Nonbiological factors affecting survival in younger patients with acute myeloid leukemia.

BACKGROUND: Progress has been made in determining the biological variants of acute myelogenous leukemia (AML) and their prognostic implications. However, to the authors' knowledge, little is known regarding the impact of nonbiological factors (NBFs) on the survival of patients with AML. METHODS: The impact of NBFs (marital status, insurance status, county-level income, and education) on survival was assessed along with biological factors (disease subtype, sex, age, and race/ethnicity) using a cohort of patients aged 19 to 64 years who were diagnosed with AML between 2007 and 2011 and reported to the Surveillance, Epidemiology, and End Results program registry (SEER 18). RESULTS: There were 5541 patients included. The median overall survival for the entire study population was 16 months. On multivariate analysis, an increased risk of death was independently linked to being a Medicaid beneficiary, uninsured, single, divorced, and residing in a county within the lower 3 quintiles of median household income. NBFs affected the risk of early (<2 months) and late mortality and their impact was confirmed among patients known to have received chemotherapy. CONCLUSIONS: Insurance status, marital status, and county-level income were found to independently affect the survival of younger patients with AML and should be integrated into outcome comparisons. Interventions are needed to mitigate the impact of social factors on survival among patients with AML.

Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center.

BACKGROUND: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. METHODS: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. RESULTS: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). CONCLUSIONS: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Aspects of mTOR biology and the use of mTOR inhibitors in non-Hodgkin's lymphoma.

The mammalian target of rapamycin (mTOR) is a large and highly conserved kinase that integrates growth factor stimulation, energy and nutrient availability to modulate translation of proteins responsible for cellular growth and proliferation. Its importance in malignant cells provides strong rationale for the development of mTOR inhibitors (mTORi) in a broad variety of solid tumors and hematological malignancies. However several questions regarding mTOR biology and its interaction with pharmacological inhibitors remain unanswered and are relevant for further development of this novel family of cancer drugs. Nevertheless, mTORi have demonstrated activity in lymphoma cells either alone or in combination with cytotoxic agents. The most promising results have been seen in mantle cell lymphoma (MCL), likely because of its dependence on Cyclin D, the translation of which is largely regulated by mTOR activity. The currently knowledge of mTOR biology will here be reviewed along with the status of clinical development of mTORi in non-Hodgkin's lymphomas.

Missed diagnosis in hematological patients-an autopsy study.

Autopsy findings of missed diagnoses that would probably have changed management or prognosis occur in up to 29% of cases in general hospitals. Such proportions may be higher in subsets of patients with complex diseases. We reviewed 2908 consecutive autopsies performed over a period of 29 months in a large-volume hospital, analyzing 118 autopsies of patients with hematological malignancies or severe aplastic anemia. A review of macroscopic reports as well as microscopic examination of tissue samples was performed. Medical records were reviewed for clinical diagnoses. Discordances between clinical and autopsy diagnoses were classified using Goldman's criteria. Additionally, we searched for clinical parameters correlated with occurrence of class-I discrepancy using a multivariate method. Median age was 46.5 years, and 25.4% had received a hematopoietic stem-cell transplant. Overall, 11.9% (6.6-19.1%) of patients died before conclusion of the hematological diagnosis and 33% (24.6-42.3%) died with no active hematological disease. We found class-I discrepancy in 31.3% (23.1-40.5 %) of cases. The most common among these diagnoses were hematological disease, pneumonia and gastrointestinal bleeding. In a univariate analysis, being elderly (P=0.04) was positively correlated with the finding of class-I discrepancies; while, having received previous specific hematological treatment (P=0.0005) or hematopoietic stem-cell transplants (P=0.013), or being admitted to a specialized hematology unit (P=0.0006) were negatively correlated to the occurrence of such discrepancies. Multivariate analysis showed that care in a specialized hematology unit (OR 0.34, 0.12-0.93) was independently associated with lower occurrence of discrepancies. We concluded that critical diagnoses are often missed in highly complex hematological patients especially in the absence of admission to specialized hematology units.

Weight changes during chemotherapy for breast cancer.

CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8), adjuvant (n = 74) or palliative (n = 24) chemotherapy. INTERVENTION: Review of medical records and gathering of clinical information, including patients' body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 +/- 1.42% (p = 0.21) of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001). In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 +/- 1.19 % (p < 0.00001) per month, whereas in the metastatic (palliative) group, we observed a mean loss of 0.52 +/- 1.21% (p = 0.11) of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy.

[Evaluation of non-oncologist physician's knowledge and attitude towards cancer screening and preventive actions]. / Estudo da atitude e do conhecimento dos médicos não oncologistas em relação às medidas de prevenção e rastreamento do câncer.

BACKGROUND: New cancer cases are most often diagnosed by non-oncologist physicians. It is therefore essential for all physicians to be aware of cancer preventive practices and use them appropriately with their patients. METHODS: Questionnaires were administered to 120 non-oncologist physicians of various specialties attending the "Faculdade de Medicina do ABC" who deal directly with adult patients. Replies were collected and classified as appropriate or not according to one of these three cancer prevention guidelines: INCA, American Cancer Society and Canadian Task Force. RESULTS: The percentage of replied questionnaires was 58.3% (70 questionnaires). Mean age of physicians was 33.9 years; 57.1% were women and 10% smokers. Most of the current preventive practices adopted by the participating physicians (45.72% to 100%) regarding the most common and preventable tumors (breast, cervix, prostate, colon and rectum and non-melanoma skin cancer) did not agree with any of the guidelines mentioned above. When questioned about possible impediments for the appropriate practice of cancer prevention, 82.86% reported absence of health education agents working with the population, 77.14% scarceness of knowledge or training concerning prevention, and 70.15% lack of financial support for ordering tests. Frequently, whenever there was disagreement between the guidelines and the physician's current practices, preventive tests were ordered in excess of those recommended by the guidelines. CONCLUSIONS: Physicians had a tendency to order excessive laboratory tests, an action which can be related to lack of knowledge and to divergence among guidelines. A more intensive educational effort regarding cancer prevention, directed towards teaching physicians in training, seems to be warranted.

Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center

ABSTRACT Background: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. Methods: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. Results: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). Conclusions: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Ratio between positive lymph nodes and total dissected axillaries lymph nodes as an independent prognostic factor for disease-free survival in patients with breast cancer.

The number of positive axillary lymph nodes involved by tumor is one of the main prognostic factors for women with locoregional breast cancer (BC) for whom adjuvant chemotherapy is being considered. The prognostic importance of the ratio (P/D) between positive lymph nodes (P) and total dissected lymph nodes (D), previously demonstrated in the high-dose chemotherapy (HDC) setting has not yet been tested, however, in the conventional adjuvant chemotherapy setting. The data of 168 patients who were from 2 institutions and who were treated with adjuvant chemotherapy for BC were retrospectively analyzed, and univariate and multivariate analysis were performed, including the other traditional prognostic factors and P/D ratio as possible predictors of disease free survival (DFS). Disease-free survival for quartile 4 of P/D ratio (ratio >0.30) was statistically different from that for the other quartiles (log-rank test p < 0.001). Mean DFS for this series was not reached as well as for quartiles 1, 2, and 3, while mean DFS for quartile 4 was 44.5 months. In univariate analysis, number of positive lymph nodes (r2 = 0.055; p = 0.023), P/D ratio (r2 = 0.213; p < 0.001), and stage (r2 = 0.105; p = 0.002) were predictive of relapse, while in multivariate analysis, only P/D ratio remained an independent predictor of relapse (r2 = 0.213; p < 0.001). It is concluded that P/D ratio could become a simple, inexpensive, and easily available prognostic factor for patients undergoing conventional chemotherapy for BC.

Weight changes during chemotherapy for breast cancer

CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8), adjuvant (n = 74) or palliative (n = 24) chemotherapy. INTERVETION: Review of medical records and gathering of clinical information, including patientsÆ body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 ± 1.42 percent (p = 0.21) of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001). In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 ± 1.19 percent (p < 0.00001) per month, whereas in the metastatic (palliative) group, we observed a mean loss of 0.52 ± 1.21 percent (p = 0.11) of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy

Estudo da atitude e do conhecimento dos médicos não oncologistas em relação às medidas de prevenção e rastreamento do câncer / Evaluation of non-oncologist physician's knowledge and attitude towards cancer screening and preventive actions

OBJETIVO: Avaliar o nível de informação e as atitudes preventivas em uso corrente pelos médicos ligados à FMABC. MÉTODOS: Foram entregues questionários para 120 médicos não oncologistas que lidam diretamente com pacientes adultos. RESULTADOS: A taxa de resposta foi de 58,3 por cento. A idade média dos médicos foi de 33,9 anos, sendo 57,1 por cento mulheres e 10 por cento tabagistas. As práticas preventivas para os cânceres mais comuns (mama, colo de útero, próstata, colorretal e pele não-melanoma) foram analisadas e comparadas com as recomendadas pelos consensos adotados (INCA, Sociedade Americana de Cancerologia e Força-Tarefa Canadense). Observou-se que a maioria das práticas (45,72 por cento a 100 por cento) não se adequou a nenhum deles. Sobre possíveis barreiras para o adequado exercício da prevenção do câncer, 82,86 por cento considerou falta de agentes educadores em saúde para a população, 77,14 por cento poucos conhecimento ou treinamento e 70,15 por cento falta de verba para custear exames. Houve uma tendência ao excesso de pedidos de exames de rastreamento. CONCLUSÕES: As práticas preventivas utilizadas pelos médicos entrevistados são heterogêneas e, em sua maioria, não preconizadas pelos consensos de condutas preventivas consultados, o que pode ser relacionado tanto à sua falta de conhecimento em relação a estes consensos como às divergências entre eles. Dessa forma, faz-se necessário um esforço educativo enfatizando a importância da prevenção do câncer no aprendizado e na prática médica.

Modulação da sinalização celular e do complexo de início de tradução como estratégias para o tratamento do carcinoma de células renais / Cell sinaling and translation initiation complex modulation as strategies to the treatment of renal cell carcinoma

O carcinoma de células renais (CCR) é uma causa crescente de morte por câncer. Melhor entendimento da biologia tumoral pode levar a terapias mais eficientes. Estudou-se a sinalização celular originada de EGFR em CCR e o efeito de um inibidor de EGFR (gefitinibe), um inibidor de MAPK (UO126) e um inibidor de mTOR (rapamicina) na fosforilação de intermediários da via de MAPK, em componentes do complexo de início de tradução (CIT) e no crescimento de culturas celulares. UO126 promoveu defosforilação de substratos de mTOR revelando comunicação entre MAPK e CIT. Gefitinibe bloqueou a sinalização entre EGFR e as vias PI3K e MAPK. Rapamicina foi um potente inibidor do crescimento na maioria das linhagens celulares e seu efeito foi frequentemente potencializado por UO126 ou gefitinibe. EGFR, MAPK e CIT são alvos promissores no tratamento do CCR / Summary Renal cell carcinoma (RCC) is a rising cause of cancer death. Better understanding of tumor biology may lead to more efficient therapy based on biological agents. We studied EGFR driven cell signaling in RCC as well as the effect of an EGFR inhibitor (gefitinib) a MAPK inhibitor (UO126) and a mTOR inhibitor (rapamycin) on phosphorylation of MAPK pathway intermediates, translation initiation complex (TIC) components and growth of cell cultures. UO126 caused dephosphorylation of downstream targets of mTOR revealing a cross talk between MAPK and TIC. Gefitinib blocked EGFR signaling though PI3K and MAPK pathways. Rapamycin was found to be a potent growth inhibitor in most cell lines and its effect was often potentiated by UO126 or gefitinib. EGFR, MAPK and TIC are suitable targets...