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Biomedical subjects

J W Koten

Publications and source records attributed to J W Koten.

At least 19 recordsLinked to original sources
PubMed1996

Second primary tumors in patients with hereditary retinoblastoma: a register-based follow-up study, 1945-1994.

The aim of this register-based follow-up study was to evaluate the long-term cumulative incidence of second primary tumors (SPT) among survivors of hereditary retinoblastoma, with special interest for the incidence of pineoblastoma in retinoblastoma patients born after 1970. The Dutch Retinoblastoma Register was completed and updated: in the period 1945-1994, 639 retinoblastoma patients were registered. The vital status of each patient was obtained from the municipal registries and the Central Office of Genealogy. SPT were traced and histopathologically confirmed. Survival curves and cumulative incidence of SPT were calculated by the Kaplan-Meier method. The survival of patients with hereditary retinoblastoma was significantly shorter than that of patients with non-hereditary retinoblastoma. The cumulative incidence of SPT in hereditary patients was 3.7 and 17.7% at the ages of 10 and 35 years, respectively. Long-term follow-up revealed a high proportion of melanomas (7 melanomas out of 28 SPT). In the sub-cohort of the hereditary-retinoblastoma patient group born after 1970, the cumulative incidence of pineoblastomas at the age of 5 years was 9.3%. Our results suggest that patients with hereditary retinoblastoma should have careful follow-up, and procedures for diagnosing SPT and pineoblastomas at an early and potentially treatable stage should be developed.

Adolescent↗
PubMed1996

High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862-1994.

We wished to determine the influence of parental age at the birth of a retinoblastoma patient on the risk of sporadic hereditary retinoblastoma. The parental age at birth of 941 patients of the Dutch retinoblastoma register (1862-1994) was identified and compared between sporadic hereditary and nonhereditary patients. In a subcohort (1936-1994), a comparison was made with parental age at birth in the general population, as obtained from the Central Bureau of Statistics. Missing birth dates of the parents of retinoblastoma patients were traced with the help of the municipal registries and the Central Bureau of Genealogy. The mean paternal age was 10.7 months higher and the mean maternal age was 11.0 months higher in the sporadic hereditary retinoblastoma patients than in parents of nonhereditary patients. In the subcohort, the mean paternal and maternal ages of sporadic hereditary patients were also higher (12.4 and 11.5 months, respectively) than those of the general population. All differences were statistically significant. This study shows that a high parental age is associated with an enhanced risk of sporadic hereditary retinoblastoma.

Adult↗
PubMed1996

Three histopathological types of retinoblastoma and their relation to heredity and age of enucleation.

The histopathology of 61 eyes was studied with special attention to the morphology of the retina adjacent to the main tumour. Three retinal types were distinguished. Retina type 1 (RT-1, 28 specimens) contained a single tumour that was sharply demarcated from surrounding normal retina. In retina type 2 (RT-2, 29 specimens) large parts of the retina were affected and the main tumour mass gradually blended with the adjacent pathological retina. Retina type 3 (RT-3, four specimens) was characterised by a retina almost entirely affected by diffuse tumour growth. RT-1 correlated significantly with early enucleation (0-3 years) both in hereditary and non-hereditary cases. RT-2 was seen in eyes enucleated later (2-5 years). The progressing tumour may release growth factors in the intraocular space that stimulate the cells of the adjacent retina and lead to multiple new primary tumours in the adjacent retinal area. RT-3 was only present in non-hereditary cases with late enucleation (at 2-5 years). Hereditary retinoblastoma cases are usually detected early. Therefore in hereditary cases RT-1 is significantly more common than RT-2. In 25 eyes of the 44 patients with unilateral sporadic retinoblastoma, multifocal tumours of the retina were observed. Such cases should not mistakenly be classified as hereditary cases on the basis of the histological pattern of multifocality of the tumour process.

Age Factors↗
PubMed1995

Therapy of bovine ocular squamous-cell carcinoma with local doses of interleukin-2: 67% complete regressions after 20 months of follow-up.

We have tested the therapeutic potency of peritumorally injected low doses of interleukin-2 (IL-2). Seventy tumours of the bovine ocular squamous-cell carcinoma (BOSCC), 1-3 cm in diameter, were treated with 5000, 20,000 or 200,000 U IL-2 from Eurocetus (Chiron) to find the optimal dose for treatment. Injections were given peritumorally on Monday to Friday on 2 consecutive weeks. The size of the tumours was measured before treatment and 1, 3, 4, 9 and 20 months after treatment. After 9 months complete regression was observed in 89% of the tumours treated with 5000 U IL-2, 80% treated with 20,000 U and 67% treated with 200,000 U. After 20 months, there was complete regression of 35%, 31% and 67% of the tumours respectively. The 9- and 20-month results of the 200,000-U treatment are significantly better than those of the 5000-U and 20,000-U treatments taken together. This protocol may be useful to treat advanced inoperable tumours (e.g. of the nasopharynx or skin) of human patients.

Animals↗
PubMed1995

Ocular squamous cell carcinoma in Simmental cattle in Zimbabwe.

In Zimbabwe, ocular squamous cell carcinoma (OSCC) was frequently observed in 5 breeding herds of Simmental cattle, a Bos taurus breed originating from Switzerland. In these herds, initial signs of OSCC were already noticeable in cattle about 3 years old. Gradually, OSCC prevalence increased, and 36 to 53% of cattle over 7 years old had 1 or more tumors. More tumors developed in Simmental cattle with periorbital white skin than in cattle with periorbital pigmented skin. Other breeds of cattle (eg, Friesian) also are partly white-faced and live in Zimbabwe in a comparable environment; yet, OSCC prevalence was lower in those breeds.

Aging↗
PubMed1994

Local bacillus Calmette-Guérin therapy for bovine vulval papilloma and carcinoma.

Thirty cows from a pedigree Friesian dairy herd with bovine vulva papilloma and carcinoma were treated by intralesional injections of live bacillus Calmette-Guérin (BCG). This treatment induced total regression of all of six carcinomas. Whilst, after treatment, limited regression was also observed in advanced papillomas, BCG has little or no effect on the early stages of papillomas. This is the first study of BCG therapy in this type of cancer.

Animals↗
PubMed1994

Antitumor effect of locally injected low doses of recombinant human interleukin-2 in bovine vulval papilloma and carcinoma.

In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.

Animals↗
PubMed1993

Histological analysis of IL-2 induced regression of murine solid SL2-tumors.

When DBA/2 mice are inoculated both intraperitoneally (i.p.) and subcutaneously (s.c.) with syngeneic SL2 lymphoma cells and treated i.p. on day 10-14 with 20,000 units IL-2/day, about 50% of the mice reject both the ascitic tumour and the s.c. tumour. During IL-2 therapy large areas of necrosis appear in the solid SL2 tumours between day 12 and 15. Immunohistochemical studies show that only a small number of infiltrating cells is present in the tumours. The percentage of macrophages (MHC-II+) in the tumours is about 1 and the percentage of T-lymphocytes (alpha beta-TCR+) about 0.5. No differences in the numbers of infiltrating cells are seen in untreated and IL-2 treated tumour bearing mice. The tumour surrounding infiltrate consists mainly of mononuclear cells: about 50% macrophages, 20% CD8+ cells, and 15% CD4+ cells. No tumour-infiltrating cells were found that express the IL-2 receptor. We conclude that direct cytotoxic activity of tumour infiltrating cells cannot account for the rapid occurrence of necrosis. When L3T4+ cells were eliminated by treating the mice with alpha-L3T4 monoclonal antibodies before tumor inoculation and treatment with rIL-2, tumor eradication did not occur. So, L3T4+ helper T-cells are essential for IL-2-mediated tumour regression. Exogenous rIL-2 is not directly responsible for the induced tumour regression. A significant stagnation of intratumoural bloodflow is observed after histological analysis; yet it still needs to be determined whether this is the primary cause or consequence of the observed necrosis.

Animals↗
PubMed1990

Parental age in sporadic hereditary retinoblastoma.

Of 104 children with sporadic hereditary retinoblastoma born between 1945 and 1970, we studied the age of their parents at the birth and compared this age with the mean age of parents at the birth of their children during the same period in The Netherlands. The mean age of fathers at the birth of their children with sporadic hereditary retinoblastoma (33.7 years) was significantly higher than the mean age of fathers at the birth of their children in the general population (32.5 years) (P less than .05, one sided). Similarly, the mean age of mothers at the birth of their children with sporadic hereditary retinoblastoma (31.2 years) was significantly higher than the mean age of mothers at the birth of their children in the general population (29.5 years) (P less than .05, one sided). We further analyzed this parental age factor by measuring the relative risk of age groups and comparing the incidence of sporadic hereditary retinoblastoma in the various parental age groups with the incidence of sporadic hereditary retinoblastoma in the total population. Mothers 35 years of age or older had a relative risk of 1.7 to have a child with sporadic hereditary retinoblastoma compared with mothers in the population in general (P = .006, one sided). Similarly, fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general (P = .04, one sided). No parental age effect was found in children with nonhereditary retinoblastoma. We conclude that a high paternal and a high maternal age are significant risk factors for sporadic hereditary retinoblastoma.

Adult↗
PubMed1989

Early diagnosis of bilateral retinoblastoma reduces death and blindness.

The influence of early diagnosis on sight and survival was studied in 130 patients with bilateral retinoblastoma. Nineteen patients died of this condition. Statistical analysis predicted that 12 of these 19 early deaths could have been prevented if doctors' delay had been less than 1 week. Consequently, a reduction of 65% in mortality is possible. Similarly, statistical analysis also predicted that the number of patients with resulting blindness could be reduced by 40%. Central registration and monitoring of retinoblastoma families would greatly improve early diagnosis.

Adolescent↗
PubMed1989

Heritability of breast cancer and its role in pre-menopausal cases.

The causes for the pre-menopausal incidence peak in breast cancer are still controversial. Other cancers also show an early incidence peak. Since the mammary tissue only starts to develop in puberty, the pre-menopausal incidence peak for breast cancer is comparable to the 'juvenile' peak in other cancers (retina, kidney). The four-mutation model for oncogenesis can explain pre-menopausal breast cancer. The model suggests that malignant transformation of a cell is due to four specific oncogenic mutations. These specific mutations accumulate during the proliferation of somatic cells. According to the model, one inherited oncogenic mutation can cause hereditary cancer. In this case only three additional specific mutations have to be accumulated during somatic cell proliferation. Epidemiological data and mathematical calculations indicate that in this case tumors occur early in life. Thus, the four-mutation model for oncogenesis predicts that the impact of heritability in pre-menopausal breast cancer is more significant than is generally believed. At this point, molecular biological studies are needed, to identify the involved specific mutations. Other implications of the model are an increased incidence of second primary tumors and an increased sensitivity for mutagenic factors in these patients.

Adult↗
PubMed1988

Non-ocular cancer in patients with hereditary retinoblastoma and their relatives.

In The Netherlands, retinoblastoma patients have been registered in the Utrecht national retinoblastoma registry since 1862. This register is virtually complete from 1945 onwards. We describe a unique epidemiological survey of the occurrence of non-ocular cancer in all patients registered during the period 1945-1970. The occurrence of non-ocular cancer in relatives of patients with hereditary retinoblastoma is also reported. One hundred and forty-one patients with hereditary retinoblastoma were studied for non-ocular second primary cancer. Nineteen patients died of retinoblastoma. The median follow-up of the surviving 122 patients was 25 years. Seventeen of these patients developed a second primary cancer, most frequently soft-tissue sarcoma. The cumulative incidence of non-ocular cancer was 19% at the age of 35, i.e., a 14-fold increase as compared to the general population. Twelve patients with hereditary retinoblastoma died of non-ocular cancer whereas none of 252 patients with non-hereditary retinoblastoma died of non-ocular cancer. Furthermore, among the parents of our hereditary retinoblastoma patients, 24 (born before 1945) had also been affected by retinoblastoma or had affected sibs. In the parents, 4 tumors occurred, of which 2 were rhabdomyosarcomas and 2 were urinary bladder cancers. Both types of non-ocular cancer were also encountered among the 122 patients with hereditary retinoblastoma. In 103 fathers and 103 mothers of patients with hereditary retinoblastoma who did not have retinoblastoma themselves, there was no previous family history of retinoblastoma. The fathers had a relative risk of 8.3 for pancreatic cancer compared to the general population. There was no significant increase in the number of non-ocular tumors in 332 sibs of patients with hereditary retinoblastoma.

Adolescent↗