Biomedical subjects

V M Kosma

Publications and source records attributed to V M Kosma.

At least 127 records · Page 7Linked to original sources

PubMed1993

Tumour induction in mouse epidermal cells irradiated by hot particles.

We have shown elsewhere that highly non-uniform exposure to ionizing radiation from authentic Chernobyl-released and artificially-produced hot particles (fragments of nuclear fuel) transform fibroblastic 10T1/2 cells in vitro effectively. We have also shown that hot-particle exposure leads to mutation and overexpression of the tumour suppressor gene p53 (and some other growth-related genes) in mouse skin in vivo at a high frequency. In the present paper it is shown that hot-particles produced by irradiating natural uranium with slow neutrons, when implanted (immobilized) under the skin of hairless and nude mice, induce epidermal tumours in excess compared with the conventional non-threshold stochastic model of radiation-induced cancer. One explanation for the effectiveness of the hot-particle exposure, under the present assay conditions, is that the same cells in which specific radiation-induced DNA damage is most likely to occur, are forced into sustained mitotic activity in the chronic wound which develops around the radiation source (combined genotoxic and nongenotoxic effects). The results are consistent with a role for cell proliferation in multistage carcinogenesis in mouse skin.

Accidents↗

PubMed1993

Predictive value of a morphometric prognostic index in female breast cancer.

Survival data of the patients were correlated to tumour size, axillary lymph node (pN) status, mitotic frequency and morphometric prognostic index (MPI) in a series of 611 women with a primary breast carcinoma treated and followed-up for over 12 years in Kuopio University Hospital. The pN status, tumour size, mitotic activity index (MAI), volume-corrected mitotic index (M/V index) and MPI all predicted recurrence-free survival and cancer survival (p < 0.001). In pN(-) patients, the MPI was the most important predictor of recurrence-free survival and cancer survival (p < 0.001) followed by the mitotic frequency. In pN(+) patients, tumour diameter and MPI were equal predictors (p < 0.001) of survival followed by M/V index. In Cox's analysis, MPI, pN status and mitotic frequency independently predicted survival in the whole series. In the separate analysis of pN(-) and in pN(+) tumours, the MPI and MAI independently predicted survival. The M/V index was independently related to recurrence-free survival in pN(+) tumours. In multivariate analysis, MPI was an independent predictor although it does not include all the prognostic information. The results suggest that the decisions on adjuvant therapy in breast cancer can be based on the MPI, particularly in pN(-) patients.

Breast Neoplasms↗

PubMed1992

The changing importance of prognostic factors in breast cancer during long-term follow-up.

A cohort of 464 breast-cancer patients were followed up for over 10 years and the clinical, histological and morphometric factors were related to survival within different time periods during follow-up. Tumor diameter, axillary lymph-node status (pN), tubule formation and the fraction of intraductal growth as determined from the primary tumor biopsy specimen had prognostic value up to 5 years. Histological grade, morphometric nuclear factors and the M/V index had only short-term prognostic value immediately after the primary therapy. In axillary lymph-node-negative (ANN) tumors tubule formation, intraductal growth, tumor necrosis and tumor diameter had prognostic value during the first 3 postoperative years. In axillary lymph-node-positive (ANP) tumors, tumor diameter, intraductal growth and tubule formation had long-term prognostic value whereas the M/V index had prognostic value only for 1 postoperative year. Tumor diameter, axillary lymph-node status, tubule formation and the proportion of intraductal growth also had independent long-term prognostic value in a multivariate analysis and accordingly these factors can categorize breast-cancer patients into prognostic groups after several years of follow-up. In contrast, mitotic frequency loses its prognostic power within 2 postoperative years, while morphometric nuclear factors and histological grade have no practical prognostic value after 1 year of follow-up.

Breast Neoplasms↗

PubMed1992

DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer.

Clinical features, 8 histological variables, 7 nuclear morphometric variables, 2 mitotic indices, oestrogen-receptor (ER) and progesterone-receptor content (PR), DNA ploidy and S-phase fraction (SPF) were entered in a Cox's model to assess their independent predictive value in 216 breast-cancer patients followed up for over 9 years. In the whole series, histological type (p = 0.007), volume-corrected mitotic index (M/V index) (p = 0.01), axillary-lymph-node (pN) status (p = 0.024) and the year of treatment (p = 0.045) predicted independently the recurrence-free survival (RFS). In a sub-analysis including SPF (n = 148), the year of treatment (p = 0.003), tumour diameter (p = 0.004), SPF (p = 0.022) and nuclear pleomorphism (p = 0.056) independently predicted the RFS. In a Cox's analysis of the whole series, tumour diameter (p less than 0.001), pN status (p = 0.001), PR status (p = 0.002) and the year of treatment (p = 0.021) were independent predictors of survival. In a separate analysis including also SPF (n = 148), tumour diameter (p less than 0.001), SPF (p = 0.003), pN status (p = 0.008) and the year of treatment (p = 0.015) proved to be independent prognostic factors. The results show that tumour diameter, pN status, M/V-index, histological type, SPF and PR status comprise a sufficient combination of prognostic factors in female breast cancer. In pN patients, age and SDPE may be of additional prognostic significance. The prognostic scores combining the independent prognostic variables reflecting both the proliferative rate and metastatic potential of the tumours are accurate predictors of the RFS and overall survival.

Adult↗

PubMed1992

Mitotic indexes as prognostic predictors in female breast cancer.

A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, axillary lymph node status, histological grade, histological type and two mitotic indexes (M/V; MAI) were assessed and related to disease outcome. Primary tumour size (P less than 0.0001), the volume-corrected mitotic index (M/V) (P less than 0.0001), the mitotic activity index (MAI) (P = 0.0001), and histological grade (P = 0.0074) predicted axillary lymph node status. Recurrence as well as recurrence-free survival was significantly related to the axillary lymph node status (P less than 0.0001), M/V index (P less than 0.0001), MAI (P less than 0.0001), tumour size (P = 0.0031) and histological grade (P = 0.0208). Multivariate analyses disclosed the tumour size and M/V index as independent predictors of axillary metastasis at diagnosis. Recurrence was related independently to M/V index, axillary metastasis and tumour size. Independent predictors of recurrence-free survival in Cox's analysis were M/V index and axillary lymph node status. Axillary lymph node status (P less than 0.0001), tumour size (P less than 0.0001), M/V index (P less than 0.0001), MAI (P less than 0.0001) and histological grade (P = 0.0009) predicted survival in that order. Cox's analysis showed that axillary lymph node status was the most important independent predictor of survival followed by tumour size and M/V index. In a separate Cox's analysis of axillary-lymph-node-negative patients the M/V index and tumour size were independently related to survival. In conclusion the M/V index is an important prognostic factor in breast cancer and also in axillary-lymph-node-negative breast tumours.

Breast Neoplasms↗

PubMed1992

Lymphocyte infiltrates as a prognostic variable in female breast cancer.

The predictive value of lymphocyte infiltrates (LI) was studied in 489 patients with breast cancer followed-up for over 10 years. LI were positively correlated to axillary lymph-node status, tumour diameter and histological and morphometric variables (P less than 0.001). In a multivariate analysis LI were independently related to axillary lymph-node status. LI predicted recurrence-free survival (RFS) in rapidly proliferating tumours (P = 0.0269). LI predicted RFS (P = 0.08) and breast cancer related survival (BS) (P = 0.0164) in rapidly proliferating, axillary lymph-node negative tumours. In a multivariate analysis LI independently predicted BS (P = 0.08) in rapidly proliferating tumours. LI independently predicted BS in rapidly (P = 0.025) and slowly (P = 0.09) proliferating, axillary lymph-node negative tumours. If the tumours were not categorised according to proliferation rate, LI and outcome were not significantly related. The results clearly confirm the presence of efficient immunological antitumour defence mechanisms in human breast cancer. Consequently tumour-host interactions are subject to further studies particularly in axillary lymph-node negative breast cancer.

Aged↗

PubMed1992

Tumor size, nuclear morphometry, mitotic indices as prognostic factors in axillary-lymph-node-positive breast cancer.

The biopsy specimens from the primary tumors of 234 women with axillary-lymph-node-positive breast carcinomas (followed up for a mean of 10.9 years) were subjected to interactive morphometric analysis of nine nuclear factors. The proliferative activity of the tumors was estimated by determining two different mitotic indices. Morphometrically determined nuclear factors and mitotic indices showed a significant correlation to the histological grading (p less than 0.0001). Mitotic activity index (MAI; p = 0.018) and volume-corrected mitotic index (M/V index; p = 0.005) accurately predicted the tumor recurrence. Recurrence-free survival was related to the M/V index (p = 0.0003), MAI (p = 0.0024) and tumor size (p = 0.0144). Disease-related survival was determined by the tumor size (p less than 0.0001), M/V index (p = 0.0142) and MAI (p = 0.0492) in that order. On the other hand, the nuclear factors analyzed and the histological grading used had no predictive value (i.e. tumor recurrence, recurrence-free survival or tumor-related survival) in these women. The results indicate that mitotic indices can be successfully applied in place for subjective grading and nuclear morphometry in predicting the disease outcome in patients with axillary-lymph-node-positive breast carcinomas. The mitotic indices provide independent prognostic information in addition to tumor size. The major clinical implications of these results would be to accurately disclose among these women the high-risk patients (i.e. those with high mitotic indices), who might benefit from more agressive adjuvant therapies.

Axilla↗

PubMed1992

Histological assessment of the prognostic factors in female breast cancer.

Paraffin-embedded biopsy specimens from the primary breast carcinoma of 653 women were subjected to histopathological assessments of the potential prognostic factors. Histological type, histological grade, nuclear pleomorphism, tubule formation, intraductal growth pattern, tumour margin circumscription, tumour necrosis and inflammatory cell reaction were semiquantitatively analysed with special reference to disease outcome during the mean follow-up 12.8 years. Histological grade, nuclear grade and inflammatory cell reaction were related to axillary lymph node involvement at operation (p less than 0.001). Intensity of the inflammatory cell reaction was directly correlated to histological grade, histological type, nuclear pleomorphism and tumour necrosis (p less than 0.001). Tubule formation and tumour necrosis were significant predictors for tumour recurrence. Recurrence-free survival was related to tubule formation (p = 0.0048), histological grade (p = 0.0208) and intraductal growth pattern (p = 0.0441). Tubule formation accurately predicted the recurrence-free survival in axillary lymph node-negative tumours (p = 0.0386). In small (diameter less than or equal to 20 mm) axillary lymph node-negative tumours, the inflammatory cell reaction (p = 0.0377) as well as intraductal growth pattern (p = 0.0632) were related to recurrence-free survival. Cancer-related patient survival was predicted in decreasing order of significance by tubule formation (p = 0.0002), nuclear pleomorphism (p = 0.0010), intraductal growth (p = 0.0077), tumour necrosis (p = 0.0117) and histological type (p = 0.0651). In axillary lymph node-negative tumours, tubule formation (p = 0.0409), inflammatory cell infiltration (p = 0.0790) and intraductal growth (p = 0.0958) predicted the cancer-related survival. The results indicate that despite an intense search for a diversity of prognostic factors by increasingly sophisticated techniques (e.g., morphometric measurements, flow cytometry, immunohistochemistry, and DNA hybridization techniques), the relatively simple light microscopic assessment of the above morphological features seems to be still advocated in predicting the disease outcome in female breast cancer.

Adult↗

PubMed1992

Prognostic factors after 5 years follow-up in female breast cancer.

A consecutive series of breast carcinomas (n = 595) followed up for a minimum of 7.5 years was analyzed for clinical, histological and morphometric prognostic factors after 5-years' follow-up. Tumor size, nodal status, mitotic frequency and patients' age at diagnosis predicted survival at 7.5 years highly significantly (p less than 0.0001). Tubule formation (p = 0.002), histological grade (p = 0.026) and nuclear pleomorphism (p = 0.046) were related to prognosis as well. In N--patients mitotic frequency (p = 0.018) was the best predictor of survival at 7.5 years whereas in N + tumors tumor size (p = 0.0013), tubule formation (p = 0.003) and mitotic frequency (p = 0.0049) were the best predictors of survival at 7.5 years. In univariate survival analysis the age of the patients (p = 0.002), tubule formation (p = 0.005), axillary lymph node status (p = 0.008), lymphocyte infiltration (p = 0.049), mitotic frequency (p = 0.06) and tumor size (p = 0.08) predicted survival after 5 years' follow-up. Tubule formation predicted survival (p = 0.025) in N - patients and in N + tumors the age of the patients was the most important predictor (p = 0.006). In Cox's analysis tubule formation (p = 0.13), axillary lymph node status (p = 0.033), SD of nuclear perimetry (p = 0.046) and intraductal growth (p = 0.059) predicted survival independently after 5 years' follow-up.

Age Factors↗

PubMed1992

Xanthogranuloma juvenile--a rare cause of orbital swelling in adulthood.

Juvenile xanthogranuloma, a non-Langerhans-type benign proliferation, in adulthood is a rare condition. This article reports the second known case in the western literature of solitary orbital involvement. The diagnosis was confirmed by orbital biopsy, and symptoms were dramatically relieved by corticoids, although a relapse occurred after their withdrawal. The importance of differentiating benign conditions from malignancies is discussed.

Edema↗

PubMed1992

Prediction of outcome after first recurrence of breast cancer.

OBJECTIVE: To assess the independent power of certain clinical, histological, and morphometric variables to predict survival after first recurrence of breast cancer. DESIGN: Long term follow up study. SETTING: Departments of surgery and pathology, University Hospital. SUBJECTS: 212 patients (from a consecutive series of 517) who developed recurrence after primary treatment of breast cancer between 1968 and 1990. INTERVENTIONS: Re-examination of histology of primary tumours, follow up of patients, and calculation of predictive score by Cox's regression analysis. RESULTS: The nodal status at the time of diagnosis (p less than 0.001), the SD of the nuclear area (p = 0.01), the degree of tubule formation (p = 0.003), and the age of patient, were all independent predictors. The most important predictor of survival was the prognostic score derived from the coefficients of the Cox's model (p less than 0.0001). CONCLUSION: Survival after first recurrence can be accurately predicted by advanced histological analysis of the primary tumour tissue. Combination of independent predictors permits even more accurate estimation of survival time.

Breast↗

PubMed1992

Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast cancer.

OBJECTIVE: To evaluate the predictive value of traditional prognostic factors, nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN: Open study. SETTING: One university hospital in Finland. SUBJECTS: 248 women with invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES: Univariate and multivariate analysis of factors thought to indicate prognosis. RESULTS: Diameter of the tumour, lymph node status, S phase fraction. DNA index, the age of the patient, and the SD of nuclear perimeter were significant independent predictors in the whole series in a multivariate analysis. In node negative patients the SED of the nuclear perimeter and diameter of the tumour had independent prognostic value, whereas in node positive patients diameter of the tumour and the S phase fraction were independently related to survival. CONCLUSIONS: Diameter of the tumour is an important prognostic factor in breast carcinomas. Histoquantitative methods are superior to conventional histological techniques for the prediction of outcome in women with breast cancer.

Adult↗

PubMed1992

Primary malignant schwannoma of the small bowel.

Primary malignant schwannoma of the small intestine is an extremely rare disease. We report a primary malignant intestinal schwannoma of the small bowel in a 66-year-old woman, who was admitted to the hospital because of fatigue and anaemia. On clinical examination there was a solid mass at the abdomen. Ultrasound scanning showed an abdominal tumour. Computed tomography showed a mass in the area of the pancreatic tail involving the small intestine. At laparotomy a 10 x 10 cm tumour was found in the proximal jejunum, and 50 cm of the small intestine was resected. The histology of the lesion corresponded to a malignant intestinal schwannoma. The results of previous studies and of our report suggest that the diagnosis of malignant intestinal schwannoma may be difficult, and to exclude malignant conditions laparotomy and surgical excision of the tumour are adequate in the management of this type of lesion.

Aged↗

PubMed1991

Prognostic scores combining clinical, histological and morphometric variables in assessment of the disease outcome in female breast cancer.

Clinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a Cox's model to assess their independent predictive power in a series of 517 breast cancer patients followed up for over 10 years. The volume-corrected mitotic index (M/V index) (p less than 0.001), axillary lymph-node status (p = 0.002), the shortest nuclear axis (p = 0.006) and the degree of tubule formation (p = 0.02) predicted independently the recurrence-free survival. In N- tumours (n = 293), the M/V index (p = 0.005), the degree of tubule formation (p = 0.016) and tumour size (p = 0.023) were independent prognostic predictors, whereas in N+ tumours (n = 224), only the M/V index (p = 0.004) and the maximum nuclear axis (p = 0.004) had independent prognostic value. The corrected survival was predicted independently by the axillary lymph-node status, degree of tubule formation, M/V index, tumour size (p less than 0.001), age (p = 0.002) and year of treatment (p = 0.008). In N- tumours, the degree of tubule formation (p = 0.005) and intraductal growth pattern (p = 0.015) exhibited independent predictive value. In N+ tumours, patient survival was related to the M/V index (p less than 0.001), tumour size (p = 0.005) and patient age (p = 0.005). The results show that the assessment of the M/V index, axillary lymph-node status, tumour size, intraductal growth pattern and tubule formation are reliable factors in predicting the prognosis of breast cancer. The conventional mitotic activity index (MAI) and histological grading should be replaced by the M/V index in histological assessment of malignancy in breast cancer. The prognostic scores combining the independent variables reflecting the proliferative rate and metastatic potential of the tumours are more accurate predictors of the recurrence-free survival and overall survival (p less than 0.0001) than the single variables used alone.

Breast Neoplasms↗

PubMed1991

Urinary excretion of ethylenethiourea and kidney morphology in rats after continuous oral exposure to nabam or ethylenethiourea.

Nabam, an ethylenebisdithiocarbamate (EBDC), is an agricultural fungicide. Ethylenethiourea (ETU), widely used in the rubber industry, is a degradation and byproduct of metabolism and of storage and production of EBDCs. Kidney function and morphology, and urinary excretion of ETU, were studied in rats exposed to nabam or ETU in drinking water for 28 days. The concentrations of nabam in drinking water were 0, 50, 100 or 200 mg/l, and of ETU 0, 100, 200 or 300 mg/l. Both compounds decreased body weight gain but did not significantly affect urinary sodium, potassium, glucose, or protein excretion, or urinary osmolality. Urinary vasopressin was also unaltered after exposure to nabam or ETU. High doses of ETU resulted in ultrastructural alterations in epithelial cells of renal proximal tubuli. ETU was excreted in urine after exposure to both nabam and ETU. There seemed to be a threshold dose of ETU below which no ultrastructural alterations in kidney occurred.

Administration, Oral↗

PubMed1991

Mesenchymoma of the chest wall in children.

Benign chest wall mesenchymoma in children is an extremely rare disease. Only 20 patients have been reported in the world literature. We report a chest wall mesenchymoma in a 2-year-old boy who was admitted to the hospital after a routine chest roentgenogram showed a mass in the right upper chest wall. The patient was asymptomatic. Clinical examination was negative, but chest roentgenograms and computed tomography showed a mass in the right upper chest wall involving the third rib. A 2 x 2 x 1.5-cm tumor was excised totally with partial resection of the third rib. The histology of the lesion corresponded to a mesenchymoma (hamartoma) of the chest wall. Our patient has been followed up for 8 years without recurrence.

Bone Neoplasms↗

PubMed1991

Prognostic factors in axillary lymph node-negative (pN-) breast carcinomas.

Axillary lymph node-negative (pN-) breast carcinomas (n = 281) were analysed histoquantitatively for two mitotic indexes (MAI, mitotic activity index; M/V, volume corrected mitotic index) and nine nuclear factors with special emphasis on disclosing prognostic factors during a follow-up of 12 years. The M/V index (P = 0.0018), tumour size (P = 0.0052), MAI (P = 0.0115) and histological grade (P = 0.0565) predicted the recurrence-free survival. MAI (P = 0.0007), M/V index (P = 0.0046), tumour size (P = 0.0133), histological grade (P = 0.0528) and S.D. of the nuclear perimetry (P = 0.07) predicted the disease-related survival. In Cox's analysis, MAI (P = 0.004), adjuvant therapy (P = 0.03) and tumour size (P = 0.09) predicted survival independently. Recurrence-free survival was related independently to nuclear perimetry (P less than 0.001), SD of nuclear area (P = 0.01) and MAI (P = 0.019) in Cox's analysis. In small (diameter less than or equal to 20 mm) tumours, S.D. of nuclear perimetry predicted recurrence-free survival (P = 0.03) in Cox's analysis. The results advocate the use of mitotic indexes and nuclear factors in place or in combination with conventional histological grading in predicting the survival and tumour recurrence in axillary lymph node-negative breast carcinomas.

Breast Neoplasms↗

PubMed1991

Dithranol (anthralin)-induced skin irritation in C57BL/6, NMRI and SENCAR mice.

Dithranol-induced skin irritation was compared in C57BL/6, NMRI and SENCAR mice, the strains representing different sensitivity to tumour promotion. Skin irritation was assessed using ear thickness and skin weight measurements, visual estimation of back skin irritation and histopathology. Both single and repeated applications of dithranol caused a delayed skin irritation resulting in the maximal response between 7-11 days after the beginning of the treatment. Contrary to the findings with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), C57BL/6 mice were the most sensitive and SENCAR mice the most resistant to the dithranol-induced skin irritation up to 30 days from the beginning of the treatment. NMRI mice were intermediate. Differences were found in the ear swelling, epidermal hyperplasia, amount of inflammatory cell infiltrate and skin ulceration. During repeated treatment of about 40 days, however, the responsiveness of SENCAR mice increased over that of C57BL/6 and NMRI mice. SENCAR mice had also more epidermal hyperplasia than the other strains at the end of the 74 day period of 3 times weekly applications. The magnitude of epidermal hyperplasia after long term treatment seems to correlate with the sensitivity to tumor promotion in the different mouse strains.

Animals↗