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R Jakesz

Publications and source records attributed to R Jakesz.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Primary (preoperative, neoadjuvant) chemotherapy of colon cancer--a therapeutic alternative?].

Primary chemotherapy is an established treatment in selected patients with osteosarcoma and locally advanced breast cancer. In several other tumor entities this therapeutic approach is under clinical investigation. In contrast, colon carcinoma has been believed to be chemoresistant for a long period of time. Thus, no therapeutic approaches dealing with preoperative therapy have been initiated yet. Recent studies showing remission rates as high as 40% in advanced colon cancer and the proof of efficacy for postoperative adjuvant chemotherapy must now lead to reevaluation of the therapeutic approach to this tumor entity. Data from animal models as well as several tumor biologic hypotheses also point to a possible advantage for preoperative therapy in order to ameliorate relapse-free survival and overall survival in these patients. In this work we discuss potential advantages and disadvantages of primary, neoadjuvant strategies of treatment for colon cancer. Based on these pros and cons, clinical studies for a preoperative therapeutic approach appear to be justified and necessary in patients with locally advanced disease and in patients with metastases at the time of diagnosis.

Antineoplastic Agents↗
PubMed1993

Aneuploidy fraction but not DNA index is important for the prognosis of patients with stage I and II breast cancer--10-year results.

BACKGROUND: Individual assessment of the prognosis of patients with breast cancer is crucial for the selection of risk-adapted adjuvant therapy and in follow-up. Parameters from DNA flow-cytometry have been shown to provide significant prognostic information, but published results are in conflict and there are only a few investigations with long-term follow-up. The aim of this study is to clarify the impact of tumor DNA data on the clinical course of stage I and stage II breast cancer patients. PATIENTS AND METHODS: Several flow-cytometry DNA analyses were performed on tumor samples derived from 191 breast cancer patients entered in a controlled clinical trial after a median follow-up of more than 10 years. In addition to DNA index (DNI) and the percentage of cells in S phase (SPF), an index, designated aneuploidy fraction (AF), was determined. It ascertains the percentage of aneuploid cells out of all cells in the DNA flow-cytometry histogram, and its reproducibility has been tested by measurements of AF in two different samples of the same tumor. Univariate analyses and, in the 122 patients for whom complete information was available, a Cox model, were performed to investigate the individual prognostic impact of flow-cytometry parameters compared with established clinical factors. RESULTS: AF proved to be a very valuable prognostic indicator both in univariate and multivariate analyses, whereas DNI and SPF failed to provide independent prognostic information. The combination of AF and lymph node status clearly identifies different prognostic subgroups in operable breast cancer. CONCLUSIONS: Routine evaluation of patients with breast cancer should include tumor DNA flow-cytometry. Aneuploidy fraction is a valuable tool in assessing an individual patient's prognosis and thus can help in the choice of the appropriate adjuvant treatment strategy. Whether it, rather than DNI and SPF should be used, as we found, needs to be validated in a larger prospective investigation.

Aged↗
PubMed1993

GM-CSF in the treatment of a patient with severe methotrexate intoxication.

This case report describes the successful treatment of severe methotrexate intoxication in a 72-year-old female patient. Following two prior uneventful courses of a polychemotherapy regimen including low-dose intravenous (i.v.) methotrexate, the patient presented with fever, polymucositis, incipient pyodermia, acute renal failure and pancytopenia 9 days after the third application. Severe methotrexate overdose was confirmed by serum levels. Using a polypragmatic treatment approach focusing on renal function and including granulocyte-macrophage-colony-stimulating factor (GM-CSF) this life threatening and nearly fatal intoxication was successfully treated. This case report demonstrates that GM-CSF might contribute to rapid reconstitution of leukopoiesis once methotrexate serum levels are in the subtoxic range.

Acute Disease↗
PubMed1992

Breast cancer and timing of surgery during menstrual cycle. A 5-year analysis of 385 pre-menopausal women.

It has been proposed that the timing of breast-cancer surgery in relation to menstrual phase has a prognostic impact on outcome. We carefully evaluated a combined 2-center series of 385 pre-menopausal women operated on for stage-I and stage-II breast cancer with a median follow-up of 5 years for a possible impact on outcome of the date of their last menstrual period (LMP) before surgery. The distribution of risk factors of the study cohort as well as prognostic indicators corresponded to previously published results. Nodal status, grading, and (in part) hormone-receptor status differentiate well between patient subgroups with high and low risk of relapse and death after breast-cancer surgery. In neither univariate nor multivariate analysis was any impact of the so-called "unopposed" estrogen secretion detected. We did not observe any effect of LMP on long-term survival in any of several prognostic subgroups, in particular in hormone-receptor-positive patients. From our results and from the literature, we conclude that LMP does not provide any prognostic information for outcome after breast-cancer surgery and therefore the proposed modification of scheduling of breast-cancer operations is not justified.

Age Factors↗
PubMed1992

Expression of p43 in breast cancer tissue, correlation with prognostic parameters.

Placental isoferritin (PLF) and its unique superheavy chain p43 have been recently described as being synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue and the degree of differentiation and prognosis, we have determined p43 in the cytosol of 122 breast cancer samples by use of the new monoclonal antibody CM-H-9. The synthesis of p43 showed a significantly negative correlation with tumor size (P = 0.0001), histologic grading (P = 0.0038), nuclear pleomorphism (P = 0.0019), rate of mitosis (P = 0.0002), lymphocytic reaction (P = 0.0001) and a significantly direct correlation with estrogen receptor status (P = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multiple Cox model. Therefore it seems that p43's prognostic impact is linked to the highly significant correlation with features of differentiation although a statistical bias in the Cox model due to the limited number of patients must also be taken into account. On the other hand, the significant correlation of p43 expression with factors for good prognosis was striking and consistent and warrants further research of this tumor product.

Breast Neoplasms↗
PubMed1992

Placental isoferritin associated p43 antigen correlates with features of high differentiation in breast cancer.

Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain p43 have been recently described to be synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue, degree of differentiation, and prognosis, we have tried to evaluate the correlation of p43 in the cytosol of 122 breast cancer samples with commonly applied prognostic factors and features of proliferation and differentiation. In parallel, we investigated the correlation of p43 expression in MCF-7 and T47-D breast cancer cell lines during proliferation induced by estradiol plus fetal calf serum (assessed by 3H-thymidine incorporation), compared to p43 expression in stationary non-stimulated cell cultures. The levels of p43 in breast cancer cytosols correlated significantly negatively with tumor size (p = 0.0001), histologic grading (p = 0.0038), nuclear pleomorphism (p = 0.0019), rate of mitosis (p = 0.0002), and lymphocytic reaction (p = 0.0001), and significantly directly with the estrogen receptor status (p = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multivariate Cox model. In accordance with the observed negative correlation of features of differentiation vs. p43 expression, induction of proliferation by estradiol plus FCS added to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. Expression of p43 in estrogen and FCS-absent media revealed also a decrease in relation to a low spontaneous proliferation. However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen-stimulated proliferation. Our in vitro and cytosol results confirm recent clinical observations describing an inverse correlation of p43 synthesis with the degree of proliferation and differentiation in breast cancer. However, the pathologic mechanisms leading to this phenomenon as well as the negative correlation with lymphocytic infiltration are still unclear and need to be further elucidated.

Breast Neoplasms↗
PubMed1992

DNA ploidy and other results of DNA flow cytometry as prognostic factors in operable breast cancer: 10 year results of a randomised study.

We evaluated breast cancer specimens from 241 patients of a controlled clinical trial by means of DNA flow cytometry. We report the correlations between DNA index (DNI) and fraction of cells in S-phase (SPF) and other prognostic parameters. Both univariately and in a Cox model, the predictive power of these factors is evaluated after a follow-up of more than 10 years. There are strong correlations between DNI and SPF (P = 0.0001) and between flow cytometry parameters and clinical and histopathological factors such as axillary lymph node involvement, tumour size and histological grade. In univariate analysis DNI fails to provide prognostic information, whereas SPF turns out to be able to differentiate between patients at high and low risk for relapse and death (P = 0.002). In the multivariate Cox model, too, SPF is an important prognostic parameter with respect to patient survival (relative risk: +86%), only surpassed by nodal involvement. DNI, however, turns out to be an independent predictor of relapse free survival and distant recurrence free survival. By combination of DNI and SPF, patients can be divided into three prognostic subgroups. We conclude that data from DNA flow cytometry can be of great importance for the decision on the level of aggressiveness of adjuvant therapy for an individual patient and therefore may help to avoid overtreatment and toxicity.

Adult↗
PubMed1992

[Epidermal growth factor receptor in human breast cancer: correlation with steroid receptors, tumor stage, grading and menopausal status].

In this study, correlations between the epidermal growth factor receptor (EGF-R), steroid receptors, and other prognostic parameters (grading, pTNM-status, menopausal status) were analysed in 326 primary breast carcinomas. 19% of the tumour samples were EGF-R positive, 63% were estrogen receptor (ER) and 54% progesteron receptor (PR) positive. Both steroid receptors were positive in 46% of all samples. We found a highly significant inverse correlation between EGF-R and steroid receptors. 88% of the ER positive tumours were EGF-R negative (p less than 5 x 10(-5)), 90% of the PR positive tumours were EGF-R negative (p less than 5 x 10(-5)) and 91% of the ER plus PR positive tumours were ERF-R negative (p less than 1 x 10(-6)). Grading was available in 170 cases. Six (4%) of the carcinomas were highly differentiated (G1), 82 (48%) were classified as G2, and another 82 (48%) were poorly differentiated (G3). A combination of negative ER and positive EGF-R was found more often in the population of G3 tumours. EGF-R was also positively correlated to tumour size. With regard to receptor status, we did not find a correlation with lymph node involvement. The ER correlated negatively (p less than 1.3 x 10(-5) and the EGF-R positively (p less than 0.042) with menopausal status. Thus, EGF-R overexpression seems to be a marker of morphological and functional dedifferentiation which is associated with a loss of steroid dependency and an increase of an autostimulatory-paracrine growth control. These changes seem to be related to poor prognosis.

Breast↗
PubMed1992

[Differential prognosis of patients with breast cancer with pleuritis carcinomatosa and with pulmonary lymphangiosis carcinomatosa].

The retrospective analysis of 672 consecutive patients with breast cancer revealed malignant pleural effusion and lymphangitic carcinomatosis of the lung to be the sites of first relapse of the disease in only 2% and 1%, respectively. In half of the 10 patients with malignant pleural effusions evaluable for survival, generalization of the disease was recorded at 51 months (range 0-197 months); the corresponding data for patients with lymphangitic carcinomatosis of the lung (n = 7) were 19 months (range 9-44 months). This difference was statistically significant (p < 0.05). The median survival of patients with pleural effusions and with lymphangitic carcinomatosis of the lung was 22 and 8 months, respectively (n.s.).

Adult↗
PubMed1991

[Steroid hormone receptors in mammary carcinoma. Immunohistochemical detection and prognostic significance].

Estrogen and progesterone receptors were immunohistochemically recorded from 426 cases of primary mammary carcinoma. Immunohistochemical detection was based on monoclonal antibodies to estrogen receptor (H222) and progesterone receptor (KD68). Immunohistochemical and biochemical tests were correlated to each other with significance (p less than 0.0001) for either receptor. Some of the histological parameters exhibited relationships with the immunohistochemical receptor status. Receptor positivity of lobular, mucoid, tubular, and papillary carcinomas was more frequent than that of ductal carcinoma, whereas that of medullary carcinoma fell below ductal cases. A straight forward correlation of statistical significance was found to exist between histological tumor grade and steroid hormone receptor status. Receptor positivity of carcinomas with sizeable stroma components proved to be more frequent than that of carcinomas with lower stroma levels. Steroid hormone receptors can be immunohistochemically identified from cytological specimens, as well, though some limiting factors are implied in the latter. Thirteen percent of fine-needle aspirates provided falsely negative steroid hormone receptor findings, as compared to histological biopsy. This problem was encountered primarily in cases of low receptor positivity and high stroma content of carcinoma, factors for which only minor amounts of cell material could be obtained from puncturing. Clinical follow-up checks and evaluation of survival data revealed the immunohistochemically determined steroid hormone receptor status to be of significant importance to prognostication (ER-ICA p less than 0.00001; PgR-ICA p = 0.004). The prognosis of patients with negative estrogen and progesterone receptors was found to be worse than that of patients with positive receptor status. These studies are likely to confirm immunohistochemical determination of steroid hormone receptors, using monoclonal antibodies, to be a reliable method of great prognostic importance.

Adenocarcinoma↗
PubMed1991

[Current status of adjuvant therapy in patients with colorectal cancer: report and commentary on the Consensus Conference, 16-18 April 1990, National Cancer Institute, Bethesda, Maryland].

This is a report on the Consensus Development Conference on adjuvant therapy for patients with colorectal carcinoma, which was held at the National Cancer Institute of the National Institutes of Health (NIH) in Bethesda, Maryland between April 16th and 18th 1990. Based on statistically significant results of a clinical trial adjuvant therapy with 5-fluorouracil (5-FU) and levamisole was recommended outside controlled clinical studies for patients with Dukes C colon carcinoma, but because no optimal form of adjuvant therapy yet exists there is still the need for further trials. No recommendations were given for patients with Dukes B colon carcinoma. For patients with Dukes B + C rectal cancer combined radiation therapy and 5-FU-based chemotherapy was considered "standard therapy" according to the consensus panel, but this recommendation seems to be still worth discussing. Since there is need of further evaluation of newly-recognized prognostic factors and also to optimize adjuvant strategies the panel stated that further prospective randomized studies are warranted. Hence, the establishment of a multicentre study group also in Austria appears to be an essential application of such trials in order to contribute towards ameliorating the prognosis of patients with colorectal carcinoma.

Colorectal Neoplasms↗
PubMed1990

Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer.

An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.

Adult↗
PubMed1990

[Importance and problems of intraperitoneal chemotherapy].

Intraperitoneal chemotherapy for prophylaxis and treatment of peritoneal carcinosis is a new treatment modality. Due to a very difficult definition of remission for peritoneal carcinosis, results of this treatment modality are difficult to state. The total remission rates are currently between 30 and 50% in minimal residual disease. The major advantage of intraperitoneal chemotherapy is the augmentation of the local concentration of the cytotoxic agent which exceeds the serum level in some cases by a factor of 1000. Due to totally implantable systems the high risk of infection in patients with Tenckhoff catheters could be reduced to nearly zero. After perfusion of the peritoneal cavity with a cytotoxic agent the concentration in the portal vein can exceed that in the peripheral blood by a factor of 10. Results of two adjuvant trials could not show a survival benefit of treated patients, however the incidence of peritoneal carcinosis was significantly decreased. New treatment options are a perfusion of the peritoneal cavity with effective cytotoxic drugs in the very early postoperative time period. The combined treatment of cytostatics and "biological response modifiers" could further increase the effectiveness of this treatment modality.

Antineoplastic Agents↗
PubMed1990

[Breast cancer in the male. A long-term follow-up study of 55 patients].

Between 1964 and 1988, 55 male patients were treated for breast cancer. Fifty-one patients were treated by radical mastectomy; only four patients underwent a simple mastectomy. Nineteen cases received postoperative radiotherapy, eleven cases chemotherapy, six cases adjuvant hormonal therapy, and one patient was submitted to orchiectomy. The five-year survival rate for tumors with nodal metastases was 37%, as compared with 57% for patients with negative nodes.

Adult↗
PubMed1990

HER-2 oncogene amplification and overall survival of breast carcinoma patients.

DNA was extracted from tumour samples of 77 patients with primary breast carcinoma and HER-2 proto-oncogene amplification was assessed. Prognostic indices such as number of positive lymph nodes, tumour size and histological grading were strongly associated with overall survival. No statistically significant correlation between amplification of HER-2 and overall survival was observed. In addition, prognostic indices, HER-2 amplification and disease-free interval was not correlated. Analysis of HER-2 amplification alone is not a useful guide in the management of patients with mammary carcinoma.

Breast Neoplasms↗
PubMed1990

[Interstitial radiotherapy of breast cancer. Preliminary report of a prospective study of 165 cases subjected to breast-conserving treatment].

UNLABELLED: The results of a prospective study on breast conserving therapy in early stage breast cancer are presented. From January 1983 to June 1987 165 patients were treated by a standardized therapy-protocol. The criteria for entering the trial were stage T1 to T2 and N0 to N1. Surgical breast conservation was achieved by segmental resection in 148 cases and by tumorectomy in 17 cases. 160 patients underwent axillary lymph node dissection. Obligatory 45 to 50 Gy were delivered percutaneously to the operated breast and optional 50 Gy to the regional lymph nodes (axillary lymph node involvement greater than 3 nodes). In addition, the area of the primary breast lesion itself was boosted interstitially by an Iridium 192 implant (LDR-technique: 15 to 20 Gy, HDR-technique: 10 to 12 Gy). RESULTS: Progression of disease in 10% of the patients (16/165), local recurrence rate in the operated breast: 2% (3/165), axillary recurrence: 0.5% (1/165). 5% of the patients (8/165) died from metastatic disease, two patients died free of recurrence for reasons unrelated to cancer, two other patients died on unknown reasons. Because of the low number of local recurrences and the observation period of 32 months, no statistically contribution on high risk factors for local failure could be found.

Adult↗