Pathophysiology of cancer cachexia

A caquexia é uma complicação freqüentemente observada em pacientes portadores de tumores malignos. Apesar de várias décadas transcorrerem desde a descrição inicial das disfunções metabólicas associadas ao câncer, poucas medidas terapêuticas foram induzidas com sucesso na prática médica. O presente estudo apresenta uma revisão detalhada da fisiopatologia básica da caquexia em câncer, e as opções terapêuticas desenvolvidas nesta área. Estudos experimentais, assim como clínicos, são avaliados individualmente para esclarecer as alterações complexas observadas em pacientes portadores de tumores. As dificuldades encontradas para introduzir manipulações metabólicas e terapias de suporte nutricional eficientes são discutidas nesta revisão.Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluated individually in order to clarify the intricate alterations observed in tumor-bearing patients. The difficulties in introducing sound and effective nutritional support or metabolic manipulation to reverse cancer cachexia are outlined in this review

Solução hipertônica hiperoncótica em pacientes com hipovolemia: experiência na sala de admissão

As soluções hipertônicas têm sido estudadas no tratamento de choque hipovolêmico, tanto em protocolos experimentais quanto clínicos. A eficácia, a segurança e os efeitos a longo prazo em animais e pacientes foram avaliados. O presente estudo apresenta uma revisão da literatura sobre as indicações, as taxas de morbidade e de mortalidade e a evolução de pacientes com choque hipovolêmico, admitidos e tratados com soluções hipertônicas/hiperoncóticas, admitidos e tratados sob observação contínua na sala de emergência do pronto socorro.Hypertonic solutions have been studied extensively in the treatment of hypovolemic shock, both in experimental and clinical models. Safety, efficacy, and long-term effects on animals and patients have been evaluated. The present article reviews indications, safety, mortality rates, and outcome in patients with hemorrhagic hypovolemic shock who were treated after admission with a hypertonic/hyperoncotic solution under strict observation in the emergency room

Biópsia de lesões pulmonares por agulha cortante guiada pela tomografia computadorizada

PURPOSE: To report the experience of a radiology department in the use of computed tomography - guided cutting needle biopsy of pulmonary nodules, by evaluating diagnostic yield and incidence of complications. METHODS: This is a retrospective analysis of 52 consecutive patients who underwent lung lesion biopsy guided by computed tomography, performed between May 1997 and May 2000. Thirty-five patients were male and 17 were female, with ages ranging from 5 to 85 years (median, 62 years). The size of the lesions ranged from 1.8 to 15 cm (median, 5.4 cm). RESULTS: In a total of 52 biopsies of lung lesions, 51 biopsies (98.1%) supplied appropriate material for histopathological diagnosis, with 9 diagnosed (17.3%) as benign and 42 (80.8%) as malignant lesions. Specific diagnosis was obtained in 44 (84.6%) biopsies: 4 benign (9.1%) and 40 (90.9%) malignant lesions. The sensitivity, specificity, and accuracy of the cutting needle biopsies for determining presence of malignancy were 96.8%, 100%, and 97.2%, respectively. Complications occurred in 9 cases (17.3%), including 6 cases (11.5%) of small pneumothorax, 1 (1.9%) of hemoptysis, 1 (1.9%) of pulmonary hematoma, and 1 (1.9%) of thoracic wall hematoma. All had spontaneous resolution. There were no complications requiring subsequent intervention. CONCLUSION: The high sensitivity and specificity of the method and the low rate of complications have established cutting needle biopsy as an efficient and safe tool for the diagnosis of lung lesions. In our hospital, cutting needle biopsy is considered a reliable procedure for the evaluation of indeterminate pulmonary nodules.OBJETIVO: Apresentar a experiência inicial de um serviço de radiologia, no uso de biópsia de lesões pulmonares por agulha cortante guiada por tomografia computadorizada, avaliando o valor diagnóstico e incidência de complicações. MÉTODOS: Realizamos análise retrospectiva de 52 pacientes submetidos à biópsia de lesão pulmonar guiada pela tomografia computadorizada. Analisamos o período de maio de 1997 até maio de 2000. Trinta e cinco pacientes eram de sexo masculino e 17 feminino, com idade variando de cinco a 85 anos (mediana de 62 anos). O tamanho das lesões pulmonares variou de 1,8 a 15 cm (mediana de 5,4 cm). RESULTADOS: Entre os 52 casos, 51 (98,1%) forneceram material adequado para diagnóstico histopatológico, com nove diagnósticos (17,3%) de lesão benigna e 42 (80,8%) de lesão maligna. Quarenta e quatro (84,6%) obtiveram diagnósticos específicos a partir de análise histopatológica, sendo quatro benignos e 40 malignos. A sensibilidade, a especificidade e a acurácia do método para lesões malignas foi de 96,8%, 100% e 97,2%, respectivamente. Nove casos (17,3%) de complicações ocorreram, sendo seis casos (11,5%) de pneumotórax pequeno, um (1,9%) de hemoptise, um (1,9%) de hematoma intrapulmonar e um outro caso (1,9%) de hematoma na parede torácica. Não houve complicação que necessitasse de intervenção posterior. CONCLUSÃO: As altas sensibilidade e especificidade, e o baixo índice de complicações tornam o método de biópsia por agulhas cortantes uma ferramenta eficiente e segura para diagnóstico de lesões pulmonares. Em nosso hospital é considerado um procedimento confiável para a avaliação de nódulos pulmonares indeterminados

Biópsia de massas mediastinais guiadas por tomografia computadorizada: agulhas finas versus cortantes

PURPOSE: To report the experience of a radiology department in the use of computed tomography guided biopsies of mediastinal lesions with fine and cutting needles, describing the differences between them. The results of adequacy of the sample and histologic diagnoses are presented according to the type of needle used. METHODS: We present a retrospective study of mediastinal biopsies guided by computed tomography performed from January 1993 to December 1999. Eighty-six patients underwent mediastinal biopsy in this period, 37 with cutting needles, 38 with fine needles, and 11 with both types (total of 97 biopsies). RESULTS: In most cases, it was possible to obtain an adequate sample (82.5%) and specific diagnosis (67.0%). Cutting-needle biopsy produced a higher percentage of adequate samples (89.6% versus 75.5%, P = 0.068) and of specific diagnosis (81.3% versus 53.1%, P = 0.003) than fine-needle biopsy. There were no complications that required intervention in either group. CONCLUSION: Because they are practical, safe, and can provide accurate diagnoses, image-guided biopsies should be considered the procedure of choice in the initial exploration of patients with mediastinal masses. In our experience, cutting needles gave higher quality samples and diagnostic rates. We recommend the use of cutting needles as the preferred procedure.OBJETIVO: Apresentar a experiência de um serviço de radiologia na prática de punções biópsias de massas mediastinais guiadas por tomografia computadorizada com agulhas finas ou cortantes, descrevendo as diferenças entre elas. Os resultados referentes a material suficiente e diagnóstico histológico são apresentados de acordo com o tipo de agulha utilizado. MÉTODOS: Apresentamos um estudo retrospectivo de biópsias mediastinais guiadas por tomografia computadorizada realizadas em nosso hospital no período de janeiro de 1993 a dezembro de 1999. Oitenta e seis pacientes foram submetidos a biópsia mediastinal neste período, sendo 37 realizadas com agulhas cortantes, 38 com agulhas finas e 11 com ambas, (total de 97 biópsias). RESULTADOS: Na maioria dos casos foi possível se obter material adequado (82.5% ) e diagnóstico específico (67 %). As agulhas cortantes apresentaram maior porcentagem de material suficiente (89.6% versus 75,5%, P=0,068) e de diagnóstico específico (81,3% versus 53,1%, p=0,003 ) do que as agulhas finas. Não houveram complicações que requisessem intervenção em nenhum dos grupos. CONCLUSÃO: Pela praticidade, segurança e grande probabilidade de diagnóstico acurado sem procedimentos mais invasivos, as biópsias guiadas por imagem devem ser consideradas como a primeira etapa na investigação de massas mediastinais. Pela nossa experiência as agulhas cortantes fornecem material de maior qualidade e maior taxa de diagnóstico. Nós recomendamos o uso das agulhas cortantes como procedimento preferencial

Carcinoma de pulmão não pequena células: validação do sistema de estadiamento em uma única instituição (1990-200)

OBJECTIVE: To analyze surgical and pathological parameters and outcome and prognostic factors of patients with nonsmall cell lung cancer (NSCLC) who were admitted to a single institution, as well as to correlate these findings to the current staging system. METHOD: Seven hundred and thirty seven patients were diagnosed with NSCLC and admitted to Hospital do Cancer A. C. Camargo from 1990 to 2000. All patients were included in a continuous prospective database, and their data was analyzed. Following staging, a multidisciplinary team decision on adequate management was established. Variables included in this analysis were age, gender, histology, Karnofsky index, weight loss, clinical stage, surgical stage, chemotherapy, radiotherapy, and survival rates. RESULTS: 75.5% of patients were males. The distribution of histologic type was squamous cell carcinoma 51.8%, adenocarcinoma 43.1%, and undifferentiated large cell carcinoma 5.1%. Most patients (73%) presented significant weight loss and a Karnofsky index of 80%. Clinical staging was IA 3.8%, IB 9.2%, IIA 1.4%, IIB 8.1%, IIIA 20.9%, IIIB 22.4%, IV 30.9%. Complete tumor resection was performed in 24.6% of all patients. Surgical stage distribution was IA 25.3%, IB 1.4%, IIB 17.1%, IIIA 16.1%, IIIB 20.3%, IV 11.5%. Chemotherapy and radiotherapy were considered therapeutic options in 43% and 72%, respectively. The overall 5-year survival rate of nonsmall cell lung cancer patients in our study was 28%. Median survival was 18.9 months. CONCLUSIONS: Patients with NSCLC who were admitted to our institution presented with histopathologic and clinical characteristics that were similar to previously published series in cancer hospitals. The best prognosis was associated with complete tumor resection with lymph node dissection, which is only achievable in earlier clinical stages.OBJETIVO: Analisar o resultado e fatores prognósticos de patients com CPNPC admitidos em uma única instituição e correlacionar os dados com o sistema atual de estadiamento. MÉTODO: Setecentos e trinta e sete pacientes com diagnóstico de CPNPC foram admitidos ao Hospital do Cancer A. C. Camargo entre 1990 e 2000. Todos os pacientes foram incluídos em um banco de dados contínuo prospectivo e seus dados foram analisados. Após o estadiamento, uma equipe multidisciplinar estabeleceu decisões sobre o manejo adequado para o caso. Variáveis analisadas incluíram idade, sexo, tipo histológico, índice de Karnofsky, perda de peso, estadio clínico, estadio cirúrgico, quimioterapia, radioterapia e taxa de sobrevida. RESULTADOS: 75,5% dos pacientes eram do sexo masculino. A distribuição dos tipos histológicos foi carcinoma espino celular 51,8%, adenocarcinoma 43,% e carcinoma indiferenciado de grandes células 5,1%. A maior parte apresentou perda de peso significativa e um Karnofsky Index de 80%. O estadiamento clínico foi IA 3,8%, IB 9,2%, IIA 1,4%, IIB 8,1%, IIIA 20,9%, IIIB 22,4%, IV 30,9%. A ressecção total do tumor foi possível em 24,6% dos casos. A distribuição do estadiamento cirúrgico foi IA 25,3%, IB 1,4%, IIA 1,4%, IIB 17,1%, IIIA 16,1%, IIIB 20,3%, IV 11,5%. Quimioterapia e radioterapia também foram consideradas opções terapêuticas. A sobrevida global de 5 anos em nosso estudo foi de 28%, sendo a sobrevida mediana de18,9 meses. CONCLUSÕES: CPNPC é uma doença que requer atenção especial, devido aos altos índices de morbi-mortalidade. Melhor prognóstico está associado à ressecção completa do tumor, com dissecção de linfonodos. Todavia, isso só é possível em estadios clínicos mais precoces

Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain

Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care ), and Group B (n=47 -- treated with systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks) in Group A and 55 weeks (range 7.4 -- 213 weeks) in Group B (p=0.0018). In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.O câncer de pulmão de células não pequenas em estádio IV é uma doença fatal, com uma sobrevida mediana de seis meses. Quimioterapia é a abordagem mais freqüente, apresentando um impacto na sobrevida controverso e questionável alteração na qualidade de vida. OBJETIVOS: Comparar o impacto na sobrevida global e na qualidade de vida em pacientes portadores de câncer de pulmão de células não pequenas, estádio IV, tratados com suporte clínico ou quimioterapia. PACIENTES: Entre fevereiro de 1990 e dezembro de 1995, 78 pacientes (pts) portadores de câncer de pulmão de células não pequenas estádio IV foram admitidos. Os pacientes foram divididos em dois grupos: grupo A (n=31 -- tratados com suporte clínico) e grupo B (n=47, tratados com quimioterapia). RESULTADOS: A sobrevida mediana no grupo tratado com suporte clínico foi de 23 semanas (variando de 5-153 semanas) e de 55 semanas no grupo tratado com quimioterapia (variando de 7,4 a 213 semanas), p= 0,0018 -- Qui-quadrada. Em ambos grupos, a incidência de internações hospitalares para a administração intravenosa de antibióticos e hemoderivados foi similar. Pacientes recebendo quimioterapia, foram estratificados entre àqueles que receberam mitomicina, vinblastina e cisplatina, n=25 e àqueles recebendo outros regimes (derivados de platina, associados à outras drogas, n= 22). Pacientes recebendo mitomicina, vinblastina e cisplatina, n=25 apresentaram uma incidência mais alta de neutropenia febril e tiveram atrasos mais longos entre os ciclos de quimioterapia, quando comparados aos pacientes do outro grupo. Pacientes recebendo mitomicina, vinblastina e cisplatina, n=25, também apresentaram uma pior sobrevida mediana (51 versus 66 semanas, p= 0,005 -- Qui-quadrado). CONCLUSÕES: Em pacientes com câncer de pulmão de células não pequenas, estádio IV, não metastático para os pulmões, o uso de quimioterapia aumenta a sobrevida de maneira estatisticamente significativa, quando comparado aos cuidados de suporte

Surgical Resection of Lung Metastases: Results from 529 Patients

OBJECTIVE: The aim of this study is to determine clinical, pathological, and treatment-relevant variables associated with long-term (90-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy. METHODS: A retrospective review was performed of patients who were admitted with lung metastases, and who underwent thoracotomy for resection, after treatment of a primary tumor. Data were collected regarding demographics, tumor features, treatment, and outcome. RESULTS: Patients (n = 529) were submitted to a total of 776 thoracotomies. Median follow-up time across all patients was 21.6 months (range: 0-192 months). The postoperative complication rate was 9.3%, and the 30-day mortality rate was 0.2%. The ninety-month overall survival rate for all patients was 30.4%. Multivariate analysis identified the number of pulmonary nodules detected on preoperative CT-scan, the number of malignant nodules resected, and complete resection as the independent prognostic factors for overall survival. CONCLUSION: These results confirm that lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after resection

Evaluation of the effects of ozone therapy in the treatment of intra-abdominal infection in rats

INTRODUCTION: The antibacterial effect of ozone (O3) has been described in the extant literature, but the role of O3 therapy in the treatment of certain types of infection remains controversial. OBJECTIVES: To evaluate the effect of intraperitoneal (i.p.) O3 application in a cecal ligation/puncture rat model on interleukins (IL-6, IL-10) and cytokine-induced neutrophil chemoattractant (CINC)-1 serum levels, acute lung injury and survival rates. METHODS: Four animal groups were used for the study: a) the SHAM group underwent laparotomy; b) the cecal ligation/puncture group underwent cecal ligation/puncture procedures; and c) the CLP+O2 and CLP+O3 groups underwent CLP+ corresponding gas mixture infusions (i.p.) throughout the observation period. IL-6, CINC-1 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Acute lung injury was evaluated with the Evans blue dye lung leakage method and by lung histology. P<0.05 was considered significant. RESULTS: CINC-1 was at the lowest level in the SHAM group and was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group. IL-10 was lower for the SHAM group vs. the other three groups, which were similar compared to each other. IL-6 was lower for the SHAM group vs. all other groups, was lower for the CLP+O3 or CLP+O2 group vs. the cecal ligation/puncture group, and was similar for the CLP+O3 group vs. the CLP+O2 group. The lung histology score was lower for the SHAM group vs. the other groups. The Evans blue dye result was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group but similar to that of the SHAM group. The survival rate for the CLP+O3 group was lower than for the SHAM group and similar to that for the other 2 groups (CLP and CLP+O2). CONCLUSION: Ozone therapy modulated the inflammatory response and acute lung injury in the cecal ligation/puncture infection model in rats, although there was no improvement on survival rates

A isquemia/reperfusão intestinal provoca hiper-reatividade brônquica e aumento do TNF-alfa sérico em ratos

INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF)- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia), or sham procedures (control), followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4) was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue) showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL) concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains to be determined.INTRODUCÃO: A isquemia/reperfusão intestinal ou hepática induz lesão pulmonar aguda em modelos animais de falência de múltiplos órgãos. O fator de necrose tumoral (TNF-alfa) está envolvido no mecanismo inflamatório da síndrome da angústia respiratória aguda. Embora a cascata inflamatória que leva à síndrome da angústia respiratória aguda tenha sido extensamente investigada, os componentes mecânicos desta ainda não são completamente compreendidos. Nós levantamos a hipótese de que a isquemia/reperfusão esplâncnica provoca aumento da reatividade contráctil das vias aéreas, bem como aumento do TNF-alfa sérico. OBJETIVO: avaliar a reatividade da musculatura lisa brônquica sob estimulação com metacolina, e medir os níveis séricos de TNF-alfa após isquemia/reperfusão intestinal e/ou hepática em ratos. MÉTODO: Ratos Wistar foram submetidos a 45 min de isquemia intestinal, ou 20 minutos de isquemia hepática, ou a ambas (isquemia dupla), ou controle, seguidos por 120 min de reperfusão. A resposta brônquica a concentrações molares (10-7 to 3x10-4) de metacolina foi avaliada usando-se uma preparação ex-vivo de musculatura brônquica. RESULTADOS: A resposta brônquica (g/100mg de tecido) mostrou reatividade aumentada a concentrações crescentes de metacolina na isquemia intestinal e isquemia dupla, mas não na isquemia hepática. Similarmente, o TNF-alfa sérico aumentou na isquemia intestinal e isquemia dupla, mas não na isquemia hepática. CONCLUSÃO: Isquemia intestinal, quer isolada ou associada à hepática, provocou hiper-reatividade da musculatura brônquica, sugerindo um possível papel da constrição brônquica na disfunção respiratória conseqüente à isquemia/reperfusão esplâncnica. Este aumento foi simultâneo ao do TNF-alfa sérico, porém o possível efeito causal do TNF-alfa na contractilidade brônquica permanece a ser determinado