Norbert P. Koper

Bladder cancer incidence and survival in the south-eastern part of the Netherlands, 1975-1989

Trends in cancer occurrence and survival may reflect changing risks and prognosis, respectively, but may also be caused by changes in detection, classification and registration. Changed classification of low-stage papillary carcinomas may have a material effect on observed trends in the occurrence of bladder cancer. We studied the effect of the implementation of the WHO grading system and the third edition of the TNM staging system on bladder cancer incidence in the south-eastern part of the Netherlands. Data on superficial and invasive bladder cancer incidence between 1975 and 1989 were derived from the population-based Eindhoven cancer registry. Data on survival of patients with stages I-IV bladder cancer were derived from the municipal population registers. Age-adjusted bladder cancer incidence per 100,000 person-years rose from 25.9 to 40.7 in males and from 3.1 to 8.5 in females. This increasing trend was caused almost entirely by non-invasive pTa papillary carcinoma. A considerable shift was observed towards lower disease stages, which was less evident within the group of invasive tumours. The relative 5-year survival of patients with stages I-IV invasive bladder cancer was 59% in 1975-1977 and 70% in 1984-1986. After stratification by stage, however, no striking improvement was observed in the prognosis. We conclude that the increasing trend of bladder cancer occurrence in the Netherlands since 1975 has largely been caused by changed classification systems and reporting procedures for pTa tumours (formerly classified as papillomas).

Ovarian cancer incidence (1989-1991) and mortality (1954-1993) in the Netherlands

Objective To examine ovarian cancer incidence and mortality in the Netherlands, and to relate trends in mortality to changes in parity and use of oral contraceptives. Methods Age-standardized and age-specific incidence and mortality rates are presented using incidence data from the Netherlands Cancer Registry, 1989–1991, and mortality data from the Netherlands Central Bureau of Statistics, 1954–1993. Results In the period 1989–1991, age-standardized incidence of ovarian cancer was 14.9 per 105 woman-years. The majority (89%) of these tumors had an epithelial origin. Two-thirds of all newly diagnosed ovarian cancers already showed extension to the pelvis or beyond at diagnosis. From the period 1954–1958 to 1969–1973, age-standardized mortality rates increased from 10.6 to 13.1 per 105 woman-years. Thereafter, a decline was noted to 11.4 per 105 woman-years in the period 1989–1993. Age-specific mortality rates showed a pattern of rising mortality in the elderly, whereas mortality in the younger age categories was declining. The number of live births has declined gradually, and oral contraceptive use has increased. Conclusion Incidence of ovarian cancer is high in the Netherlands, but comparable to other countries in north-western Europe and North America. Mortality rates are rising in the elderly and declining in the young. Further research is needed concerning the effects of oral contraceptives, fertility drugs, and hormone replacement therapy on the incidence and mortality of ovarian cancer.

An illustration of the clinical relevance of detecting human antimouse antibody interference by affinity chromatography

Elevated Cancer antigen 125 (CA 125) serum concentrations (up to 221 kU/1) were measured in a 39 year old woman with a positive family history of breast cancer. The serum determinations were performed with the automated Immulite OM-MA chemiluminescent enzyme immunoassay system (Diagnostic Products). Laparoscopic evaluation of the ovaries did not reveal any abnormalities. CA 125 measurements in the same patient using the automated IMx immunoassay system (Abbott) demonstrated normal serum levels. Using a previously reported chromatography procedure IgG type human antimouse antibody activity was found to be present in the serum samples explaining the falsely elevated levels. To prevent this interference the manufacturer modified the assay system by replacing the monoclonal M11 detection antibody with a rabbit polyclonal antibody. Using the modified OM-MA CA 125 assay results were comparable with the IMx values.

Quantitation of IgG and IgM human anti-mouse antibodies (HAMA) interference in CA 125 measurements using affinity chromatography

Abstract Currently no available immunoassay system offers complete protection against spuriously elevated or lowered results due to interference by Human Anti-Mouse Antibodies (HAMA). Although routine use of chromatography procedures is not an acceptable option because of the extra cost and workload involved, such a procedure would be highly desirable to ensure accurate immunoassay results. The present report describes a relatively simple affinity chromatography procedure using a HiTrap Protein G column to isolate immunoglobulin G (IgG) HAMA, followed by a HiTrap N-hydroxy-succinimide(NHS)-activated column coupled to goat-anti human immunoglobulin M (IgM) to bind IgM HAMA. To examine the usefulness of this purification procedure we determined CA 125 in forty serum samples prior to and following chromatography. Pre- and post-injection samples were obtained from 20 patients injected with 1 mg of 111In-Iabelled murine OC 125 F(ab′)2 fragments in an immunoscintigraphy study. It is shown that this analytical procedure provides a technique to determine the extent and the nature of the existing HAMA interference in samples of patients after in vivo use of monoclonal antibodies for diagnostic or therapeutic purposes. The procedure can also contribute to the clarification of clinically discordant CA 125 results. Finally, the availability of such a procedure in the clinical laboratory provides an opportunity to test the robustness of newly developed immunoassay systems towards HAMA interference.

Mutagen sensitivity in patients with familial and non-familial urothelial cell carcinoma.

Due to variation in individual susceptibility, only a fraction of all individuals exposed to environmental carcinogens will develop cancer. Our aim was to assess whether mutagen sensitivity plays a role in developing urothelial cell carcinoma (UCC) and whether this sensitivity is different in familial and non‐familial cases. Intrinsic susceptibility was quantified by a mutagen sensitivity assay (mean number of chromatid breaks per cell after damage induction with bleomycin in the late S–G2 phase of the cell cycle). Patients were classified as sporadic (n = 25), familial (2 patients in 1 nuclear family, n = 23) or hereditary (2 patients <60 years or 3 patients in 1 nuclear family, n = 13) and compared with control subjects without a history of cancer. Information on demographic factors, smoking history and family history of UCC was collected by postal questionnaires. Differences in mutagen sensitivity were assessed by ANOVA and logistic regression analysis. Overall, UCC patients showed a higher mutagen sensitivity score compared with control subjects [mean number of chromatid breaks per cell 0.91, 95% confidence interval (CI) 0.84–0.97, and 0.74, 95% CI 0.69–0.79, respectively; p = 0.001). Sporadic and familial patients exhibited the highest susceptibility (0.94, 95% CI 0.82–1.06, and 0.93, 95% CI 0.83–1.03, respectively). Hereditary patients (0.79, 95% CI 0.72–0.86) showed a susceptibility similar to controls. Mutagen sensitivity increases the risk of non‐hereditary UCC. The relatively low mutagen sensitivity score among hereditary patients points to a different carcinogenic pathway. Int. J. Cancer 88:493–496, 2000.