Meta-analysis of colorectal cancer follow-up after potentially curative resection.

BACKGROUND: After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier. METHODS: A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer. RESULTS: There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11). CONCLUSION: Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

Role of adenosine deaminase and the influence of age on the diagnosis of pleural tuberculosis.

OBJECTIVE: 1) To determine factors affecting adenosine deaminase (ADA) levels in pleural fluid (PF), and 2) to establish the optimal ADA cut-off level for a Brazilian population. DESIGN: ADA levels in PF of 309 patients were analysed to investigate pleural effusion. All patients were evaluated for age, sex and presence of tuberculosis (TB) based on a positive pleural biopsy. Differences in ADA levels between groups were analysed using Kruskal-Wallis one-way analysis of variance. Logistic regression analysis was also carried out to predict the occurrence of TB. ADA cut-off levels were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean PF ADA level was significantly higher in the tuberculous pleural group than in non-tuberculous pleural patients (63.3 ± 29 IU/l vs. 19 ± 31 IU/l, P < 0.001). There was a significant correlation between PF ADA levels and age: for patients aged ⩾45 years, the ROC curve for ADA had an area under the curve of 0.91. An ADA level of 29 IU/l resulted in a sensitivity of 88.6% and specificity of 91.5%. CONCLUSIONS: There is a significant negative correlation between PF ADA level and age. The use of a lower ADA cut-off reduces the number of false-negative results.

Pulmonary metastasectomy for colorectal cancer: long-term survival and prognostic factors.

BACKGROUND: Despite the development of novel chemotherapy and biological agents, surgery is still an important option for patients with pulmonary metastases. Predictors of survival usually include disease-free interval, histology of the primary tumor, number of metastases and complete resection. The aim of this study was to report the outcomes of patients with pulmonary metastases from colorectal carcinoma submitted to surgical resection, and to identify prognostic factors that significantly affect overall survival. METHODS: We retrospectively analyzed 120 patients with previously treated colorectal carcinoma that had developed pulmonary metastases, admitted between 1990 and 2006. Overall survival was estimated using Kaplan-Meier analysis. The log-rank and Breslow tests were used to compare survival differences for each variable. Multivariate analyses to determine the independent prognostic factors for overall survival were performed using the Cox proportional hazard model as identified by the univariate analyses. RESULTS: The median follow-up was 20.3 months (range: 3.27-134.2 months). The patients included in this study underwent a total of 165 thoracotomies (mean of 1.37 thoracotomies/patient). The median overall survival for all patients was 34.73 months, with an estimated 5-year survival rate of 24.39%. Multivariate analyses identified unilateral lesions, neoadjuvant chemotherapy at lung resection and complete resection as independent prognostic factors for overall survival. CONCLUSIONS: These results indicate that prognostic factors identified in studies on pulmonary metastasectomy for all primary tumors should be interpreted carefully for patients with possibility of pulmonary metastasectomy from colorectal carcinoma.

Pulmonary metastasectomy from head and neck tumors.

AIM: Isolated pulmonary metastases from head and neck cancer occur in 20%-30% of patients affected by head and neck neoplasms. Surgical resection is well accepted as a standard approach to treat metastases from head and neck cancer isolated to the lungs. Many studies reported overall five-year survival ranging from 20% to 30%. The aim of this study is to determine demographics and clinical treatment-related variables associated with long-term (60-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from head and neck tumors. METHODS: A retrospective review was performed of patients who were admitted with lung metastases and underwent thoracotomy for resection after treatment of the primary tumor. Data were collected regarding primary tumor features, demographics, treatment, and outcome. RESULTS: Median follow-up time of all patients was 36.4 months (range: 0-288 months). The postoperative complication rate was 14.4%, and the 30-day mortality rate was 0%. The 60-month overall survival rate for all patients was 35.5%. Multivariate analysis identified the number of nodules at CT scan, the disease-free interval, and histological type as independent prognostic factors for overall survival. CONCLUSION: 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 lung resection.

ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas.

SUMMARY: Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies. METHODS: This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis. RESULTS: Strong correlation among the expression of ErbB family receptors was found (ErbB1-ErbB2 P = 0.008, ErbB1-ErbB4 P = 0.018, EbB2-ErbB3 P = 0.001, ErbB2-ErbB4 P = 0.006, ErbB3-ErbB4 P=0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006). CONCLUSIONS: The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1-ErbB2, ErbB1-ErbB4, ErbB2-ErbB3, ErbB2-ErbB4, and ErbB3-ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.

Management of neuroendocrine tumors: a meeting of experts from Latin America.

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.

High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer.

INTRODUCTION: Antigen-presenting cells, like dendritic cells (DCs) and macrophages, play a significant role in the induction of an immune response and an imbalance in the proportion of macrophages, immature and mature DCs within the tumor could affect significantly the immune response to cancer. DCs and macrophages can differentiate from monocytes, depending on the milieu, where cytokines, like interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce DC differentiation and tumor necrosis factor (TNF)-alpha induce DC maturation. Thus, the aim of this work was to analyze by immunohistochemistry the presence of DCs (S100+ or CD1a+), macrophages (CD68+), IL-4 and TNF-alpha within the microenvironment of primary lung carcinomas. RESULTS: Higher frequencies of both immature DCs and macrophages were detected in the tumor-affected lung, when compared to the non-affected lung. Also, TNF-alpha-positive cells were more frequent, while IL-4-positive cells were less frequent in neoplastic tissues. This decreased frequency of mature DCs within the tumor was further confirmed by the lower frequency of CD14-CD80+ cells in cell suspensions obtained from the same lung tissues analyzed by flow cytometry. CONCLUSION: These data are discussed and interpreted as the result of an environment that does not oppose monocyte differentiation into DCs, but that could impair DC maturation, thus affecting the induction of effective immune responses against the tumor.

Expression of a dendritic cell maturation marker CD83 on tumor cells from lung cancer patients and several human tumor cell lines: is there a biological meaning behind it?

The present paper shows, for the first time, the membrane expression of the dendritic cell maturation marker CD83 on tumor cells from lung cancer patients. CD83 was also detected on freshly cultured fibroblast-like cells from these tissues and on several adherent human tumor cell lines (lung adenocarcinomas P9, A459 and A549, melanomas A375 and C81-61, breast adenocarcinomas SKBR-3 and MCF-7 and colon carcinoma AR42-J), but not in the non-adherent MOT leukemia cell line. CD83 may have immunosuppressive properties and its expression by cancer cells could have a role in facilitating tumor growth.

In vitro breast cancer cell lethality of Brazilian plant extracts.

In this study we screened the cytotoxicity of 1220 plant extracts obtained from 351 plants belonging to 74 families occurring in the Amazon and Atlantic rain forests against MCF-7 human breast adenocarcinoma cell lines. All extracts were tested at a dose of 100 microg/mL. Only 11 aqueous or organic extracts belonging to the Annonaceae, Apocynaceae, Araceae, Clusiaceae, Flacourtiaceae, Leguminosae, Olacaceae and Violaceae showed marked lethal activity. Vismia guianensis and Annona hypoglauca extracts showed the greatest lethal activity.

In vitro prostate cancer cell growth inhibition by Brazilian plant extracts.

In the present study, 1220 plant extracts obtained from 352 plants belonging to 73 families that grow in the Amazon and Atlantic rain forests were screened for cytotoxicity against PC-3 prostate cancer cell lines. Extracts were tested in the single dose of 100 microg/mL. Activity was observed in 17 aqueous or organic extracts belonging to Annonaceae, Apocynaceae, Araceae, Capparaceae, Commelinaceae, Flacourtiaceae, Lecythidaceae, Leguminosae, Passifloraceae, Rutaceae, and Violaceae.

Response to chemotherapy in patients with lung metastases: how many nodules should be measured?

OBJECTIVE: With the introduction of cross-sectional imaging methods the number of lesions per patient that can be evaluated is frequently large and most oncologists and study protocols use only one lesion or a few 'representative' lesions to evaluate chemotherapy response. Intra-patient response variability can therefore affect evaluation reproducibility. This study evaluates intra-individual variation in response to chemotherapy in patients with multiple lung metastases. METHODS: We prospectively studied chest CT images of patients with solid tumors and pulmonary metastases under systemic chemotherapy being evaluated for tumor response. The response of 566 pulmonary nodules in 41 evaluations was determined by both WHO and RECIST criteria in order to determine intra-individual tumor response variation. RESULTS: There was almost perfect agreement between the WHO and the RECIST criteria for the evaluation of tumor response. High intra-individual variability of tumor response was observed in a significant proportion of the evaluations. A new nodule was the main criterion for determination of disease progression. A mean of 35% of the total number of nodules of a patient have a response evaluation different from that calculated with all the nodules together. CONCLUSIONS: Intra-individual variation in tumor response of pulmonary metastases is elevated in some patients. Selecting any or some nodules for response evaluation could significantly influence therapeutic response perception.

Analysis of the toxic potential of Palicourea corymbifera (Müll. Arg.) Standl. in laboratory animals.

Palicourea species may produce bovine toxicity. Palicourea corymbifera grows in terra firme forests within the Amazon rain forest and in Tropical America, particularly in spots that gave place to gazing areas. The lyophilized extract done with the aerial organs of P. corymbifera were analyzed in male and female mice. Results revealed a significant toxicity: LD50 was 1.10 (1.04-1.15)g/kg for male mice, and 1.05 (1.00-1.10)g/kg for female mice. Locomotion was affected as well as there were reflexes linked to environmental stimuli in addition to changes in posture. Progressive central nervous system stimulus signs such as trembling and convulsions were detected, the latter followed by the animal's death. Macroscopic histopathological exams performed on the liver, kidneys and lungs of mice submitted to necropsy did not indicate the existence of lesions. General activity of animals, measured in an open field, was reduced as a result of the administration of the extract. Duration of locomotion and rearing frequency were reduced, in opposition to an increase in the duration of immobility. Thin layer chromatography analysis showed that monofluoroacetic acid is present in the lyophilized extract, but other qualitative techniques as gas chromatography/mass spectrometry and 19F nuclear magnetic resonance showed that the MFAA was not present in the extract, and that the toxicity is related to other compound, although the toxic profile is very similar to that of MFAA. P. corymbifera was shown to be significantly toxic to laboratory animals and investigation of the possible toxic substance shall be done.

Screening of antibacterial extracts from plants native to the Brazilian Amazon Rain Forest and Atlantic Forest.

More than 20% of the world's biodiversity is located in Brazilian forests and only a few plant extracts have been evaluated for potential antibacterial activity. In the present study, 705 organic and aqueous extracts of plants obtained from different Amazon Rain Forest and Atlantic Forest plants were screened for antibacterial activity at 100 microg/ml, using a microdilution broth assay against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. One extract, VO581, was active against S. aureus (minimum inhibitory concentration (MIC)=140 microg/ml and minimal bactericidal concentration (MBC)=160 microg/ml, organic extract obtained from stems) and two extracts were active against E. faecalis, SM053 (MIC=80 microg/ml and MBC=90 microg/ml, organic extract obtained from aerial parts), and MY841 (MIC=30 microg/ml and MBC=50 microg/ml, organic extract obtained from stems). The most active fractions are being fractionated to identify their active substances. Higher concentrations of other extracts are currently being evaluated against the same microorganisms.

Screening of antibacterial extracts from plants native to the Brazilian Amazon Rain Forest and Atlantic Forest

More than 20 percent of the world's biodiversity is located in Brazilian forests and only a few plant extracts have been evaluated for potential antibacterial activity. In the present study, 705 organic and aqueous extracts of plants obtained from different Amazon Rain Forest and Atlantic Forest plants were screened for antibacterial activity at 100 µg/ml, using a microdilution broth assay against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. One extract, VO581, was active against S. aureus (minimum inhibitory concentration (MIC) = 140 µg/ml and minimal bactericidal concentration (MBC) = 160 µg/ml, organic extract obtained from stems) and two extracts were active against E. faecalis, SM053 (MIC = 80 µg/ml and MBC = 90 µg/ml, organic extract obtained from aerial parts), and MY841 (MIC = 30 µg/ml and MBC = 50 µg/ml, organic extract obtained from stems). The most active fractions are being fractionated to identify their active substances. Higher concentrations of other extracts are currently being evaluated against the same microorganisms.

Atividade antibacteriana e fracionamento direcionado do extrato orgânico obtido de Tovomita sp

O extrato orgânico obtido do caule de Tovomita sp. apresentou atividade antibacteriana significativa contra Staphylococcus aureus (CIM = 460 ?µg/mL e CBM = 490 µg/mL), Enterococcus faecalis (CIM = 500 ?µg/mL e CBM = 540 µg/mL) e Pseudomonas aeruginosa (CIM = 300 ?µg/mL e CBM = 400 µg/mL). As frações obtidas do extrato orgânico apresentaram atividade antimicrobiana contra E. faecalis (CIM F1 = 570 µg/mL e CBM F1 = 840 µg/mL; CIM F2 = 480 µg/mL e CBM F2 = 720 µg/mL, respectivamente) e contra P. aeruginosa (CIM F1 = 310 µg/mL e CBM F1 = 570 µg/mL; CIM F2 = 310 µg/mL e CBM F2 = 460 µg/mL, respectivamente).

The organic extract obtained of the stem of Tovomita sp. did it present significant antibacterial activity against Staphylococcus aureus (CIM = 460 µg/mL and CBM = 490 µg/mL), Enterococcus faecalis (CIM = 500 µg/mL and CBM = 540 µg/mL) and Pseudomonas aeruginosa (CIM = 300 µg/mL and CBM = 400 µg/mL). The obtained fractions of the organic extract present antibacterial activity against E. faecalis (CIM F1 = 570 µg/mL and CBM F1 = 840 µg/mL; CIM F2 = 480 µg/mL and CBM F2 = 720 µg/mL, respectively) and against P. aeruginosa (CIM F1 = 310 µg/mL and CBM F1 = 570 µg/mL; CIM F2 = 310 µg/mL and CBM F2 = 460 µg/mL, respectively).

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

UNLABELLED: 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.

Pathophysiology of cancer cachexia.

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.

Stereological estimates of nuclear star volume and vessels as predictors of chemotherapy response in small cell carcinoma of the lung: a preliminary report.

AIMS: This study was designed to evaluate the role of morphometric and clinical parameters in predicting chemotherapy responder patients with small cell carcinoma of the lung. METHODS AND RESULTS: Morphometric studies were performed by means of point counting techniques. Forty-six patients were included in this study. Group 1 patients (n = 19) were those without response to chemotherapy; Group 2 (n = 27) was composed by patients with partial or complete response to chemotherapy. Logistic regression analysis was used to attain the best separation of non-responder from responder patients. Star volume of the nuclei and vessel were selected during the backward procedure as relevant variables to characterize the two groups of patients. The overall sensitivity of the model was 80.43%. CONCLUSIONS: Our results indicate that histopathological data may help to predict the chemotherapy response in patients with small cell lung carcinoma, and encourage the use of morphometric procedures in histopathological analysis of this type of lung tumours.

Follow-up in lung cancer: how often and for what purpose?

OBJECTIVES: The present study evaluates the cost-effectiveness of two follow-up routines: a strict follow-up with frequent visits, imaging, and laboratory examinations was compared to a follow-up with infrequent visits that were scheduled mainly on the basis of the patient's symptoms. METHODS: A retrospective evaluation was undertaken of 130 patients who underwent a complete resection of non-small cell lung cancer (NSCLC). All patients had complete follow-up for at least 2 years after their operation. The patients were separated into two groups: strict (n = 67), with a routine follow-up policy; and symptom (n = 63), seen on a symptom-oriented basis. The costs of the follow-up routines and the yield of each schedule were compared between the two groups. RESULTS: There were no significant differences in the disease-free interval until the first detection of recurrence. In most patients, metastatic diseases were diagnosed on the basis of symptoms, rather than by routine tests. The patients who had recurrent cancer diagnosed after surgery had a dismal survival rate irrespective of the follow-up schedule. The majority of patients with recurrence died of malignancy within a 2-year period. The costs of strict vs symptom follow-up were significantly different, because of the greater number of routine imaging procedures performed in patients having strict follow-up. On the other hand, when we analyzed only the frequency of hospitalization and the cost per day of hospital treatment for medical problems other than cancer recurrence, the patients in the strict group had a less expensive follow-up than the patients in the symptom group. CONCLUSIONS: The present study showed that a more cost-effective routine follow-up scheme should be advised for patients with completely resected NSCLC, without affecting overall outcome. Routine imaging follow-up is of questionable value, and it may be indicated only in academic settings.