Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets.

The Eph/ephrin system regulates many developmental processes and adult tissue homeostasis. In colorectal cancer (CRC), it is involved in different processes including tumorigenesis, tumor angiogenesis, metastasis development, and cancer stem cell regeneration. However, conflicting data regarding Eph receptors in CRC, especially in its putative role as an oncogene or a suppressor gene, make the precise role of Eph-ephrin interaction confusing in CRC development. In this review, we provide an overview of the literature and highlight evidence that collaborates with these ambiguous roles of the Eph/ephrin system in CRC, as well as the molecular findings that represent promising therapeutic targets.

Síndrome Dress relacionada ao uso de Alopurinol: relato de caso / Dress Syndrome related to the use of allopurinol: case report

A síndrome DRESS é uma reação adversa a medicamentos pouco conhecida dentro da prática clínica, porém com grande potencial de letalidade devido a combinação de manifestações cutâneas e envolvimento de múltiplos órgãos. Objetivo: identificar possíveis reações adversas graves e incomuns secundárias ao uso de medicações usadas frequentemente na prática clínica. Métodos: Trata-se de um relato de caso construído com base em levantamento de dados do prontuário do paciente e análise a partir de um referencial teórico para comprovação de sua relevância na prática clínica. Resultado: Enfatizou-se a importância de um reconhecimento precoce dessa condição, a fim de evitar desfechos graves

The DRESS syndrome is an adverse drug reaction that is unsual in clinical practice, but with a high potential for lethality, due to the combination of cutaneous manifestations and involvement of multiple organs. Objective: identify possible serious and unusual adverse reactions secondary to the use of medications frequently used in clinical practice. Methods: This is a case report built on the basis of data collection from the patient's medical record and analysis from a theoretical framework to prove its source in clinical practice. Outcome: The importance of early recognition of this condition was emphasized, in order to avoid serious outcomes

Differential Diagnosis of Diarrhea in Patients With Neuroendocrine Tumors.

Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience diarrhea that can have a debilitating effect on quality of life. Diarrhea also may develop in response to other hormonal syndromes associated with NETs, surgical complications, medical comorbidities, medications, or food sensitivities. Limited guidance on the practical approach to the differential diagnosis of diarrhea in these patients can lead to delays in appropriate treatment. This clinical review and commentary underscore the complexity in identifying the etiology of diarrhea in patients with NETs. Based on our collective experience and expertise, we offer a practical algorithm to guide medical oncologists and other care providers to expedite effective management of diarrhea and related symptoms in patients with NETs.

Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico.

Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.

Immunocytochemical detection of epithelial cells in the bone marrow of primary breast cancer patients: a meta-analysis.

PURPOSE: The immunocytochemical detection of epithelial cells in the bone marrow (BM) of breast cancer (BC) patients has been shown to have prognostic importance in several studies. We conducted a systematic review of the literature and a meta-analysis to assess the specificity, rate of positivity and correlation with known prognostic variables as well as with disease free (DFS) and overall survival (OS). DESIGN: We performed a systematic review from the published literature. We included studies with at least 20 previously untreated BC patients as well as non-BC controls that evaluated the presence of epithelial cells in BM using immunocytochemistry (IC). RESULTS: We identified 14 eligible studies with 3253 BC patients and 532 controls. Our results showed that IC has an overall rate of positivity of 31% (95% CI: 30-33%), and specificity of 96% (compared to normal patients) (95% CI: 0.94-0.98). We observed significant direct correlations between IC BM positivity and the primary tumor's presence with expression of estrogen receptors, larger size and higher histologic grade as well as with the presence of more than 3 positive axillary lymph nodes. At 5 years of follow up IC positivity correlated directly with a lower DFS (relative risk=1.60; 95% CI: 1.39-1.83) and OS (relative risk=1.73; 95% CI: 1.29-2.31). The prognostic impact of BM positivity seemed to decrease with time. CONCLUSIONS: We conclude that the finding of epithelial cells in BM of BC patients correlates with several known prognostic factors and has adverse impact in the DFS and OS of these patients that seems, however, to decrease with time.

Praying correlates with higher quality of life: results from a survey on complementary/alternative medicine use among a group of Brazilian cancer patients.

CONTEXT: The use of complementary/alternative medicine has been little studied in Brazil. OBJECTIVE: The purpose of this study was to determine the prevalence of complementary/alternative medicine use among a group of Brazilian cancer patients and correlate these findings with the patients' quality of life. TYPE OF STUDY: Descriptive. SETTING: Oncology Institute of the Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil. PARTICIPANTS: 100 cancer patients. PROCEDURES: The EORTC QLQ C-30 quality of life questionnaire was applied together with another questionnaire on the use of complementary/alternative medicine. MAIN MEASUREMENTS: Use of complementary/alternative medicine and quality of life. RESULTS: 89% of the patients had already used complementary/alternative medicine, 63% were currently using it and most of them (77.7%) believed in the efficacy of complementary/alternative medicine for their treatment. The type most used was individual prayer (77.5%). We found a significant association between believing in the efficacy of complementary/alternative medicine and praying (individually or in groups), in comparison with better scores on the functional (p = 0.001) and overall health (p = 0.001) quality of life scales. Multivariate analysis confirmed these findings regarding praying and also showed that believing in complementary/alternative medicine correlated significantly with functional and symptom quality of life scores. CONCLUSION: The prevalence of complementary/alternative medicine use in this group of cancer patients was high. Praying and belief in the efficacy of complementary/alternative medicine correlated significantly with an overall better quality of life, and therefore these practices should not be discouraged by physicians. New prospective studies should be conducted in order to better characterize the efficacy of such alternative therapeutic approaches.

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.

Praying correlates with higher quality of life: results from a survey on complementary/alternative medicine use among a group of Brazilian cancer patients

CONTEXTO: O uso da medicina alternativa/complementar no Brasil é pouco estudado. OBJETIVO: Verificar a prevalência do uso de medicina alternativa/complementar por pacientes oncológicos e correlacionar os achados com a qualidade de vida. TIPO DE ESTUDO: Descritivo. LOCAL: Instituto de Oncologia da Faculdade de Medicina da Fundação do ABC. PARTICIPANTES: 100 pacientes com câncer. PROCEDIMENTOS: Aplicamos questionário de qualidade de vida da EORTC QLQ C-30 quality of life e um questionário sobre o uso de medicina alternativa/complementar. VARIAVEIS ESTUDADAS: Uso de medicina alternativa/complementar e qualidade de vida. RESULTADOS: 89% dos pacientes já usaram medicina alternativa/complementar alguma vez, 63% estavam usando no momento do estudo e a maioria dos pacientes (77,7%) acredita na eficácia da medicina alternativa/complementar para o seu tratamento. O tipo de medicina alternativa/complementar mais utilizado foi a oração individual (77,5%). Encontramos associação significativa entre acreditar em medicina alternativa/complementar e a prática de orações (individual ou em grupo) com uma melhor qualidade de vida em relação à escala funcional (p = 0,001) e saúde global (p = 0,001). A análise multivariada confirmou estes achados, mostrando que rezar e acreditar na medicina alternativa/complementar se correlacionam significativamente com uma melhor qualidade de vida nas escalas funcionais e de sintomas. CONCLUSAO: A utilização de medicina alternativa/complementar em nosso meio é freqüente em pacientes com câncer e a crença na sua eficácia e a prática de orações se correlacionaram significativamente com uma melhor qualidade de vida, de forma que tais práticas não devem ser desestimuladas pelos profissionais da área médica. Novos trabalhos prospectivos devem ser conduzidos para melhor caracterizar a eficácia destas práticas terapêuticas alternativas.

Qualidade de vida, depressão e câncer de mama: um estudo piloto da Faculdade de Medicina do ABC / Quality of life, depression and breast cancer: a pilot study of ABC School of Medicine

Muitas mulheres com diagnóstico de câncer de mama se deparam com conflitos pessoais. Há estudos na literatura que associam câncer de mama com pior qualidade de vida e depressão. Objetivo: Nosso objetivo neste trabalho foi avaliar qualidade de vida e depressão das pacientes com câncer de mama em quimioterapia (QT) e compará-las com um grupo de controle e com um grupo de pacientes em seguimento após terem completado a sua QT. Métodos: Aplicar questionário geral, questionário de qualidade de vida (QV), versão WHOQL-brief, e o questionário Beck para avaliação de depressão em pacientes: ao diagnóstico (grupo 1), antes do início da QT (D0), após uma semana do primeiro ciclo de QT (D1-7) e após uma semana do segundo ciclo de QT (D2-7); em pacientes em seguimento clínico (grupo 2); e no grupo de controle (grupo 3). Resultados: 1) Pacientes em QT apresentaram uma pontuação significativamente inferior apenas no domínio físico do questionário WHOQL quando comparadas ao grupo de controle (p<0,05), não apresentando alterados os domínios psicológico, social e ambiental, e pontuação total do questionário WHOQL; 2) não evidenciamos depressão quando analisamos diferenças de pontuação no questionário de Beck entre grupos 1 e 2 e entre os grupos 1 e 3. Conclusão: Não encontramos evidências de que a quimioterapia induza um nível significativo de depressão nas pacientes com câncer de mama a ela submetidas. À exceção de significativa mudança na pontuação do domínio físico, o início do tratamento quimioterápico parece não implicar em piora de qualidade de vida das mulheres com câncer de mama quando comparadas às mulheres em seguimento ou mulheres sem doença.

Many women after a diagnosis of breast cancer (BC) come across personal conflicts. Some studies have associated breast cancer with worsening quality of life (QOL) and depression. Aims: Evaluating the quality of life and depression of breast cancer patients treated with chemotherapy (CH) and comparing it with normal women and patients who already finished their chemotherapy. Methods: We employed a general questionare, a quality of life questionnaire WHOQL and the Beck depression questionnaire in the following groups of patients: group 1 - women with BC before chemotherapy (DO), one week after the first cycle (D1-7) and one week after the second cycle; group 2 - patients in the follow-up; and group 3 - control group of normal women. Results: 1) Group 1 reported poorer physical domain scores in the questionnaire WHOQL when compared with the contro group (p<0,05); 2) there was no evidence of significant differences in the Beck depression questionnaire scores between groups 1 and 2 or between groups 1 and 3. Conclusion: We believe that beginning chemotherapy does not produce a significant level of depression in BC patients who undergo this treatment acutely. Except for a significant decrease in the physical domain scores of the QOL questionnaire, beginning chemotherapy seems not to worsen overall QOL in women with BC when compared to women who already finished treatment or to normal healthy women.

Peripheral blood c-erbB-2 expression by reverse transcriptase-polymerase chain reaction in breast cancer patients receiving chemotherapy.

Minimal residual disease (MRD) evaluation in breast cancer patients is a promising tool to improve current staging procedures. In a previous work employing a CK-19-based reverse transcriptase-polymerase chain reaction (RT-PCR) technique for MRD detection, we identified a group of women who exhibited persistent negativity for this assay and for whom this technique was considered noninformative. In order to improve the yield of MRD detection in these patients, we evaluated the usefulness of RT-PCR detection of c-erbB-2 expression. We were able to detect up to 1 MCF-7 cell (positive for c-erbB-2 expression) in a mixture of 1,000,000 CCRF-CEM cells (negative for c-erbB-2 expression). We evaluated the specificity of this technique in the peripheral-blood mononuclear cells (PBMCs) of 20 healthy women and found that 2 of these women were positive for c-erbB-2 expression. In the PBMCs of a group of 16 women with breast cancer, 25% of the samples were positive for c-erbB-2 expression before chemotherapy. Except for race (P = 0.017), no other significant correlations were found, including c-erbB-2 expression in the primary tumor by immunoperoxidase. Interestingly, in the subgroup of 6 patients for whom this technique was informative, we found that 80% of the samples obtained while on chemotherapy were negative compared to only 10% obtained off treatment (P = 0.017). Additionally, 2 patients for whom CK-19 expression was noninformative had at least 1 c-erbB-2-positive sample. We conclude that this technique might be useful for MRD detection in breast cancer patients, but further studies are necessary to confirm our findings.

Pancreatic islet isolation by mechanical-enzymatic separation, stationary collagenase digestion and dextran discontinuous density gradient purification: experimental study in dogs

The prospects for allotransplantation of pancreatic islets in man depend on the development of methods that provide sufficient quantities of pancreatic islets from a single donor, which are capable, when transplanted, of achieve the normalization of carbohydrate metabolism. Objective: Evaluate the efficacy of the isolation of Langerhans islets from dogs, by means of mechanical-enzymatic separation technique with stationary digestion using collagenase, and purification with a discontinuous dextran density gradient. Methods: The counting of islet numbers and evaluation of their sizes was accomplished by staining with diphenylthiocarbazone and using stereoscopic microscopes equipped with eyepiece reticule for the measurement of average diameters of stained islets. Results: The results disclosed that the average number of islets isolated was 81032.20 ñ 24736.79 and the average number of islets isolated per kg of body weight was 6938.70 1392.43. The average number of islets isolated per kg of body weight showed significant correlation with body weight and weight of the pancreas resected. Conclusion: The number of islets isolated, of a single donor, by mechanical-enzymatic separation, stationary collagenase digestion and discontinuous dextran density gradient purification can be sufficient to success of pancreatic islets transplant in dogs.

Pancreatic islet isolation by mechanical-enzymatic separation, stationary collagenase digestion and dextran discontinuous density gradient purification: experimental study in dogs

The prospects for allotransplantation of pancreatic islets in man depend on the development of methods that provide sufficient quantities of pancreatic islets from a single donor, which are capable, when transplanted, of achieve the normalization of carbohydrate metabolism. Objective: Evaluate the efficacy of the isolation of Langerhans islets from dogs, by means of mechanical-enzymatic separation technique with stationary digestion using collagenase, and purification with a discontinuous dextran density gradient. Methods: The counting of islet numbers and evaluation of their sizes was accomplished by staining with diphenylthiocarbazone and using stereoscopic microscopes equipped with eyepiece reticule for the measurement of average diameters of stained islets. Results: The results disclosed that the average number of islets isolated was 81032.20 ± 24736.79 and the average number of islets isolated per kg of body weight was 6938.70 ± 1392.43. The average number of islets isolated per kg of body weight showed significant correlation with body weight and weight of the pancreas resected. Conclusion: The number of islets isolated, of a single donor, by mechanical-enzymatic separation, stationary collagenase digestion and discontinuous dextran density gradient purification can be sufficient to success of pancreatic islets transplant in dogs.

A perspectiva do alotransplante de ilhotas pancreáticas no homem está na dependência do desenvolvimento de métodos que propiciem quantidades suficientes de ilhotas pancreáticas, originadas de doador único, capazes de, quando transplantadas, levarem à normalização do metabolismo dos hidratos de carbono. Objetivo: Avaliar, em cães, a eficácia do isolamento das ilhotas de Langerhans por meio da técnica de separação mecânica-enzimática, digestão estacionária com colagenase e purificação pelo gradiente de densidade descontínua de dextran. Métodos: A contagem do número e avaliação do tamanho das ilhotas foi realizada pela coloração com difeniltiocarbazona e exame em microscópio estereoscópico munido de retícula ocular para medição do diâmetro médio das ilhotas coradas. Resultados: O número médio de ilhotas isoladas foi de 81032,20 ± 24736.79 e o número médio de ilhotas/kg de peso corpóreo foi de 6938,70± 1392,43. O número médio de ilhotas/kg de peso corpóreo obtido mostrou correlação significativa com peso corpóreo e peso do pâncreas extirpado. Conclusão: Estes resultados sugerem que o número de ilhotas isoladas, de um único doador, por meio da separação mecânica-enzimática, digestão estacionária com colagenase e purificação pelo gradiente de densidade descontínua de dextran pode ser suficiente para o sucesso do transplante de ilhotas pancreáticas em cães.

Atividade proliferativa do carcinoma colo-retal: relaçäo com o estadiamento, localizaçäo e padräo de crescimentro. Estudo imuno-histoquímico com anticorpo anti-pcna / The prolifetative activity of colorectal tumor: relation with staging, localization and growth pattern. Immunohistochemical study with anti-PCNA antibody

Objetivo: analisar a atividade proliferativa das células tumorais do carcinoma colo-retal extirpado. Pacientes e métodos: foram estudados 78 doentes (50 mulheres e 28 homens), com carcinoma colo-retal. A média de idade foi 59,29 anos (28 a 86 anos). Dezesseis doentes foram classificados com Dukes A, 438 como B e 14 como C. A neoplasia estava localizada no colo proximal em 19 enfermos,no distal em 32 e no reto em 27. Os blocos parafinados obtidos das lesões neoplásicas foram submetidos ao estudo imuno-histoquímico com anticorpo anti`-PCNA. O estudo histológico foi realizado na margem invasiva mais profunda de cada lesäo. O índice de expressäo do PCNA foi quantificado pela observaçäo do núcleo celular marcado com anticorpo anti-PCNA em 1000 células na lâmina obtida de cada lesäo. A reaçäo foi considerada positiva quando a marcaçäo nuclear ocorreu de modo difuso, com pontos de intensidade variável, ou de modo granular com distribuiçäo homogênea, independente da intensidade. Resultados: houve ausência de diferença significativa entre o índice de expressäo do PCNA e a idade, sexo, estadiamento e padräo de crescimento. A localizaçäo da lesäo no segmento colo-retal e o índice de expressäo do PCNA apresentaram diferença significativa apenas antre as lesões situadas no reto e aquelas localizadas no colo proximal (p<0,001). Conclusões: a expressäo do PCNA no carcinoma colo-retal näo apresenta relaçäo com os diferentes estádios da classificaçäo de Dukes e com o padräo de crescimento infiltrativo ou expansivo da lesäo. Os carcinomas retais mostram maior atividade proliferativa que os situados no colo proximal

Detection of Helicobacter pylori in gastric cancer

Considering the high prevalence of stomach cancer in the northern region of Brazil and the recognized relationship between chronic gastric inflammation caused by Helicobacter pylori, and its carcinogenic potential, the objective we had with this study was to investigate the presence of the microorganism in macro and microscopic presentations of neoplasm in different regions of the stomach, and in non-malignant lesions concomitant to the adenocarcinoma in patients originating from the metropolitan area of Belem (State of Para, Brazil). METHODS: Examinations were made on 172 patients divided into two groups: group I, formed by 75 patients with gastric carcinoma, and group II, formed by 97 patients with mild enanthematic gastritis, considered control group. The diagnosis was obtained during endoscopic examination and the respective biopsy. Gastric neoplasms were classified macroscopically in accordance with Borrmann's classification, and microscopically in accordance with Lauren's classification. In group I, 54 patients were male and 21 female while in group II, 22 patients were male and 75 female. The average age in group I was 61.2 years (range 27 to 86 years), while in group II it was 37.5 years (range 16 to 69 years). Thin sections were prepared and stained using the hematoxylin-eosin method. In the Helicobacter pylori research, the modified Gram stain was utilized. Statistical analysis was done by utilizing the chi-squared (chi 2) test, Mann-Whitney test (U), and Fisher's exact test. RESULTS: The results showed the detection of Helicobacter pylori were significantly greater in patients with mild enanthematic gastritis than in patients with gastric carcinoma...