.2% of T4a and 19.2% of T4b. Forty-four percent of cases were N0; 20% N1a and 36.6% of N1b. Twelve patients were considered non-responsive to radioiodine. Only one of the patients did not have distant metastases. The most common metastatic site was the lung in 69.7%. The majority of deaths were due to pulmonary complications related to lung metastases (17 patients, 51.5%), followed by post-operative complications in 5 cases, neurological disease progression in 3 cases, local invasion and airway obstruction in one patient. Median survival between diagnosis and death was reached in 49 months while between disease progression and death it was at 22 months. Conclusion Mortality from DTC is extremely rare but persists, and the main causes of death derive from distant metastasis, especially respiratory failure due to lung metastasis. Once disease progression is established, median survival was only 22 months.

Emerging radiotherapy technology in a developing country: A single Brazilian institution assessment of stereotactic body radiotherapy application / Tecnologias emergentes em radioterapia em um país em desenvolvimento: perfil do uso de radiocirurgia extracraniana em uma instituição filantrópica privada

Summary Objective: To provide a quantitative profile of the indications and use of stereotactic body radiotherapy (SBRT) in a developing country oncology-based institution. In addition, to describe the patients' and treatment characteristics, and to provide a temporal analysis. Method: SBRT patients treated from 2007 to 2015 were retrospectively evaluated by two independently investigators. Data were stratified and compared in two periods: first experience (FE) (May 2007 to April 2011), and following experience (FollowE) (May 2011 to April 2015). The following parameters were compared between the groups: total number of treated patients and lesions, treatment site, additional image fusion used, formal protocol adoption, and SBRT planning technique. Results: One hundred and seventy-six (176) patients with 191 lesions were treated: 34 (18%) lesions in the FE and 157 (82%) lesions in FollowE. The majority of lesions were metastases (60.3%), and lung (60.2%) was the most common treatment site, followed by spine (31%), and others (8.8%). An average of 1.4 (±0.6) additional imaging exams for delineation was performed. Conformal 3D radiotherapy planning technique was used in 64.4%, and intensity modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT) in the remaining 35.6% (p=0.0001). Higher rates of curative treatments were observed in FE, as well as more lung lesions, patients ≥ 70 years, 3D conformal, number of additional images and ECOG 0, and all presented p<0.05. The global rate of protocol statement was 79%, lung treatment being the most stated. Conclusion: SBRT application is rapidly increasing in our setting. Treatment sites and planning techniques are becoming more diversified and complex.

Resumo Objetivo: realizar uma análise quantitativa das indicações e do uso de SBRT (stereotactic body radiotherapy) em uma instituição filantrópica. Além disso, descrever temporalmente as características dos pacientes e tratamentos. Método: retrospectivamente, foram coletados, por dois investigadores independentes, os dados de todos os pacientes tratados com SBRT na instituição no período de maio de 2007 a fevereiro de 2015. Dados foram estratificados e comparados em dois períodos: inicial (P1) (maio de 2007 a abril de 2011) e período seguinte (P2) (maio de 2011 a abril de 2015). Os seguintes parâmetros foram comparados entre os grupos: número total de pacientes e lesões tratadas, local de tratamento, uso de imagens adicionais, adoção formal de protocolo e técnica de planejamento. Resultados: foram avaliados 176 pacientes e 191 lesões, sendo 34 (18%) no P1 e 157 (82%) no P2, tratados com SBRT. A maioria das lesões eram metastáticas (60,3%), sendo pulmão o sítio mais prevalente, contabilizando 115/191 (60,2%) lesões, seguida de lesões ósseas (30,8%). Uma média de 1,4 (±0,6) exame de imagem adicional foi usada para o delineamento. Uso formal de protocolo/recomendações foi descrito em 79% das lesões. A técnica 3D-conformada (3DCRT - three-dimensional conformal radiotherapy) foi a mais utilizada para planejamento [123/191 (64,4%) lesões] quando comparada à intensidade modulada e ao arco dinâmico (p=0.0001). O P1 esteve associado a maior número de lesões primárias tratadas (OR 2,09; p=0,0005), lesões pulmonares (OR 3,85; p=0,0198), pacientes ≥ 70 anos (OR 2,77; p=0,0005), uso de planejamento 3D (OR 16; p=0,0001), menor uso de imagens adicionais [0 ou 1 (versus > 1)] (OR 7,5; p=0,0001) e ECOG 0 (vs. > 0) (OR 0,21; p=0,0431). Conclusão: o uso de SBRT aumentou ao longo do tempo na instituição. No P2, notou-se uma evolução técnica, com indicações mais diferenciadas, maior uso de imagens auxiliares para definição do alvo e técnicas de planejamento mais sofisticadas.

Melanoma as a surprising solution to the puzzle of intestinal obstruction

Abstract We present a case of a 71-year-old man with an advanced melanoma of the right colon. The final diagnosis was determined based on histopathological examination of the material collected during urgent laparotomy performed due to ileus. Although we considered the tumor to be a disseminated primary melanoma of the colon, the possibility of unknown primary origin could not be excluded. Palliative chemotherapy and radiotherapy reduced symptoms associated with the disease and prolonged patient's survival.

Pneumatosis intestinalis after etoposide-based chemotherapy in a patient with metastatic small cell lung cancer: successful conservative management of a rare condition / Pneumatose intestinal após quimioterapia com etoposídeo em paciente com câncer de pulmão de pequenas células: sucesso com conduta conservadora em uma condição rara

ABSTRACT A 69-year-old male patient, smoker, was diagnosed with small cell lung cancer metastatic to lung, liver and central nervous system. He received chemotherapy with carboplatin AUC 5 on day 1 and etoposide 100mg/m2 on days 1, 2 and 3. During the first cycle, the patient presented with febrile neutropenia and abdominal distension. Chest, abdomen and pelvis computed tomography scan was performed and detected gas dissecting the wall of sigmoid colon extending to the mesosigmoid. Patient had no abdominal pain, nausea, vomiting, and on physical examination he had no peritoneal irritation, tachycardia or hemodynamic instability compatible with perforation or acute abdomen. Therefore, the radiological finding was interpreted as pneumatosis intestinalis caused by chemotherapy with etoposide. Pneumatosis resolved after continuous oxygen therapy. The second cycle was administered after a complete resolution of the clinical condition and etoposide dose was reduced by 30%. The patient experienced a remarkable evolution.

RESUMO Paciente do gênero masculino, 69 anos, fumante, diagnosticado com câncer de pulmão de pequenas células, metastático para pulmão, fígado e sistema nervoso central. Foi administrada quimioterapia com carboplatina AUC 5 no dia 1 e etoposídeo 100mg/m2 nos dias 1, 2 e 3. Durante o primeiro ciclo, o paciente apresentou neutropenia febril e distensão abdominal. Tomografias de tórax, abdome e pelve detectaram gás dissecando a parede do cólon sigmoide, com extensão para o mesossigmoide. O paciente não apresentava dor abdominal, náusea, vômito e não tinha sinais de irritação peritoneal, taquicardia ou instabilidade hemodinâmica compatíveis com perfuração ou abdome agudo. O achado radiológico foi interpretado como pneumatose intestinal causada por etoposídeo. A resolução do quadro ocorreu após suplementação de oxigênio. O segundo ciclo foi administrado após resolução completa do quadro, com redução da dose do quimioterápico em 30%. O paciente evoluiu de forma bastante satisfatória.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.