Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 19 recordsLinked to original sources

PubMed2005

Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer.

Preoperative staging of gastric cancer is difficult and not optimal. The TNM stage is an important prognostic factor, but it can only be assessed reliably after surgery. Therefore, there is need for additional, reliable prognostic factors that can be determined preoperatively in order to select patients who might benefit from (neo) adjuvant treatment. Expression of immunohistochemical markers was demonstrated to be associated with tumour progression and metastasis. The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300 patients from the Dutch Gastric Cancer Trial, investigating the value of extended lymphadenectomy compared to that of limited lymphadenectomy). The expression of tumour markers was analysed with respect to patient survival. Patients without loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10-year survival (P<0.0001) compared to patients with any loss: 42% (s.e.=7%) vs 22% (s.e.=3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour cells (69% of the patients) also had a significantly better survival (P=0.01) compared to patients with expression in less than 25% of the tumour cells: 10 year survival rate of 29% (s.e.=3%) vs 19% (s.e.=4%). The prognostic value of both markers was stronger in stages I and II, and independent of the TNM stage. Ep-CAM and CD44v6-expression provides prognostic information additional to the TNM stage. Loss of Ep-CAM-expression identifies aggressive tumours especially in patients with stage I and II disease. This information may be helpful in selecting patients suitable for surgery or for additional treatment pre- or postoperatively.

Adenocarcinoma↗

PubMed2004

Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study.

PURPOSE: To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically proven NSCLC, performance score <2, weight loss <10%, and normal organ functions were randomized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone (both 60 Gy). Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria (NCI CTC) and the Radiation Therapy Oncology Group (RTOG) criteria. Quality of life was measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/LC13 questionnaires. RESULTS: One-hundred and sixty patients were included. Pathologically confirmed persistent tumor was present in 53% of patients in the combination arm versus 58% in the radiotherapy alone arm (P=0.5). Median survival in the combination arm was 11.8 [95% confidence interval (CI) 9.3-14.2] months and in the radiotherapy alone arm 11.7 (95% CI 8.1-15.5) months; progression-free survival was not different between arms [6.8 and 7.5 months, respectively (P=0.28)]. Acute toxicity was mild, late toxicity was radiation-induced cardiomyopathy (three patients) and pulmonary fibrosis (five patients). Quality of life was not different between arms, but in all measured patients cough and dyspnea improved, pain became less, and slight paresthesia developed 3 months after treatment. CONCLUSION: Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996).

Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25-30% of patients treatment still fails. The objectives of the DCLSG study ALL 8 were to decrease the toxicity and to increase the effectivity of BFM-oriented treatment. Decrease of toxicity was aimed at by confirmation of the results of the previous DCLSG study ALL-7, showing that the majority (94%) of children with ALL can successfully be treated with BFM-oriented therapy without cranial irradiation, and by reduction of treatment for standard risk (SRG) patients. To increase the cure rate in medium risk (MRG) patients the efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during protocol M and in SRG patients the efficacy of high doses of L-asparaginase (HD-L-ASP) during maintenance treatment was studied in randomized studies. Patient stratification and treatment were identical to protocol ALL-BFM90, with the following differences: no prophylactic cranial irradiation, SRG patients received only phase 1 of protocol I. Four hundred and sixty-seven patients entered the protocol: 170 SRG, 241 MRG and 56 HRG patients. The 5 years event-free survival rate for all patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%), 73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients >1 year of age at diagnosis unfavorable prognostic factors were male sex, >25% blasts in the bone marrow at day 15 and initial white blood cell count (WBC) >50 x 10(9)/l. The cumulative risk of CNS relapse rate was 5% (s.e. 1%) at 5 years. These results confirm that the omission of cranial irradiation in BFM-oriented treatment does not jeopardize the overall good treatment results, nor does early reduction of chemotherapy in SRG patients. No benefit was observed from treatment intensification with HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Quantum mechanics simulation of protein dynamics on long timescale.

Protein structure and dynamics are the keys to a wide range of problems in biology. In principle, both can be fully understood by using quantum mechanics as the ultimate tool to unveil the molecular interactions involved. Indeed, quantum mechanics of atoms and molecules have come to play a central role in chemistry and physics. In practice, however, direct application of quantum mechanics to protein systems has been prohibited by the large molecular size of proteins. As a consequence, there is no general quantum mechanical treatment that not only exceeds the accuracy of state-of-the-art empirical models for proteins but also maintains the efficiency needed for extensive sampling in the conformational space, a requirement mandated by the complexity of protein systems. Here we show that, given recent developments in methods, a general quantum mechanical-based treatment can be constructed. We report a molecular dynamics simulation of a protein, crambin, in solution for 350 ps in which we combine a semiempirical quantum-mechanical description of the entire protein with a description of the surrounding solvent, and solvent-protein interactions based on a molecular mechanics force field. Comparison with a recent very high-resolution crystal structure of crambin (Jelsch et al., Proc Natl Acad Sci USA 2000;102:2246-2251) shows that geometrical detail is better reproduced in this simulation than when several alternate molecular mechanics force fields are used to describe the entire system of protein and solvent, even though the structure is no less flexible. Individual atomic charges deviate in both directions from "canonical" values, and some charge transfer is found between the N and C-termini. The capability of simulating protein dynamics on and beyond the few hundred ps timescale with a demonstrably accurate quantum mechanical model will bring new opportunities to extend our understanding of a range of basic processes in biology such as molecular recognition and enzyme catalysis.

Alanine↗

PubMed2001

Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect--a histopathological and immunohistochemical study.

BACKGROUND: Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host response. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. PATIENTS AND METHODS: The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. RESULTS: Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). CONCLUSIONS: We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer.

Adenocarcinoma↗

PubMed2001

Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction.

The vertebrate immune system has evolved to protect against infections that threaten survival before reproduction. Clinically manifest tumours mostly arise after the reproductive years and somatic mutations allow even otherwise antigenic tumours to evade the attention of the immune system. Moreover, the lack of immunological co-stimulatory molecules on solid tumours could result in T-cell tolerance; that is, the failure of T cells to respond. However, this may not generally apply. Here we report several important findings regarding the immune response to tumours, on the basis of studies of several tumour types. First, tumour-specific induction of protective cytotoxic T cells (CTLs) depends on sufficient tumour cells reaching secondary lymphatic organs early and for a long enough duration. Second, diffusely invading systemic tumours delete CTLs. Third, tumours that stay strictly outside secondary lymphatic organs, or that are within these organs but separated from T cells by barriers, are ignored by T cells but do not delete them. Fourth, co-stimulatory molecules on tumour cells do not influence CTL priming but enhance primed CTL responses in peripheral solid tumours. Last, cross priming of CTLs by tumour antigens, mediated by major histocompatibility complex (MHC) class I molecules of antigen-presenting host cells, is inefficient and not protective. These rules of T-cell induction and maintenance not only change previous views but also rationales for anti-tumour immunotherapy.

Animals↗

PubMed2001

Less medical intervention after sharp demarcation of Grade 1-2 cervical intraepithelial neoplasia smears by neural network screening.

BACKGROUND: Neural network technology has been used for the daily screening of cervical smears in The Netherlands since 1992. The authors believe this method might have the potential to demarcate diagnoses of Grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). METHODS: Of 133,196 women who were screened between 1992-1995, there were 2236 CIN 1-2 smears; 1128 of which were detected by means of neural network screening (NNS) (n = 83,404 women) and 1108 of which were diagnosed by conventional screening (n = 49,792 women). Cytologic and clinical outcomes (first cytologic or histologic follow-up diagnosis) were retrieved for all the women in the study population (n = 1920). Stratification based on clinical outcome resulted in the cases being grouped as overdiagnosed, concordant, or underdiagnosed. The smears were performed by general practitioners, whereas the biopsies were obtained by gynecologists. RESULTS: The prevalence rate for CIN 1-2 was 1.15% (95% confidence interval [95% CI], 1.08-1.23%) for NNS and 1.92% (95% CI, 1.80-2.04%) for conventional diagnosis (P < 0.001). Concordance with histology was significantly higher for NNS (53.9%; 95% CI, 50.7-57.0%) compared with conventional screening (29.2%; 95% CI, 26.4-32.2%). In addition, overdiagnosis was significantly lower for cases diagnosed by NNS (39.4%; 95% CI, 36.3-42.4%) compared with cases diagnosed by conventional screening (62.4%; 95% CI, 59.3-65.5%). CONCLUSIONS: Neural network-based screening can lead to fewer women being burdened unnecessarily with a cytologic diagnosis of CIN 1-2 by resulting in a sharp demarcation in these diagnoses and a corresponding reduction in unnecessary medical interventions. [See editorial on pages 171-172, this issue.]

Cytogenetic Analysis↗

PubMed2001

Induction of cross-protection in mice against dolphin Erysipelothrix rhusiopathiae isolates with a swine commercial vaccine.

Erysipelothrix rhusiopathiae is well known to cause disease in dolphins. This disease occurs either in an peracute way, leading to mortality even before clinical signs are observed or in a sub-acute way, characterized by rhomboidal skin lesions, that can be treated with penicillin or its derivatives. Commercial swine vaccines, containing inactivated serotype 2 strains, are currently used for vaccination but it is not known whether these vaccines induce protection against E. rhusiopathiae isolates from dolphins. In the present study, it was demonstrated in a mouse model that vaccination with a commercial swine vaccine (Eurovac Ery, Eurovet, Belgium) containing inactivated serotype 2 E. rhusiopathiae strains induced protection against challenge with three E. rhusiopathiae isolates from dolphins. The duration of the protection varied, depending on the challenging isolate, between 8 and >23 weeks. There was however no positive correlation between the amount of antibodies at the moment of challenge and the observed protection. In conclusion, vaccination trials in mice indicate that commercial serotype 2 swine Erysipelothrix vaccines induce protection against erysipelas caused by dolphin pathogenic isolates.

Animals↗

PubMed2001

Isolated late local recurrences with high mitotic count and early local recurrences following breast-conserving therapy are associated with increased risk on distant metastasis.

PURPOSE: Local recurrence (LR) after breast-conserving therapy (BCT) is associated with an increased risk for the development of distant metastasis. We studied risk factors for distant metastasis risk (DMR) and poor prognosis within a group of patients with LR as first event. PATIENTS AND METHODS: From a cohort of 1481 breast carcinomas treated with BCT in the period 1980-1994, a total of 68 pT1-3 N0-1 patients developed LR as first event. We have studied risk factors for the development of distant metastasis within this group of patients with LR. In addition to clinical factors (age at BCT and LR, mode of detection, location of LR, and treatment of LR), the histology slides of the primary and the recurrent tumor were reviewed. Immunohistochemical staining was performed for the following proteins: bcl-2, cyclin D1, E-cadherin, EGF receptor, ER, PR, Ki-67, c-erbB-2/neu, and p53. Statistical analyses were performed using conditional logistic regression. RESULTS: At a median follow-up after LR of 5.6 years, the 5-year DMR was 53%. In univariate analysis, none of the factors of the primary tumor was found to be associated with DMR after LR. Of the recurrent tumor the following factors were found to be risk factors for high DMR after LR: interval between treatment of the primary tumor and LR at 2 years or less (relative risk, 2.38; 95% confidence interval, 1.22-4.76; p = 0.008) and high mitotic count (relative risk, 2.51; 95% confidence interval, 1.03-6.15; p = 0.04). All patients with noninvasive recurrent tumor were alive at the time of analysis. Patients with an interval of greater than 2 years and a recurrent tumor with high mitotic count were found to have an equally poor prognosis compared to patients with LRs detected after a short interval. CONCLUSION: LR after BCT is associated with higher DMR and poor prognosis. Patients with LR within 2 years after BCT are especially at high risk. Late recurrences with high mitotic count have the same poor prognosis as early recurrences. For these patients, systemic treatment at time of the detection of LR should be considered.

Analysis of Variance↗

PubMed2001

No downstaging after short-term preoperative radiotherapy in rectal cancer patients.

PURPOSE: In retrospective studies, total mesorectal excision (TME) surgery has been demonstrated to result in a reduction in the number of local recurrences of rectal cancer. Reports on improved local control after preoperative, hypofractionated radiotherapy have led to the introduction of a randomized multicenter trial to evaluate the effect of TME surgery with and without preoperative radiotherapy. Treatment with preoperative radiotherapy might have an effect on the pathologic characteristics that determine staging of rectal cancer. We investigated the occurrence of downstaging in rectal cancer patients treated with and without preoperative radiotherapy. PATIENTS AND METHODS: We analyzed the differences in tumor size, number of examined lymph nodes, tumor-node-metastasis stage, and histopathologic features in 1,321 patients entered onto a randomized trial. The trial compared preoperative radiotherapy (5 x 5 Gy) followed by TME surgery with TME surgery alone. Patients who had an interval of more than 10 days between the start of radiotherapy and surgery were excluded from analysis. RESULTS: Differences were observed in tumor size (P <.001) and total number of examined lymph nodes (P <.001). No difference in tumor or node classification was detected. The irradiated group demonstrated more poorly differentiated tumors as well as more mucinous tumors. CONCLUSION: In rectal cancer patients, short-term, preoperative radiotherapy with 5 x 5 Gy does not lead to downstaging if the interval between the start of radiotherapy and surgery does not exceed 10 days.

Adult↗

PubMed2001

Evaluation of the 5th edition of the TNM classification for gastric cancer: improved prognostic value.

The main change in the 5th edition (1997) of the TNM classification for gastric cancer compared to the 4th edition (1987) is the use of the number of involved nodes instead of the location of positive nodes. As a result stage grouping is also altered. A second change is the requirement for the examination of at least 15 nodes to justify the N0 status. Patients with fewer examined negative nodes are unclassifiable (Nx). Data were retrieved from a randomized trial database comparing D1 and D2 dissection and 633 curatively operated patients were included. According to the criteria of the 5th edition, 39% of the node-positive patients had another N stage compared to the 4th: 21% had a lower and 18% had a higher stage. 5-year survival rates according to the 4th edition N0, N1 and N2 groups were respectively 72%, 34% and 27%. According to the 5th edition these percentages were for the N0, N1, N2, N3 and Nx groups respectively 75%, 38%, 19%, 8% and 65%. The former 1987 N1 and N2 group were significantly split into three new N 1997 groups (P = 0.006, respectively P< 0.0005). The Cox's regression analysis showed the N 1997 classification to be the most important prognostic variable, with a higher prognostic value than N 1987. In addition, the new TNM stage was also a better prognosticator. The requirement for examining at least 15 nodes, however, could not be fulfilled in 38% of all node-negative patients and we found that a minimum of 5 consecutive negative lymph nodes is a reliable number for staging purposes. We conclude that the 5th edition of the TNM classification provides a better estimation of prognosis, however, examination of at least 15 negative regional lymph nodes is too high a threshold and 5 gives similar prognostic value.

Humans↗

PubMed2001

Expression of genetic markers in lymph node metastases compared with their primary tumours in head and neck cancer.

Regional metastasis is an important factor in the prognosis and treatment of head and neck squamous cell carcinoma (HNSCC). The results of earlier studies suggested the possibility of predicting nodal metastasis in HNSCC using biological markers. To identify which factors may be relevant in the metastatic behaviour of these tumours, the expression of several markers involved in tumour progression was studied in both nodal metastases and their corresponding primary tumours. Expression of p53, Rb, cyclin D1, myc, bcl-2, EGFR, neu, E-cadherin, epithelial cell adhesion molecule (Ep-CAM), and nm23 was studied in 54 primary tumours and their corresponding metastases in patients with HNSCC. The expression of most genes involved in tumourigenesis (p53, Rb, cyclin D1, myc, bcl-2, EGFR, neu, and E-cadherin) was similar in primary tumours and metastases. The expression of nm23 and Ep-CAM was found to be more frequently lower than higher in metastases, compared with their primary tumours. Whereas most genetic alterations of primary tumours remain unchanged in metastases, expression of the cell adhesion molecule Ep-CAM and of nm23 is more frequently reduced than increased in metastases, compared with their primary tumours, suggesting relevance to the process of metastasis. This also implies differences in the regulation of markers involved in tumourigenesis and the process of metastasis.

Adult↗

PubMed2001

Hospital admissions and readmissions for asthma in the age group 0-4 years.

SUMMARY. Childhood rates for admission and readmission for asthma are highest under the age of 5 years. From a registration study in 0-4-year-olds, 100 patients (68 male) were admitted to hospital for asthma and followed for 1 year, yielding a total of 136 admissions. To examine factors that may play a role in admissions and readmissions, histories and laboratory tests for atopic status at initial presentation, and clinical data on admission were evaluated. Age groups 0-1 year (n = 54) and 2-4 years (n = 46) were analyzed separately, of whom 20 (37%) and 9 (20%) patients, respectively, had at least one readmission. In the age group 2-4 years, patients with antibodies against inhalant allergens, determined by radioallergosorbent test (RAST), had a significantly higher risk of readmission (RR = 1.54; 95% CI, 1.22-1.95). In the age group 0-1, year prevalence of sensitization to inhalant allergens was low (20% vs. 72% in age group 2-4 years) and constituted only a slight risk (P = 0.097) for readmission. A history of eczema showed a negative association in the age group 0-1 year. Treatment of the first admission did not differ between children only admitted once and those requiring readmission. In both age groups, clinical features at admission did not differ significantly between first and subsequent admissions, and neither did length of stay. Number of readmissions were higher in the age group 0-1 year than in the age group 2-4 years (27/81 (33%) vs. 9/55 (16%), P = 0.028), with no indication of a lower threshold for admission. In the age group 0-1 year, 60% of the readmissions occurred within 2 months of first hospitalization. Moreover, in the age group 0-1 year a trend was observed that inhaled steroids were prescribed less frequently on discharge following first admission in those children who were readmitted than in the children who had a first admission only (4/20 (20%) vs. 15/34 (44%), P = 0.073). More "aggressive" therapy with anti-inflammatory drugs and close medical follow-up after discharge seem to be indicated.

Adrenal Cortex Hormones↗

PubMed2001

Prediction of survival in patients with head and neck cancer.

BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC) the estimated prognosis is usually based on the TNM classification. The relative weight of the three contributing parameters is often not completely clear. Moreover, the impact of other important clinical variables such as age, gender, prior malignancies, etc is very difficult to substantiate in daily clinical practice. The Cox-regression model allows us to estimate the effect of different variables simultaneously. The purpose of this study was to design a model for application in new HNSCC patients. In our historical data-base of patients with HNSCC, patient, treatment, and follow-up data are stored by trained oncological data managers. With these hospital-based data, we developed a statistical model for risk assessment and prediction of overall survival. This model serves in clinical decision making and appropriate counseling of patients with HNSCC. PATIENTS AND METHODS: All patients with HNSCC of the oral cavity, the pharynx, and the larynx diagnosed in our hospital between 1981 and 1998 were included. In these 1396 patients, the prognostic value of site of the primary tumor, age at diagnosis, gender, T-, N-, and M-stage, and prior malignancies were studied univariately by Kaplan-Meier curves and the log-rank test. The Cox-regression model was used to investigate the effect of these variables simultaneously on overall survival and to develop a prediction model for individual patients. RESULTS: In the univariate analyses, all variables except gender contributed significantly to overall survival. Their contribution remained significant in the multivariate Cox model. Based on the relative risks and the baseline survival curve, the expected survival for a new HNSCC patient can be calculated. CONCLUSIONS: It is possible to predict survival probabilities in a new patient with HNSCC based on historical results from a data-set analyzed with the Cox-regression model. The model is supplied with hospital-based data. Our model can be extended by other prognostic factors such as co-morbidity, histological data, molecular biology markers, etc. The results of the Cox-regression may be used in patient counseling, clinical decision making, and quality maintenance.

Aged↗

PubMed2001

Mechanisms of oncogenesis in colon versus rectal cancer.

Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2, p53, E-cadherin and beta-catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear beta-catenin expression (p=0.75). Rectal cancers showed significantly more nuclear beta-catenin than colon cancers (65% versus 40%, p=0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry (p<0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p=0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease-free survival (p=0.008), but not in colon cancers. Cox regression showed that p53-expression (p=0.03) was an independent predictor for disease-free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear beta-catenin in the APC/beta-catenin pathway than colon cancer and/or nuclear beta-catenin may have another role in rectal cancer independently of APC. The p53-pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered.

Adult↗

PubMed2001

Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Dukes C colon cancer.

PURPOSE: Mutations in K-ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibility in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by K-ras and TP53 mutations. METHODS: Mutation screening of the hot spots of the K-ras gene and of the evolutionarily conserved regions of the TP53 gene was performed by denaturing gradient gel electrophoresis technique in formalin-fixed paraffin-embedded specimens of 55 consecutive patients with Dukes C colon cancer treated with adjuvant 5-fluorouracil-based chemotherapy. The median follow-up was 47 (range, 32-66) months. RESULTS: Alterations in the mutation hot spots of K-ras were found at codon 12 (n = 11) and 13 (n = 4) in 15 of the 55 carcinomas (27 percent). No mutation was found at codon 61. Mutations of a probably causative nature in the evolutionarily conserved regions (exons 5-8) of the TP53 gene were found in 24 tumors (44 percent). K-ras and TP53 mutations were found equally in the group with recurrent disease (7/26 (26 percent) and 12/27 (44 percent), respectively) and in the group without recurrences (8/28 (24 percent) and 12/28 (43 percent), respectively). Cancer-specific survival did not differ significantly between patients with K-ras or TP53 or both mutated and nonmutated tumors, respectively (log-rank test: K-ras, P = 0.72 and TP53, P = 0.77; K-ras and TP53, P = 0.8). Also, potentially aggressive K-ras codon 12 and 13 mutations had the same survival as tumors without these mutations (log-rank test; P = 0.73). CONCLUSIONS: Patients with K-ras or TP53 or both mutated Dukes C colon tumors have the same survival as nonmutated tumors when treated with adjuvant chemotherapy. These data suggest that mutations in K-ras or TP53 alone are not prognostic indicators in patients with Dukes C colon cancer receiving adjuvant 5-Fluorouracil-based therapy.

Adult↗

PubMed2001

[Benign diseases in radiotherapy: a practice survey in Belgium. Peer review of radiotherapy in Belgium].

In 1996 and 2000, a survey of radiation practice in Belgium was performed by sending a questionnaire to the different centers asking their opinion and number of patients treated. There was a great similarity between the two surveys both for indications and total number of patients irradiated. For the most common indications (prevention of cheloids, heterotopic bone formation, hyperthyroidy ophthalmopathy), there was a trend to use similar radiation technique following recent publications. In contrast, if the number of cases of macular degeneration is declining, the prevention of vessels restenosis is becoming more and more an indication.

Belgium↗

PubMed2001

Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation.

Transplantation with histocompatible identical siblings is a curative treatment for patients with myelodysplastic syndromes (MDS). Alternative treatments, such as transplantation with other family donors, are an option for patients without HLA-identical siblings. This study evaluated transplantation with genotypically nonidentical family donors and compared the results to those obtained with unrelated donors and autologous stem cell transplantation. Overall 3-year survival was 35% for the 79 patients transplanted using genotypically nonidentical donors, DFS was 31%, relapse risk 16%, and the treatment-related mortality (TRM) 62%. Patients transplanted using phenotypically identical family donors had a significantly superior survival and a lower TRM than patients transplanted with mismatched family donors. Age had no influence on the outcome of transplantation. The DFS of patients transplanted in early stage of the disease was 42% compared to 28% in patients transplanted with more advanced disease (P = 0.03). The results of transplantation with mismatched family donors were comparable to those obtained with unrelated donor transplantation. This suggests that nonidentical family donors may be considered if a fully matched unrelated donor is not available. The TRM of patients transplanted with nonidentical family donors is significantly higher than the TRM of patients transplanted with autologous stem cells. The disease-free survival of ASCT is not inferior to allogeneic transplantation using nonidentical family donors, and the intensity of the treatment is much lower. The choice of ASCT or alternative donor transplantation must be influenced by the age of the patient and the risk of relapse. For patients under the age of 20 years the treatment of choice may indeed be an alternative donor transplantation.

Adolescent↗