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Biomedical subjects

M R Christiaens

Publications and source records attributed to M R Christiaens.

At least 19 recordsLinked to original sources
PubMed2007

Body mass index and HER-2 overexpression in breast cancer patients over 50 years of age.

PURPOSE: In breast cancer, in vitro as well as in vivo experiments have shown an inverse relationship between HER-2 and steroid hormone receptors. It is unknown whether circulating estrogens affect HER-2 expression. We hypothesize that the postmenopausal body mass index (BMI) as a surrogate marker for bio-available estrogens, is inversely associated with HER-2 over-expression. PATIENTS AND METHODS: A total of 535 women over age 50 or with known postmenopausal status, with a unilateral, not previously treated, operable breast cancer were evaluated the evening prior to surgery for body weight, height, abdominal and hip circumference over a 3 years period. Waist-to-hip ratio (WHR) and BMI were calculated. HER-2, estrogen receptor and progesterone receptor staining was done by immunohistochemistry. All tumours with DAKO 2+ staining were submitted for HER-2 detection by FISH analysis. HER-2 was defined as positive if DAKO 3+ or FISH positive. We assessed the frequency of HER-2 positivity in each of 6 quantiles for all parameters of body composition and tested for a trend in HER-2 expression across the 6 quantiles. Furthermore, we investigated whether BMI contributed, together with other known predictors for HER-2, in a standard multivariate logistic regression model that predicts HER-2 over-expression. RESULTS: There is a decrease in HER-2 over-expression per increasing quantile of BMI. In a multivariate model-including both steroid receptors-BMI remains an independent predictor for HER-2 over-expression. CONCLUSION: In women over age 50 or with known postmenopausal status with an operable breast cancer, there is an inverse association between BMI and HER-2 over-expression.

Age Factors↗
PubMed2005

Hormone receptors do not predict the HER2/neu status in all age groups of women with an operable breast cancer.

BACKGROUND: In breast cancer, there is an inverse relationship between HER2/neu overexpression and receptors for estrogen (ER) or progesterone (PR). Some clinical observations such as the age-related association between hormone receptors and tumour grade, which predicts HER2/neu overexpression, suggest an age-related relationship. PATIENTS AND METHODS: Our study population consisted of 1362 consecutive women receiving primary surgery for non-metastatic invasive breast cancer. We compared the relationship between both hormone receptors and HER2/neu overexpression in different age groups taking other tumour characteristics into account. RESULTS: In a multivariate model, considering the overall group, a negative ER, a negative PR and a high tumour grade were predictive for HER2/neu overexpression (P <0.001). Considering 246 women aged < or =45 years, the only predictor for HER2/neu overexpression in this age category was a high tumour grade (P = 0.003). Considering the 1116 women aged >45 years, ER (P = 0.001), PR (P = 0.001) and tumour grade (P <0.001) were associated with HER2/neu (P <0.001). CONCLUSION: Our findings indicate that the association between ER, PR and HER2/neu overexpression varies with age. The hormone receptors are not an independent predictor for the HER2/neu status in young women while they are in elder patients.

Age Distribution↗
PubMed2005

Actinomycosis, a rare and unsuspected cause of anal fistulous abscess: report of three cases and review of the literature.

Primary perianal actinomycosis is rare. Sporadic cases, with lesions varying in extent have been reported. The infection is caused by the bacterium Actinomyces, which often is a saprophyte. Male gender and diabetes are risk factors, but the exact pathogenic mechanism remains speculative. The diagnosis is a challenge and often delayed, with a protracted history of masses and sinuses extending into the gluteal and genital region. The treatment, a combination of surgery and antibiotics, is poorly standardized. We report three cases and compare their characteristics to those of published cases, found by a computerized literature search (1968-2002). The lesions, a simple fistula-in-ano or a mass, were diagnosed in an early stage in all three patients. The infection always spread into the scrotum. There were no risk factors other than gender, except in one patient. The diagnosis was suspected by the observation of draining sulfur granules and promptly confirmed by histology in the three cases. All patients healed with antibiotics in addition to simple surgical procedures. Treatment consisted of amoxicillin for two weeks in two cases and more extended antimicrobial treatment in the third. These findings are contrasting with the classic picture of perianal actinomycosis. It is concluded that perianal actinomycosis can occur in the absence of risk factors and that early diagnosis requires a high degree of suspicion. An infection with Actinomyces should be suspected in the presence of lesions containing watery purulent material with sulfur granules. The indication for extended antibiotherapy combined with sphincter damaging surgery may need to be revised in the presence of early detection.

Abscess↗
PubMed2005

Plasma gelatinase levels in patients with primary breast cancer in relation to axillary lymph node status, Her2/neu expression and other clinicopathological variables.

Matrix metalloproteinases (MMPs), in particular the gelatinases MMP2 and MMP9, are important mediators of tumour invasion and metastasis. We examined whether plasma gelatinase levels could predict lymph node metastasis in breast cancer patients. Further, we investigated the relationship of plasma gelatinase levels with Her2/neu expression, recently acknowledged as an important prognostic factor for recurrence, and with various clinicopathological factors. Preoperative plasma samples from 81 breast cancer patients were collected. Total and active gelatinase levels were measured by enzyme immunoassays and activity assays, respectively. Neither total nor active plasma MMP2 levels correlated with nodal status or with any of the classical clinicopathological factors including histological tumour type, tumour size and grade and hormone receptor status. Patients with Her2/neu overexpressing tumours showed an increase of 27% (P=0.007) in plasma MMP2 activity, but not in total MMP2, compared with patients without overexpression. MMP9 levels, total and active, did not correlate with any of the investigated variables. In contrast to MMP9, total MMP2 levels correlated significantly with active MMP2 levels. In summary, total and active plasma gelatinase levels failed to identify high risk for axillary lymph node metastasis. Active plasma MMP2 was significantly increased in patients with Her2/neu overexpressing tumours, suggesting a role for Her2/neu in the signalling pathways of MMP2 activation in carcinogenesis. However, this increase was too small to be of clinical use. Furthermore, no relationship was found between plasma gelatinase levels, total or active, and any of the clinicopathological prognostic factors.

Axilla↗
PubMed2005

Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer.

AIMS: To investigate the association between tumour characteristics and HER-2/neu by immunohistochemistry in primary operable breast cancer. METHODS: The association between HER-2/neu and other clinicopathological factors was evaluated in 1362 consecutive patients with primary breast cancer treated between 2000 and July 2003 in one centre. Microscopic tumour size, tumour grade, lymph node status, patient's age, oestrogen receptor (ER), progesterone receptor (PR), and joint ER/PR status were evaluated, using the chi2 test for univariate analysis and logistic regression for multivariate analysis. The hormone receptors and HER-2/neu were studied immunohistochemically. Using the HER-2/neu DAKO scoring system, scores of 0, 1+, or 2+ were defined as negative and 3+ as positive. Data for DAKO scores 2+/3+ versus 0/1+ are also presented. RESULTS: Hormone receptor negative breast cancers were more often HER-2/neu positive than hormone receptor positive cancers, both for ER (28.7% v 6.8%) and PR (19.9% v 5.9%). In multivariate analysis, both ER, PR, and tumour grade were independently associated with HER-2/neu. In ER+ tumours, HER-2/neu overexpression was significantly lower in PR+ than in PR- cases (11.5% v 5.4%). HER-2/neu overexpression (2.7%) was lowest in the large subgroup of ER+PR+ tumours with low tumour grade (grade 1-2), comprising 46.1% of all patients. CONCLUSIONS: ER, PR, and tumour grade are independent predictors for HER-2/neu overexpression in women with primary operable breast cancer. ER and PR are negatively associated with HER-2/neu, whereas tumour grade is positively associated with HER-2/neu. In women with ER+ tumours, PR status also affects the likelihood of HER-2/neu expression.

Adult↗
PubMed2003

Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions.

BACKGROUND: We previously developed a real-time quantitative RT-PCR technique to detect breast carcinoma cells in peripheral blood (PB). The aim of the current study was to improve cytokeratin 19 (CK19) quantification using plasmid dilutions of cloned PCR fragments to obtain a more reliable and reproducible quantification of CK19 transcripts. MATERIALS AND METHODS: PB samples of 14 stage IV breast cancer patients and 23 healthy controls were examined with RT-PCR using plasmid quantification. RESULTS: Median CK19+ copy numbers of one and 11 were detected in the control group and stage IV breast cancer patients, respectively (Mann-Whitney, P </=0.0001). When comparing the results obtained using cell line dilutions with those obtained using plasmid dilutions, a good correlation was observed (r(2) = 0.98). CONCLUSIONS: Plasmid dilutions are more reliable than cell line dilutions for quantification of gene expression, and more objective criteria for positivity could be defined based on the characteristics of the standard curve (slope and intercept). A more universally accepted agreement on the definition of the cut-off value for positivity is needed.

Breast Neoplasms↗
PubMed2001

A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood.

BACKGROUND: The detection of occult carcinoma cells in patients with breast cancer has been shown to predict disease recurrence and metastasis. MATERIALS AND METHODS: To improve on molecular detection of breast carcinoma cells in blood, we have developed a sensitive and quantitative assay using real-time quantitative RT-PCR identifying transcripts of the cytokeratin-19 (CK19) gene. RESULTS: This real-time quantitative RT-PCR is sensitive, accurate and has a high reproducibility within a wide dynamic range, which permits simultaneous quantitative analysis of samples with varying input concentrations. Furthermore, the procedure offers several technical advantages over classic quantitative PCR methods (competitive RT-PCR, Northern blotting) such as decreased likelihood of contamination due to absence of post-PCR manipulations, high sample throughput because of absence of post-PCR processing time (no agarose gel electrophoresis). In this pilot study, we detected significantly elevated CK19 transcript levels in < 10% of the volunteers, in +/- 30% of stage I-IIIa patients preoperatively and in > 70% of the and stage IV breast cancer patients. CONCLUSIONS: Analyses using this real time quantitative RT-PCR for CK19 mRNA may prove to have clinical implications in the assessment of circulating tumour cells in peripheral blood, micrometastases in bone marrow or lymph nodes in breast cancer patients. Application of this technique in a clinical population may improve diagnosis and monitoring of metastatic breast cancer and its validation is currently ongoing.

Adult↗
PubMed1998

Relationship between potential doubling time (Tpot), labeling index and duration of DNA synthesis in 60 esophageal and 35 breast tumors: Is it worthwhile to measure Tpot?

BACKGROUND: In recent years Tpot (potential doubling time) has been measured before treatment in human tumors in an attempt to estimate the proliferation taking place during a course of irradiation. Tpot is defined as Ts/LI, where Ts is the duration of DNA synthesis and LI is the labeling index (proportion of cells synthesizing DNA). Ts is more difficult to measure than LI, so the question arises whether variation introduced during the determination of Ts is compensated by the theoretically better relevance of the quotient Tpot than of LI alone. It is not clear from comparisons with clinical outcome whether Tpot is a useful indicator of proliferation or whether LI is more prognostic, as suggested by a currently ongoing multicenter analysis elsewhere. Therefore, we investigated intercomparisons between Tpot and its components LI and Ts in two in their proliferation rates contrasting types of tumor where multiple biopsies were taken from each tumor. MATERIALS AND METHODS: Sixty patients with esophageal carcinoma and 57 patients with breast cancer were included in this study. All patients were injected with IUdR 6-8 h before surgery. From each tumor three to five biopsies were taken at surgery. Using flow cytometry, LI and Ts were measured on all biopsies in order to calculate Tpot. Logarithmic transformations of the distributions were used to examine correlations. Kappa-tests were used to assess how reliable an LI value could be in predicting the corresponding Tpot. RESULTS: Ts and LI were not completely independent, based on the within-tumor coefficients of variation (CVw). The ratio of between-tumor coefficient of variation (CVb) to the CVw suggested that the discriminative power of Tpot was higher than LI for esophagus, but the reverse in breast tumors, which had a larger range. Pearson correlation coefficients were high for log Tpot versus log LI in both types of tumor, but the predictive power was low, as shown by kappa-values of only 0.3-0.41 starting with LI and trying to predict the corresponding value of Tpot. Increasing widths of a central 'gray zone' were investigated for improved discrimination between fast and slow proliferation. Multiples of the within-tumor standard deviation, equally on each side of the median, were used to vary the width of the gray zone. Without a gray zone no more than 70% successful matching was obtained in esophagus tumors, compared with 80% in breast tumors. However, by excluding about half of the esophageal tumors an 80% success rate was achieved. In breast tumors over 90% matching was obtained more easily, keeping 80% of the tumors classifiable. For both tumor types correlations between Ts and Tpot were weak, with a trend towards short Ts associated with short Tpot and also with low LI. The latter correlation was significant for esophageal tumors and resulted in Tpot values having a smaller range than the LIs. CONCLUSION: Although there were good correlation coefficients between Tpot and LI, the predictive power of either from the other was not reliable, except by excluding a significant number of tumors close to the medians. The predictive value of LI for Tpot was higher for breast tumors because the spread in cell kinetic measurements was wide. Until more clinical data become available on outcome in comparison with LI or Tpot, it is still worthwhile to measure Tpot and to assess the prognostic value of both LI and Tpot in relation to outcome.

Adenocarcinoma↗
PubMed1996

Comparison of the surgical procedures for breast conserving treatment of early breast cancer in seven EORTC centres.

The aim of this study was to develop a standardised surgical report for breast-conserving procedures, supporting the systematic documentation of the different aspects of the surgery. The surgical procedure for tumourectomy and axillary clearance was translated into a series of steps that could be quantitatively documented. This description was submitted twice to a group of surgeons from different departments to ensure that all steps that are considered to have relevance for outcome were included and that no superfluous data were collected. After two corrective phases, a first test format was developed. Between February 1993 and May 1994, seven surgical departments, participating in EORTC trials, completed this questionnaire for a number of their patients. The data collected related to general information on the department, the tumour excision itself, the axillary dissection and, in a later phase, on pathology. 269 questionnaires (264 tumour excisions, 259 axillary dissections and 189 pathology reports) were collected and analysed. Even though the participating departments were involved in a single trial on breast-conserving surgery and had previously developed regular contacts about the practical aspects of treatment, many differences were detected. In general, variations were found in the waiting time between treatment prescription and execution, experience of the surgeon, duration of the procedure, and the use of prophylactic antibiotics. Also, in the practical execution of the procedure, major variations in the type of incision, width of tumour excision, closure of the breast tissue and skin, the use of frozen sections and the extent of the axillary dissection were found. The most relevant differences and their possible consequences are discussed. It has been proven possible and feasible to document quantitatively a surgical procedure. The fact that within a group of surgeons participating in the same clinical trials, many differences in the surgical techniques are observed, stresses the need to reach a consensus on a stricter set of guidelines for breast-conserving procedures and their documentation, especially when conducting clinical trials.

Axilla↗
PubMed1996

More detailed documentation of operative procedures in breast conserving treatment: what good will it do us?

When researching the literature, many differences within surgical techniques for breast conservation, tumour excision and axillary dissection are described in the smallest detail. Most authors have their own preferences but little clinical research has been done to evaluate the impact of those differences on outcome: local control, cosmesis, complications or costs. Even when prospective, randomized clinical trial protocols provide many instructions to perform the surgery, the case report forms almost never document the surgery actually performed. This is in contrast to radiotherapy and chemotherapy regimens, which have had higher standards of quality of care implemented. The development of more detailed and standardized procedural information should lead to more accurate and specific information, which can be easily transferred in a learning process, and enable more reliable clinical research. Documentation and guidelines for surgery are essential tools in implementing a process of quality audit for a type of surgery where accuracy is essential.

Axilla↗
PubMed1995

Primary leiomyosarcoma of the diaphragm.

Primary leiomyosarcoma of the diaphragm is extremely rare and only five cases have so far been reported. In the early stages clinical signs are scarce and diagnosis is difficult. The advent of MR-imaging has helped in detecting the origin of a diaphragmatic tumour and its relationship to the adjacent tissues. The highly malignant character of this tumour accounts for the poor prognosis even when radical surgery is performed.

Diagnosis, Differential↗
PubMed1995

A single-center multiple regression analysis of covariates associated with long-term cadaveric renal allograft survival: further improvement of long-term results with CsA.

This single center analysis shows further improvement in the already excellent long-term, cadaveric renal allograft survival with Aza since the introduction of CsA. In contrast to the findings from the UCLA/UNOS multicenter registries, these results support other observations that the type of maintenance immunosuppression does indeed influence the long-term attrition rate of cadaveric, renal allografts.

Adult↗