Biomedical subjects
R Holland
Publications and source records attributed to R Holland.
Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ.
To assess the potential of breast-conserving treatment for ductal carcinoma in situ (DCIS), 82 mastectomy specimens were studied by Egan's serial subgross method. 42 (51%) of the tumours were larger than 50 mm and only 12 (15%) were smaller than 20 mm; the size distribution was not affected by the mode of detection (mammography 52 cases, clinical examination 30). All but 1 case showed only 1 region of tumour. 66% of tumours involved one breast quadrant, 23% extended over more than one quadrant, and 11% were centrally located. Mammographic estimates, based on the extent of microcalcifications, frequently underestimated the histological size of tumours, the extent of the discrepancy being related to the histological type--8/50 predominantly micropapillary/cribriform. In view of the frequently large size, adequate excision of many DCIS will require a wide excision involving up to a whole quadrant.
[Observed effects of the mass screening program for breast cancer in Nijmegen in 1975-1986].
Since January 1975, the start of the screening programme for breast cancer in the city of Nijmegen, The Netherlands, over 14 years have elapsed. Data up to the end of 1986 have been processed and are presented in this article. The younger the birth cohort, the higher the attendance rate. In the course of the screening programme, attendance rates decline. Referral rates are highest in the first screening round and for the eldest birth cohort. Detection rates increased during the most recent screening rounds, after an initial decrease during the earliest rounds. They are higher for the eldest birth cohort also. The relative number of interval carcinomas is highest among younger women (as related to the screening-detected carcinomas).
The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast.
Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.
Prognostic assessment in node-negative breast cancer patients.
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[Presence of debris in the apical region of dog teeth after biomechanical preparation with or without the use of an auxiliary cream substance].
The subject of this work is to observe if the employment of a cream (ENDO-PTC) during the root canal preparation contributes or not to the condensation of debris in the apical region. Twenty root canals of dogs teeth were divided into two experimental groups: in the first one, the biomechanical preparation was carried out up to the n. 50 Kerr file by using irrigation and aspiration with sodium hypochlorite. In the second experimental group the canal negotiation was done in the same way but using a cream (ENDO-PTC) with sodium hypochlorite as a lubrication substance. A final irrigation and aspiration with sodium hypochlorite was also done in this group. The animal was killed and the pieces prepared for histological analysis. The histological results show us that the employment of a cream during the negotiation of the root canal contributes to a higher condensation of debris in the apical area.
[Hardening treatment for gutta-percha cones].
The subject of this work was to study a hardening procedure for gutta-percha points, in order to make ease their introduction in very curved root canals. Gutta-percha points of different brands and dimensions were submitted to treatment with alcohol 96 degrees for 1 to 3 days. After this treatment the weight necessary to make a bending of 35 degrees on the tip of the gutta-percha was evaluated. The obtained results were submitted to statistic analysis and the following conclusions can be observed: a. The treatment with alcohol make hard the gutta-percha points in a significant level. b. There was not significant differences between the results obtained with more than one day of alcohol treatment. c. The treatment with alcohol do not make hard all the brands of gutta-percha points.
[Behavior of periapical tissue of dog teeth after canal obturation with Sealapex with or without iodoform].
Some endodontists use iodoform in Sealapex in order to rend it more radiopac. This procedure is empiric and for this reason we decided to observe, histologically, if the iodoform introduces some modification in the biological properties of Sealapex. Thirty root canals of dogs' teeth were overinstrumented and filled, by lateral condensation technique, with gutta percha points and Sealapex, with or without iodoform. The iodoform was added in two different proportions: 30 mg or 112 mg for one centimeter of the base and one centimeter of the catalyst of Sealapex. The pieces were removed for histological studies, 6 months after the treatment. The histological results showed that Sealapex encourages apical closure by cementum deposition and that the addition of iodoform does not change that biological property.
Cyclic AMP calcium and the growth of mastocytoma cells.
Arresting P815 mastocytoma cell growth with N6, O2'-dibutyryladenosine 3':5' cyclic monophosphate (db cAMP) and theophylline increased 45Ca2+ uptake and efflux by the cells (i.e, Ca2+ cycling) without altering cytoplasmic free Ca2+ concentrations or the amount or distribution of protein kinase C in the cells. Attempts to identify the Ca2+ channels involved using a wide variety of drugs were unsuccessful. However, the inhibitory effect of db cAMP on growth was greatly increase in medium containing low Ca2+ concentrations, confirming that interactions between Ca2+ and cyclic AMP can affect mastocytoma cell growth.
Chronic fatigue syndrome.
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Premenstrual syndrome.
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In-situ breast cancer: the EORTC consensus meeting.
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Treatment of premenstrual syndrome.
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Chronic fatigue syndrome.
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Hyperactivity in children.
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The occurrence of interval cancers in the Nijmegen screening programme.
Since January 1975 a population-based screening programme for the early detection of breast cancer has been carried out in the city of Nijmegen. During five interscreening periods of 2 years each a total of 158 so-called interval cancers were diagnosed. Careful revision of all screening and diagnostic mammograms was executed. Of all interval cancers 26% were 'missed' at the previous screening examination (due to technical or observer error), 16% were radiographically occult at the time of diagnosis and 58% were 'true' interval cancers. Interval cancers were regarded as 'true' when an obvious lesion was observed on the diagnostic mammogram while no suspect signs were seen on the previous screening mammogram. The prevalence of 'missed' cancers did not decline in the course of the screening programme. Radiographically occult tumours were localised, mostly in Wolfe's P2/DY breast parenchyma (83%), 33% were lobular invasive and 25% ductal non-invasive. 'True' interval cancer cases (58%) showed the same overall survival as control breast cancer patients, diagnosed in a non-screening situation. Shortening the screening interval would reduce interval cancer rates and probably further decrease breast cancer mortality in a screened population. However, from the present series of interval cancers 63% would not have been prevented by an annual screening examination. As regards women under age 50 annual screening would still leave 66% of all interval cancers in this age group undetected. Probably more benefit will be gained by searching for new imaging techniques to reduce numbers of 'missed' cancers and to detect lobular invasive and ductal non-invasive cancers in dense breast parenchyma.
Evaluation of overdiagnosis of breast cancer in screening with mammography: results of the Nijmegen programme.
After 12 years of screening for breast cancer in Nijmegen (1975-86), during which period six mammographic examination rounds were carried out, the extent of overdiagnosis was evaluated. Overdiagnosis is defined as a histologically established diagnosis of invasive or intraductal breast cancer that would never have developed into a clinically manifest tumour during the patient's normal life expectancy if no screening examination had been carried out. The whole 12-year period shows an excess of 11% of breast cancer cases in Nijmegen, compared with the neighbouring city of Arnhem, where no mass screening was performed. The incidence of breast cancers in Nijmegen in the period 1975-78 is higher, compared with the incidence rates in Arnhem; the rate ratio is 1.30. For the time-intervals 1979-82 and 1983-86 the rate ratios are 1.03 and 1.01 respectively with (0.89; 1.18) and (0.86; 1.16) as 95% confidence intervals. This leads to the conclusion that there is no evidence that screening programmes using modern mammography constitute a significant risk for overdiagnosis of breast cancers.
Treatment and survival of female patients with nonpalpable breast carcinoma.
Since 1971, 151 nonpalpable breast cancers (100 invasive carcinomas, 39 in situ ductal carcinomas, and twelve lobular carcinomas in situ) have been diagnosed and treated at the St. Radboud University Hospital. Of the 100 clinically occult invasive carcinomas, 53 had pathologic diameters of more than 10 mm, 29 were of sizes between 6 and 10 mm, and 18 were tumors of 5 mm or less. Residual tumor outside the "excisional" biopsy cavity was encountered in 76 of the 118 mastectomy specimens (64.4%) fully capable of evaluation. Invasive residual tumor would have been left behind in 34 of 86 mastectomy specimens (39.5%). Of 27 axillas studied, no patient with in situ carcinoma had evidence of axillary lymph node metastases. Invasive carcinoma, however, showed axillary lymph node involvement in 7.7% of mastectomy specimens when the size of the primary tumor was not more than 5 mm, in 12.5% when the size was between 6 and 10 mm, and in 29.5% when the primary tumor was more than 10 mm in diameter. The 10-year recurrence-free survival (RFS) of patients with clinically occult invasive carcinomas greater than 10 mm in size was 71.9% and differed significantly from the 90.9% for patients with the invasive tumors less than or equal to 5 mm, as well as from the 100% RFS of patients with invasive tumors of between 6 and 10 mm and noninvasive tumors. Although the 10-year RFS was 92.6% for the patients with negative axillary nodes and 80.0% for the patients with positive axillary nodes, this difference did not reach statistical significance. However, the disease-specific overall survival after 10 years was significantly different between node-negative patients (96.4%) and node-positive patients (78.8%). Multivariate analysis disclosed that the relationship between size of the primary tumor and RFS was independent of the presence of axillary lymph node metastases. In conclusion, the validity of the concept of minimal breast cancer has been re-enforced. However, the results of this study suggest that the upper limit of the original definition of minimal breast cancer is too narrow and should be extended, so that, apart from the noninvasive tumors--regardless of their size--all invasive tumors having a maximum diameter less than or equal to 10 mm should be regarded as minimal breast cancers.