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Biomedical subjects

M Eskelinen

Publications and source records attributed to M Eskelinen.

At least 109 records · Page 6Linked to original sources

Carcinoma of the breast in children.

Carcinoma of the breast in children is an extremely rare disease, only 44 patients have been reported in the world literature. We report on a case of breast cancer in a 9-year-old girl, who was admitted to the hospital because of a four-month history of a painless mass in the right breast. Clinical examination and mammography resulted in a strong suspicion of malignancy. The histology corresponded to juvenile secretory carcinoma, the histological type without the characteristics of prepubertal cancer cases. Electron microscopy demonstrated intracellular large vacuoles and acini filled with secretory material. The mitotic index was low, the highest measured value was 4 mitotic figures per 10 high power fields corresponding to 2.78 mitotic figures per mm2 of epithelium in the microscope field. Flow cytometry showed that the neoplastic cells were diploid and had a low S-phase fraction. A simple mastectomy including axillary evacuation was performed. No lymph node or distant metastases were found. Postoperative radiation treatment or chemotherapy were not administered. Our patient has been in follow-up for six years without recurrence. In this case simple mastectomy with axillary evacuation seems to have given a cancer-free development into adulthood. Earlier reports have also shown a favourable outcome in these tumours.

Breast↗

Potential of nuclear morphometry and volume-corrected mitotic index in grading transitional cell carcinoma of the urinary bladder.

The potential of nuclear morphometry and volume-corrected mitotic index (M/V index) in grading cases of transitional cell carcinoma of the urinary bladder was studied. 30 cases of bladder cancer including all three WHO grades were evaluated. Four investigators selected independently the most atypical field from paraffin sections, and one investigator measured the nuclear areas from these fields using the IBAS 1&2 image analyzer system. Following the same sampling rule, four investigators counted the mitotic figures per area of neoplastic tissue in the microscopic image at an objective magnification of X40. The mean nuclear areas covered values from 28.1 to 139.0 microns 2 (mean +/- SD 57.2 +/- 18.9). The total variance of measurements was 359.1 and the mean variance between corresponding fields 110.2 (about 30% of the total variation). The efficiency was evaluated by estimating the fraction of falsely classified cases. Instrumental morphometry of nuclear area in a three-grade system gave an efficiency of 79% and of 90%, in a two-grade system. The M/V index varied from 0 to 54 (mean +/- SD 12.3 +/- 10.9). The total variance was 119.8 and the methodological variance 15.5 (about 13% of total variance). In a three-grade system this would correspond to an efficiency of about 75%; in a two-grade system the efficiency would be 88%. The results suggest that nuclear area and M/V index estimates constitute efficient grading systems in bladder carcinoma.

Carcinoma, Transitional Cell↗

Nuclear morphometry in human pancreatic adenocarcinoma; relation to histological grade, clinical stage, and survival.

A retrospective study was performed on 63 pancreatic cancer patients diagnosed during the years 1970-1988. The mean follow-up time of all individual patients was 6.9 months (range 0-37 months). Histological grade, clinical stage, and 12 morphometric nuclear variables were correlated to the survival of patients. Clinical stage (p = 0.066), histological grade (p = 0.095), and morphometric variables (p = 0.155) predicted survival in survival analysis. Clinical stage (p = 0.029), morphometric variables (p = 0.157), and histological grade (p = 0.306) predicted survival at one year after diagnosis. Morphometric variables divided grade II tumours into two prognostically different groups (p = 0.008) when the mean survival time was used as a classifier. Also the metastasizing potential of pancreatic cancer and lymph node involvement were associated with morphometric variables. Histological grade and morphometric variables were positively correlated (p less than 0.001). On the basis of our results, it seems that nuclear morphometric variables are more efficient or equal to subjective histological grade in predicting survival of pancreatic cancer patients. This result suggests the potential use of nuclear morphometric variables in grading pancreatic adenocarcinomas, and selecting patients for different modes of therapy.

Adult↗

An improved prognostic index of axillary node involvement in breast cancer incorporating DNA ploidy and tumour size.

A multivariate prognostic index based on clinical data and the results of flow cytometry for the grading of breast cancer was evaluated in 117 patients whose disease had been detected and treated by mastectomy with axillary clearance between 1974 and 1976. Survival analysis with Cox's regression model pointed to three important prognostic factors: lymph node involvement (p less than 0.001), DNA ploidy (p less than 0.01) and tumour size (p less than 0.01). These factors were incorporated into a prognostic index, in which the lymph node involvement, DNA ploidy, and tumour size contributed to the index in that order. Logistic discriminant analysis with five year follow-up as the fixed end point (70 alive, 47 dead) gave the same result; lymph node involvement, tumour size, and DNA ploidy were the best prognostic indicators of survival. The result showed that our multivariate prognostic index was more powerful than lymph node involvement alone. The use of this prognostic index is recommended for selecting patients for different treatments.

Adult↗

Factors associated with risk of breast cancer and persistence of symptoms in women with breast problems.

Risk factors in breast cancer were analysed in a series of 293 women who were first seen at the Surgical Outpatient Department of Savonlinna Central Hospital in 1982-1983 for breast problems and were alive and willing to participate in a control examination and interview 4-5 years later. In 1986 and 1987 the patients were examined clinically and underwent mammography and interview. They were divided into three groups: 1) 49 patients with breast cancer in 1982 and 1983, 2) 49 with breast symptoms after primary treatment of benign disease, and 3) 195 patients without breast symptoms after primary treatment of benign disease. The groups were compared in terms of 18 suggested risk factors for breast cancer. Two factors were significantly associated with breast cancer (compared with all benign breast diseases): higher age of the patient and higher age at first delivery. Use of contraceptives was significantly associated with the presence of breast symptoms after treatment of benign breast disease (as compared with the absence of symptoms) (RR = 1.70 P less than 0.001). Hysterectomy and/or oophorectomy was significantly associated with the absence of breast symptoms among patients with benign breast disease (RR = 0.76, P less than 0.05). Our results suggest that symptoms after treatment of benign breast disease are associated with the levels of female sex hormones.

Breast Diseases↗

Potential of morphometry in grading transitional cell carcinoma of the urinary bladder.

The potential of morphometry in grading cases of transitional cell carcinoma of the urinary bladder was evaluated. Thirty cases of bladder cancer including all three WHO grades were studied. Three investigators measured the nuclear areas using the IBAS 1&2 image analyser system. The means, the standard deviations and the variances of the measurements were calculated. The nuclear areas covered values from 25.1 to 107.4 square micrometers, the mean +/- SD being 52.6 +/- 17.5. The total variance of measurements, including biological and methodological variation, was 304.6, and the methodological variance 10.4 (about 3.5% of the total variation). In a 3-grade grading system this would correspond to an efficiency of about 92%, and in a 2-grade system of about 96%, which are the percentages correctly graded by the grading system.

Carcinoma, Transitional Cell↗

The flow-cytometric analysis of DNA content and S-phase fraction (SPF) of human breast cancer.

The DNA ploidy of breast cancer tissue from paraffin blocks was measured by flow cytometry in 122 patients. In this material there was a difference in lymph node involvement and in the presence of distant metastases between diploid and aneuploid tumors. Diploid tumors were smaller than aneuploid tumors. Aneuploid tumors were more common in postmenopausal than in premenopausal women. Near tetraploid tumors were found in older patients rather than tumors with other ploidy patterns. The ploidy pattern was not associated with survival during the mean follow-up of 4.1 years. We specially studied the S-phase fraction (SPF) which was distinctly higher in aneuploid tumors than in diploid tumors. Also near tetraploid, hypertetraploid and multiploid tumors showed higher SPF than diploid tumors. The median of SPF in our material was 8.5%. Positive axillary lymph nodes were found in 32% of the patients who had tumors with an SPF below the median and in 46% of those with tumors above the median (SPF greater than 8.5%). The difference, however, was not statistically significant. In our material the SPF of the tumor did not show a significant association with survival. However, longer follow up time is needed for firm conclusions on the predictive value of cell DNA on survival.

Breast Neoplasms↗

Frozen section diagnosis of breast cancer.

In Savonlinna Central Hospital, Southeastern Finland, 371 frozen section examinations were made from September 1981 to December 1986 to detect breast cancer. There was one false positive diagnosis (0.7%) among the 147 lesions interpreted as carcinoma. Among the 224 biopsies, which were benign on frozen section investigation, four showed carcinoma in paraffin sections (1.8%). Thus, the diagnostic sensitivity of frozen section method was 97.3% (146/150) and the clinical diagnostic specificity 99.5% (220/221) when the diagnosis in the paraffin sections was used as reference. In the four false negative cases the tumour was small and limited to the breast without any evidence of metastases. Two of them were ductal carcinomas, one was microinvasive lobular carcinoma, and one intraductal non-invasive papillary carcinoma. The false positive case had benign intraductal papillomatosis. Our results suggest that the probability of a false diagnosis in frozen section examination increases with diminishing size of the lesion. We suggest that small lesions (less than 1 cm in diameter, or non-palpable) should not be subjected to frozen section examination to avoid unnecessary loss of neoplastic tissue during the preparation process. Instead surgically radical lumpectomy and careful investigation of paraffin-embedded tissue are recommended.

Adult↗

Lymphoma of the breast.

Three cases of malignant lymphoma of the breast are described, seen over a 14 year period in the district of Kuopio University Central Hospital. The neoplasms were either of high or intermediate grade of malignancy: one immunoblastic, one Burkitt-type, and one centroblastic-centrocytic malignant lymphoma. The patient with centroblastic-centrocytic malignant lymphoma had advanced disease with pulmonary and adenoidal involvement and died 15 months after the detection of the breast tumor. The two other neoplasms were confined to the breast with no evidence of further dissemination. The patient with immunoblastic malignant lymphoma developed intestinal lymphoma 3 years later which was treated with surgery and cytostatic therapy. The patient has since been in remission for a period of 10.5 years. The patient with Burkitt-type malignant lymphoma was subjected to surgical resection which was followed by cytostatic treatment. The patient has remained in good health during the 20-month follow-up. The correct diagnosis is especially important in breast lymphoma because without it the appropriate treatment cannot be applied.

Adult↗

Cancer-associated antigen CA 15-3 in the diagnostics of breast tumours.

The serum concentration of the new marker CA 15-3 was determined by a kit method, which is based on the use of two different monoclonal antibodies 115D8 and DF3, in a coated tube immunoradiometric technique. The mean CA 15-3 values in breast cancer patients (n = 40) were significantly higher than in patients with benign breast disease (n = 52, p less than 0.001) and in control subjects (n = 32, p less than 0.001). When we used the cut-off level 35 kU/l for CA 15-3, 0/32 of control subjects, 1/52 (2%) of patients with benign breast disease, 8/40 (20%) of all breast cancer patients, 6/19 (32%) of breast cancer patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were above this level. Among the same patients the CEA serum test was positive at a cut-off level of 5 micrograms/l in 7/40 (18%) cancer cases, and in 6/19 (32%) of cancer patients with nodal involvement. When we used the cut-off level 35 kU/l for CA 15-3 and 5 micrograms/l for CEA 1/52 (2%) of patients with benign breast disease, 10/40 (25%) of all breast cancer patients, 7/19 (37%) patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were positive in one or both of the tests. The serum CA 15-3 and CEA values were higher in patients with tumour size above 2 cm in diameter than in patients with smaller tumours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Receiver-operating characteristic (ROC) curve analysis of cathepsin D and pS2 in breast disease; results from a prospective study.

The cytosol values of estrogen-regulated proteins cathepsin D and pS2 were evaluated in 166 patients with breast diseases by a receiver-operating characteristic (ROC) curve analysis. Our aim was to compare their diagnostic accuracy and to define optimal cut-off levels for the cytosol values of these proteins in breast cancer (n = 133). The preoperative mean cytosol cathepsin D values in the breast cancer group were higher than in patients with benign breast disease (p < 0.001). The correlation coefficient (Pearson's r) between Cathepsin D and pS2 measurements was 0.286 (p < 0.001) in breast cancer patients. The ROC analysis indicated that the cathepsin D test was more sensitive than the pS2 test at all specificity levels, and the cathepsin D test reached considerably high sensitivity (86%) at the specificity level of 80%. According to present study, it would seem optimal to use the cut-off level of 33.0 pmol/mg for cathepsin D analysis and the level of 31.0 ng/mg for pS2 in breast cancer. In conclusion, the results of ROC curve analysis suggest that the cathepsin D test has advantage over pS2 because of its higher sensitivity in breast cancer.

Adolescent↗

Preoperative high type I collagen degradation marker ICTP reflects advanced breast cancer.

Type I collagen synthesis (PINP, PICP) and degradation (ICTP) markers were analysed from preoperative serum samples of 138 women with breast cancer (BC), 94 women with benign breast disease (BBD) and 100 healthy controls to evaluate the levels of these markers and the stage of BC at the time of diagnosis. We also compared the clinical utility of these markers in detecting BC with CA15-3 and CEA. The mean value of ICTP was statistically significantly elevated in the BC group (p < 0.001), as compared with the control group, but the elevated values in BC group were due to stage IV disease. The sensitivity of ICTP in detecting BC was 0.23, which was equal with CA15-3(0.24) or CEA(0.23). The sensitivity of both PICP and PINP for diagnosing BC was poor, but a tendency to higher serum levels of PINP and low PICP/PINP ratio was detected in patients with advanced stage IV disease. These results indicate that high preoperative serum levels of ICTP are associated with advanced BC, but like CA15-3 and CEA, its clinical value in diagnosing purpose is poor.

Biomarkers, Tumor↗

A prospective study of tissue polypeptide specific antigen (TPS) in breast cancer diagnosis.

The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in sera from patients with breast cancer and patients with benign breast disease. The results for TPS were compared with those for TAG 12, CA 15-3 and MCA. The cutoff levels (90% specificity) determined for each test were 108.0 U/1 for TPS, 57.5 KU/1 for TAG 12, 24.8 KU/1 for CA 15-3 and 9.7 KU/1 for MCA. The diagnostic sensitivity of the TPS test was 0.21, for the TAG 12 test it was 0.2, 0.13 for the CA 15-3 test and 0.12 for the MCA test in detecting breast cancer. TPS, TAG 12, CA 15-3 and MCA tests were tested in a multivariate analysis to find the best combination of independent predictors of breast cancer. The most important predictor of breast cancer was TAG 12 followed by TPS. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The diagnostic score (DS) was: DS = TPS x 0.0085 x TAG 12 x 0.0596 - CA 15-3 x 0.0866 - MCA x 0.2938 + 0.1738. The sensitivity of the DS in detecting breast cancer was 55% with a specificity of 90% and an efficiency of 64%. In conclusion, new tumour markers TPS and TAG 12 may have some value in breast cancer diagnosis. In particular, the results indicate the usefulness of computer assistance and a simple diagnostic score when tumour markers are used in breast cancer diagnosis.

Adult↗

A prospective study of the value of imaging, serum markers and their combination in the diagnosis of pancreatic carcinoma in symptomatic patients.

The diagnostic accuracy of ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and tumour markers CEA, CA 50 and CA 242 in pancreatic cancer (n = 26) was studied in 113 patients with jaundice, in 20 patients with unjaundiced cholestasis, and in 60 patients with the suspicion of chronic pancreatitis or a pancreatic tumour. The sensitivities of US, CT and ERCP were 61.9%, 95.2% and 82.3%, the specificities 93.9%, 92.9% and 94.1%, and the efficiencies 91.6%, 96.6% and 92.1%, respectively. The sensitivities of CEA, CA 50 and CA 242 were 92.3%, 96.1% and 61.5%, the specificities 59.2%, 58.0% and 95.2%, and the efficiencies 63.7%, 63.2% and 90.6% respectively. The combined use of the imaging methods and tumour markers was also analysed. When either the imaging method or the serum marker test was required to be positive, the sensitivities of the combinations were clearly better than those of US and CA 242 alone, but only slightly better than those of CT, ERCP or the tumour markers CEA and CA 50 alone. When both the imaging test and the marker test were required to be positive, the specificities of the combinations were clearly better than those of CEA and CA 50 alone, but they did not exceed the specificity of the imaging methods or CA 242 alone. We conclude that CT, ERCP and CEA and CA 50 are highly sensitive in the diagnosis of pancreatic cancer in symptomatic patients, while the sensitivity of US and CA 242 is lower. The specificity of the imaging methods and CA 242 is high, but that of CEA and CA 50 is low. Imaging methods and serum tumour markers could be more used in clinical practice in a complementary manner. In patients with jaundice and/or cholestasis or with a suspicion of pancreatic tumour or chronic pancreatitis, the combined use may yield higher sensitivity than US alone and higher specificity than CEA or CA 50 alone.

Antigens, Tumor-Associated, Carbohydrate↗

Clinical value of serum tumour markers CEA, CA 50 and CA 242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis; results from a prospective study.

A prospective study of 113 patients with jaundice and 20 patients with unjaundiced cholestasis was carried out to evaluate the value of serum tumour markers, carcinoembryonic antigen (CEA) and monoclonal antibodies CA 50 and CA 242, in the distinction between benign and malignant diseases causing jaundice and/or cholestasis. In the patients with malignant disease (n = 37) the serum values of all tumour markers were significantly higher than in the patients with benign disease (n = 96). The sensitivities of CEA, CA 50 and CA 242 in detecting malignancy were 70.2%, 94.5% and 56.7%, respectively, while the specificities were 57.2%, 33.3% and 77.0%, respectively. Serum alkaline phosphatase and bilirubin levels had a high positive correlation with CA 50, and CA 242 correlated positively with serum bilirubin levels. No correlation was seen between CEA and alkaline phosphatase or bilirubin levels. The CEA, CA 50 and CA 242 tests may be used as useful complements to other investigative methods in the distinction between benign and malignant causes of jaundice and/or cholestasis. In particular, the rather high specificity of the CA 242 test for malignant diseases seems promising.

Acute Disease↗

A decision support system for predicting a recurrence of breast cancer; a prospective study of serum tumour markers TAG 12, CA 15-3 and MCA.

The aim of the present study was to evaluate the clinical value of the preoperative serum tumour markers TAG 12, CA 15-3 and MCA in predicting a recurrence of breast cancer patients. The sensitivity of the TAG 12 test was 54%, that of the CA 15-3 test 15% and that of the MCA test 15% in predicting a recurrence of breast cancer. The most important predictor of breast cancer recurrence was TAG 12. In order to evaluate the contributions of different tumour marker serum test, a stepwise discriminant analysis was carried out. The discriminant function (DF) is DF = TAG 12 x 0.061 - CA 15-3 x 0.1336 - 0.396. The sensitivity of the DF in detecting recurrence of breast cancer was 63% with a specificity of 90% and an efficiency of 75%. In conclusion, the results indicate that a new tumour marker TAG 12 is superior to CA 15-3 and MCA in predicting breast cancer recurrence. In this study the discriminant function including TAG 12 and CA 15-3 was superior to single preoperative tumour marker tests. The results speak for the use of a decision support system to aid in predicting a recurrence of breast cancer.

Antigens, Neoplasm↗

Clinical, histological and quantitative prognostic factors in cutaneous malignant melanoma.

A retrospective study including 55 cutaneous melanoma patients with 9.5 years follow-up was carried out to assess the significance of various prognostic factors. The histological samples were evaluated according to Clark's and Breslow's classifications and six nuclear features were measured by interactive morphometry. Mitotic activity was assessed by two different methods: mitotic activity index (MAI) and volume corrected mitotic index (M/V index). The overall disease-related five-year survival of patients was 76.4%. TNM stage (p = 0.0001), sex (p = 0.0024), M/V index (p = 0.003), standard deviation of nuclear form factor (p = 0.023), MAI (p = 0.02), shortest nuclear axis (p = 0.023) and Breslow's classification (p = 0.044) predicted survival in univariate analysis. A multivariate analysis including clinical, histological and morphometric features pointed the Clark's classification as the most important predictor of survival (p = 0.002), while the other variables included had no independent prognostic value. The prognostic importance of mitotic indices and morphometric features is clearly a subject for further studies in superficial melanomas.

Female↗

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer.

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment.

Analysis of Variance↗