Folke Pettersson

Radiation dose and second cancer risk in patients treated for cancer of the cervix

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkins lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkins disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Leukemia Following Chemotherapy for Ovarian Cancer

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.

Prognostic significance of cell cycle- and invasion-related molecular markers and genomic instability in primary carcinoma of the vagina.

Objective This study aimed to analyze the prognostic value of DNA content and biological markers for cell cycle regulation and invasion in primary carcinoma of the vagina (PCV). Material and Methods Seventy-two consecutive patients with PCV, categorized as short-term (≤2 years) and long-term (≥8 years) survivors, were evaluated for DNA content by image cytometry, and for expression of p53, p21, cyclin A, Ki67, E-cadherin, and laminin-5γ2 chain by immunohistochemistry. The relationship between these biological markers and histopathological and clinical parameters was assessed. Results All PCV showed aneuploid DNA content. Most of the PCV patients showed no overexpression of p53 and high expression of p21, cyclin A, and Ki67. Loss or underexpression of E-cadherin was found in 94% (68/72) of PCV patients, and all patients showed immunopositivity for the laminin-5γ2 chain. Tumors with a vaginal longitudinal location in the lower third or in the entire vagina more often had overexpression of p53, high expression of Ki67 (P = 0.044), and underexpression of E-cadherin (P = 0.038), than tumors confined only to the upper third. Overexpression of p53 was significantly associated with short-term survival in the univariate analysis, but not in the multivariate analysis adjusted for age at diagnosis and tumor size. Conclusions The expression level of some markers was related to tumor location, which might be indicative of different genesis. Overexpression of p53 was associated with short-term survival, but the only independent predictors of survival were age at diagnosis and tumor size.

Evaluation of the Pulse Wash Sampling Technique for Screening of Uterine Cervical Carcinoma

The efficacy of a new sampling technique performed for early detection of cervical carcinoma is compared with Pap smears with the swab-and-wooden spatula technique in 312 women. In this new method, sampling of cytologic material is achieved by using a pulse wash instrument described in a previous article. Cells are rinsed and detached by liquid jets of 0.2 mm in diameter which are produced by a spray nozzle connected with a pressure hose to a high pressure pump. The liquid molecules pass through the spray nozzle at a speed of 20 m/s thus creating a successful rinsing effect on cervical epithelium due to high kinetic energy. Rinsed cells are mixed with the small amount of the flushing liquid. The suspension of cells and liquid accumulated in the speculum is then transported to a small container by a suction pump. The results of this work suggest that the pulse wash technique gives a more representative cell sample than the Pap smear sampling technique, thus offering a simple method to decrease false negative diagnoses in the detection of carcinoma of the uterine cervix. Samples by the new technique give an abundance of cells for slide preparation for cytodiagnostic techniques as well as for additional cytochemical, immunocytochemical and microbiologic diagnostic techniques.

Leukemia following chemotherapy for ovarian cancer

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.

The Pulse Wash Instrument A New Sampling Method for Uterine Cervical Cancer Detection

A new sampling method for uterine cervical cancer detection is described. In this method, sampling of cytologic material is done by using a pulse wash instrument. Liquid jets with a diameter of 0.2 mm at a speed of 20 m/s create a successful rinsing effect of cervical epithelial cells due to the high kinetic energy produced. Because cells are suspended in the flushing liquid it is possible to collect material for additional cytochemical, immunocytochemical, and microbiologic diagnostic techniques in addition to a conventional smear technique. Compared to a conventional Papanicolaou smear technique performed in 75 women at two cervical atypia clinics at the Karolinska Hospital, the pulse wash technique is suggested to result in a more representative cellular sample, thus offering a method to decrease false negative diagnoses in uterine cervical cancer detection.

Granulosa-Cell and Theca-Cell Tumors: The Clinical Picture and Long-Term Outcome for the Radiumhemmet Series

Over the period 1923--72 a total of 305 patients with granulosa-cell, theca-cell tumor and mixed tumor were seen at Radiumhemmet. The commonest symptom was abnormal uterine bleeding. Twenty-three per cent of married women were nulliparous. The menarche seems to have occurred earlier in this group than in the general population. Eight of the granulosa-cell tumor group gave birth to 12 children after treatment for the tumor. Nineteen women with granulosa-cell tumor and 4 with thecoma had received radiotherapy earlier in life for benign lesions. The risk of endometrial cancer was approximately 10 times greater for the women with granulosa- or theca-cell tumor than for the general population. Two hundred and fifty-two patients were given both surgical treatment and radiotherapy. Fifty-three received only surgery (37 granulosa-cell and 16 theca-cell tumors). None of the thecoma patients but 21 per cent of those with granulosa-cell tumor died from their disease. The 5-year survival for the latter group, all stages, was 85 per cent.