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K Haustermans

Publications and source records attributed to K Haustermans.

29 records · Page 2Linked to original sources
PubMed1997

Do cell kinetics have prognostic and/or predictive value in oesophageal cancer treated by surgery?

Tumour cell kinetics could help in predicting the optimal duration of treatment for the individual patient. In order to assess the importance of cell kinetics in oesophageal cancer, 63 patients with cancer of the oesophagus and/or gastro-oesophageal junction were studied. Seven patients had T1 tumours, six T2, 47 T3, and three T4. Twenty patients had no pathological nodes, while 43 patients had node-positive disease. Thirty-one patients had squamous cell carcinoma, 31 patients suffered from adenocarcinoma and one patient had signet ring cell carcinoma. The primary treatment was surgery. 5-iodo-2'-deoxyuridine (IUdR) was injected 6 to 10 h before surgery, and five biopsies per tumour were taken. The labelling index (LI), S-phase duration (Ts) and potential doubling time (Tpot) on the 305 biopsies taken were measured using flow cytometry. Overall, 1-year disease-free survival (DFS) was 57%, with the 2-year DFS being 38%. T-stage, pathological node status and sex significantly influenced the DFS. The mean Tpot from our 63 patients was 5.6 days, with a standard deviation of 3.6 days. When DFS was studied as a function of Tpot, no statistically significant difference was found between fast- and slow-proliferating tumours (log-rank, P = 0.84). A trend developed with fast-proliferating tumours recurring earlier than slow-proliferating ones. From our results it was also clear that intratumour variability exists, and is a confounding factor using Tpot as a predictor for treatment outcome. When tumours were classified into two categories, 'fast' or 'slow', according to their mean Tpot value (with the median Tpot (4.6 days) as the cut-off value), the trend for fast tumours recurring earlier was less clear than when the classification of tumours was based on the confidence interval (CI) being situated entirely below or above the mean. This classification into 'fast' or 'slow' included 27 of 63 tumours. The other tumours (n = 36) had a CI which included the cut-off, and could thus not be classified in this way. DFS at 1 year was 55% for the fast-proliferating tumours (n = 32) vs 63% for the slow-proliferating ones (n = 31). DFS at 1 year on the basis of the CI, however, was 38% for the fast-proliferating tumours (n = 17) vs 45% for the slow-proliferating ones (n = 10). Tumour cell kinetics have the greatest chance of predicting outcome in relatively long treatment schedules, where proliferation will have more time to occur. The fact that oesophageal tumours are almost all fast-proliferating tumours means that for new treatment schedules overall treatment time should not be unduly prolonged, whichever combination of surgery, radiotherapy and chemotherapy is used.

Adenocarcinoma↗
PubMed1997

Microscopic vascular invasion is the most relevant prognosticator after radical nephrectomy for clinically nonmetastatic renal cell carcinoma.

PURPOSE: Although many factors have been considered to predict the outcome after radical nephrectomy, renal cell carcinoma continues to behave unpredictably. In a retrospective study the correlation between microvascular tumor invasion and disease-free survival after surgery for renal cell carcinoma was analyzed. MATERIALS AND METHODS: Between 1980 and 1993, 180 patients (mean age 60 years) were followed for a mean of 52 months after radical or partial nephrectomy for clinically localized renal cell carcinoma. The relevance of microscopic vascular invasion was compared to classical tumor staging, grade and tumor diameter. RESULTS: Microscopic vascular invasion was found in 51 patients (28.3%), including 20 (39.2%) with progression (mean interval to progression 72 months). Of 129 patients with no pathological evidence of microscopic vascular invasion only 8 (6.2%) showed progression at a mean interval of more than 160 months. The difference in disease-free survival as a function of microvascular invasion was statistically highly significant (log rank p < 0.00001) and on multivariate analysis this parameter was by far the most relevant predictor of progression. CONCLUSIONS: In patients who underwent radical nephrectomy for clinically nonmetastatic renal cell carcinoma with microvascular invasion but without lymph node involvement or macroscopic vascular invasion the chance of disease progression is estimated at 45% within 1 year. Microvascular invasion is the single most relevant prognosticator after presumed curative radical nephrectomy for renal cell carcinoma.

Adolescent↗
PubMed1997

A clinical quality management support system.

In the CONQUEST Quality Management System, assessment and improvement of the quality of treatment process and outcome is done by introducing a Clinical Quality Management Support System. Initially the treatment of breast cancer was chosen to illustrate the potential benefits of introducing quality management in the treatment process. The main objective of the CONQUEST Quality Management System is to provide a flexible framework for supplying quality management of the treatment process and enable comparison of clinical results, despite differences in the local best clinical practice guidelines used in the participating treatment centres.

Breast Neoplasms↗
PubMed1996

Enrichment of tumor cells for cell kinetic analysis in human tumor biopsies using cytokeratin gating.

PURPOSE: To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies. MATERIAL AND METHODS: A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor. RESULTS: The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors. CONCLUSIONS: We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements.

Aneuploidy↗
PubMed1995

Can measurements of potential doubling time (Tpot) be compared between laboratories? A quality control study.

The purpose of this study was to investigate the reproducibility of potential doubling time measurements of human tumors in different laboratories and to distinguish which steps in the measurement procedure were subject to the greatest variation. This was achieved by comparing measurements on the same source material in two different laboratories in which three aspects of the technique were separately studied, namely, preparation and staining of the nuclear suspensions, running the samples on the flow cytometer (FCM), and analyzing the two-parameter FCM data. This involved exchange between the two centers of fixed tumor material, stained nuclear suspensions, and FCM data on floppy disks. The analysis step was found to be the least variable step. For DNA synthesis time, Ts, and the labeling index, LI, the coefficients of determination (R2) ranged from 92% to 95.4%. A small systematic bias was observed, with one center measuring approximately 15% higher values for both LI and Ts. Different criteria for window placements were found to be a contributing factor. Variations in the FCM step were approximately equal to those for analysis, with no systematic deviations. Variations for the preparation and staining step were the largest (R2 = 60.5% and 38.1% for LI and Ts, respectively). However, this step was the only one subject to intratumoral variability, which was the largest contributing factor to the variations observed. In addition, however, LI was on average 41% higher in one center compared to the other, resulting in a systematic bias. Differences in the level of green fluorescence of the labeled cells implicated antibody differences as a possible cause. The variations found here for the three procedural aspects were significantly smaller than variations observed between tumors, a requirement for a predictive assay. Suggestions for implementation of quality control procedures include objective (computer-assisted) data analysis on two-parameter histograms and optimization of antibody combinations.

Carcinoma, Squamous Cell↗
PubMed1994

Influence of combined use of nicotinamide and carbogen on rat spinal cord radiation tolerance.

The effect of combining oxygen or carbogen breathing with the systemic administration of nicotinamide (NA) on spinal cord tolerance in Ethrane anesthetised male WAG/Rij rats has been investigated. Ten fraction experiments were carried out with daily (24 h between fractions) and twice a day fractionation (8 h between fractions). Nicotinamide (500 mg/kg) was injected 1 h prior to each irradiation. In addition, a 10-fraction experiment with daily intervals was carried out in which NA was added immediately after irradiation under carbogen breathing conditions. Single dose irradiations showed a minimal decrease in ED50 from 21 Gy in oxygen conditions to 19.9 Gy in carbogen conditions and 19.4 Gy when combined with NA. In the fractionation experiments, comparing the response to irradiation in oxygen (O) and nicotinamide oxygen (NO) conditions for the 24-h interval experiment, the ED50 for O was 61.6 Gy compared with 54.5 Gy for NO. When carbogen (C) was compared with nicotinamide carbogen (NC), the ED50 for C was 62.3 Gy and 53.9 Gy for NC. When NA was administered immediately after irradiation under carbogen breathing conditions the ED50 increased to 57.8 Gy. For twice a day fractionation the modifying effect of nicotinamide was similar to that observed for daily fractionation (ED50 of 57.9 Gy for O, 57 Gy for C and 50.9 Gy for CN), when corrected for incomplete repair in between the two fractions given on 1 day.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

In vivo cell kinetic measurements in human oesophageal cancer: what can be learned from multiple biopsies?

The importance of intratumour variability of cell kinetics was studied in 60 patients with cancer of the oesophagus. Five biopsies per tumour were taken. The labelling index, S-phase duration and potential doubling time (Tpot) were measured using flow cytometry. The mean Tpot value was 5.56 +/- 4.43 days (+/- 1S.D.) for adenocarcinomas and 4.40 +/- 2.45 days (+/- 1S.D.) for squamous cell carcinomas. These values were statistically significantly different. Although intratumour variation in Tpot measurements occurred, the intertumour variability was more important (P < 0.00001). This feature permits classification of tumours into slow and fast proliferating groups, leaving an intermediate group of tumours that could not be unequivocally categorised. The relative distribution of tumours into these three categories depends on the intratumour and intertumour variability of Tpot, and on the cut-off values used. Increasing the number of biopsies from one to five reduces the number of non-classifiable tumours.

Adenocarcinoma↗
PubMed1994

Mucin-secreting adenocarcinoma of the prostate with neuroendocrine differentiation and Paneth-like cells.

We present an unusual variant of prostatic adenocarcinoma with obvious mucinous and neuroendocrine features, arising in the transition zone. The neuroendocrine component is largely represented by Paneth-like cells (PLCs). These cells correspond to previously described eosinophilic cells and are amphicrine. We could demonstrate immunohistochemically the presence of calcitonin in some of these PLCs. The prognostic significance of these special characteristics is not well known, but it is most likely that this type of prostate cancer will not respond well to hormonal therapy.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Survival of rectal cancer patients in Belgium 1997-98 and the potential benefit of a national project.

BACKGROUND: PROCARE, a Belgian multidisciplinary project on rectal cancer (RC), will be launched in 2006. Guidelines have been developed, but remain to be implemented. AIM: A population-based study on RC treatment and outcome in Belgium and comparison with recent international benchmarks in order to better define targets that should be reached. PATIENTS AND METHODS: Anonymous data of 3079 patients with rectal cancer registered in the National Cancer Registry in 1997 and 1998 were analysed. Observed (OS) and relative survival (RS) were compared with figures from nationwide projects and multi-centre studies. RESULTS: The 5-yr OS and RS were 46.6% and 58.5%, respectively. For patients with stage I-III tumours 5-yr OS was 57.1% and 5-yr RS 70.1%. Adjuvant or neo-adjuvant treatment was given in 54.8% stage II-III patients who were < 70 years old. There were marked differences between the provinces in the use of radiotherapy for stage II-III patients and in 5-yr RS for all stages. In stage IV, the median OS was 13 months and the 2-yr OS was 28%. Comparison with recent multi-centre trials indicates significant potential benefits from the PROCARE project: an absolute increase of the 5-yr OS by 10 to 20% after chemoradiotherapy and TME in stage II-III patients 75 years old or less, a 7-month increase of the median OS and an absolute 15% increase of the 2-yr OS in unresectable stage IV patients with combined chemotherapy. CONCLUSION: Significant improvement seems to be achievable. Implementation of the PROCARE guidelines with quality assurance through prospective registration in a specific database, however, is a crucial prerequisite for credible audit of performance and feedback to individual teams.

Adolescent↗
PubMedDate not supplied

The medical treatment of colorectal cancer: actual status and new developments.

Colorectal cancer is one of the most frequent malignancies and one of the greatest causes of cancer death in the Western world. The prognosis is determined by the stage at diagnosis. Patients with metastatic colon cancer have a bad prognosis. Chemotherapeutic treatment with 5-Fluorouracil (5-FU) and folinic acid is actually considered as the standard treatment in patients with metastatic disease. Although the survival benefit is relatively small, many patients can benefit from this treatment in terms of tumor regression or symptom improvement. Several new drugs are actually in development and create hope for improved tumor or symptom control and longer survival. Thymidylate synthase inhibitors (raltitrexed), topoisomerase I inhibitors (irinotecan), the oral 5-FU prodrugs (capecitabine, UFT), ethynyluracil, and oxaliplatin are promising new drugs. The challenge will be to determine the best combination of these new drugs and the exact sequence in which these drugs will be used. Adjuvant post-operative chemotherapy in colon cancer is one of the most important advances in oncology that has been introduced into the clinic during the last years. For rectal cancer, an adjuvant treatment should consist of a combined chemo-radiotherapy. The search for better prognostic factors for recurrence should help to focus on a better adjuvant treatment for patients with the highest risk for recurrence.

Antineoplastic Agents↗