Lasse Teerenhovi

Effects of supplemental α-tocopherol and β-carotene on colorectal cancer: results from a controlled trial (Finland)

AbstractBackground:Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and β-carotene might be associated with reduced risk of colorectal cancer. Methods:We tested the effects of α-tocopherol and β-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50–69-year-old male cigarette smokers. Participants were randomly assigned to receive α-tocopherol (50 mg), β-carotene (20 mg), both agents, or a placebo daily for 5–8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. Results:Colorectal cancer incidence was somewhat lower in the α-tocopherol arm compared to the no α-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55–1.09; log-rank test p = 0.15). β-Carotene had no effect on colorectal cancer incidence (RR=1.05, 95% CI 0.75–1.47; log-rank test p = 0.78). There was no interaction between the two substances. Conclusion:Our study found no evidence of a beneficial or harmful effect for β-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.

Gain of 3q and deletion of 11q22 are frequent aberrations in mantle cell lymphoma

We used comparative genomic hybridization (CGH) to screen for DNA copy number changes in 34 specimens from 27 cases of mantle cell lymphoma (MCL). The most common gains were detected at 3q (52%), 8q (30%), and 15q (26%), whereas the most frequent losses involved 13q (41%), 1p (33%), 6q (30%), 9p (30%), and 11q (30%). The gain of 3q, with a minimal common region at 3q26.1‐27, appeared in more than half of the lymphomas, suggesting the location of an important oncogene here. A common deleted region at 11q22 was found in one‐third of the patients, which suggests that this region may harbor a tumor suppressor gene important in the tumorigenesis of MCL. The mean number of changes was higher in more aggressive blastoid variants of MCL than in lymphomas with typical morphology. Our results show that the chromosomal regions affected in MCL are highly consistent and are different from those seen in other types of non‐Hodgkins lymphoma. Genes Chromosomes Cancer 21:298–307, 1998.

Ki-67 expression level, histological subtype, and the International Prognostic Index as outcome predictors in mantle cell lymphoma

Abstract: Objectives : Mantle cell lymphoma (MCL) is characterised by translocation t(11;14) (q13;q32) leading to rearrangement of bcl1/CCND1 and overexpression of the cell‐cycle regulatory protein cyclin D1. We assessed the significance of the cell proliferation rate as an outcome predictor with the five components of the International Prognostic Index (IPI) and the histological subtypes of MCL. Patients and methods : The hospital case records and histopathological material of 127 patients diagnosed with MCL in a single centre were reviewed. The cell proliferation rate was assessed by Ki‐67 immunostaining and mitosis counting. Coxs multivariate regression model was used in multivariate survival analyses. The median follow‐up time was 87 months. Results : The mantle zone/nodular subtype of the common variant (19%) was associated with median survival of 70 months, the diffuse subtype of the common variant (64%) of 35 months, and the blastoid subtype (17%) of 11 months ( P  < 0.001). Patients with Ki‐67 expression in ≥ 26% (the upper tertile) of the lymphoma cells had median survival of only 13 months as compared with 45 months in the rest of the patients ( P  < 0.001). In a multivariate analysis high Ki‐67 expression, Ann Arbor stage III–IV, and age over 60 yr had independent influence on survival, whereas serum lactate dehydrogenase level, the number of extranodal disease sites, and performance status did not. Conclusions : The IPI may not be an optimal tool for outcome prediction in MCL, and a better prognostic index may be obtained by including Ki‐67 expression and possibly the histological subtype in the index.

Trisomy 12 in B cells of patients with B-cell chronic lymphocytic leukemia.

Trisomy 12 is the most frequently reported chromosome abnormality in patients with B-cell chronic lymphocytic leukemia, but only normal karyotypes are found in one third of patients with that disorder. Moreover, samples from patients with trisomy 12 also have many normal metaphases. To identify immunologically the cells in which both the trisomy 12 and the normal karyotypes occur, we studied two patients with B-cell chronic lymphocytic leukemia--one whose neoplastic cells demonstrated lambda light-chain clonality and one whose cells had kappa light-chain clonality. We used a recently developed cytogenetic method that allows simultaneous analysis of cell morphology, immunologic phenotype, and karyotype in the same mitotic cell. In cultures of blood cells stimulated with pokeweed mitogen and tetradecanoylphorbol acetate, all the mitotic cells with either the lambda or the kappa immunoglobulin had trisomy 12, whereas all the cells that lacked these light chains or that had T-cell markers (OKT8 or OKT4) had normal karyotypes. These results show that trisomy 12 in B-cell chronic lymphocytic leukemia occurs in the neoplastic B cells, but not in the T cells, and they thus provide an explanation for the common finding of mitoses with normal karyotypes in patients with B-cell chronic lymphocytic leukemia.

5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy—A randomised study

166 patients receiving moderately emetogenic chemotherapy were entered into a randomised prospective study in which the efficacy of single dose ondansetron 8 mg, tropisetron 5 mg and granisetron 3 mg in the prophylaxis of acute vomiting was evaluated. 130 patients were evaluable for analysis. During the 24 h following the start of chemotherapy complete control of vomiting was achieved in 80% [95% confidence interval (CI) 73.1; 86.9] of patients receiving granisetron compared with 75% (95% CI 67.1; 82.1) of those on tropisetron and 69% (95% CI 60.5; 76.5) on ondansetron. The patients experienced significantly fewer failures with granisetron (6.2%, 95% CI 2.1; 10.3) than with either ondansetron (14.6%, 95% CI 8.5; 20.6) or tropisetron (13.8%, 95% CI 7.9; 19.7). When asked, 34 (26%) patients out of 130 expressed no preference, 54 (42%) preferred granisetron, 22 (17%) preferred ondansetron and 20 (15%) preferred tropisetron. All the 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy. The observed differences in the control of emesis, although statistically significant, may not have clinical significance.

Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkins lymphoma recently recognised as a distinct disease entity. Little is known about the prognostic factors and optimal treatment of MCL. The aim of this study was to analyse retrospectively the clinical features and effect of treatment in 94 MCL patients diagnosed and treated in one centre between 1980 and 1996, and to find out different factors influencing the treatment results and prognosis. The median age of the patients was 66 years, and 77% were over 60 years old. Of the patients, 76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B symptoms were present in 35% of the cases. Bone marrow infiltration was found in 61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved complete remission with first- or second-line therapy. The median duration of remission, time to treatment failure (TTF), and survival were 28, 18, and 41 months, respectively. In multivariate analyses, age, stage and leukaemic disease were significantly associated with TTF, and age, stage, leukaemic disease and lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL. None of the conventional chemotherapies seems curative. A prospective randomised trial should be made to evaluate the benefit of anthracycline-containing regimens in MCL.

Cytogenetic and immunologic characterization of mitotic cells in chronic lymphocytic leukaemia.

Lymphocytes from 14 patients with chronic B‐cell leukaemia (B‐CLL) and one with chronic T‐cell leukaemia (T‐CLL) were studied by the MAC (Morphology, Antibodies, Chromosomes) method, which allows simultaneous analysis of the morphology, immunologic phenotype and karyotype of the same mitotic cell. Use of the MAC‐method in present studies has yielded new information about the cytogenetics of CLL. Although most of the interphase cells from patients with B‐CLL were positive for B‐cell markers, many of the mitotic cells turned out to be T cells, supporting the notion that the cells studied by conventional chromosome analysis are often non‐neoplastic T cells. In some B‐CLL cases with normal karyotype in the conventional chromosome study, however, most of the mitotic cells were B cells, indicating that neoplastic B cells may also have a normal karyotype. The patient with T‐CLL had normal karyotype even though most of the mitoses were T cells. The chromosome abnormalities found were restricted to cells with light chain clonality. Our results show that clonal chromosome abnormalities do occur in neoplastic B cells of patients with B‐CLL.

Clinical implications of monosomy 7 in acute nonlymphocytic leukemia

Abstract A group of 18 patients with acute nonlymphocytic leukemia and the chromosomal aberration monosomy 7 in their bone marrow cells was compared to a group of control patients with the same disease but normal bone marrow chromosomes. The monosomy 7 group of patients had a higher incidence of fever and infections, and a higher white blood cell and granulocyte count compared to the control group at the time of diagnosis. The clinical difference between the groups continued over the first month of hospitalization. Complete remission was obtained in 12% of the monosomy 7 group and in 59% of the control group. Survival was clearly longer in the control group of patients. Monosomy 7 of the bone marrow in acute nonlymphocytic leukemia is therefore to be considered a bad prognostic sign.

Elevated Serum Endostatin Is Associated with Poor Outcome in Patients with Non-Hodgkin Lymphoma

Endostatin is a cleaved fragment of collagen Type XVIII and has antiangiogenic activity. The clinical significance of circulating, soluble endostatin (S‐endostatin) is not known.

Oral sources of septicaemia in patients with malignancies

This article reviews papers dealing with oral infections of adult septicaemia patients, searched from MEDLINE, Current Contents and Core Biomedical Collection databases from January 1966 to November 1996. Case reports were excluded. The systematic review of literature revealed that our knowledge of the topic is mostly based on very small patient material. There are no multicentre studies on the effects of various oral health treatment modes on the prevention of septicaemia of oral origin. The number of controlled and comparative studies on the efficacy of the different treatment protocols of oral infections is also small. Current recommendations in this respect are mainly empirical and not evidence based. Clinical practice guidelines are therefore urgently needed. Nevertheless, close co-operation between oncological and oral health units is emphasised because many studies have shown that the oral cavity is indeed an important source of bacteraemia. Life-threatening infections may follow if maintenance of oral health is neglected during anticancer therapy and if potential oral infection foci are left untreated before immunosuppressive therapy.