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C J H van de Velde

Publications and source records attributed to C J H van de Velde.

At least 19 recordsLinked to original sources

Gastric cancers in young and elderly patients show different genomic profiles.

Although most gastric cancers occur in elderly patients, a substantial number of cases of this common disease occur in young patients. Gastric cancer is a heterogeneous disease at the genomic level and different patterns of DNA copy number alterations are associated with different clinical behaviour. The aim of the present study was to explore differences in DNA copy number alterations in relation to age of onset of gastric cancer. DNA isolated from 46 paraffin-embedded gastric cancer tissue samples from 17 patients less than 50 years of age [median 43 (21-49) years] and 29 patients greater than or equal to 70 years of age [median 75 (70-83) years] was analysed by genome-wide microarray comparative genomic hybridization (array CGH) using an array of 5000 BAC clones. Patterns of DNA copy number aberrations were analysed by hierarchical cluster analysis of the mode-normalized and smoothed log(2) ratios of tumour to normal reference fluorescence signal intensities using TMEV software, after which cluster membership was correlated with age group. In addition, supervised analysis was performed using CGH Multi-array. Hierarchical cluster analysis of the array CGH data revealed three clusters with different genomic profiles that correlated significantly with age (p = 0.006). Cluster 1 mainly contained young patients, while elderly patients were divided over clusters 2 and 3. Chromosome regions 11q23.3 and 19p13.3 contributed most to age-related differences in tumour profiles. Gastric cancers of young and old patients belong to groups with different genomic profiles, which likely reflect different pathogenic mechanisms of the disease.

Adult↗

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↗

How important is the opinion of significant others to cancer patients' adjuvant chemotherapy decision-making?

GOALS: Decisions regarding adjuvant chemotherapy are difficult, since value tradeoffs are involved. Little is known about the importance of the significant others in patients' decision-making regarding adjuvant treatment. We surveyed patients with breast and colorectal cancer about the importance they assigned to the opinions of their significant others and assessed correlates of these importance scores. MATERIALS AND METHODS: One hundred and twenty-three patients rated on a five-point scale how much they cared about the opinion of six significant others. MAIN RESULTS: Most important was the opinion of their treating specialist, followed by that of their partner, children, other family, friends, and colleagues. Women assigned higher scores to the opinion of their children, younger patients to that of their specialist, and patients who were about to undergo chemotherapy to that of their family. Patients with breast cancer and patients without paid employment assigned slightly more importance to the opinion of their partner. CONCLUSIONS: Information on the influence of significant others may help clinicians when involving patients in treatment decision-making and discussing patients' treatment preferences.

Adult↗

Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer.

Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7(-181A>G). In addition, the genotype distribution of MMP-7(-181A>G) was associated with Helicobacter pylori status (chi(2) 7.8, P=0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2(303C>T) correlated significantly with the WHO classification (chi(2) 5.9, P=0.03) and also strongly with tumour-related survival (log rank 11.74, P=0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2(-1306C>T) polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7(-181A>G) and TIMP-2(303C>T) polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7(-181A>G) and TIMP-2(303C>T), may be helpful in identifying gastric cancer patients with a poor clinical outcome.

Adult↗

Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer.

In a pioneer study, we showed 10 years ago that enhanced tissue levels of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in gastric cancers, as determined by zymography, were related with worse overall survival of the patients. To corroborate these observations, we now assessed MMP-2 and MMP-9 with new techniques in an expanded group of gastric cancer patients (n = 81) and included for comparison MMP-7, MMP-8 and the tissue inhibitors of MMPs, TIMP-1 and -2. All MMPs and TIMP-1 were significantly increased in tumour tissue compared to normal gastric mucosa. Matrix metalloproteinase-7, -8 and -9, and the TIMPs showed some correlations with the clinicopathologic parameters TNM, WHO and Laurén classification, but their levels were not related with survival. Regardless of the determination method used, that is, enzyme-linked immunosorbent assay or bioactivity assay, an enhanced tumour MMP-2 level did not show a significant correlation with any of the clinicopathological parameters, but was confirmed to be an independent prognostic factor in gastric cancer.

Adult↗

Prognostic relevance of occult tumour cells in lymph nodes in colorectal cancer.

AIMS: Presently, in Europe the treatment of node-negative colorectal cancer (CRC) patients consists of surgical resection of the primary tumour without adjuvant systemic therapy. However, up to 30% of these patients will develop disease recurrence. These high-risk patients are possibly identified by occult tumour cell (OTC) assessment in lymph nodes. In this paper, studies on the clinical relevance of OTC in lymph nodes are reviewed. METHODS: A literature search was conducted in the National Library of Medicine by using the keywords colonic, rectal, colorectal, neoplasm, adenocarcinoma, cancer, lymph node, polymerase chain reaction, mRNA, immunohistochemistry, micrometastases and isolated tumour cells. Additional articles were identified by cross-referencing from papers retrieved in the initial search. RESULTS: The upstaging percentages through OTC assessment and the prognostic relevance of OTC in lymph nodes vary among studies, which is related to differences in techniques used to detect OTC. CONCLUSIONS: We conclude that OTC examination techniques should be standardized to illuminate whether OTC in lymph nodes can reliably identify high-risk node-negative patients.

Antibodies, Neoplasm↗

Recent trends and future perspectives in isolated hepatic perfusion in the treatment of liver tumors.

Isolated hepatic perfusion (IHP) involves a method of complete vascular isolation of the liver to enable treatment of liver tumors with high drug doses without systemic toxicity. Recent clinical studies have mainly employed IHP with melphalan with or without tumor necrosis factor-alpha and mild hyperthermia. The results of these studies demonstrate that high response and survival rates can be achieved with IHP. The current status, recent developments and future perspectives of IHP are discussed in this review.

Animals↗

Long-term survival with non-proportional hazards: results from the Dutch Gastric Cancer Trial.

Randomized clinical trials with long-term survival data comparing two treatments often show Kaplan-Meier plots with crossing survival curves. Such behaviour implies a violation of the proportional hazards assumption for treatment. The Cox proportional hazards regression model with treatment as a fixed effect can therefore not be used to assess the influence of treatment of survival. In this paper we analyse long-term follow-up data from the Dutch Gastric Cancer Trial, a randomized study comparing limited (D1) lymph node dissection with extended (D2) lymph node dissection. We illustrate a number of ways of dealing with survival data that do not obey the proportional hazards assumption, each of which can be easily implemented in standard statistical packages.

Aged↗

Explaining differences in attitude toward adjuvant chemotherapy between experienced and inexperienced breast cancer patients.

PURPOSE: Previous studies have shown that patients who have experienced adjuvant chemotherapy (experienced patients) have a more favorable attitude towards chemotherapy than those who have not (inexperienced patients). However, not much is known about the reasons underlying this difference. According to the Theory of Planned Behavior, the attitude towards a particular behavior (eg, accepting chemotherapy) is based on beliefs about the likelihood of outcomes of the behavior and the evaluations of these outcomes. We used this theory to explore in what way the beliefs of experienced patients differed from those of inexperienced patients. PATIENTS AND METHODS: A cross-sectional survey was undertaken among 719 patients who had been treated for early-stage breast cancer between 1998 and 2003. Patients were asked, first, to indicate the likelihood of six positive and six negative outcomes of undergoing chemotherapy and, second, to give their evaluation of these outcomes. RESULTS: Four hundred forty-six women filled in the questionnaire (response rate, 62%). As hypothesized, experienced patients (ie, patients who had been treated with adjuvant chemotherapy as part of their primary treatment plan) had a more positive attitude towards chemotherapy. Experienced patients provided higher likelihood estimates of treatment advantages, such as life prolongation. In addition, they evaluated the positive outcomes of chemotherapy more favorably. With regard to the negative outcomes of chemotherapy, few differences were observed between treatment groups. CONCLUSION: Experienced patients have more confidence in the positive outcomes of chemotherapy than inexperienced patients. This might be the result of a cognitive mechanism to justify the way in which patients were treated.

Adaptation, Physiological↗

[The 4th large meta-analysis of all trials of the treatment of operable breast cancer: increased survival after a longer follow-up].

The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) was founded in 1983. The EBCTCG coordinates the quinquennial worldwide meta-analyses of centrally located data on women in all randomised trials of early breast cancer. This 4th meta-analysis, with a follow-up of 15 years, showed an increased survival after the use of adjuvant hormonal or chemotherapy. The EBCTCG analyses have been responsible for major changes in the treatment of breast cancer in the past. However, we do not need another meta-analysis before implementing, for example, the improvement of chemotherapy with taxoids and the improvement of hormonal treatment with aromatase inhibitors. Nowadays, new treatments are implemented before the 5-year follow-up and are aimed more specifically at certain tumour characteristics.

Antineoplastic Agents↗

Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study.

PURPOSE: Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision (TME). This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 x 5 Gy radiotherapy and TME. Also, hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment. PATIENTS AND METHODS: Long-term morbidity was assessed in patients from the prospective randomized TME trial, which investigated the efficacy of 5 x 5 Gy before TME surgery for mobile rectal cancer. Dutch patients without recurrent disease were sent a questionnaire. RESULTS: Results were obtained from 597 patients, with a median follow-up of 5.1 years. Stoma function, urinary function, and hospital treatment rates did not differ significantly between the treatment arms. However, irradiated patients, compared with nonirradiated patients, reported increased rates of fecal incontinence (62% v 38%, respectively; P < .001), pad wearing as a result of incontinence (56% v 33%, respectively; P < .001), anal blood loss (11% v 3%, respectively; P = .004), and mucus loss (27% v 15%, respectively; P = .005). Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone. CONCLUSION: Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.

Adult↗

[The multidisciplinary breast cancer care team: promoting better care].

Breast cancer is the most commonly diagnosed form of cancer in women in the Western world. Various sorts of therapies are available and treatment plans are becoming more and more complex. The treatment of breast cancer is based on several prognostic and predictive factors, of which the TNM-classification is the best known. However, several new factors have been discovered and implemented over the past decade. As well as these, economic factors and doctor- and patient-related factors are also important. As a consequence of the multitude of factors and the ensuing complexity of treatment, it has become impossible for a single doctor to coordinate the complete treatment of a patient. Therefore, it seems obvious that patients with breast cancer should be managed by a breast cancer care team. Specialists and nurses from different disciplines are represented within this team, with the advanced practice nurse as the primary contact person. This type of team helps to lower mortality, improve quality of care and lower associated costs.

Breast Neoplasms↗

Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer.

We have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At 10 years from the date of salvage treatment, the overall survival rate for the 226 patients with invasive local recurrence was 39% (95% CI, 32-46), the distant recurrence-free survival rate was 36% (95% CI, 29-42), and the local control rate (i.e., survival without subsequent local recurrence or local progression) was 68% (95% CI, 62-75). Among patients with a local recurrence at or near the original tumour site a better distant disease-free survival was observed for patients with recurrences measuring 1cm or less, compared to those with larger recurrences. This suggests, though does not prove, that early detection of local recurrence can improve the treatment outcome but might as well point towards a different biologic behaviour, facilitating early detection.

Adult↗

[The abdominal compartment syndrome].

In two patients, a man aged 67 and a woman aged 80, an abdominal compartment syndrome was diagnosed. The man had been treated surgically for an abdominal aortic aneurysm; he recovered after re-operation. The woman had been treated by sigmoidectomy because of ileus. A Bogota bag and a vacuum-assisted wound-closure system were applied to the abdominal wound. Her condition deteriorated, an intestinal perforation became apparent, of which she did not recover and died. An abdominal compartment syndrome should always be kept in mind when a patient at risk presents with increased intra-abdominal pressure and at least one of the following symptoms: oliguria, decreased cardiac output, increased pulmonary-artery pressure, hypotension and acidosis. Measurement of the bladder pressure remains the method of choice to establish the abdominal pressure level. However, there is a lack of correlation between the measured pressure and the clinical condition of the patient. Therefore, the combination of clinical findings and the observed trend in serial measurements of the bladder pressure is preferred to a single pressure measurement.

Abdomen↗

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↗

[The treatment of patients with gastric carcinoma based on the results of Dutch studies].

--The extent of lymph-node dissection in gastrectomy for gastric carcinoma and the use of adjuvant or neo-adjuvant chemotherapy is a matter still under discussion. Only radical resection can offer a cure. --Non-randomised studies show that extended lymph-node dissections are more advantageous than less extended dissections. None of the randomised trials confirms this. The associated statistically significant higher morbidity and mortality offsets its long-term advantageous effect on survival. --If procedures that increase morbidity and mortality such as pancreatectomy and splenectomy can be avoided, then extended lymph-node dissections are more advantageous. --In cases of inadequate dissection (i.e. less than 15 lymph nodes removed) adjuvant radiochemotherapy confers an advantage. If adequate dissection is carried out, this advantage is not present. --To date there is no indication for adjuvant or neo-adjuvant chemotherapy. --To improve the results of treatment for gastric carcinoma in Western countries and to simplify trial participation, treatment for patients with gastric carcinoma should be centralised.

Carcinoma↗

Risk factors for anastomotic failure after total mesorectal excision of rectal cancer.

BACKGROUND: Anastomotic leakage is a major complication of rectal cancer surgery. The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision (TME). METHODS: Between 1996 and 1999, patients with operable rectal cancer were randomized to receive short-term radiotherapy followed by TME or to undergo TME alone. Eligible Dutch patients who underwent an anterior resection (924 patients) were studied retrospectively. RESULTS: Symptomatic anastomotic leakage occurred in 107 patients (11.6 per cent). Pelvic drainage and the use of a defunctioning stoma were significantly associated with a lower anastomotic failure rate. A significant correlation between the absence of a stoma and anastomotic dehiscence was observed in both men and women, for both distal and proximal rectal tumours. In patients with anastomotic failure, the presence of pelvic drains and a covering stoma were both related to a lower requirement for surgical reintervention. CONCLUSION: Placement of one or more pelvic drains after TME may limit the consequences of anastomotic failure. The clinical decision to construct a defunctioning stoma is supported by this study.

Adult↗