Biomedical subjects

M Gnant

Publications and source records attributed to M Gnant.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Indications and contraindications for breast preservation in patients with breast cancer].

Roughly 70% of all patients with breast cancer can be treated by breast-preserving procedures under optimal circumstances. Risk factors for the development of local recurrences are age, angioinvasion, poor differentiation of the tumor, negative steroid hormone receptors, extensive intraductal component and positive margins. Contraindications for breast preservation are large tumors without remission after preoperative chemotherapy, multicentricity, extensive intraductal component, large ductal carcinoma in situ, inflammatory breast cancer after preoperative chemotherapy, Paget disease and local recurrence after breast-conserving surgery. Preoperative needle biopsy allows determination of nearly all of the risk factors. To further increase the rate of breast conservation, preoperative chemotherapy should be used more extensively.

Breast Neoplasms↗

PubMed1999

Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients. Austrian Breast Cancer Study Group.

The aim of our study was to evaluate if p53 mutations, especially those in the L2/L3 domains of the p53 gene, add prognostic information for node-positive and steroid receptor positive breast cancer patients. Two hundred and five tumour samples from a randomised clinical trial of 596 lymph node- and steroid receptor positive breast cancer patients were included. All patients had been randomly allocated to receive 20 mg of adjuvant tamoxifen (TAM) daily for 2 years or TAM plus one cycle of low-dose, short-term chemotherapy. For detection of p53 mutations we used in vitro amplification by polymerase chain reaction and consecutively performed temperature gradient gel electrophoresis (PCR-TGGE) and direct sequencing. We found p53 mutations in 42/205 (20%) cases: 16/42 (38%) p53 mutations occurred within the L2/L3 domains of the p53 gene, and 26/42 (62%) outside the L2/L3 domains. p53 mutation served as a statistically significant parameter in predicting disease-free survival in univariate (P = 0.02) and multivariate (P = 0.009) analysis. For overall survival, no significant differences were observed. Patients with tumours that had p53 mutations within the L2/L3 domains of the gene showed no significant difference to those with mutations outside the L2/L3 domains for disease-free survival. For overall survival, mutations in the L2/L3 domains showed a marginally significant difference (P = 0.05) in multivariate analysis, but not in univariate analysis (P = 0.13). We conclude that mutation in the L2/L3 domains of the p53 gene is not an independent prognostic indicator of disease outcome for patients suffering from breast cancer with lymph node metastases and positive steroid receptors.

Adult↗

PubMed1999

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Age Factors↗

PubMed1998

Outcomes of surgical, percutaneous endoscopic, and percutaneous radiologic gastrostomies.

OBJECTIVES: To evaluate and compare outcomes and complications in patients having undergone gastrostomy by surgical (SG), percutaneous endoscopic (PEG), or percutaneous radiological (PRG) procedure. DESIGN: Retrospective analysis. SETTING: University-based tertiary care center. PATIENTS: Of 82 patients who met inclusion criteria, 14 patients (median age, 40 years) received a surgical tube placement (SG), in 24 patients (median age, 55 years) a PEG procedure was performed, and in 44 patients (median age, 57 years) the tube was placed under fluoroscopic guidance (PRG). Indications for gastrostomy were similar in all groups, representing mainly cancer of the oropharyngeal, head and neck region (51 [61%]) as well as the upper gastrointestinal tract (6 [8%]), neurological disorders (15 [18%]), and others (10 [13%]). MAIN OUTCOME MEASURES: Catheter function rates, major and minor procedure-related complications, and survival. RESULTS: Median follow-up was 17.2 months. Ten patients (71%) died in the SG group 7 to 855 days (median, 67 days) after the procedure, 7 patients (29%) died 5 to 263 days (median, 103 days) after PEG placement, and 30 patients (68%) died within 3 to 621 days (median, 112 days) after PRG, of their underlying disease or disease-related complications; 1 procedure-related death occurred 6 days after radiological tube placement. We observed a rate of minor complications of 43% (6 patients), 33% (8), and 36% (16) and a major complication rate of 14% (2 patients), 17% (4), and 11% (5) in the SG, PEG, and PRG groups, respectively. Tube function rates at 1 year were 67% (9 patients) and 68% (20) in the SG and PEG groups, respectively, and 10% lower (39) in the PRG group, although the difference was not statistically significant. CONCLUSIONS: There is no major difference between SG, PEG, and PRG concerning procedure-related complications. Tube function tends to be inferior after radiological tube placement.

Adolescent↗

PubMed1998

[Value of punch biopsy in diagnosis of palpable breast tumors. A prospective analysis of 150 patients].

To reduce the need for excisional biopsies in the diagnosis of breast masses, the accuracy of core needle biopsy (CNB) was determined in a university hospital setting. 150 consecutive women with solitary palpable breast masses underwent CNB over a 2-year period. Histological diagnosis was established, and in the case of cancer the type, grade and estrogen and progesterone receptors were determined. CNB findings were compared with those independently obtained from the subsequently excised lesions. There were 103 malignant and 47 benign lesions. CNB diagnosed 136 lesions (90.7%) correctly. Fourteen biopsies were inconclusive. Histological type was correct in all cases and grading in 83.5%. Correct hormone receptor status was obtained in 97.1% of cases for estrogen and 91.3% for progesterone. Diagnosis of histological type, grading, and hormone receptors obtained from CNB material is a safe way to analyze palpable breast lesions and therefore a useful tool to select patients for preoperative treatment.

Adult↗

PubMed1998

Preoperative TNM-classification is a better prognostic indicator for recurrence of hepatocellular carcinoma after liver transplantation than albumin mRNA in peripheral blood. Liver Transplant Oncology Group.

BACKGROUND/AIM: Survival after orthotopic liver transplantation for hepatocellular carcinoma is limited by a high rate of tumor recurrence. A polymerase chain reaction assay based on the detection of albumin mRNA expression in peripheral blood for detection of hematogenous micrometastasis of hepatocellular carcinoma has been described, which may help to select candidates for orthotopic liver transplantation. METHODS: The prognostic value of a highly sensitive nested reverse transcription-polymerase chain reaction assay was evaluated in comparison with the TNM-classification of the International Union against Cancer in a population of liver transplant candidates. RESULTS: Eighty patients with liver disease and 42 control patients were evaluated. Six of 21 patients with hepatocellular carcinoma and 11 of 59 patients with other diseases of the liver were positive for albumin reverse transcription-polymerase chain reaction, making this assay an indicator of ongoing liver damage without absolute specificity for hepatocellular carcinoma. Twelve patients with hepatoma were followed after liver transplantation and seven of those patients had a tumor recurrence within 12 months. Six of these patients with recurrence had International Union against Cancer stage IV A tumors preoperatively, while only one of them was positive for albumin reverse transcription-polymerase chain reaction before transplantation. Only one patient with a stage I to III tumor had a recurrence within 12 months. CONCLUSIONS: Detection of albumin mRNA in peripheral blood by reverse transcription-polymerase chain reaction seems to be an unreliable marker for assessing hematogenous spread of hepatocellular carcinoma. With International Union against Cancer stage IV A being a much better predictor of tumor recurrence, the practical value of albumin mRNA reverse transcription-polymerase chain reaction for patient selection in liver transplant candidates seems to be very limited.

Adult↗

PubMed1998

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

Adult↗

PubMed1998

It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients.

The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery. Between 1983 and May 1994, 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy. We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates. After a median follow-up of 60 months the multivariate model revealed lymph node status (p = 0.002) as highly significant with regard to local recurrence free survival. We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status: both patient groups with or without irradiation had similar locoregional recurrence rates of 3%. In a subgroup of patients who were lymph node negative, receptor positive, and received adjuvant tamoxifen therapy, the local recurrence rates were as low as 2% in both groups. Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery (T1, N0, positive hormone receptor, adjuvant tamoxifen) without increasing risk of locoregional recurrence. These data have to be confirmed in a prospectively randomized fashion.

Aged↗

PubMed1998

Haemophilus parainfluenzae liver abscess after successful liver transplantation.

Haemophilus parainfluenzae was isolated from a bile specimen and from an aspirate of a liver abscess in a 58-year-old liver-transplanted woman that was indicative of an invasion of the graft by an ascending route. Drug therapy, immunosuppression, rejection therapy, and Roux-en-Y choledochojejunostomy may have contributed to the septic course. Interdisciplinary cooperation was instrumental in diagnosis and successful management in this case.

Bile↗

PubMed1998

Evaluation of needle size for breast biopsy: comparison of 14-, 16-, and 18-gauge biopsy needles.

OBJECTIVE: The purpose of our study was to compare the quantity and quality of tissue harvested from breast biopsy when using 14-, 16-, and 18-gauge "long-throw" needles. SUBJECTS AND METHODS: We performed a prospective randomized study in 64 patients with 66 breast lesions. Under stereotactic guidance, passes were made in random order with each of the three biopsy needles in each lesion. Samples were measured for tissue area and scored for their quality. All lesions, including benign and malignant lesions and lesions with and without microcalcifications, were analyzed. Findings of the biopsy samples were compared with the final diagnoses made at surgical excision. RESULTS: In all 66 lesions, 14-gauge biopsy needles obtained significantly larger specimens (14-gauge, 13.14 mm2; 16-gauge, 9.6 mm2; 18-gauge, 6.41 mm2; p < .05) and scored significantly better (14-gauge, 8.37; 16-gauge, 7.56; 18-gauge, 7.14; p < .016) than either of the smaller needles. The results for malignant and benign lesions and for lesions with and without microcalcifications were similar but not equal to the overall results. However, benign lesions and areas with microcalcifications seem to be more problematic for both smaller needles than for 14-gauge needles. CONCLUSION: Our results indicate that the quantity and quality of breast biopsy specimens depend on the needle size. Of the three needle sizes tested, only 14-gauge long-throw biopsy needles can be recommended for breast biopsy.

Biopsy, Needle↗

PubMed1998

[Neoadjuvant chemotherapy of patients with breast carcinoma].

Adjuvant therapy has shown to be of significant benefit in patients with breast cancer. Among the possibilities to further improve the results, preoperative chemotherapy is a promising tool. So far, we have treated 178 patients and found that downstaging permits breast conservation in 60% of patients who would otherwise undergo mastectomy. The significance of this method for further improvement of survival has to await results of ongoing trials.

Adult↗

PubMed1997

5-fluorouracil kinetics in the interstitial tumor space: clinical response in breast cancer patients.

Several anticancer drugs fail to exhibit sufficient activity against solid tumors in vivo despite effective inhibition of tumor cell growth in vitro. This may be due to impaired drug transfer from plasma into solid tumors. The present study, therefore, aimed at measuring interstitial tumor 5-fluorouracil (5-FU) pharmacokinetics and 5-FU transfer rates from plasma into the tumor interstitium in breast cancer patients. Microdialysis probes were inserted into the primary tumor and the periumbilical s.c. adipose layer of 10 breast cancer patients (8 females and 2 males) scheduled to receive neoadjuvant chemotherapy due to locally advanced breast cancer. Thereafter, patients received 5-FU (600 mg/m2, i.v). 5-FU kinetics were followed in plasma and tumor and s.c. interstitial fluid. Mean interstitial 5-FU load, expressed as area under curve (AUC), in breast tumors was 61 +/- 11% (means +/- SE) of the mean plasma 5-FU load. 5-FU displayed similar kinetics in the interstitial space of s.c. adipose tissue and tumor tissue. A high interstitial tumor AUC was associated with increased tumor response. There was no association with tumor response for s.c. or plasma AUC of 5-FU. Measurement of interstitial drug concentrations in breast tumors by in vivo microdialysis may predict response to chemotherapy. This information may explain drug resistance in some patients and help to optimize dosing and administration schedules. In the future, selection of novel cytotoxic compounds with favorable tumor penetration characteristics may become possible.

Adipose Tissue↗

PubMed1997

Differentiation of benign and malignant breast lesions: MR imaging versus Tc-99m sestamibi scintimammography.

PURPOSE: To compare the accuracies of magnetic resonance (MR) imaging and scintimammography in differentiating benign from malignant breast lesions. MATERIALS AND METHODS: MR imaging was performed in 66 women with 75 lesions during intravenous administration of gadopentetate dimeglumine. Planar and single photon emission computed tomographic (SPECT) scintimammography were performed (with 740 MBq technetium-99m sestamibi administered intravenously) in all 66 patients with 75 lesions and in 64 patients with 73 lesions, respectively. MR imaging and scintimammographic studies were independently evaluated by using signal intensity measurements versus time or focal tracer uptake to differentiate benign from malignant lesions. Histopathologic proof was obtained in 63 lesions. Twelve lesions were monitored with follow-up. RESULTS: MR imaging was false-negative in one and false-positive in nine lesions. Planar scintimammography was false-negative in 10 and false-positive in six lesions. SPECT scintimammography was false-negative in four and false-positive in 10 lesions. Sensitivities and specificities for malignancy were, respectively, 96% and 82% for MR imaging, 62% and 88% for planar scintimammography, and 83% and 80% for SPECT scintimammography. CONCLUSION: Both MR imaging and scintimammography are useful in the evaluation of breast cancer. MR imaging is more sensitive and as specific as scintimammography.

Adult↗

PubMed1996

The importance of the effect of underlying disease on rejection outcomes following orthotopic liver transplantation.

Despite major advances in immunopharmacology, virtually all patients receive the same center-specific immunosuppressive regimen following orthotopic liver transplantation (OLT). The present analysis was performed on the hypothesis that the original disease representing the indication for OLT leads to a different initial immunological situation of the patient. The type of original disease might therefore be a predisposing factor for acute rejection episodes and influence graft and patient survival. From January 1988 to July 1994, 34 patients received OLT at our institution for end-stage primary biliary cirrhosis (group 1) and 66 patients for end-stage alcoholic cirrhosis (group 2). Overall survivals at 1 and 5 years in group 1 versus group 2 were 67% versus 80% and 50% versus 68%, respectively (P<0.04). Retransplantation was performed in 21% of patients from group 1 and in 6% from group 2. The estimated risk for freedom from acute rejection amounts to 38% in group 1 compared with 59% in group 2 (P<0.02). Multivariate regression analysis of potential risk factors identified only the underlying disease as independent predictor. Analysis of cumulative rates of clinically relevant rejection episodes stratified by group revealed 0.29 and 0.05 episodes per patient at one month and 0.80 and 0.06 at six months (P<0.009) respectively. In our clinical experience it was possible to confirm the hypothesis that the underlying disease is the reason for a significantly different incidence of acute rejection episodes and that it subsequently influences graft and patient survival. This approach to an individually adapted immunosuppressive therapy should be taken into consideration and other appropriate parameters investigated.

Acute Disease↗

PubMed1996

Tumor recurrence after oLTX.

Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this condition. The aim of this retrospective analysis was to examine the influence of risk factors on the development of early tumor recurrence. Between December 1982 and June 1995, 480 liver transplantations were performed at a single institution. Out of these, 103 patients had unresectable primary hepatic cancer (88 hepatocellular cancer; HCCA; 20%) and 15 had cholangiocellular cancer (CHCA; 4%). The influence of the following tumor-associated risk factors was assessed: tumor size, tumor distribution within the liver, grading, pseudocapsular formation, vascular invasion, lymph node metastasis, and cirrhotic alteration. The diagnosis of tumor recurrence was made using various radiological imaging techniques, reelevation of serum alphafetoprotein, or autopsy. For patient survival and disease-free period, data analysis was performed by the method of Kaplan-Meier. The Cox model was used for multivariate analysis; a P-value of less than 0.05 was considered to be significant. The mean age of the 103 patients was 54 years (range 15-63a). There were 22 female and 81 male patients. The follow-up period ranged between 4 and 108 months. Twenty-nine patients (50%) died during the follow-up period due to recurrence of disease. The survival rates of the 88 patients with HCCA were 57%, 34%, and 26% at 1, 3, and 5 years, respectively, after orthotopic liver transplantation (oLTX; follow-up 36 month). Of the 15 pts with CHCA the rates were 53%, 33%, and 33%, respectively, with a median follow-up of 60 months. The influence of the risk factors studied showed a significantly longer disease-free period for the following tumor characteristics: grading below or equal 2 (P = 0.009) and absence of vascular invasion (P = 0.04). Regarding a median survival rate of 2-4 months for patients with unresectable malignant liver tumors, these results confirmed the indication for oLTX, especially if the patient does not compete with someone on the waiting list for benign liver disease.

Adolescent↗

PubMed1996

Molecular genetic differentiation between primary lung cancers and lung metastases of other tumors.

When solitary pulmonary tumors are observed in patients with a history of cancer, differentiation between metastasis and primary lung cancer is crucial for appropriate therapy. Assuming that p53 mutations are conserved in metastases, mutation analysis of the p53 gene would be a valuable tool in differentiating metastases from primary carcinomas of the lung. In nine of 267 resected lung tumors, the origin of the lung tumor could not be defined histologically. Five patients had a history of colorectal carcinoma, one had a history of breast carcinoma, one had a history of soft-tissue carcinoma, and one had a history of head and neck carcinoma. One patient with a clear cell carcinoma of the lung had been surgically treated for both renal and thyroid cancer. Material from one patient with adenocarcinoma of the lung, histologically defined regional lymph nodes, and distant brain metastasis served as a control. We extracted deoxyribonucleic acid from the snap-frozen tissue of the unclassified lung tumors, from paraffin-embedded tissue of the previously removed primary cancers, and also from peripheral blood of the patients. Exons 2 to 11 of the p53 gene were amplified in separated polymerase chain reactions and directly sequenced. In all cases, the presence of germline mutations was excluded by analysis of peripheral blood deoxyribonucleic acid. The p53 mutation detected in the deoxyribonucleic acid of the lung tumor of the control patient proved to be conserved in the lymph nodes as well as in the brain metastasis. In two cases, the lung tumors exhibited a p53 mutation not present in the previously removed primary tumor and were therefore classified as new primary lung cancers. In five cases, the lung tumors proved to be metastases of the first tumor, exhibiting the identical p53 mutation. One of these lung tumor samples could be identified as a metastasis from the renal cancer, but the corresponding thyroid cancer material was different. For two cases, molecular analysis remained inconclusive. In one case, no p53 mutation could be found in the compared samples; in the other, no deoxyribonucleic acid could be extracted. Analysis of p53 mutations allowed exact classification in tumors for which standard methods failed to distinguish between metastasis or primary tumor. More than two thirds of lung tumors in patients with previous gastrointestinal carcinoma were revealed to be metastases, but second primary lung cancer could also be diagnosed. This diagnosis allowed correct surgical and adjuvant treatment of these patients.

Adenocarcinoma↗

PubMed1995

Platelet disorders in uraemia before and after haemodialysis under the influence of low dose aspirin.

Thrombocyte dysfunction and increased bleeding time (BT) are well documented in uraemic patients. However, these patients are frequently medicated with low dose aspirin (ASA) in order to maintain shunt patency and prevent cardiovascular events. Recently, life- threatening gastrointestinal haemorrhage in an uraemic subject taking low dose aspirin has been reported. In this work ASA related bleeding risk in uraemic patients and the effect of haemodialysis on their bleeding tendency was studied by measuring in vitro bleeding time (BT) using the Thrombostat 4000 in 34 uraemic patients on chronic haemodialysis compared to 50 healthy subjects. Our results indicate that low dose aspirin does not influence uraemic thrombopathia 8 to 10h after ingestion but seems to increase bleeding risk shortly after ingestion. Moreover, haemodialysis alters uraemic in vitro BT with regard to the time after ingestion of ASA.

Adult↗

PubMed1995

Interphase cytogenetics reveals a high incidence of aneuploidy and intra-tumour heterogeneity in breast cancer.

The occurrence of aberrations involving chromosomes 11 and 17 in malignant tissues of breast cancer patients has not yet been studied systematically. Using fluorescence in situ hybridisation (FISH) with centromere-specific probes, we determined chromosome 11 and 17 status in interphase nuclei from primary and/or metastatic breast cancer cells. In all cancerous specimens obtained from 30 patients, FISH identified cells with clonal chromosomal abnormalities, with aneuploidy rates ranging from 6% to 92% (median 59%). There was a gain of centromeric signals for chromosome 11, most likely corresponding to hyperploidy; aberrations of chromosome 17 in specimens from 26 patients (87%) were hyperploid as well; however, four cases (13%) showed loss of chromosome 17 centromeres. All specimens contained heterogeneous aneuploid cell populations with excessive gain of signals in some cases. The pattern of aneuploidy did not appear to correlate with tumour grade/stage and was comparable in primary tumours and corresponding metastatic axillary lymph nodes, indicative of genetic instability early in tumour development. Screening with a panel of FISH probes may lead to enhanced sensitivity and specificity in detecting malignant cells, as demonstrated in this study with effusions which could not be conclusively interpreted as being malignant by cytological criteria.

Adult↗