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Biomedical subjects

C J van de Velde

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

At least 19 recordsLinked to original sources
PubMed2005

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↗
PubMed2001

Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902.

PURPOSE: To evaluate whether preoperative neoadjuvant chemotherapy in patients with primary operable breast cancer results in better overall survival (OS) and relapse-free survival rates and whether preoperative chemotherapy permits more breast-conserving surgery procedures than postoperative chemotherapy. PATIENTS AND METHODS: Six hundred ninety-eight breast cancer patients (T1c, T2, T3, T4b, N0 to 1, and M0) were enrolled onto a randomized phase III trial that compared four cycles of fluorouracil, epirubicin, and cyclophosphamide administered preoperatively versus the same regimen administered postoperatively (the first cycle administered within 36 hours after surgery). Patients were followed up for OS, progression-free survival (PFS), and locoregional recurrence (LRR). RESULTS: At a median follow-up of 56 months, there was no significant difference in terms of OS (hazards ratio, 1.16; P =.38), PFS (hazards ratio, 1.15; P =.27), and time to LRR (hazards ratio, 1.13; P =.61). Fifty-seven patients (23%) were downstaged by the preoperative chemotherapy, whereas 14 patients (18%) underwent mastectomy and not the planned breast-conserving therapy. CONCLUSION: The use of preoperative chemotherapy yields similar results in terms of PFS, OS, and locoregional control compared with conventional postoperative chemotherapy. In addition, preoperative chemotherapy enables more patients to be treated with breast-conserving surgery. Because preoperative chemotherapy does not improve disease outcome compared with postoperative chemotherapy, future trials should involve quality-of-life studies to investigate whether patients will benefit from this treatment modality.

Aged↗
PubMed2001

Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.

BACKGROUND: Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision. METHODS: We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and quality-control measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques. RESULTS: Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001). CONCLUSIONS: Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.

Adenocarcinoma↗
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

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

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

Tumor structure and extracellular matrix as a possible barrier for therapeutic approaches using immune cells or adenoviruses in colorectal cancer.

In this article we report about the role that tumor structure and extracellular matrix (ECM) may play in immunotherapy and in gene therapy using adenoviruses. We performed studies in a rat model for colorectal cancer, CC531, and in specimens of human colorectal cancer. The tumors were composed of two compartments, tumor cell nests surrounded by stromal cells. ECM proteins were expressed in the stromal part, where the blood vessels were also located. Furthermore, in several tumors, the tumor cell nests were surrounded by basal membrane-like structures. Therefore, in vascular approaches to treat cancer, therapeutic agents on their route to tumor cells may be hampered by ECM to reach tumor cells. We found that immune cells were abundantly present in tumors from colorectal origin. These cells were, however, not found in direct contact with tumor cells, but mainly in the stromal part of the tumor. Adenoviruses, when intravascularly injected, did not reach tumor cells in the CC531 rat model. Tumor cells were only infected, and even then in limited numbers, in cases of intratumoral injection. We hypothesize that ECM in a tumor is a barrier both for immune cells and for adenoviruses to make direct contact with these tumor cells, and thus limits colorectal tumor therapy.

Adenoviridae↗
PubMed2001

Quality assurance in surgical oncology (QASO) within the European Organization for Research and Treatment of Cancer (EORTC): current status and future prospects.

The European Organization for Research and Treatment of Cancer (EORTC) has a long history in the development of quality assurance, in particular in radio- and chemotherapy. Quality assurance in surgical oncology is considered to be more complicated, because it is a multistep procedure depending on the individual. Because of the growing importance of the quality of surgical intervention in the multi-modality treatment approach of most cancers, the EORTC recently decided to investigate the current status of quality assurance programmes, both outside and within, the EORTC. The review of EORTC involvement in this area has been conducted on the basis of interviews with subcommittee chairmen and Data Center teams of the EORTC clinical research groups. In addition, clinical trial protocols, case report forms (CRFs) and publications by the EORTC groups related to this field were considered as possible sources of information. Several methods have been used or are currently under investigation to ensure the quality of surgery within clinical trials. These include review of reported data, standardisation of surgery and pathology forms, training sessions and site visits. However, there has been no attempt to harmonise these initiatives across the different medical specialties. The EORTC will have to address this problem within its short-term scientific strategy.

Clinical Protocols↗
PubMed2001

Improved survival after one course of perioperative chemotherapy in early breast cancer patients. long-term results from the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854.

The aim of this study was to examine whether one course of perioperative polychemotherapy yields better results in terms of survival, progression-free survival (PFS) and locoregional control than surgery alone in early stage breast cancer. From 1986 to 1991, 2795 patients with stage I/II breast cancer were randomised to receive either one perioperative course of an anthracycline-containing chemotherapeutic regimen within 36 h after surgery or surgery alone. Patients were followed-up for overall survival, PFS and locoregional recurrence. The median follow-up period at time of the analysis was 11 years. PFS and locoregional control were significantly better (P=0.025 and P=0.004, respectively) in the perioperative chemotherapy arm. Node-negative patients seemed to benefit most from the perioperative FAC. Patients who received perioperative chemotherapy and locoregional therapy alone had significantly better overall survival rates than patients who received locoregional therapy alone (P=0.004). Patients who received additional systemic therapy did not seem to benefit from one course of perioperative chemotherapy (P=0.65). One course of perioperative polychemotherapy does improve PFS and locoregional control in early stage breast cancers. This effect is still present after 11 years of follow-up.

Adult↗
PubMed2001

Role of NK cells in adoptive immunotherapy of metastatic colorectal cancer in a syngeneic rat model.

This article reviews our immunotherapy research with natural killer (NK) cells in a syngeneic rat colorectal cancer liver and lung metastasis model. Using adoptive transfer of interleukin (IL)-2-activated NK cells, NK cells were shown to selectively infiltrate the tumors. More NK cells were found in tumors when the NK cells were directly injected into tumor-draining blood vessels than when the cells were injected in systemic blood vessels. Under optimal conditions, a limited, though significant, effect of adoptively transferred NK cells on tumor growth was shown. We observed that both endogenous and adoptively transferred NK cells were predominantly present in the stroma surrounding the tumor cell nodules. It is possible that they did not penetrate the nodules containing the tumor cells because of the presence of a basal membrane-like structure around these nodules. Adoptively transferred NK cells may initiate elimination of tumor cells by activating other effector cells, whereas some may eliminate tumor cells by direct cell-cell contact. A diverse array of molecules was shown to be involved in this process. CD45 on NK cells was found to be important in initiating the lysis-inhibitory signal upon binding of 'self' major histocompatibility complex (MHC) class I on potential target cells. Our results indicate that NK-cell cancer therapy is still promising and needs improvement.

Animals↗
PubMed2001

Major liver resection results in a changed plasma amino acid pattern as reflected by a decreased Fischer ratio which improves by bactericidal/permeability increasing protein.

BACKGROUND/AIMS: Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). PATIENTS AND METHODS: Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day. RESULTS: In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure. CONCLUSIONS: Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.

Adult↗
PubMed2001

Caspase-3 activity as a prognostic factor in colorectal carcinoma.

Several techniques to determine apoptotic frequencies in tumors have been described. In this study, we report that biochemical detection of enzymatic caspase-3 activity is a simple and quantitative technique to measure apoptosis in colorectal tumor cells. The relevance of the level of apoptosis in colorectal cancer for the clinical course remains unclear. Therefore, we studied the correlation between caspase-3 activity and prognosis of the disease in relation to different factors known to be involved in apoptosis induction. High caspase-3 activity significantly correlated with a higher risk of recurrence and was preferentially found in tumors of the right side of the colon. No correlation was detected between high caspase-3 activity and altered protein expression of p53, beta-catenin, or proteins of mismatched repair genes. This indicates that high caspase-3 activity has no evident correlation with the genetic Wnt-signaling or the mismatch repair mutational pathways. The caspase-3 activity significantly correlated with CD57(+) tumor infiltrating cells. Therefore, high caspase-3 activity in right-sided tumors might be induced by a specific lymphocytic reaction.

Apoptosis↗
PubMed2001

The phenotypic heterogeneity of human natural killer cells: presence of at least 48 different subsets in the peripheral blood.

Peripheral blood natural killer (NK) cells are usually defined as a homogeneous cell population. However, NK cells show heterogeneous expression of a diversity of cell surface molecules, which might reflect the diversity of NK-cell functions. Therefore, a more specific phenotypic definition of NK cells is necessary. In this study, we made an inventory of phenotypic subsets that are present within the peripheral blood NK-cell population of healthy donors based on differential expression of nine cell-surface markers. Using three-colour flow cytometric analysis we were able to define at least 48 different CD56(+) NK-cell subsets within the peripheral blood. This phenotypic heterogeneity appeared to be stable among healthy individuals, and was also steady within CD56(dim) and CD56(bright) NK populations, indicating a possible role for these subsets in NK-cell function or differentiation.

Adult↗
PubMed2001

Primary pheochromocytoma extending into the right atrium: report of a case and review of the literature.

Pheochromocytoma rarely extends locally into the vena cava or the right atrium. We report a case of malignant pheochromocytoma with growth into the inferior vena cava, extending into the right atrium, address clinical aspects of this tumour and review the literature on this malignancy. Pre-operative work-up of this tumour should include measurements of urinary vanillyl mandelic acid and cathecholamine excretion, MRI and spiral CT of the abdomen and thorax. After the diagnosis is made the patient should be treated with catecholamine alpha-receptor blockade and if necessary with subsequent beta-receptor blockade. An aggressive surgical approach is always warranted, even in cases with very large localized tumours, because surgery has been shown to lead to relief of symptoms and to prolong survival in cases otherwise deemed irresectable. The optimal surgical exposure is obtained via a transsternal midline thoraco-laparotomy. If feasible, a combination of cardiopulmonary bypass, hypothermia, cardiac arrest and exsanguination procedures should be used. In case of local of tumour remnants after surgery or distant metastases treatment options are secondary surgery, tumour embolization, or treatment with radioactive labelled drugs, including(131)I-MIBG.

Adrenal Gland Neoplasms↗
PubMed2001

Genetic cancer syndromes and large-scale gene expression analysis: applications in surgical oncology.

The last decade of the 20th century was characterized by an explosion in genetic discoveries. The Human Genome Project and technical advances have made it possible to unravel many genetic abnormalities underlying cancer. Many genes responsible for inherited cancer syndromes have been identified and diagnostic tests are readily available. The clinical implications of these tests are currently under debate. Large-scale gene expression analysis enables simultaneous monitoring of expression of thousands of genes, in vitro and in vivo. The identification of high risk patients and drug responsiveness, can be studied within the framework of complex molecular networks. This article will focus on the possibilities for surgical oncology.

Breast Neoplasms↗
PubMed2001

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.

Abdomen↗