Diagnostic outcome of repeated mammography screening

Mammographic screening for breast cancer within health service routines was evaluated for the years 1987–1992, with special focus on repeated screening during 1989–1992. The overall attendance rate by women aged 40 to 74 years was 82.8%. During 1989–1992 malignancy was found in 2.6/1000 screened women, giving a 87.4% positive predictive rate at surgery and 95.9% efficiency. Among women aged 45, the positive predictive rate was >94%. Fine-needle aspiration (FNA) biopsy showed invasive cancers in 84% and highly suspected cancer in another 15%; 60% of the lesions were nonpalpable. For first-time (prevalence) screening (1987–1988) the positive predictive rate was 86% and the malignancy yield 6.4/1000. In women aged 40–44 years there were few surgical referrals (1.6%), but the positive predictive rate at surgery was only 48.3%, indicating diagnostic difficulties in young women. The median size of all invasive cancers was 12 mm: 84% were classified as pT1, and 23% had lymph node involvement. Stage II disease was found in 27% of all malignancies. The use of FNA in the diagnostic workup for breast cancer screening is of crucial importance to the maintenance of high positive predictive rates at surgery. Moreover, regular analysis is important even when mammographic screening is incorporated into the routine work of health services.

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Resumen El tamizaje mamográfico para cáncer del seno como parte de las rutinas de los servicios de salud fue evaluado para los años 1987–1992, con especial énfasis en el tamizaje repetido en el período 1989–1992. La tasa de cumplimiento por parte de las pacientes en las edades 40–74 años fue de 82.8%. En 1989–92 se halló neoplasia maligna en 2.6/1000 mujeres tamizadas, lo cual significó un índice de predicción de positividad en la cirugía de 87.4% y de eficiencia de 95.9%. Entre las mujeres con edad 45 años el valor de predicción de positividad fue >94%. La biopsia por aspiración con aguja fina demostró cánceres invasores en 84% y alta sospecha de cáncer en un 15% adicional; 60% de las lesiones fueron no palpables. En el tamizaje de primera vez (prevalencia, 1987–1988) el valor de predicción de positividad fue de 86% y el rendimiento de 6.4/1000. En las mujeres con edades 40–44 años se hicieron menos referencias para cirugía (1.6%) pero el valor de predicción de positividad en la cirugía fue apenas de 48.3%, lo cual indica dificultades diagnósticas en las pacientes más jóvenes. El tamaño promedio de los cánceres invasores fue 12 mm; 84% fueron clasificados como pT1 y 25% presentaban invasión ganglionar; 27% de todos los tumores malignos fueron estado II. La aspiración con aguja fina en la evaluación diagnóstica del tamizaje para cáncer mamario es de importancia crucial para el mantenimiento de un alto valor de predicción de positividad en la cirugía y el análisis regular es importante aun cuando el tamizaje mamográfico quede incorporado en el trabajo rutinario de los servicios de salud.

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Résumé Le dépistage systématique des cancers du sein par mammographie effectuée par les services de santé a été évalué entre 1987–1992, en particulier le dépistage répété pratiqué entre 1989–1992. Le taux de participation des femmes âgées entre 40–74 ans a été de 82.8%. Dans la période 1989–1992, une tumeur maligne a été retrouvée chez 2.6/1000 femmes, la chirurgie permettant de calculer une valeur prédictive positive de 87.4% et une efficacité de 95.9%. Chez les femmes âgées de plus de 45 ans, la valeur prédictive positive a dépassé 94%. La ponction biopsie a fourni la preuve de cancer invasif dans 84% des cas et celle d'une forte suspicion dans 15% des cas, alors que 60% des lésions n'étaient pas palpables. Par comparaison, la valeur prédictive positive pendant la période de dépistage entre 1987–88 a été de 96% pour une prévalence de cancer de 6.4/1000. Chez la femme âgée entre 40–44 ans, très peu de femmes ont été opérées, avec une valeur prédictive positive de 48.3%, ce qui démontre les difficultés de diagnostic chez la femme jeune. La taille médiane de tous les cancers invasifs était de 12 mm: 84% étaient classés comme pT1 et 23% avaient un envahissement lymphatique. On a trouvé un stade II chez 27% des patientes tous cancers confondus. L'utilisation de ponction biopsie est capitale pour le diagnostic de cancer de sein pour maintenir une valeur prédictive positive élevée lors de la chirurgie et une analyse régulière est nécessaire même lorsque le dépistage systématique par mammographie est inclu dans le programme des service de santé.

     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Biological monitoring of isocyanates and related amines

Summary Five men were exposed to toluene diisocyanate (TDI) atmospheres for 7.5 h. The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m3 stainless-steel test chamber. The mean air concentration of TDI was ca. 40 g/m³, which corresponds to the threshold limit value (TLV) of Sweden. The inhaled doses of 2,4- and 2,6-TDI were ca. 120 g. TDI in the test chamber air was determined by an HPLC method using the 9-(N-methyl-aminomethyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. After hydrolysis of plasma and urine, the related amines, 2,4- and 2,6-toluenediamine 2,4-, and 2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas-chromatography using selected ion monitoring (SIM) in the electron-impact mode. The urinary elimination of the TDAs showed a possible biphasic pattern, with rapid first phases for 2,4-TDA (mean t _1/2 for the concentration in urine, 1.9 h) and for 2,6-TDA (mean t _1/2 for the concentration in urine, 1.6 h). The cumulative amount of 2,4-TDA excreted in urine within 28 h ranged from 8% to 14% of the estimated dose of 2,4-TDI, and the cumulative amount of 2,6-TDA in urine ranged from 14% to 18% of the 2,6-TDI dose. The average urinary level of 2,4-TDA was 5 g/l in the 6 to 8-h sample (range 2.8–9.6 g/l), and the corresponding value for 2,6-TDA was 8.6 g/l (range, 5.6–16.6 g/l). Biological monitoring of exposure to 2,4- and 2,6-TDI by analysis of 2,4- and 2,6-TDA in urine is feasible.     

Effectiveness of low-dose contrimoxazole prophylaxis against Pneumocystis carinii pneumonia after renal and/or pancreas transplantation

We retrospectively examined the effectiveness of prophylaxis with cotrimoxazole in preventing Pneumocystis carnii pneumonia in recipients of kidney and combined kidney-pancreas transplants between 1985 and 1989. Cotrimoxazole prophylaxis (480 mg daily or 300 mg/m²), when used, was started within 2 months after transplantation and usually continued until 6 months after surgery. Eight (3.7%) of the 214 patients who were not given prophylaxis were infected with Pneumocystis carinii, and there were 4 fatalities (50% mortality). There were no cases among the 161 patients given prophylaxis (P 0.03). No serious adverse effects were noted in the prophylaxis group. It is concluded that prophylaxis against Pneumocystis carinii infection is well tolerated and should be given as soon as possible to all organ transplant recipients for at least 6 months.     

A Systematic Overview of Radiation Therapy Effects in Cervical Cancer (Cervix Uteri)

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for cervical cancer is based on data from 1 meta-analysis and 34 randomized trials. In total, 35 scientific articles are included, involving 7 952 patients. The results were compared with those of a similar overview from 1996 including 34 024 patients. The conclusions reached can be summarized in these points: There are limited scientific data supporting that postoperative pelvic radiotherapy improves disease-free survival in early cervical cancer. No firm conclusion can be drawn.There is moderate scientific evidence that external beam radiotherapy combined with brachytherapy gives a similar disease-free and overall survival rate as radical hysterectomy in early cervical cancer.There is strong scientific evidence that concomitant radiochemotherapy improves disease-free and overall survival compared to radiotherapy alone in early cervical cancer.The NCI has recently published an announcement stating that cisplantin-based chemotherapy should be used concomitantly with radiotherapy in cervical cancer. No solid documentation for this statement can be found concerning locally advanced stages (>IIB).There is a strong scientific evidence that cisplatin-based chemotherapy given concomitantly with radiotherapy is superior to concomitant chemotherapy with hydroxyurea.There is no scientific evidence to show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free or overall survival compared to radiotherapy alone in patients with localized cervical cancer.There is moderate scientific evidence that high-dose-rate brachytherapy gives the same local control rate as low-dose-rate brachytherapy but with fewer rectal complications.     

Uptake and disposition of inhaled methanol vapor in humans.

Methanol is a widely used solvent and a potential fuel for motor vehicles. Human kinetic data of methanol are sparse. As a basis for biological exposure monitoring and risk assessment, we studied the inhalation toxicokinetics of methanol vapor in four female and four male human volunteers during light physical exercise (50 W) in an exposure chamber. The relative uptake of methanol was about 50% (range 47-53%). Methanol in blood increased from a background level of about 20 to 116 and 244 microM after 2 h exposure at 0, 100 ppm (131 mg/m3) and 200 ppm (262 mg/m3), respectively. Saliva showed substantially higher levels than blood immediately after exposure. This difference disappeared in a few minutes; thereafter the concentrations and time courses in blood, urine, and saliva were similar, with half times of 1.4, 1.7, and 1.3 h, respectively. The postexposure decrease of methanol in exhaled air was faster, with a half time of 0.8 h. The methanol concentrations were approximately twice as high in all four types of biological samples at 200 compared to 100 ppm. No increase in urinary formic acid was seen in exposed subjects. Our study indicates non-saturated, dose-proportional kinetics of methanol up to 200 ppm for 2 h. No gender differences were detected. Similar, parallel patterns were seen with regard to the methanol time courses in blood, urine, and saliva, whereas the concentration in exhaled air decreased markedly faster. Thus, apart from blood and urine, saliva also seems suitable for biomonitoring of methanol exposure.     

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.     

TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

Background  

Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive.