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Biomedical subjects

J Carstensen

Publications and source records attributed to J Carstensen.

At least 73 records · Page 4Linked to original sources

Deferred treatment in clinically localised prostatic carcinoma.

A series of 122 patients with a cytological diagnosis of well or moderately differentiated and clinically localised (T1-2) prostatic carcinoma were followed up without any initial anti-tumour therapy. The median observation time was 91 months. During follow-up the local tumour progressed to stage T3 in 67 patients (55%) and distant metastases developed in 17 (14%); 47 patients died (38%), 9 of them (7%) from prostatic carcinoma. The risk of dying from prostatic carcinoma was 1% after 5 years and 16% after 10 years for patients not dying from other causes.

Adult↗

Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Stockholm Breast Cancer Study Group.

The prognostic significance of the number of metastatic axillary lymph nodes in relation to the number of identified nodes among 1,622 patients with operable breast cancer was assessed. We present a Cox's analysis of the prognostic significance of nodal status in relation to loco-regional recurrence, axillary recurrence, distant metastasis and death due to breast cancer respectively. As expected, the relative risks were generally higher for patients with nodal involvement, particularly those with 4 or more positive nodes or with few examined nodes. However, among those with more than 4 positive nodes the risk of distant metastases and death due to breast cancer was about the same irrespective of the number of nodes examined.

Antineoplastic Agents↗

Interrelations between cellular DNA content, S-phase fraction, hormone receptor status and age in primary breast cancer. A series of 1,342 consecutively detected tumors. South-East Sweden Breast Cancer Group.

Estrogen and progesterone receptors were assessed by an immuno-biochemical method and DNA content was analysed by flow cytometry in a consecutive series of 1,342 frozen breast cancer samples. Forty-six percent of the ER-positive tumors were DNA diploid compared to 23% among ER-negative cases. The proportion of ER-/PR- cases was highest among hypertetraploid tumors (45%) and lowest among DNA diploids (13%). While receptor positivity and DNA ploidy were strongly related, no differences in mean receptor levels were detected when comparing DNA diploid and aneuploid cases of receptor positive tumors. In receptor positive tumors ER content--but not PR content--increased with age. S-phase fraction (SPF) was estimated in 1,165 cases (87%) with an overall mean of 8.6%. Tumors with high S-phase levels and DNA hypodiploid tumors were significantly more often found in younger than in older patients. The frequency of DNA hypodiploidy was less than 1% among women older than 75 years, while it was 8% among those aged 40 years or younger. S-phase fraction was inversely related to ER and PR status. However, while mean SPF gradually decreased with increasing levels of PR, no significant difference in S-phase fraction was seen for ER concentrations just above the cut-off level for receptor positivity. Tumors positive for both receptors showed the same pattern of DNA ploidy as ER+/PR- tumors while differences in S-phase fraction were observed between the groups. These results support that PR status better than ER status reflects hormone dependent growth in breast cancer.

Age Factors↗

Natural course of clinically localized prostate adenocarcinoma in men less than 70 years old.

A total of 61 patients, less than 70 years old at diagnosis, with clinical stage T1-2, NX, M0, cytologically well or moderately differentiated prostate adenocarcinoma was prospectively included in a surveillance study. Median patient age was 63 years (range 38 to 69 years). Mean followup was 96 +/- 24 months. The probability of local progression to stage T3 disease after 5 and 10 years was 49 and 72%, respectively. The probability of metastases developing after 5 and 10 years was 8 and 23%, respectively. The probability of dying of prostate adenocarcinoma was 2 and 8%, respectively. Moderately differentiated cancer progressed locally significantly faster than well differentiated disease. The relative number of patients who had metastases or died of prostate adenocarcinoma found in our study was comparable to the relative numbers reported after radical prostatectomy and radiation therapy. Therefore, deferred therapy may be an alternative to active therapy in patients with clinically localized prostate adenocarcinoma and with a life expectancy of less than 10 years.

Adenocarcinoma↗

Adenoid cystic carcinoma: DNA as a prognostic indicator.

A retrospective study was performed on 20 patients with adenoid cystic carcinomas of major salivary glands to see if DNA patterns correlated with their prognoses. Fourteen tumors were found to be DNA diploid; 6 were DNA aneuploid. Histologically, all DNA-aneuploid tumors had solid components, compared with only 5 of the DNA-diploid tumors. All of the DNA-aneuploid tumors recurred, in contrast to only 2 of the DNA-diploid tumors; the difference was highly significant (P less than 0.001). All of the patients with no recurrences had DNA-diploid tumors. In our study, DNA measurements of adenoid cystic carcinomas gave statistically significant information about prognosis and correlated to histological grading. We propose that evaluation of DNA content may be performed before planning the treatment of adenoid cystic carcinomas.

Adult↗

Cytometric and histopathologic features of tumors detected in a randomized mammography screening program: correlation and relative prognostic influence.

Cytometric determination of S-phase fraction and ploidy type was performed on 430 tumors detected within a randomized trial of mammographic screening. The results were compared to several histopathologic features. A high S-phase fraction was estimated in tumors with a high grade of malignancy and other histopathologic findings related to rapid tumor progression, including lack of tubule formation, a high mitotic index, marked nuclear pleomorphism, multifocal cancer growth, tumor emboli in lymphatic and blood vessels, tumor necrosis, and inflammatory reaction. DNA aneuploidy was correlated with a high malignancy grade, frequent mitoses, a high degree of nuclear pleomorphism, vascular invasion, necrosis, and the presence of noninvasive ductal carcinoma. Both cytometric variables were inversely related to the degree of elastosis. Positive nodes, large tumor size, DNA aneuploidy, a high S-phase fraction, high grade of malignancy, lack of tubule formation, as well as high mitotic index and pleomorphism, presence of multifocal cancer, and vascular invasion, predicted a significantly shorter distant recurrence-free interval after a median follow-up time of 46.6 months. Elastosis and the presence of estrogen and progesterone receptors indicated favorable prognosis. In the multivariate analysis, only lymph node status, tumor size, S-phase fraction, and multifocal growth pattern had independent prognostic value.

Adult↗

The prognostic value of modal deoxyribonucleic acid in low grade, low stage untreated prostate cancer.

We selected for a prospective surveillance study 167 patients with untreated grades 1 and 2 prostate cancer. The tumors were classified regarding modal deoxyribonucleic acid value (ploidy) by flow cytometry, cytological grade by transrectal fine needle aspiration biopsy and local tumor stage. Of the patients 146 could be evaluated. Mean followup was 50 months. The initial ploidy was statistically correlated to cytological grade but not to initial local tumor stage, prostatic acid phosphatase activity or patient age. Initial ploidy and cytological grade had a prognostic value regarding local tumor progression when considered as single predictors and in combination. Two patients with diploid and 8 with nondiploid tumors initially had metastases during the surveillance. Five patients (1 with diploid and 4 with nondiploid disease) died of prostatic cancer. Modal deoxyribonucleic acid value and cytological grade were of prognostic value in untreated prostate cancer.

Adenocarcinoma↗

The natural course of low grade, non-metastatic prostatic carcinoma.

A surveillance study was carried out on 167 patients with low grade, low stage prostatic carcinoma without known metastases; of these, 146 were evaluated, the mean follow-up time being 50 months. Local tumour progression occurred in 77 patients (53%), corresponding to a 5-year cumulative probability of progression of 67%. Ten patients developed metastases, 5 died of prostatic carcinoma and 24 died of other causes. Cox's regression analysis showed that the initial cytological grade of the tumour was of prognostic importance, but initial local tumour stage, prostatic acid phosphatase activity and age had no statistically significant prognostic value. Although the number of patients developing metastases and dying of prostatic carcinoma was low, most tumours seemed to progress locally.

Aged↗

Heterochromatin variants in 109 ovarian cancer patients and 192 healthy subjects.

Aberrations of the C-band region of chromosome no. 1 (1qh) were studied in 109 patients with ovarian cancer and 192 healthy subjects. The groups were compared for heterochromatin size variations, intrapair size asymmetry, and inversion. No significant correlation was found between the size of 1qh and ovarian cancer. Heterochromatin size asymmetry was estimated visually and determined by objective measurement of 1qh length or area; the methods show strong correlation. The measurements were normalised by comparison with the length or area of 16p or the entire chromosome no. 1. However, since good reliability was found by simply relating the 1qh size difference to the mean 1qh size, this was considered an appropriate and simpler method of normalisation. Asymmetry indices of length and area measurements correlated well, implying that the simpler method of length measurements can be readily used. 1qh asymmetry, measured objectively or estimated visually, was significantly increased in the cancer patient group. The incidence of C-band inversion was significantly increased in the patient group. Moreover, inversion increased significantly with increasing 1qh asymmetry.

Adolescent↗

Cytometric characterization and clinical course of breast cancer diagnosed in a population-based screening program.

A randomized controlled trial evaluating mammographic screening was started in two Swedish counties in 1977. In one of these, Ostergötland county, the authors performed static cytofluorometry on 161 cancers detected at the second and third screening rounds, 50 interval cancers, and 219 cancers appearing in the nonscreened control group during the same time period. The median follow-up time was 42 months. No difference in mean S-phase was found between screening and control group cancers, but interval cancers, appearing between two screenings, had increased mean S-phase levels (P = 0.01) compared to both of the other groups. A high S-phase fraction was associated with distant recurrence in both node-negative and node-positive tumors. Aneuploid tumors were more often found in the control group (67%) and among interval cancers (72%) than among screening detected cancers (55%, P = 0.02). In Cox's multivariate analysis, including all patients, the lymph node status, tumor size, estrogen receptor content, and S-phase all contributed independent prognostic information about the clinical course. DNA ploidy predicted the outcome in simple but not in multivariate Cox's analysis. When analyzing screening-detected cancers separately, only the S-phase significantly predicted distant recurrence in multivariate analysis. In tumors with local recurrence, a high S-phase implicated an increased, although not statistically significant, risk for distant recurrence. Survival with metastatic disease was significantly influenced by the S-phase level (P = 0.002). The authors conclude that S-phase fraction provides valuable kinetic information related to the clinical outcome for all stages of the disease and serves as a prognostic factor in screened populations, which have tumors predominantly in early stages.

Adult↗

Influence of S-phase fraction on metastatic pattern and post-recurrence survival in a randomized mammography screening trial.

Using static cytofluorometry, S-phase was determined on the primary tumors of 421 patients with breast carcinomas in stages I-III diagnosed 1981-85 during the second and third screening rounds of a randomized trial evaluating the effect of mammographic screening. Through December 1988, 82 patients had developed local and/or distant recurrence, 51 of whom had died of cancer during the same period. The distribution among sites of recurrence differed between patients with tumors detected by mammography screening and cancers diagnosed due to clinical symptoms. The mean S-phase fraction was highest in patients with liver or brain metastases and lowest in patients with metastases in subcutaneous and cutaneous tissue and lymph nodes only. In univariate analysis, survival after first recurrence was significantly associated with the site of primary recurrence, the disease-free interval, and node status and tumor size at diagnosis, as well as the S-phase level. The median survival period was 31.3. months for patients with a S-phase fraction below 6%, and 10.7 months in cases with S-phase exceeding 10%. Neither ploidy nor the estrogen receptor content had significant influence on post-recurrence survival. In Cox's multiple regression analysis, only metastatic site, disease-free interval, and S-phase fraction showed significantly independent prognostic value.

Breast Neoplasms↗

Prognostic value of nuclear DNA content in breast cancer in relation to tumor size, nodal status, and estrogen receptor content.

The prognostic value of nuclear DNA distribution pattern in relation to tumor size, axillary lymph node status, and estrogen receptor (ER) content was studied in 464 patients with primary, operable mammary adenocarcinoma. The median follow-up time was 3 1/2 years. Slide cytophotometric DNA analysis was performed on morphologically identified Feulgen-stained tumor cells. The tumors were classified into four subgroups according to their DNA histogram type. DNA content was significantly related to tumor size and ER level but not to nodal status. When all variables were stimultaneously introduced into Cox's proportional hazards model, tumor size, nodal status, and DNA profile remained as significant predictors of recurrence. Restricting the analysis to node-negative patients, both DNA profile and tumor size showed a significant prognostic value. DNA did not contribute significant prognostic information in node-positive patients. However, the trends in recurrence-free survival were similar to those in the node-negative subgroup: patients with aneuploid tumors tended to fare worse than those with euploid carcinomas.

Biomarkers, Tumor↗

Prognostic value of DNA ploidy and S-phase fraction in relation to estrogen receptor content and clinicopathological variables in primary breast cancer.

Tumors from 472 women with primary breast cancer were analyzed by flow cytometry. Divided into four categories, DNA ploidy showed significant association with disease recurrence and mortality. When allowance was made for its correlation with nodal status and estrogen receptor (ER) content, DNA ploidy did not add prognostic information. S-phase fraction was estimated in 290 DNA histograms. In contrast, it was significantly related to recurrence and mortality when controlling for nodal status, tumor size and ER content. When the follow-up was divided into two periods DNA ploidy and S-phase fraction showed association with disease recurrence in the first period only (less than 2.5 years), while the association with mortality was valid for both periods. Light scatter was measured in 234 samples. A low light scatter variability for the stemline nuclei was related to a high recurrence rate during the early follow-up period. In conclusion, DNA flow cytometry adds prognostic information concerning breast cancer patients.

Aged↗

Cytophotometric estimation of cell proliferation in breast cancer. Correlation to the clinical course during long-term follow-up.

Tumours from 117 patients with breast cancer operated during a 5-month period 1975-1976 were investigated by absorbance scanning cytophotometry. The relations of these data to breast cancer recurrence and death during a follow-up period of 8.5 years were analysed using Cox's proportional hazards model. When individually tested, nodal status, grade of malignancy and high rates of proliferation, as indicated by cells in S-phase, were statistically significant predictors of the clinical outcome. The risk ratio associated with S-phase decreased significantly over time from primary treatment. No significant relation was found between DNA-ploidy or tumour size and the clinical course. In the multivariate analysis, based on 76 patients, nodal status alone was a significant prognostic factor.

Adult↗

Childhood mortality in relation to nutritional status and water supply--a prospective study from rural Malawi.

In connection with the introduction of an improved method of water supply in rural Malawi, the nutritional status, morbidity, and mortality among 1,178 children under five were studied during three rainy and three dry seasons. Data were collected at fortnightly home interviews. Nutritional assessment was made twice a year. One hundred and thirty-seven of the children died during the study period, and the probability of dying before the age of five was estimated to 270 per 1,000 children. The mortality risk was related to weight for height (p less than 0.001) and height for age (p less than 0.01) as well as to upper arm circumference (p less than 0.001) and triceps skinfold (p less than 0.05). Mortality among children living in households using the new, piped-water supply tended to be lower than mortality for those using traditional water sources, although the difference was not statistically significant (relative risk 0.4, 95% confidence interval 0.1-1.3).

Child Nutritional Physiological Phenomena↗

DNA flow cytometry and histopathological grading of paraffin-embedded prostate biopsy specimens in a survival study.

Methods to disintegrate old paraffin-embedded tissue blocks for the application of DNA flow cytometry open up new possibilities for retrospective studies on the correlation between tumor cell nuclear DNA pattern and prognosis of the neoplastic disease. In the present work we used such a method to study the relationship between DNA ploidy, histopathological grade, and survival for 50 patients with prostate carcinomas diagnosed 1958-1974. Plugs of histologically identified tissue from benign and tumor areas were sampled from paraffin blocks of prostate biopsy specimens by using a 4-mm skin biopsy punch. Thirty-micron sections were cut from each plug for dewaxing and disintegration. The cell suspensions obtained were stained with 4',6-diamidino-2-phenylindole dihydrochloride and analyzed by flow cytometry. In about one-half of the cases where two or more plugs were analyzed we found a heterogeneous tumor cell nuclear DNA pattern. No apparent correlation was found between the histopathological grade and the DNA ploidy. Using Cox's multiple regression analysis, we found a significant correlation between DNA ploidy and survival of these patients (P = 0.043) when we controlled for histopathological grade (Dhom grade), acid phosphatase level, occurrence of metastases, age, year of diagnosis, and type of biopsy. The correlation between DNA ploidy and survival was just above the level of significance (P = 0.059) when Gleason grade was substituted for Dhom grade in the regression model.

Acid Phosphatase↗