European Journal of Cancer and Clinical Oncology最新文献

A sample of 176 808 Pap smears, taken from 70 236 women, was constructed from the records of a large cytopathology laboratory between 1962 and 1981. The prevalence of cervical dysplasia, based on the distribution of initial smear results, rose from 42.7 to 94.9 per 1000 during the study period. The relative risks (RR) for the manifestation of a malignancy (carcinoma in situ or worse) in a subsequent cervical smear were 1.48, 3.42, 20.9 and 71.5 for women with minimal, mild, moderate and severe dysplasia, respectively, compared with the entire cohort. The initial degree of dysplasia for women developing a malignancy was much more likely to be interpreted as moderate (RR = 5.0) or severe (RR = 42.3) than were those for controls. These results are strongly supportive of the hypothesis that the degree of dysplasia is related to the risk of development of cancer of the cervix.

To prospectively assess the role of the MDR1 gene in breast carcinomas, MDR1 RNA levels of breast carcinoma specimens were determined by slot blot analysis. In 59 evaluable patients with primary breast carcinomas, MDR1 RNA levels of the carcinomas were negative in 54%, low in 29% and high in 17% of the patients. No differences in age, menopause status, oestrogen and progesterone receptor levels, tumour size, lymph node involvement and c-erbB-2/neu gene expression were observed between MDR1 RNA negative patients and MDR1 RNA positive patients.

33 patients (median age 39 years) with advanced seminoma were treated with 4 courses of alternating cisplatin-containing chemotherapy PVB/BEP (cisplatin, vinblastine and bleomycin; bleomycin, etoposide and cisplatin). Patients were classified as stage IIC (n = 7), IID (n = 9), III (n = 13) and IV (n = 4). 8 had had prior radiotherapy; 9 had an elevated beta human chorionic gonadotropin (βHCG). 30 patients were evaluable for response and 33 for toxicity. During chemotherapy 3 patients died, 1 due to malignant disease, another due to a cardiac arrest, and 1 patient of a bleomycin pneumonitis. 13 (43%) had a complete remission and 17 (57%) had a clinical partial remission (residual radiographic mass). At a median follow-up of 28 months (range 16–88), 3 patients relapsed, 6–8 months after entry. After completion of therapy there were 2 deaths, 1 due to bleomycin pneumonitis and 1 neither tumour nor treatment related. 26 of 33 (79%) patients achieved a continuously disease-free status. Leucocytopenia and thrombocytopenia of WHO grade $\text{3}\text{4}$ occurred in, respectively, $\text{32}\text{33}$ (97%) and $\text{20}\text{33}$ (61%) of the patients. This study shows that alternating PVB/BEP in this group yields comparable response rates with non-alternating schedules but at the expense of considerable toxicity.

Over a 7-year period, semen analysis was performed in 92 male patients with Hodgkin's disease prior to therapy. In 67% of patients semen revealed a decreased chance for fertility (i.e. oligozoospermia, asthenozoospermia and/or teratozoospermia). The mean basal levels of follicle-stimulating hormone (FSH), luteinising hormone, testosterone and prolactin were in the normal range. In 77 patients in complete remission after alternating MOPP/ABVD (mechlorethamine, vincristine, procarbazine, prednisone; doxorubicin, bleomycin, vinblastine, dacarbazine), testicular function was assessed. 87% of patients were azoospermic, 9% had semen abnormalities and only 4% were normospermic. Recovery of spermatogenesis was documented in only 17 of 42 (40%) reassessed patients after a median time of 27 months and was generally not affected by pretreatment sperm quality. After chemotherapy, the mean value of FSH [20.45 (S.E. 1.7) mUI/ml] was significantly superior compared with that of the mean pretreatment values. No difference was documented in the mean testosterone and prolactin values tested before and after treatment. Our findings indicate that, of patients with Hodgkin's disease, about half are affected by hypogonadism before starting chemotherapy. By utilising alternating MOPP/ABVD, persistent testicular dysfunction was documented in half of the patients.

Data from a specialist registry of haematopoietic malignancies in England and Wales (1984–1988) have been analysed to investigate variations of incidence by age and diagnostic subtype of lymphoid malignancies in young people (aged 0–24 years). Attention has been focussed on the role of community lifestyle indicators for small areas, derived from routine sources, in an ecological analysis. The predominant conditions were acute lymphoblastic leukaemia (ALL)—42.4%, and Hodgkin's disease (HD)—37.5%. Lowest overall incidence at approximately 8 years of age corresponded to the termination of the childhood peak for ALL. Opposite trends of incidence rates with distance from urban centres (urban distance) were observed for the two age groups: odds ratios (OR) for areas > 20 km from towns and cities were 1.46 (95% confidence interval 1.01–2.12) for ages 0–7 and 0.75 (95% confidence interval 0.56-0.99) for ages 8–24. For the younger group this was entirely attributable to ALL. HD, which was dominant in the older group, had highest incidence in connurbations but the gradient of risk for older onset ALL followed the overall pattern for this age group. A positive relationship with socioeconomic status was evident for both age groups but this was considerably stronger for the older cases (OR = 1.16, 95% confidence interval 1.01-1.33) than for the younger for whom it was not independent of urban distance. These results display an association between expression of lymphoid malignancies in young people and urban distance which is not attributable to socioeconomic status; for urban distances the distribution is shifted towards ALL and towards younger age at onset.

Paternity before and after treatment was investigated in 177 patients with unilateral germ cell tumours of the testis. Before the cancer was diagnosed, 51% had fathered at least 1 child, 9% had a history of infertility and 40% had not wanted to have children. It was estimated that 72% of the patients would have fathered at least 1 child at the age of 40 years. After treatment 41 patients had wished to have children. Infertility was still a problem 5 years after the end of treatment in 53% of these men. No significant differences was observed between patients treated with orchiectomy alone and patients treated with cisplatin-based chemotherapy or subdiaphragmatic irradiation. In 8 patients, infertility was present in spite of an evident recovery of spermatogenesis. Congenital malformations were recorded in 3.8% of the live-born children conceived before the orchiectomy. This incidence did not exceed the Danish national rate, the relative risk being 2.5 (95% confidence limits, 0.9-5.5). No malformations were observed in the 22 children conceived after ending treatment.

Intraperitoneal treatment with interferon (IFN) for malignant ascites due to advanced ovarian carcinoma refractory to chemotherapy gave an objective response rate of 36% ($\text{7}\text{19}$ patients treated). In vitro studies demonstrated that cytotoxicity of peripheral blood monocytes/macrophages was stimulated by IFN. However, peritoneal exudate cells obtained after intraperitoneal treatment with interferon were not stimulated to kill autologous tumour cells. Clinical response was therefore most probably due to a direct inhibitory effect of IFN on growth of malignant cells rather than due to an immune modulatory effect. Using a newly established ovarian cancer cell line (UWOV1), synergy between the growth inhibitory/antitumour effects of IFN and cisplatin was demonstrated at clinically achievable concentrations of each agent. IFN plus cisplatin proved to be more effective than intraperitoneal cisplatin alone in control of peritoneal carcinomatosis. The response rate was $\text{5}\text{7}$ (77%) for combined modality therapy vs. $\text{2}\text{9}$ (22%) for intraperitoneal chemotherapy alone. Both in vitro and in vivo studies suggest a role for interperitoneal therapy for control of refractory ascites in ovarian cancer.

Camptothecin, a specific inhibitor of topoisomerase I, caused erythroid differentiation of the human leukaemia cell-line K562, as assessed by benzidine staining at 70 h recovery following a 60 min treatment of the cells. Differentiation was confirmed by increased levels of ϵ-globin and γ-globin mRNA in the treated cells and was accompanied by down-regulation of c-myb mRNA. Synchronisation of K562 cells by non-cytotoxic doses of methotrexate increased the differentiation induced by camptothecin, without affecting the camptothecin-induced inhibition of cellular proliferation. Camptothecin induction of differentiation and inhibition of proliferation may occur by independent mechanisms.