G Griffioen

Technische Universität München, München, Bavaria, Germany

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Publications (132)739.54 Total impact

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    ABSTRACT: Carcinogenesis in the human colon is associated with a marked increase in the tissue content of the urokinase-type plasmmogen activator (u-PA). This study was performed to determine the type of cells responsible for the u-PA increase in carcinomas of the colon and in their precursor lesions, the adenomas, by immunohistological evaluation applying monoclonal antibody 3689 directed to the β-chain of u-PA. Normal intestinal mucosa (n= 17) showed hardly any staining of u-PA, but some lamina propria cells were faintly positive. Carcinomas (n= 17) and adenomas (n= 16) showed a considerable and comparable staining intensity of u-PA in neoplastic columnar epithelial cells, and this staining was found to be diffuse and cytoplasmic. In a majority of the neoplastic tissues the u-PA staining was found to be patchy and not related to known risk markers of malignancy such as dysplasia in the adenomas, or to prognostic determinants such as Dukes' classification or differentiation in the carcinomas. The observation of strong u-PA positive lamina propria cells in adenomas but infrequently observed in normal mucosa and carcinomas was noteworthy. u-PA staining intensity of the tissue sections was found to correlate well with the u-PA antigen level in the tissue extracts determined by ELISA (r= 0.52, P= 0.0001) but poorly with the u-PA activity determined enzymatically (r= 0.28, P= 0.05). In conclusion, the u-PA increase in neoplasia of the human colon can be attributed to an increased diffuse cytoplasmic content of u-PA in neoplastic columnar epithelial cells.
    No preview · Article · Apr 2007 · Histopathology
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    ABSTRACT: Enhanced antigen levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are associated with clinico-pathological parameters of the tumors and survival of patients with gastric cancer. Recently, Single Nucleotide Polymorphisms (SNPs) in MMP- and TIMP-genes have been associated with susceptibility for various diseases. In this study, 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 tumor progression, patient survival, and tissue antigen expression. Genomic DNA was isolated from tissue of 81 Caucasian gastric cancer patients and from blood of 169 controls. Genotypes were analyzed by PCR based techniques. Antigen levels for MMPs and TIMPs were determined in tissue homogenates from the same patients using specific ELISAs. Genotype distribution and allele frequencies of MMP-2, -7, -8, -9, and TIMP-1 and -2 were similar in gastric cancer patients and controls, except for MMP-7-181 A>G. In addition, the genotype distribution of MMP-7-181 A>G was associated with H. pylori status (X2 7.8, P=0.005) and tumor-related survival of the patients (Log Rank 3.57, P=0.059). SNP TIMP-2303C>T correlated significantly with the WHO classification (X2 5.9, P=0.03) and strongly with tumor-related survival (Log Rank 11.74, P=0.0006). SNPs of MMP-2, -8, -9 and TIMP-1 were not associated with tumor-related survival. Only the MMP-2-1306 C>T polymorphism, located in the promoter of the gene, correlated significantly with the protein level within the tumors. First order dendrogram cluster analysis combined with Cox analysis identified the MMP-7-181 A>G and TIMP-2303C>T polymorphism combination to have a major impact on patients survival outcome. Conclusions: Determination of MMP-related SNPs, especially MMP-7-181 A>G and TIMP-2303C>T, might be a useful tool to stratify and select patients for primary resection and (neo)-adjuvant treatment of gastric cancer aiming at better outcome. In addition, upregulated protein level of MMP-2, associated with a promoter-located SNP, is a consistent independent prognostic factor in gastric cancer.
    No preview · Article · Oct 2006 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Matrix metalloproteinases (MMPs) are involved in tissue remodelling, tumour invasion and metastasis. High levels of gelatinases MMP-2 and MMP-9 in various types of cancer tissue are associated with worse survival of the patients. Complexes of MMP-9 with neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2) were found in urine from breast cancer patients but were absent in healthy controls, suggesting a possible application as tumour marker. We analyzed the presence of MMP-9/NGAL complexes in tissue from gastric cancer patients and determined their possible clinical value. MMP-9, NGAL, and MMP-9/NGAL complexes were determined in 81 tissue homogenates from gastric cancer patients using quantitative zymography, ELISAs and a specific MMP-9 bioactivity assay. The tumour levels were examined for associations with established clinico-pathological parameters including classifications according to TNM, WHO, Laurén, and survival. Gastric carcinomas were found to have significantly increased MMP-9 (P Keywords: MMP-9; lipocalin; prognosis Document Type: Research Article DOI: http://dx.doi.org/10.1111/j.1538-7836.2006.00108.x Affiliations: 1: LUMC, Gastroenterology-Hepatology, Leiden, The Netherlands 2: University of Bieleveld, Germany 3: TNO Quality of Life, Biomedical Research, Leiden, The Netherlands Publication date: October 1, 2006 $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher In this Subject: Allergy & Immunology By this author: Sier, C. ; Kubben, F. ; Hawinkels, L. ; Tschesche, H. ; van Duijn, W. ; Zuidwijk, K. ; van der Reijden, J. ; Hanemaaijer, R. ; Griffioen, G. ; Verspaget, H. GA_googleFillSlot("Horizontal_banner_bottom");
    No preview · Article · Oct 2006 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: 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.
    Full-text · Article · Sep 2006 · British Journal of Cancer
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    ABSTRACT: 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.
    Full-text · Article · May 2006 · British Journal of Cancer
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    ABSTRACT: Crohn's disease is associated with a host of factors potentially increasing the risk for osteoporosis and fractures. The aim of our study was to identify the most predictive factors for skeletal pathology in this patients. Using a cross-sectional study design, 146 randomly selected patients with Crohn's disease of variable disease activity who were given standard therapy to control disease activity, including glucocorticoids, and who attended the outpatient clinic of the Gastroenterology Unit on regular follow-up visits were studied. Bone mineral density (BMD) measurements and lateral X-rays of the spine were performed, and biochemical parameters of bone turnover, gonadal hormones and C-reactive protein (CRP) as markers of disease activity were measured in all patients. There were 61 men and 85 women, with a mean age of 43 years and mean disease duration of 20 years. The majority of patients (86%) had been treated with glucocorticoids at some stage during their illness at a median dose of 7.5 mg/day, 43% were currently using these agents and 66% had undergone an intestinal resection. Twenty-one percent of patients had below-normal 25-hydroxy vitamin D levels. Osteoporosis was documented in 26% of patients, predominantly at the femoral neck, but also at the lumbar spine or at both sites; osteopenia was documented in 45% of patients. Prevalence of vertebral and non-vertebral fractures was, respectively, 6% and 12%. Ileum resection was the most predictive factor for osteoporosis: RR 3.84 (CI 1.24-9.77, p=0.018), followed by age: RR 1.05 (CI 1.02-1.08, p<0.001) and current or past glucocorticoid use: RR 1.94 (CI 0.92-4.10, p=0.08). Our data suggest that in patients with Crohn's disease, the risk of osteoporosis is best predicted by a history of ileum resection.
    Full-text · Article · Apr 2006 · Osteoporosis International
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    ABSTRACT: Lynch syndrome families have a substantial risk of developing colorectal cancer (CRC). The recommended surveillance protocol includes colonoscopy every 2 years from age 20-25 years. It is yet unknown whether annual screening of patients aged 40-60 years is more effective than bi-annual screening, whether patients who had an adenoma removed should be re-examined after a year and whether surveillance of second-degree relatives is indicated. The aim of this study was to address these issues. All carriers of a mismatch repair gene mutation who participated in the surveillance program were selected from the Dutch Lynch syndrome registry. The results of colonoscopy were prospectively collected. A total of 666 mutation carriers were identified in 110 families. Fourty-one CRCs were detected during endoscopic follow-up, of which 34 (83%) were diagnosed between age 40 and 60 years. In five of 34 patients, CRC was diagnosed within 1 year after colonoscopy, eight cancers were diagnosed between 1 and 2 years and the remaining tumors more than 2 years after colonoscopy. All eight CRCs detected between 1 and 2 years were at local stage. At least one adenoma was diagnosed at 141 examinations. The risk of developing CRC during follow-up in carriers with an adenoma was similar as in carriers without an adenoma at the previous colonoscopy. 280 parent-child couples with at least one Lynch syndrome-related carcinoma were identified in 110 families. In only 19 (6.8%) of these couples, CRC developed earlier in the child than an Lynch syndrome-associated cancer in the parent. The current surveillance protocol, i.e., bi-annual colonoscopy in first-degree relatives independent of age and endoscopic findings, appears to be appropriate.
    No preview · Article · Feb 2006 · Familial Cancer

  • No preview · Article · Jan 2006 · European Journal of Gastroenterology & Hepatology
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    Full-text · Article · Apr 2004 · Journal of Medical Genetics
  • RA Veenendaal · G Griffioen · C B H W Lamers
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    ABSTRACT: Barrett's oesophagus develops as a consequence of severe gastro-oesophageal reflux. The importance of Barrett's oesophagus lies in the small risk of developing high-grade dysplasia and subsequent adenocarcinoma. Because of poor treatment results in patients with advanced adenocarcinoma, surveillance of patients with Barrett's oesophagus for the development of dysplasia, although not uncontroversial, is widely practised in the gastroenterological community. The aim of surveillance is to detect adenocarcinoma in an early stadium where surgical cure is possible. In recent years several endoscopic treatments for both high-grade dysplasia and intramucosal adenocarcinoma have been developed. In this review some basic aspects of Barrett's oesophagus are discussed together with endoscopic treatments such as endoscopic mucosal resection, local thermal treatments and photodynamic therapy. Although surgical resection is probably the treatment of choice in fit patients, local endoscopic treatments should be considered in patients with high-grade dysplasia or intramucosal carcinoma who are unfit or unwilling to have surgery.
    No preview · Article · Feb 2004 · Scandinavian journal of gastroenterology. Supplement
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    ABSTRACT: In view of the high risk of developing a new primary colorectal carcinoma (CRC), subtotal colectomy rather than segmental resection or hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal cancer (HNPCC) patients. Subtotal colectomy however implies a substantial decrease in quality of life. To date, colonoscopic surveillance has been shown to reduce CRC occurrence. To compare the potential health effects in terms of life expectancy (LE) for patients undergoing subtotal colectomy or hemicolectomy for CRC. A decision analysis (Markov) model was created. Information on the 10 year risk of CRC after subtotal colectomy (4%) and hemicolectomy (16%) and stages of CRCs detected within a two year surveillance interval (32% Dukes' A, 54% Dukes' B, and 14% Dukes' C) were derived from two cohort studies. Five year survival rates used for the different Dukes stages (A, B, and C) were 98%, 80%, and 60%, respectively. Remaining LE values were calculated for hypothetical cohorts with an age at CRC diagnosis of 27, 47, and 67 years, respectively. Remaining LE values were also calculated for patients with CRC of Dukes' stage A. The overall LE gain of subtotal colectomy compared with hemicolectomy at ages 27, 47, and 67 was 2.3, 1, and 0.3 years, respectively. Specifically for Dukes' stage A, this would be 3.4, 1.5, and 0.4 years. Unless surveillance results improve, subtotal colectomy still seems the preferred treatment for CRC in HNPCC in view of the difference in LE. For older patients, hemicolectomy may be an option as there is no appreciable difference in LE.
    Full-text · Article · Jan 2004 · Gut
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    ABSTRACT: Purpose: The purpose is to document the clinical, pathological, and genetic features of pancreatic carcinoma (PC) in carriers of a specific p16-Leiden mutation (a 19-bp deletion in exon 2 of the CDKN2A gene). Experimental Design: Clinical data and paraffin embedded tissue were obtained from 12 patients of p16-Leiden-positive families with PC. Because of the known 19-bp germline deletion, we could specifically analyze the genotype of the wild-type allele for loss of heterozygosity. K-ras codon 12 mutations were determined and immunohistochemical testing for p16, Tp53, Smad4, and cyclooxygenase 2 was performed. Results: The average age of subjects that developed PC (8 males) was 58 years (range, 43-74 years). Histology was considered as conventional ductal adenocarcinoma in 11 of 12 and neuroendocrine carcinoma (1 of 12). The carcinomas were-located in the head (10 of 12), corpus (1 of 12), and tail (1 of 12) of the pancreas. The specific p16-Leiden mutation was confirmed in the tissue of all subjects. Loss of heterozygosity of the wild-type allele was present in 2 of 7 tumors analyzed. Immunostaining for p16 was negative in 10 of 10. Tp53 mutations were detected in 5 of 12. Smad4 was negative in 5 of 12 and cyclooxygenase 2 was overexpressed in 11 of 12. K-ras codon 12 mutations were present in 9 of 10 and in three precursor lesions even before abrogation of p16 protein expression was seen (one of three). Conclusions: The p16-Leiden deletion was associated with progression toward conventional ductal adenocarcinomas in all cases but one. Our observations might support the feasibility of early diagnosis of PC in p16-Leiden mutation carriers and might also indicate that chemoprevention needs consideration.
    No preview · Article · Sep 2003 · Clinical Cancer Research
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    ABSTRACT: The lifetime risk of developing duodenal cancer in familial adenomatous polyposis (FAP) is about 5 per cent. When and to what extent surgical intervention should be undertaken to prevent death from invasive carcinoma is controversial. The aim of this study was to determine the effectiveness of various surgical treatments for cancer and severe duodenal adenomatosis. A questionnaire was mailed to the members of the Leeds Castle Polyposis Group to obtain data on patients with FAP, treated for duodenal cancer or severe duodenal adenomatosis after 1990. Sixty-nine patients were included. The indication for surgery was invasive cancer in 13 patients, of whom six died from metastatic disease. Fifty-six patients were initially treated for severe duodenal adenomatosis, five (9 per cent) of whom died from metastatic disease (P = 0.002). In surviving patients, adenomas recurred after ampullectomy (six of eight, at mean follow-up of 11 months), after duodenotomy with polypectomy (17 of 21, at mean 29 months) and after pancreatoduodenectomy (six of 25, at mean 47 months). None of six patients who underwent a pancreas-sparing duodenectomy had recurrence of adenoma (mean follow-up 11 months). Surgery for duodenal adenomatosis should take place before endoscopic biopsy reveals invasive cancer. Even after extensive surgical procedures, small bowel adenomas may occur, emphasizing the need for chemoprevention.
    No preview · Article · Jul 2003 · British Journal of Surgery
  • A Pikaar · J W R Nortier · G Griffioen · H F A Vasen
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    ABSTRACT: Desmoid tumours (DT) are slow-growing tumours that consist of proliferations of well-differentiated fibroblasts. Although the typical characteristics of malignant tumours, such as distant metastases, are absent, the tumours are locally aggressive and grow into neighbouring structures. The prevalence of desmoid tumours in patients with FAP is 7-12%. The lifetime risk of developing desmoid tumours is about 20%. In FAP, most tumours are intra-abdominal or located in the abdominal wall. Next to colorectal cancer, desmoid tumours are the most frequent cause of death in FAP. Possible risk factors for the development of desmoid tumours are previous surgical procedures, pregnancy, female sex, a family history of desmoid tumours, and specific mutations in the APC-gene. Both CT scanning and MRI can be used to detect the tumours. An excision biopsy is needed to establish the diagnosis. Medicinal treatment with NSAIDs is the treatment of first choice, followed by hormonal treatment (e.g., tamoxifen) in combination with NSAIDs. Both forms of treatment lead to a response in about 30-50% of the patients. Surgery is the preferred treatment for extra-abdominal tumours or tumours located in the abdominal wall. Surgical treatment of intra-abdominal tumours is only indicated in patients with obstruction of the bowel or ureter. Chemotherapy is indicated in patients with progressive desmoid tumours when non-cytotoxic treatment has failed. Radiotherapy may play a role in the treatment of irresectable extra-abdominal or abdominal wall tumours, or as adjuvant treatment of tumours with positive margins.
    No preview · Article · Aug 2002 · Nederlands tijdschrift voor geneeskunde
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    ABSTRACT: Functional impairments are frequently observed in patients with an ileoanal pouch. Meal ingestion increases pouch tone and motility. Little is known, however, about the influence of meal-stimulated pouch characteristics on pouch function. The aim was to characterize basal and postprandial pouch motor and sensory characteristics in relation to clinical pouch function in patients with an ileoanal pouch. Nineteen patients with an ileoanal pouch, without faecal incontinence but with either a high stool frequency (n = 8) or an adequate stool frequency (n = 11), underwent pressure distension of the pouch, by which pouch compliance and sensitivity characteristics were assessed using an electronic barostat. A set pressure procedure was performed to assess the influence of a meal on pouch tone and motility. Mean(s.d.) compliance was 10(6) and 11(4) ml/mmHg in the groups with poor and adequate pouch function respectively (P not significant). Mean(s.d.) visual analogue scale scores (0-10 cm) for urge at the highest pressure of 28 mmHg were 2.3(1.0) versus 2.3(2.4) cm respectively (P not significant); those for pain were 0.8(1.0) versus 0.5(0.7) (P not significant). Postprandially mean(s.d.) pouch volume decreased by 70(24) per cent in the group with poor pouch function and 29(25) per cent in the group with adequate pouch function (P < 0.01). The frequency and amplitude of phasic pouch contractions increased significantly postprandially, but no differences in motility characteristics were observed between the two groups. In patients with uniform pouch design and follow-up after pouch construction, pouch compliance and sensitivity were no different between patients with normal and high stool frequency; however, postprandial pouch tone was increased significantly in patients with a high stool frequency.
    No preview · Article · Dec 2001 · British Journal of Surgery
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    ABSTRACT: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations. Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives. Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P < .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P < .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant. Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered.
    No preview · Article · Oct 2001 · Journal of Clinical Oncology
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    ABSTRACT: The purpose of this study is to determine the effectiveness of extensive nonsurgical management of patients with clinically active Crohn's disease of the terminal ileum and to identify parameters that could predict failure of this nonsurgical approach. All consecutive patients hospitalized for the first time because of active Crohn's disease of the terminal ileum between 1985 and 1994 were included. Two groups of patients were defined. Patients who responded favorably to the extensive treatment protocol (group I), and patients in whom an ileocolic resection had been performed (group II). Treatment and patient characteristics were related to outcome. Twenty-nine (38%) of the 76 patients were treated successfully by nonsurgical management (group I) and did not have surgery until the end of follow-up (mean 8.0 years, range 3-12 years). In total, 47 patients (62%) had ileocolic resection (group II). Logistic regression analysis revealed that a longer time between onset and exacerbation of this disease, the presence of stenosis and extraintestinal manifestations were independent predictors of failure of nonsurgical treatment. Prolonged medical treatment is effective in only one third of the clinically admitted patients. It should be applied with caution particularly in patients exhibiting stenosis, extraintestinal manifestations or a known history of Crohn's disease of more than 5 years.
    No preview · Article · Feb 2001 · Digestive Surgery
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    ABSTRACT: The objective of this study was to compare laparoscopic-assisted ileocolic resection for Crohn's disease of the distal ileum with open surgery in two consecutive groups of patients. From 1995 until 1998, 48 patients underwent open ileocolic resection at the Academic Medical Center (AMC) in Amsterdam, while 30 patients had laparoscopic-assisted ileocolic resection at the Leiden University Medical Center (LUMC). Patient characteristics, perioperative course, and recovery were compared. Differences between the groups were tested using Student's t-test for independent groups and chi-square tests when appropriate. The open and the laparoscopic patient groups were comparable for age, gender, body mass index (BMI), prior abdominal surgery, and length of resected bowel. The conversion rate was 6.6%. Laparoscopic operating times (138+/-SD 36 min) were significantly longer than those observed in the open group (104+/-SD 34 min). Discharge was significantly earlier in the laparoscopic group than the open group (5.7 vs 10.2 postoperative days, p<0.007). Postoperative morbidity did not differ significantly between the patients treated traditionally (14.6%) and laparoscopically (10%). Compared to open surgery, laparoscopic ileocolic resection for Crohn's disease is associated with similar morbidity rates, a shorter hospital stay, and improved cosmetic results, justifying the laparoscopic approach as the procedure of choice.
    Full-text · Article · Aug 2000 · Surgical Endoscopy
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    ABSTRACT: The oxidant-antioxidant balance is thought to be important in the initiation, promotion, and therapy resistance of cancer. In the present study, we assessed the expression of the antioxidants manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase in gastric and esophageal carcinomas and their relation with clinical outcome. Adenocarcinomas of the stomach (n = 81) as well as squamous cell carcinomas of the esophagus (n = 10) showed an enhanced immunohistochemical expression of Mn-SOD, which was accompanied by a significantly higher tissue level (P < or = 0.007) compared with their corresponding normal mucosa. In contrast, copper/zinc superoxide dismutase was found to be marginally lower in these malignant tissues in comparison with the normal tissues. The superoxide dismutase levels were not found to be associated with major clinicopathological features of the gastric cancer patients. Univariate analysis revealed, however, that a high Mn-SOD level in gastric carcinomas, a low level in the normal gastric mucosa, and a high ratio of these two levels in gastric cancer patients are indicative of a poor overall survival. Multivariate analysis, including all clinicopathological parameters, revealed that the Mn-SOD ratio in particular is an independent prognostic parameter in gastric cancer patients.
    No preview · Article · Aug 2000 · Clinical Cancer Research
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    ABSTRACT: Despite a high frequency of pouch function disorders, most patients are satisfied with the outcome of ileo-anal pouch surgery. Aims of this study were: 1) To assess the influence of pouch function on quality of life and, 2) to determine which aspects of pouch dysfunction affect quality of life the most. Questionnaires, addressing current pouch function and quality of life (Rand-36, GIQLI), were sent to all (53) patients with intact ileo-anal pouches, operated on between 1987 and 1997 in our center. Thirty-six of 53 patients responded. Compared to reference data, Rand-36 scores for role-limitations based on a physical problem, vitality and general health perception were significantly diminished (P < 0.01). Physical and social functioning were normal. The GIQLI score was slightly decreased (111.7 vs. 125.8, P < 0.01). Overall pouch function did not correlate with the overall Rand-36 score, but correlated well with the overall GIQLI score (r = -0.47). Both quality of life scores were diminished mainly by the night-time stool frequency. 1) Quality of life after IPAA, as measured with validated questionnaires, is only slightly decreased; 2) the GIQLI questionnaire is more sensitive to pouch dysfunction than the Rand-36; 3) night-time stool frequency influences quality of life the most.
    No preview · Article · May 2000 · Hepato-gastroenterology

Publication Stats

5k Citations
739.54 Total Impact Points


  • 2007
    • Technische Universität München
      München, Bavaria, Germany
  • 2006
    • Curium-LUMC
      Leyden, South Holland, Netherlands
  • 1988-2006
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1987-2006
    • Leiden University Medical Centre
      • Department of Gastroenterology and Hepatology
      Leiden, South Holland, Netherlands
  • 1998
    • University of Groningen
      Groningen, Groningen, Netherlands
    • Bielefeld University
      Bielefeld, North Rhine-Westphalia, Germany
  • 1995
    • TNO
      's-Gravenhage, South Holland, Netherlands
  • 1994
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1989
    • Netherlands Cancer Institute
      Amsterdamo, North Holland, Netherlands