Esta seção tem por objetivo divulgar os resumos dos mais recentes artigos publicados na literatura mundial a respeito da epidemiologia, prevenção, diagnóstico, estadiamento, tratamento e prognóstico do câncer. Caso o colega deseje receber separatas dos artigos referidos (máximo cinco), imprima nosso formulário, preencha e envie por fax.

Bcl-2 and Bax expression and chlorambucil-induced apoptosis in the T-cells and leukaemic B-cells of untreated B-cell chronic lymphocytic leukaemia patients
Alun Thomas, Chris Pepper, Terry Hoy, Paul Bentley

Chlorambucil and other cytotoxic drugs kill cells, non-selectively, by inducing apoptosis. In this study, we measured the apoptotic response to chlorambucil in T- and B-cells from untreated B-CLL patients and T-cells, from normal control subjects. We found increased chemosensitivity in the T-cells of B-CLL patients compared to the controls (P = 0.0002). The chlorambucil ID 50 values for T-cells from B-CLL patients showed a direct correlation with Bcl-2 expression (P = 0.002) and an inverse correlation with CD3 cell count (P < 0.0001), suggesting a trend of increasing chemosensitivity and decreasing Bcl-2 expression with an elevated T-cell count. There was no differential expression of Bcl-2 or Bax between the CD4 + and CD8 + cells of B-CLL patients, isolated by immunomagnetic separation. We found correlations in the leukaemic B-cells between chlorambucil ID 50 values and both Bcl-2 expression (P = 0.006), and Bcl-2/Bax ratios (P = 0.002), suggesting a role for the Bcl-2/Bax ratio in predicting the response of untreated CLL patients to cytotoxic treatment. Chlorambucil produced almost identical changes in Bcl-2 and Bax expression in normal T-cells and leukaemic B-cells triggered to die by apoptosis, which together with the correlation between Bcl-2 and chemosensitivity confirms a pivotal role for Bcl-2 in regulating a distal step in the apoptotic pathway following cytotoxic cellular damage.

Key words: B-cell chronic lymphocytic leukaemia; Apoptosis; T-cells; Bcl-2; Bax; Chlorambucil.

Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia
Teresa de Souza Fernandez, Maria Helena Ornellas, Luize Otero de Carvalho, Daniel Tabak, Eliana Abdelhay

Several studies have demonstrated the prognostic value of cytogenetic analysis in MDS both for survival and progression to AML. However it is unknown which are the numerical or structural abnormalities required for leukemic transformation. In this report we studied clinically and cytogenetically 127 patients: 125 with primary MDS and two with AML with a previous history of MDS. Thirty-one patients (24%) showed evolution of the disease during the follow-up study. Chromosomal abnormalities found at diagnosis in patients that progressed toward AML included: del(5)(q15), + 6, del(6)(q21), t(5;8)(q32;q22), - 7, del(7)(q22), der(7)t(1;7)(q10;p10), t(7;11)(p15;p15), +8, del(11)(q23), del(12p), del(3)(q21), del(20)(q12) and complex karyotypes. Eight of these patients were studied cytogenetically during transformation and showed acquisition of chromosomal alterations involving dup(1q), + 8, del(11)(q23), and translocations between chromosomes 1 and 8 or 7 and 17. In addition we also observed gain of ploidy and monosomy 21. These results suggest that chromosomal alterations during evolution of the disease include special chromosome gains or abnormalities of chromosomes 1, 7, 8, 11 and 17 with involvement of ETV-1, Hox-A9, Pax 4, MLL genes besides a putative gene mapped at 17q25. We also applied the International Prognostic Scoring System (IPSS) to 114 patients, excluding those submitted to allogeneic bone marrow transplant. Our patients were classified into four distinct risk groups. The analysis of risk groups presented by 27 patients who showed evolution of the disease revealed 18 at the high risk group and four at the intermediate-2 group. From the intermediate-1 risk group only five patients showed evolution of the disease. Three of these patients evolved from RA to RAEB with gain of a del(11)(q23) or an expansion of a del(12)(p12) clone. Our results suggest that some chromosomal alterations are responsible for each step in the evolution of the disease. As the pathway of evolution is not unique it has been very difficult to define what genetic alteration comes first. However from several results in the literature and our own, it seems that some chromosomal alterations may predict the evolution of the disease and are correlated with short survival, as for example the trisomy of chromosome 8, and might be incorporated in the high risk group in the IPSS. This score system has been proved to be useful for predicting survival and evolution from MDS to AML

Key words: Chromosomal changes; Myelodysplastic syndrome; Progression to acute myeloid leukemia.

2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence based, clinical practice guidelines
By Howard Ozer, James O. Armitage, Charles L. Bennett, Jeffrey Crawford, George D. Demetri, Philip A. Pizzo, Charles A. Schiffer, Thomas J. Smith, George Somlo, James C. Wade, James L. Wade III, Rodger J. Wino, Antoinette J. Wozniak, and Mark R. Somerfield

THE AMERICAN Society of Clinical Oncology (ASCO) published evidence-based clinical practice guidelines for the use of hematopoietic colony-stimulating factors (CSFs) in 1994. ASCO guidelines are updated on a regular basis by a Review Committee of the original expert panel. The CSF guidelines were updated by the full expert panel in 2000.

For the 2000 update, an update committee, composed of members, from the full panel and selected ad hoc members, was formed to complete the review and analysis of data published since 1994. Computerized literature searches of MEDLINE and CancerLit were performed. The key phrases granulocyte-macrophage colony-stimulating factors, granulocyte colony-stimulating factors, and clinical trials were used in searches of the published English-language literature from 1994 to 1999.

The Update Committee had two face-to-face meetings to consider the evidence for each of the 1996 recommendations. The guideline was circulated in draft form to the update committee and to the full expert panel for review and approval. Each guideline from the 1996 update is listed below, followed by the 2000 update, and the 2000 recommendation.

From the American Society of Clinical Oncology. Submitted August 4, 2000: accepted August 7, 2000. Adapted on July 21, 2000, by the American Society of Clinical Oncology. Manuscript editing was completed by H. Ozer and M. Somerfield.

*The American Society of Clinical Oncology considers adherence to these guidelines to be voluntary. The ultimate determination regarding their application is to be made by the physician in light of each patient's' individual circumstances. In addition, these guidelines describe administration of therapies in clinical practice; they cannot be assumed to apply to interventions performed in the context of clinical trials. given that such clinical studies are designed to test innovative and carrel therapies for this svmptom in which better treatment is of paramount importance. In that guideline development involves it review and synthesis of the latest literature, a practice guideline also serves to identify important questions for further research and those settings in which investigational therapy should be considered.

Address reprint requests to American Society of Clinical Oncology, 1900 Duke St. Suite 200, Alexandria, VA 22314; e-mail: guidelines@asco.org
© 2000 by American Society of Clinical Oncology.
0732-183X/00/1820-3558

Prostate cancer screening: the problem of overdiagnosis and lessons to be learned from breast cancer screening
S. Ciatto, M. Zappa, R. Bonardi, G. Gervasii

Screening for prostate cancer is a relatively new procedure, still under experimental evaluation within prospective randomised trials. The design of prospective studies has been mainly based on the experience of other cancer screenings, particularly breast cancer, for which data of several controlled studies are available. Unfortunately, breast cancer is very different from prostate cancer, particularly for aspects such as early diagnosis and, thus the screening process, originally modelled on the basis of the lesson taught by breast cancer screening, needs continuous re-evaluation and adjustment, based on data which are now being produced from ongoing screening experiences. In this paper, we will consider the most controversial aspects of prostate cancer screening and compare prostate screening with breast cancer screening in order to promote a better understanding of the current problems and lessons to be learned.

Key words: Prostate cancer; Screening; Overdiagnosis.

Analysis of biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer using dose-distribution variables and tumor control probability models
Sabine Levegrün, Ph.D., Andrew Jackson, Ph.D., Michael J. Zelefsky, M.D., Ennapadam S. Venkatraman, Ph.D., Mark W. Skwarchuk, Ph.D., Wolfgang Schlegel, Ph.D., Zvi Fuks, M.D., Steven A. Leibel, M.D., and C. Clifton Ling, Ph.D.

Purpose: To investigate tumor control following three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer and to identify dose-distribution variables that correlate with local control assessed through posttreatment prostate biopsies.

Methods and Material: Data from 132 patients, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), who had a prostate biopsy 2.5 years or more after 3D-CRT for T1c-T3 prostate cancer with prescription doses of 64.8-81 Gy were analyzed. Variables derived from the dose distribution in the PTV included: minimum dose (Dmin), maximum dose (Dmax), mean dose (Dmean), dose to n% of the PTV (Dn), where n = 1%, . . . ,99%. The concept of the equivalent uniform dose (EUD) was evaluated for different values of the surviving fraction at 2 Gy (SF₂ ). Four tumor control probability (TCP) models (one phenomenologic model using a logistic function and three Poisson cell kill models) were investigated using two sets of input parameters, one for low and one for high T-stage tumors. Application of both sets to all patients was also investigated. In addition, several tumor-related prognostic variables were examined (including T-stage, Gleason score). Univariate and multivariate logistic regression analyses were performed. The ability of the logistic regression models (univariate and multivariate) to predict the biopsy result correctly was tested by performing cross-validation analyses and evaluating the results in terms of receiver operating characteristic (ROC) curves.

Results: In univariate analysis, prescription dose (Dprescr), Dmax, Dmean, dose to n% of the PTV with n of 70% or less correlate with outcome (p < 0.01). The area under the ROC curve for Dmean is 0.64. In contrast, Dmin (p = 0.6), D98 (p = 0.2) or D95 (p = 0.1) are not significantly correlated with outcome. The results for EUD depend on the input parameter SF 2 ,: EUD correlates significantly with outcome for SF 2 , of 0.4 or more, but not for lower SF 2 , values. Using either of the two input parameters sets, all TCP models correlate with outcome (p < 0.05; ROC areas 0.60-0.62). Using T-stage dependent input parameters, the correlation is improved (logistic function: p < 0.01, ROC area 0.67, Poisson models: p < 0.01, ROC areas 0.64-0.66). In comparison, the ROC area is 0.68 for the combination of Dmean and T-stage. After multivariate analysis, a model based on TCP, D20 and Gleason score is the best overall model (ROC area 0.73). However, an alternative model based on Dmean, Gleason score, and T-stage is competitive (ROC area 0.70).

Conclusion: Biopsy outcome after 3D-CRT of prostate cancer at MSKCC is not correlated with Dmin in the PTV and appears to be insensitive to cold spots in the dose distribution. This observation likely reflects the fact that much of the PTV, especially at the periphery, may not contain viable tumor cells and that the treatment margins were sufficiently large. Therefore, the predictive power of all variables which are sensitive to cold spots, like TCPs with Poisson models and EUD for low SF 2 , is limited because the low dose region may not coincide with the tumor location. Instead, for MSKCC prostate cancer patients with their standardized CTV definition, substantial target motion and small dose inhomogeneities, Dmean (or any variable that downplays the effect of cold spots) is a very good predictor of biopsy outcome. While our findings may indicate a general problem in the application of current TCP models to clinical data, these conclusions should not be extrapolated to other disease sites without careful analysis.

Association of psychological vulnerability factors to post-traumatic stress symptomatology in mothers of pediatric cancer survivors
Sharon Manne, Katherine Duhamel and William H. Redd

The current study investigated whether individual differences in coping style, lifetime experience of traumatic events, perceived social support, and perceived social constraints were associated with symptoms of post-traumatic stress among 72 mothers of children who had successfully completed cancer treatment. Results suggested that more perceived social constraints and less perceived belonging support were associated with significantly more post-traumatic stress symptomatology, and this association was present after controlling for the effects of child age. Monitoring coping style and lifetime traumatic events were not significantly predictive of post-traumatic stress symptoms. The results of this study indicate that a sense of belonging to a social network as well as comfort expressing cancer-related thoughts and feelings to fiends and family may play a key role in mothers’ long-term adjustment to this extremely difficult life experience.

Carcinoma Diferenciado da Tireóide na Infância
Childhood Differentiated Thyroid Carcinoma
Geraldo Matos de Sá, TCBC-RJ; Mauro Marques Barbosa, TCBC-RJ; Roberto R. M. de Araújo Lima, TCBC-RJ; Fernando Luiz Dias, TCBC-RJ; Terence Pires de Faria; Fábio Afonso Peixoto

Os autores apresentam uma revisão de 12 casos de carcinoma da glândula tireóide em crianças, tratados na Seção de Cirurgia de Cabeça a Pescoço do Hospital do Câncer (INCA), no período entre 1986 e 1994. Trata-se de doença pouco freqüente, pois, neste levantamento, representou apenas 1,6% das 729 afecções cirúrgicas da tireóide a 10% dos 126 casos de carcinoma papilífero da glândula tireóide atendidos no período referido. A avaliação do sexo, forma de apresentação da doença, extensão do tumor inicial a resposta ao tratamento a evolução demonstraram que estas neoplasias acometem mais freqüentemente as meninas do que os meninos e, embora apresentem-se como forma de doença avançada desde a matrícula, geralmente respondem muito bem ao tratamento cirúrgico agressivo, o que proporciona, na maioria dos casos, um prognóstico bastante favorável.

Descritores: Câncer na infância; Carcinoma diferenciado da tireóide.

Pretreatment prognostic factors for children with hepatoblastoma - results from the International Society of Paediatric Oncology (SIOP) Study SIOPEL 1
J. Brown, G. Perilongo, E. Shafford, J. Keeling, J. Pritchard, P. Brock, C. Dicks-Mireaux, A. Phillips, A. Vos, J. Plaschkes

The aim of this study was to investigate the prognostic significance of pretreatment patient and tumour characteristics for overall (OS) and event-free (EFS) survival in 154 children affected by hepatoblastoma (HB) in the first prospective liver tumour study run by the International Society of Paediatric Oncology. The pretreatment characteristics studied were age, a-fetoprotein, platelet count, histology; from radiology: intrahepatic tumour extension (PRETEXT), lung metastases, enlarged hilar lymph nodes, vena cava or extrahepatic vena porta tumour extension and tumour locality. Five-year OS was 75% (95% confidence interval (CI) 68-82%) and EFS 66% (95% CI 59-74%). Both were univariately associated with PRETEXT and the presence of metastases. Additionally tumour focality and enlargement of hilar lymph nodes at diagnosis were univariately associated with EFS. In multivariate analysis, PRETEXT was the only predictor of OS; PRETEXT and metastases were predictors of EFS. There is a need to investigate further these factors to confirm their validity.

Key words: Hepatoblastoma; Prognostic factors; Overall survival; Liver tumours; Childhood.

Smoking in Latin America: a major public health problem
Tabagismo na América Latina: problema prioritário de saúde pública
Vera Luiza da Costa a Silva, Sergio Koifman

Smoking has become a major public health problem in Latin America, and its scope varies from country to country. Despite difficulties in obtaining methodologically consistent data for the region, we analyzed the results from prevalence surveys in 14 Latin American countries. Smoking prevalence among men varied from 24.1 % (Paraguay) to 66.3% (Dominican Republic) and among women from 5.5% (Paraguay) to 26,6% (Uruguay). By applying point prevalence data to the stage model of the tobacco epidemic in developed countries, we concluded that the Latin American countries are in stage 2, i.e., with a clearly rising prevalence among men, a prevalence for women that is beginning to increase, and mortality attributable to smoking among men still not reflecting peak prevalence. None of the countries analyzed appeared to have reached stage 3, in which one observes a downward trend in prevalence of smoking among men and peak prevalence among women, with broad impact on tobacco-related mortality. The only exception appears to be Paraguay, which is still emerging from stage 1, i.e., with low prevalence rates among men, too. Nevertheless, high lung cancer mortality rates in Uruguay and Argentina are comparable to those of the developed countries.

Key words: Smoking; Public Health; Prevalence; Impacts on Health; Mortality.

Resource use in women completing treatment for breast cancer
Linda Edgar, Jean Remmer, Zeev Rosberger and Marc A. Fournier

Objective: To explore resources used by women completing treatment for breast cancer, how they learned about them, and the psychological factors that predicted their use.

Design: A questionnaire on resource use was administered as part of a randomized clinical trial which assessed subjects’ psychosocial characteristics and tested the outcomes of a psychosocial intervention.

Setting: Women completing treatment for breast cancer were recruited from the oncology departments of three university-teaching hospitals in Montreal. A questionnaire gathered data on the resources used by the subjects, how they learned about them, and the role of the health care team in their decision-making. Emotional distress, dimensions of coping effort, a sense of control and optimism were also measured.

Results: Five categories of resources were explored; professional services, informal support networks, informational resources, support organizations and complementary therapies. Most women found out about the last two resources by themselves. Women who used cancer support organizations or complementary therapies scored high on the use of problem-solving coping and low on the use of escape/ avoidance coping. In addition they were moderately optimistic, had a slightly lower sense of personal control and were somewhat more distressed than the non-users. The use of support organizations and complementary therapies appears to represent a thoughtful approach to dealing with the distress of cancer. The opinion of the oncologist regarding resource use was valued by nearly half of the sample.

An improved technique for breast cancer irradiation including the locoregional lymph nodes
Coen W. Hurkmans, M.Sc., Anne E. Saarnak, Ph.D., Bradley R. Pieters, M.D., Jacques H. Borger, M.D., Ph.D., and Iaïn A. D. Bruinvis, Ph.D.

Purpose: To find an irradiation technique for locoregional irradiation of breast cancer patients which, compared with a standard technique, improves the dose distribution to the internal mammary-medial supraclavicular (IM-MS) lymph nodes. The improved technique is intended to minimize the lung dose and reduce the dose to the heart.

Methods and Materials: The standard technique consists of an anterior mixed electron/photon IM-MS field. In the improved technique, an oblique electron and an oblique asymmetric photon field are combined to irradiate the IM lymph nodes. To irradiate the MS lymph nodes, a combination of an anterior electron and an anterior asymmetric photon field is used. For both the standard and the improved technique, tangential photon fields are used to irradiate the breast. Three-dimensional (3D) treatment planning was performed for 8 patients with various breast sizes for these two techniques. Dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) were compared for both techniques. The field dimensions and energy of the standard technique were determined at simulation, whereas for the improved technique the fields were designed by CT-based treatment planning.

Results: The dose in the breast planning target volume was essentially the same for both techniques. For the improved technique, combined with 3D localization information, an improvement in the IM-MS planning target coverage is seen. The volume within the 95% isodose surface was on average 25% (range, 0-64%) and 74% (range, 43-90%) for the standard and improved technique, respectively. The heart generally receives less dose with the improved technique. However, sometimes a small but acceptable increase in lung dose is found.

Conclusion: The improved technique, combined with localization information of the IM-MS lymph nodes, greatly improves the dose distribution in the planning target volume for a large group of patients without significantly increasing the dose to organs at risk.

Breast irradiation, Internal mammary lymph nodes, Cardiac dose, 3D dose distribution, Treatment technique.

Breast cancer risk and intake of fat
Elaine B. Feldman, M.D.

The popular hypothesis that dietary fat intake is an important risk factor for breast cancer in women has been challenged by data from numerous epidemiologic studies that show no relationship of the quantity or type of fat to disease incidence. Reasons for this discrepancy and current recommendations are discussed.

The role of dietary fat intake and the contribution of individual fatty acids to the risk of breast cancer have been a source of controversy in recent years. Epidemiologic studies' and animal work have supported the hypothesis that dietary fat intake is an important risk factor in the etiology of breast cancer. The 1989 report of the National Academy of Sciences, however, considered the data linking breast cancer and dietary fat inconclusive.

Data from 1 1 prospective cohort studies and 23 case-control studies relating total fat intake and risk of breast cancer were tabulated in a 1997 report from the American Institute of Cancer Research. Data were reviewed from publications up to 1995. This review concluded that the studies, overall, do not strongly support an etiologic link between dietary fat intake in adulthood and breast cancer. Diets high in total fat, however, may increase breast cancer risk. Prospective studies showed no relationship, and results from case-control studies are inconsistent. The data from international comparisons may be attributable to confounding factors other than fat intake, including delayed onset of menses, weight gain after age 18 years, and hormone replacement therapy.

Similar conclusions were drawn for saturated fat. Diets high in monounsaturated fat may have no relationship with the risk of breast cancer, independent of total fat; however, high consumption of olive oil may decrease the risk of breast cancer, perhaps by mechanisms unrelated to its monounsaturated fat content. In addition, diets high in polyunsaturated or vegetable fats may be unrelated to breast cancer risk. Data were considered too sparse to draw conclusions about omega-3 or traps-unsaturated fatty.

The impact of abnormal mammograms on psychosocial outcomes and subsequent screening
Isaac M. Lipkus, Susan Halabi, Tara S. Strigo and Barbara K. Rimer

Few studies have examined the impact of abnormal mammograms on subsequent mammography screening and psychosocial outcomes specifically as a function of the length of time that has passed since the abnormal test result. This cross-sectional report compared breast cancer screening practices and psychosocial outcomes among three groups of women. These groups were women who (I) never had an abnormal mammogram, (2) had an abnormal mammogram 2 or more years prior to the study’s baseline interview, and (3) had an abnormal mammogram within 2 years prior to the study’s baseline interview. Women who had an abnormal mammogram at least 2 years prior to the baseline interview expressed greater 10-year and lifetime risks of getting breast cancer than women who never had an abnormal mammogram. Women who had abnormal mammograms, independent of when they occurred, were substantially more worried about getting breast cancer than were women who never had abnormal mammograms. Women who had an abnormal mammogram within 2 years prior to the baseline interview were more likely to be on schedule for mammography, compared with women who never had an abnormal mammogram.

These results suggest that (I) few differences exist in perceived breast cancer risk and worry as a function of when an abnormal mammogram occurred, and (2) subsequent screening behavior is most affected by whether an abnormal mammogram occurred within 2 years from the interview. Not surprisingly, more recent experiences of abnormal mammograms had a greater influence on behavior.

Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk
Celia Byrne, Ph.D., James L. Connolly, M.D., Graham A. Colditz, Dr.P.H., Stuart J.Schnitt, M.D.

Background: A history of proliferative benign breast disease has been shown to increase the risk of developing breast carcinoma, but, to the authors’ knowledge, how postmenopausal exogenous female hormone use, in general, has affected breast carcinoma risk among women with a history of proliferative breast disease with or without atypia has not been well established.

Methods: In the current case-control study, nested within the Nurses' Health Study, benign breast biopsy slides of 133 postmenopausal breast carcinoma cases and 610 controls with a history of benign breast disease, were reviewed. Reviewers had no knowledge of case status.

Results: Women with proliferative disease without atypia had a relative risk for postmenopausal breast carcinoma of 1.8 (95%, confidence interval [CI]: 1.1 to 2.8), and women with atypical hyperplasia had a relative risk of 3.6 (95%, CI: 2.0 to 6.4) compared with women who had nonproliferative benign histology. Neither current postmenopausal use of exogenous female hormones nor long term use for 5 or more years further increased the risk of breast carcinoma in the study population beyond that already associated with their benign histology.

Conclusions: Women who had proliferative benign breast disease, with or without atypia, were at moderately to substantially increased risk of developing postmenopausal breast carcinoma compared with women who had nonproliferative benign conditions. In the current study, postmenopausal exogenous female hormone use in general did not further increase the breast carcinoma risk for women with proliferative benign breast disease. However, the analysis did not exclude the possibility of increased risk with a particular hormone combination or dosage.

Key words: breast carcinoma risk, benign breast disease, postmenopausal exogenous female hormones, epidemiology.

Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials
E. Mari, I. Floriani, A. Tinazzi, A. Buda, M. Belfiglio, M. Valentini, S. Cascinu, S. Barni, R. Labianca and V. Torn

Background: Several studies have investigated the possible role of the adjuvant chemotherapy after curative resection for gastric cancer failing to show a clear indication; previous meta-analyses suggested small survival benefit of adjuvant chemotherapy, but the statistical methods used were open to criticisms.

Materials and methods: Randomised trials were identified by means of Medline and CancerLit and by selecting references from relevant articles. Systematic review of all randomised clinical trials of adjuvant chemotherapy for gastric cancer compared with surgery alone, published before January 2000, were considered. Pooling of data was performed using the fixed effect model. Death for any cause was the study endpoint. The hazard ratio and its 95% confidence intervals (95% CI), derived according to the method of Parmar, were the statistics chosen for summarising the relative benefit of chemotherapy versus control.

Results: Overall 20 articles (21 comparisons) were considered for analysis. Three studies used single agent chemotherapy, seven combination of 5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU without anthracyclines. Information on 3658 patients. 2180 deaths, was collected.

Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82. 95% CI: 0.75-0.89, P < 0.001). Association of Anthracyclines to 5-FU did not show a statistically significant improvement when compared with the effect of the other regimens.

Conclusions: Chemotherapy produces a small survival benefit in patients with curatively resected gastric cancer. However, taking into account the limitations of literature based meta-analyses, adjuvant chemotherapy is still to be considered as an investigational approach.

Key words: adjuvant, chemotherapy, gastric cancer, meta-analysis, randomised clinical trial.

Presence of human B- and y-herpes virus DNA in Hodgkin's disease
Christian A. Schmidt, Helmut Oettle, R. Peng, Thomas Binder, Freimut Wilborn, Dieter Huhn, Wolfgang Siegert, Hermann Herbst

Herpes viruses have been implicated in the etiology of Hodgkin’s disease (HD). We studied the prevalence of human cytomegalovirus (CMV), human herpes viruses type-6 (HHV-6), type-7 (HHV-7) and type 8 (HHV-8) DNA in up to 88 Hodgkin’s disease biopsies in comparison to Epstein-Barr virus (EBV) DNA by polymerise chain reaction (PCR). Non-Hodgkin lymphomas (NHL) and reactive lesions served as controls. CMV and HHV-6 were found in 8/86 (9%) and 11/88 (13%) HD cases, respectively, by nested primer PCR. Except for three cases harbouring HHV-6 type-B, only HHV-6 type-A was detected in HD. HHV-7 was observed by nested PCR in 33/88 (38%) HD cases and was already detectable in 15/88 (17%) HD cases by a single-round PCR indicating elevated virus copy numbers. Seven of these cases showed co-infection with HHV-6, and 11 cases were found to contain EBV DNA. 7/8 CMV-positive HD cases also harboured EBV DNA. HHV-8 DNA was not detected by single round or nested PCR in any HD case investigated. Thus, CMV, HHV-6, and HHV-7 were present in small proportions of HD cases, with frequent co-infection of HHV-6 and HHV-7, and frequent association with EBV. In contrast to EBV, (3-herpes viruses are therefore unlikely to have a role in the aetiology of HD. Rather, the presence of these viruses seems to reflect impaired immunological surveillance.

Key words: Hodgkin’s disease; Human herpes virus type 6; Human herpes virus type 7; Cytomegalovirus; Epstein-Barr virus; Human herpes virus type 8.

Facilitating day-to-day decision making in palliative care
Joan L. Bottorff, R.N., Ph.D.; Rose Steele, R.N., Ph.D.; Betty Davies, R.N., Ph.D.; Pat Porterfield, R.N., M.S.N.; Candy Garossino, R.N., M.S.N.; Mary Shaw, R.N., M.S.N.

As part of a larger grounded theory study investigating the process by which palliative care patients make everyday choices, a secondary analysis of data was conducted to investigate the ways nurses support or restrict patients' participation in their care. Constant comparative methods were used to generate a detailed, contextually grounded description of nurses' strategies that influenced patients' participation in making everyday choices about their personal and nursing care. Data consisted of field notes derived from observations of patients and their caregivers in two hospital-based palliative care units and from 23 transcripts of interviews with participating nurses and patients. Nurses' efforts to support patients' participation in decision making were described as a four-phase process: getting to know the patient, enhancing opportunities for choice, being open to patient choice, and respecting choice. Factors influencing nurses' use of supportive behaviors and behaviors that restricted patients' participation in everyday choices were identified. Given the importance patients attributed to making choices, these findings provide a foundation for the design of nursing interventions that hold great potential for directly influencing quality of life.

Key words: Nurse-patient interaction; Palliative care; Patient autonomy; Patient participation; Supportive nursing.

Tratamento combinado de quimioterapia e radioterapia no câncer do colo uterino
Combined chemotherapy and radiotherapy in the treatment of cervical cancer
Luis Souhami

0 câncer do colo uterino permanece como um dos mais freqüentes na mulher brasileira e, na maioria dos casos, é diagnosticado nos estádios mais avançados da doença. Enquanto que a radioterapia é um tratamento extremamente eficaz para os estádios iniciais, o seu use isolado nos estádios mais avançados está associado com uma taxa de cura abaixo de 50%. A combinação de quimioterapia a radioterapia, de forma seqüencial ou concomitante, tem sido bastante explorada nestes últimos 15 anos como uma tentativa de melhorar o controle da doença. Recentemente, uma série de estudos randomizados foram publicados avaliando esta associação terapêutica. Uma seqüência de estudos positivos gerou um justificado entusiasmo num grande número de investigadores de que esta combinação terapêutica levaria a um aumento da cura nestas pacientes. Infelizmente, outros estudos randomizados não reproduziram esta melhora terapêutica, criando dúvidas no otimismo de alguns. Este artigo faz uma revisão dos estudos randomizados publicados a analisa criticamente os resultados, tanto na abordagem neoadjuvante como no use concomitante, desta combinação terapêutica.

Palavras-chave: Câncer do colo uterino, radioterapia, quimioterapia, tratamento combinado, quimioterapia neo-adjuvante.

Methylenetetrahydrofolate reductase polymorphisms, folate, and cancer risk: a paradigm of gene-nutrient interactions in carcinogenesis
Young-In Kim, M.D.

Recent epidemiologic studies suggest chat common polymorphisms of methylenetetrahydrofolate reductase (MTHFR) with allele frequencies up to 35% in the general North American population may modulate cancer risk. In some cancers, folate and other nutrients involved in the MTHFR metabolic pathway appear to interact with MTHFR polymorphisms to further modify cancer risk. In carcinogenesis, MTHFR polymorphisms thus provide a paradigm of gene-nutrient interactions, an emerging and important topic in the field of nutrition and cancer. Furthermore, MTHFR polymorphisms and MTHFR-nutrient interactions provide an opportunity to identify an ideal target group of individuals, at high risk of developing cancer, for rational, effective, and safe chemoprevention using these nutrients.

An evaluation of thallium imaging for detection of carcinoma in clinically palpable solitary, nonfunctioning thyroid nodules
P.S. Sinha, D.I. Beeby and P. Ryan

Objective: An evaluation of thallium imaging for differentiating benign from malignant lesions in clinically palpable solitary, nonfunctioning, thyroid nodules.

Methods: Seventy-eight patients presenting with a clinically palpable solitary nonfunctioning thyroid nodule were imaged with 3 mCi thallium-201 with a pinhole acquisition at 20 minutes and 3 hours after injection. Thallium uptake was assessed as grade 1, less than the rest of the gland; grade 2, same as the rest of the gland; and grade 3, more than the rest of the gland. All patients underwent surgery and the histology was compared with the thallium scan results.

Results: Of the 78 patients presenting with solitary thyroid nodule, 13 were malignant and 65 were benign. Twenty-four patients with benign disease showed no uptake of thallium at 3 hours (grade 1). Thirty-two patients with benign disease and 2 patients with malignant lesion hats grade 2 uptake at 3 hours. Eleven patients with malignant disease and 9 with benign disease had grade 3 uptake at 3 hours.

Conclusions: All malignant lesions had at least grade 2 and most had grade 3 uptake at 3 hours. All lesions with grade 1 uptake at 3 hours were benign, enabling malignancy to be excluded in one-third of cases. Thallium imaging is a useful adjunct to fine-needle cytology in evaluation of solitary thyroid nodules especially when the latter is inconclusive.