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Biomedical subjects

G H de Bock

Publications and source records attributed to G H de Bock.

At least 19 recordsLinked to original sources

Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial.

BACKGROUND: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. METHOD: Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n=1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml. RESULTS: Normal pre-operative CEA values were present in 63% (CEA<5.0) and 39% (CEA<2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA<5.0), 50% (CEA<2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed. CONCLUSION: A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.

Adult↗

EGFR expression is associated with groin node metastases in vulvar cancer, but does not improve their prediction.

OBJECTIVES: High morbidity of elective inguinofemoral lymphadenectomy in early stage vulvar cancer patients urges the need for defining a group of low-risk patients in whom inguinofemoral lymphadenectomy can be safely omitted. Aim of the study was to evaluate whether in addition to 'classic' clinicopathological factors determination of EGFR expression in vulvar cancer can be helpful in defining such a 'low-risk' group. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples of 197 surgically treated T1/2 patients were collected in a Tissue Micro Array (TMA). On this TMA, immunohistochemistry for EGFR was performed. Logistic regression analyses were performed including histopathological characteristics with the presence of nodal metastases as outcome. A predictive model was constructed, and absolute risks were calculated. RESULTS: EGFR expression was present in 68% of the vulvar tumors and related to the presence of lymph node metastases (OR 2.12, 95% CI 1.09-4.10). Our predictive model with only clinicopathological factors was able to define a group of patients with a likelihood of absence of lymph node metastases of 13% (95% CI 5-36), which could be decreased to 6% (95% CI 0-29) after inclusion of EGFR expression (p=0.07). CONCLUSIONS: EGFR expression is present in the majority of vulvar tumors and is associated with groin node metastases in vulvar cancer. Current classic clinicopathological predictive factors for inguinofemoral lymph node metastases with or without EGFR analysis are not strong enough for identification of "sufficiently low" risk T1/2 vulvar cancer patients. Our predictive model approach however is excellent for evaluation of new cell biological parameters, associated with clinical outcome.

Adult↗

Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies.

The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was determined by immunohistochemistry on tissue microarrays. Association with progression-free survival (PFS) and overall survival (OS) was analysed by univariate and multivariate Cox regression analysis. Aberrant p53 overexpression was significantly associated with PFS in the Dutch and Scottish cohorts (P=0.001 and 0.038, respectively), but not with OS in univariate analysis. In multivariate analysis, when the two groups were combined and account taken of clinical factors and country of origin of the cohort, p53 expression was not an independent prognostic predictor of PFS or OS. In this well-powered study with minimal methodological variability, p53 immunostaining is not an independent prognostic marker of clinical outcome in epithelial ovarian cancer. The data demonstrate the importance of methodological standardisation, particularly defining patient characteristics and survival end-point data, if biomarker data from multicentre studies are to be combined.

Adult↗

The clinical value of a negative multi-detector computed tomographic angiography in patients suspected of coronary artery disease: A meta-analysis.

The aim of this meta-analysis was to calculate the sensitivity of contrast-enhanced multi-detector computed tomography (MDCT) compared with coronary angiography (CAG) in incident patients suspected of coronary artery disease (CAD). We searched PubMed, Embase, bibliographies of original papers and reviews to identify original papers including > or =20 patients. Two independent reviewers selected papers and judged eligible papers on quality. Heterogeneity was assessed and homogeneous subgroups were pooled. Of the 15 included studies, ten provided moderately homogeneous patient-based analyses with absolute diagnostic numbers (n = 630 patients). Pooled sensitivity was 89% (95% confidence interval: 85-92%). Scanners with 16 detectors (n = 4) had higher sensitivities (pooled sensitivity: 91%) than four-detector scanners (n = 6; pooling not possible due to heterogeneity). Seven studies reported sensitivity for a proximal stenosis, but different definitions were used making pooling impossible; sensitivities ranged from 75 to 100%. The sensitivity of four- and 16-detector MDCT is not sufficient to rule out any stenosis in patients suspected of CAD. No conclusions can be drawn with respect to the sensitivity for clinically relevant or proximal stenoses.

Contrast Media↗

Association between the CHEK2*1100delC germ line mutation and estrogen receptor status.

Already published data were further analyzed regarding the association between the CHEK2*1100delC germ line mutation and estrogen receptor (ER) status in patients with breast cancer. The CHEK2*1100delC mutation was more prevalent among the patients with a positive ER status (4.2% versus 1.0%). An ER-negative status was beside CHEK2*1100delC mutation and independently associated with an earlier of age onset of breast cancer. There was a trend that an ER-negative status, beside the presence of a CHEK2*1100delC mutation, was associated with a worse disease-free survival. There might be an association between ER status and a CHEK2*1100delC mutation. More studies with larger number of patients are needed to further investigate the relation between CHEK2*1100delC and ER status.

Breast Neoplasms↗

Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy: long-term results of European Organisation for Research and Treatment of Cancer studies.

The aim of this study was to evaluate prognostic factors for isolated loco-regional recurrence in patients treated for invasive stage I or II breast cancer. The study population comprised 3602 women who had undergone primary surgery for early stage breast cancer, who were enrolled in European Organisation for Research and Treatment of Cancer (EORTC) trials 10801, 10854, or 10902, by breast conservation (55%) and mastectomy (45%). The median follow-up time varied from 5.3 (range: 0.6-9.5) to 11.9 years (range: 0.6-17.4). Main outcome was the occurrence of isolated loco-regional recurrence. The results of multivariate analysis showed that younger age and breast conservation were risk factors for isolated loco-regional recurrence (breast cancer under 35 years of age versus over 50 years of age: hazard ratio 2.80 (95% CI 1.41-5.60)); breast cancer age 35-50 years versus over 50 years: hazard ratio 1.72 (95% CI 1.17-2.54); breast conservation (hazard ratio: 1.82 (95% CI 1.17-2.86)). After perioperative chemotherapy, less isolated loco-regional recurrences were observed (hazard ratio 0.63 (95% CI 0.44-0.91)). No significant interaction effects were observed. It is concluded that young age and breast conserving therapy are both independent predictors for isolated loco-regional recurrence. As an isolated loco-regional recurrence is a potentially curable condition, women treated with breast conservation or diagnosed with breast cancer at a young age should be monitored closely to detect local recurrence at an early stage.

Adult↗

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ.

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696-13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126-28.926; HR=2.778, 95% CI 0.982-6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272-5.776 for time period 1992-1995 and HR=1.976, 95% CI 0.526-7.421 for time period 1996-1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS.

Adult↗

Effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences after treatment for early-stage invasive breast cancer: a meta-analysis and systematic review.

PURPOSE: To review the effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences in asymptomatic patients after treatment for early-stage invasive breast cancer. METHODS: Systematic review and meta-analysis. The proportion of isolated locoregional recurrences diagnosed during routine visits or routine tests in asymptomatic patients was compared with the proportion of isolated locoregional recurrences in symptomatic patients. RESULTS: Twelve studies that involved a total of 5,045 patients and 378 isolated locoregional recurrences were identified. Pooling data showed an overall estimate of 40% of isolated locoregional recurrences diagnosed during routine visits or routine tests in asymptomatic patients (95% CI, 35 to 45). Of these, 47% (95% CI, 39 to 54) were diagnosed after mastectomy, and 36% (95% CI, 28 to 43) were diagnosed after breast-conserving therapy (relative risk, 1.327; 95% CI, 1.014 to 1.738). Apart from differences in therapy, we have not been able to discern subgroups of patients for whom results were different. CONCLUSION: Approximately 40% of isolated locoregional recurrences are diagnosed during routine visits and routine tests in asymptomatic patients treated for early-stage invasive breast cancer. We could not assess whether these were detected by either physical examination or other tests, nor if the detection of asymptomatic isolated recurrences had any influence on potential for cure or quality of life. As the overall quality of the included studies and the overall incidence of isolated locoregional recurrences are low, this systematic review highlights the need for prospective comparative studies on cost-effective strategies for the follow-up of patients after a diagnosis of breast cancer.

Aftercare↗

Patient's needs and preferences in routine follow-up after treatment for breast cancer.

The purpose of the study was to analyse the needs of women who participated in a routine follow-up programme after treatment for primary breast cancer. A cross-sectional survey was conducted using a postal questionnaire among women without any sign of relapse during the routine follow-up period. The questionnaire was sent 2-4 years after primary surgical treatment. Most important to patients was information on long-term effects of treatment and prognosis, discussion of prevention of breast cancer and hereditary factors and changes in the untreated breast. Patients preferred additional investigations (such as X-ray and blood tests) to be part of routine follow-up visits. Less satisfaction with interpersonal aspects and higher scores on the Hospital Anxiety and Depression Scale (HADS) scale were related to stronger preferences for additional investigation. Receiving adjuvant hormonal or radiotherapy was related to a preference for a more intensive follow-up schedule. There were no significant differences between patients treated with mastectomy compared to treated with breast-conserving therapy. During routine follow-up after a diagnosis of breast cancer, not all patients needed all types of information. When introducing alternative follow-up schedules, individual patients' information needs and preferences should be identified early and incorporated into the follow-up routine care, to target resources and maximise the likelihood that positive patient outcomes will result.

Adult↗

Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant.

BACKGROUND: The germline CHEK2*1100delC variant has been associated with breast cancer in multiple case families where involvement of BRCA1 and BRCA2 has been excluded. METHODS: We have investigated the tumour characteristics and prognosis of carriers of this germline variant by means of a prospective cohort study in an unselected cohort of 1084 consecutive patients with primary breast cancer. Data were collected for 34 patients with a germline CHEK2*1100delC mutation and for 102 patients without this mutation, stratified by age and date of diagnosis of the first primary breast cancer (within 1 year). RESULTS: Carriers developed steroid receptor positive tumours (oestrogen receptor (ER): 91%; progesterone receptor (PR): 81%) more frequently than non-carriers (ER: 69%; PR: 53%; p = 0.04). Mutation carriers more frequently had a female first or second degree relative with breast cancer (p = 0.03), or had any first or second degree relative with breast or ovarian cancer (p = 0.04). Patients with the CHEK2 variant had a more unfavourable prognosis regarding the occurrence of contralateral breast cancer (relative risk (RR) = 5.74; 95% confidence interval (CI) 1.67 to 19.65), distant metastasis-free survival (RR = 2.81; 95% CI 1.20 to 6.58), and disease-free survival (RR = 3.86; 95% CI 1.91 to 7.78). As yet, no difference with respect to overall survival has been found at a median follow up of 3.8 years. CONCLUSION: We conclude that carrying the CHEK2*1100delC mutation is an adverse prognostic indicator for breast cancer. If independently confirmed by others, intensive surveillance, and possibly preventive measures, should be considered for newly diagnosed breast cancer cases carrying the CHEK2*1100delC variant.

Adult↗

Risk estimation for healthy women from breast cancer families: new insights and new strategies.

Risk estimation in breast cancer families is often estimated by use of the Claus tables. We analyzed the family histories of 196 counselees; compared the Claus tables with the Claus, the BRCA1/2, the BRCA1/2/ models; and performed linear regression analysis to extend the Claus tables with characteristics of hereditary breast cancer. Finally, we compared the Claus extended method with the Claus, the BRCA1/2, and the BRCA1/2/u models. We found 47% agreement for Claus table versus Claus model; 39% agreement for Claus table versus BRCA1/2 model; 48% agreement for Claus table versus BRCA1/2/u model; 37% agreement for Claus extended method versus Claus model; 44% agreement for Claus extended model versus BRCA1/2 model; and 66% agreement for Claus extended method versus BRCA1/2/u model. The regression formula (Claus extended method) for the lifetime risk for breast cancer was 0.08 + 0.40 (*) Claus Table + 0.07 (*) ovarian cancer + 0.08 (*) bilateral breast cancer + 0.07 (*) multiple cases. This new method for risk estimation, which is an extension of the Claus tables, incorporates information on the presence of ovarian cancer, bilateral breast cancer, and whether there are more than two affected relatives with breast cancer. This extension might offer a good alternative for breast cancer risk estimation in clinical practice.

Breast Neoplasms↗

[Summary of the Dutch College of General Practitioners' practice guideline 'Diagnosis of breast cancer'].

The general practitioner should encourage women aged 50-75 who are eligible for the national screening program for the early detection of breast cancer to participate. When any abnormalities are seen on the mammogram, the general practitioner should refer the woman for further investigations and inform her about the procedure to be followed. In the case of a lump, a mammogram or ultrasound examination of the breasts is indicated, unless the abnormality disappears during a different phase of the woman's menstrual cycle. Local pain and brown or bloody discharge from the nipples also necessitate further investigation. Women with a greater than 20% risk of ever developing breast cancer during their life based on a positive family history for breast cancer have an indication for periodic examination of the breasts and a mammogram before they are 50. If the risk is greater than 30%, consultation with a clinical geneticist can be suggested.

Age Factors↗

Possible consequences of applying guidelines to healthy women with a family history of breast cancer.

Possible effects of consistently applying published guidelines on healthy women with breast cancer in their family history were analysed. We investigated 1060 unrelated breast cancer patients and calculated the numbers of first-degree relatives that would be referred to a familial cancer clinic if the guidelines were consistently applied. A first-degree relative was considered a candidate for referral if she was female, without breast cancer at the moment of the interview, alive and over the age of 24. The criteria for referral were based on one Dutch and two British guidelines. According to the Dutch guideline, for one affected woman with breast cancer, 0.25 (95% CI 0.22-0.28) healthy first-degree female relatives should be offered a consultation at a familial cancer clinic (FCC). Application of the British guidelines would lead to a similar number of referrals. Of all healthy first-degree female relatives, who should be referred to an FCC, 34-37% had an index case among their family who was already known at a genetic department. If current guidelines are consistently applied, a sharp increase in referrals to FCCs may be expected. These guidelines, however, are arbitrary and only limited data are available on the efficacy of this surveillance for high-risk healthy women.

Aged↗

Women's interest in GP-initiated pre-conception counselling in The Netherlands.

BACKGROUND: Pre-conception counselling has the potential to reduce pregnancy complications and congenital disorders. The timing of counselling, before conception, is crucial to maximize the benefit. As many couples are unaware of their risk status and the fact that the first period of pregnancy is crucial, they do not seek information before pregnancy occurs. To reach couples with timely information, it seems that a health care worker needs to take the initiative. In The Netherlands, the GP is in an ideal position to offer pre-conception counselling. OBJECTIVE: The aim of this study was to determine the interest of women aged 18-40 in pre-conception counselling if this is offered to them by their own GP. METHOD: A cohort of women (n = 1206) received a personal letter from their own GP with an offer of pre-conception counselling. The women were requested to fill in a reply form, indicating if they were interested, might be interested (if they decided to become pregnant) or were not interested in an invitation for pre-conception counselling. When interested, they were asked to give an indication as to when they were planning a pregnancy. Women who were not interested were requested to give a reason. RESULTS: Almost 70% of the women returned the reply form. Up to the age of 29 years, at least 80% of the respondents were interested or might be interested should they decide to have children. Most women, especially the younger women, do not know exactly when they wish to become pregnant. Regardless of age, >70% of the respondents were interested. Only 11% of the respondents indicated specifically that they were not interested in advice. CONCLUSION: Women are interested in GP-initiated pre-conception counselling. Further research is needed to assess the effect of programmed and systematic pre-conception counselling, offered by GPs, on pregnancy outcome and the health of the children. A randomized controlled trial to assess these effects currently is being conducted at the Department of General Practice in Leiden.

Adolescent↗