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Biomedical subjects

E K Kranenbarg

Publications and source records attributed to E K Kranenbarg.

10 recordsLinked to original sources
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

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↗
PubMed2000

Pathology data in the central databases of multicenter randomized trials need to be based on pathology reports and controlled by trained quality managers.

PURPOSE: Randomized multicenter trials form the basis of health care development. Regarding cancer research, pathology data are crucial. To maintain the quality of these trials, the auditing of subsequent processes is necessary. The aim of the present study was to examine the completeness and accuracy of data obtained from a special-purpose standardized pathology form compared with the data available through traditional hospital pathology reports. PATIENTS AND METHODS: A retrospective comparison of pathology data case record forms with hospital pathology reports was performed using the data from 300 patients with primary rectal cancer. All of these patients had been included in a large multicenter trial in the Netherlands. Three independent audits were carried out. Special attention was given to the accuracy of parameters, which are important for prognosis and treatment decisions. Furthermore, various factors that possibly influence the occurrence of errors were investigated. RESULTS: Quality control of the pathology data revealed a high accuracy of 86.5% of all data items. However, only one third of the forms were complete and correct. Missing values were most prominent in the number of lymph nodes examined, whereas most errors were made in relation to the circumferential margin. Trained review pathologists made fewer major errors. Discrepancies were detected in all control rounds. CONCLUSION: Successive rounds of quality control are required for accuracy and completeness of pathology data in multicenter trials. In addition to the special-purpose pathology forms, original pathology reports have to be collected, and the data should also be controlled by a trained pathology quality manager.

Databases, Factual↗
PubMed1999

Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prospective randomised trial with standard operative and histopathological techniques. Dutch ColoRectal Cancer Group.

OBJECTIVE: To document local recurrence in primary rectal cancer when standardised techniques of surgery, radiotherapy, and pathology are used, and to investigate whether the local recurrence rate after total mesorectal excision permits the omission of adjuvant short term preoperative radiotherapy. DESIGN: Prospective randomised study. SETTING: Dutch (n = 80), English (n = 1), German (n = 1), Swedish (n = 9), and Swiss (n = 1) hospitals. SUBJECTS: The first 500 randomised Dutch patients with primary rectal cancer. MAIN OUTCOME MEASURES: Local recurrence, survival, operation-related factors, specific pathological tumour characteristics, short and long term morbidity, and quality of life. RESULTS: Between January 1996 and April 1998, 871 Dutch and 94 other patients were randomised. Our feasibility analysis shows that cooperation between and within the participating disciplines goes well. With regard to the surgical part, this can be confirmed by the large number of operations attended by consultant surgeons (58%). The number of abdominoperineal resections appeared to be low (30%), as did the percentage of lateral margins involved (13%). The rate of adverse effects of radiotherapy was acceptable. Apart from a larger operative blood loss and a higher infective complication rate in the irradiated group, no significant differences were found with regard to morbidity and mortality between the randomised groups. CONCLUSIONS: The accrual of our trial is going well and it is feasible; short term preoperative radiotherapy is safe even in combination with TME.

Adult↗
PubMed1998

Gastric cancer in the elderly.

The elderly population is expanding and, from the early 1990s, one-quarter of newly diagnosed gastric cancer patients are over 80 years of age. The main risk factors for post-operative complications and mortality are total gastrectomy, radical lymphadenectomy, splenectomy and/or pancreatectomy and these should, therefore, not be practised routinely. Good long-term results can be achieved with careful monitoring of concomitant disease.

Aged↗
PubMed1994

Diet composition and postexercise energy balance.

This study was aimed at investigating the effect of exercise on energy balance under dietary conditions differing by the relative lipid content of foods. Nine healthy men performed a 60-min treadmill exercise followed by a 48-h observation period during which they maintained their habitual daily activities and had free access to either a low-fat, a mixed, or a high-fat diet. Energy balance, summing up the excess of energy expended during exercise and the 48-h postexercise energy balance, was -6.4, -4.5, and 0.9 MJ under low-fat, mixed, and high-fat diet conditions, respectively. These observations suggest that exercise can induce a substantial energy deficit when a low-fat diet conforming to nutritional recommendations is consumed after exercise. They also suggest that the increase in energy intake associated with a high-fat diet is sufficient to fully compensate for the energy deficit resulting from the energy cost of exercise and the increase in postexercise energy expenditure.

Adult↗