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W Dekker

Publications and source records attributed to W Dekker.

At least 19 recordsLinked to original sources

No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis.

Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5-8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result from binding to overexpressed MDM2 protein. While these two mechanisms of p53 inactivation are considered to be mutually exclusive, no data exist as to whether MDM2 overexpression occurs during gastric carcinogenesis. MDM2 protein overexpression was therefore studied in relation to p53 protein accumulation in gastric carcinogenesis. Forty-five paraffin-embedded gastrectomy specimens from early gastric carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type was reassessed for all early carcinomas. p53 protein accumulation was examined using the monoclonal antibody DO-7. MDM2 protein overexpression was assessed with the monoclonal antibody SMP-14. Complete absence of nuclear p53 protein accumulation was observed in chronic active gastritis, chronic atrophic gastritis, and intestinal metaplasia, irrespective of the subtype. In gastric dysplasia (one mild, two moderate, one severe), only severe dysplasia was p53-positive. Intestinal-type (n = 20) and diffuse-type early gastric carcinoma (n = 25) were p53-positive in 70 and 52 per cent of the cases, respectively. MDM2 protein overexpression was not observed during gastric carcinogenesis, either in the p53-positive or in the p53-negative cases. In conclusion, it appears that functional inactivation of wild-type p53 by MDM2 protein overexpression plays no role in (early) gastric carcinogenesis.

Chronic Disease

No evidence for c-erbB-2 overexpression in gastric carcinogenesis.

AIMS: Conflicting data on c-erbB-2 overexpression in gastric carcinomas can be found in the literature with regard to overall prevalence, prognostic significance and the histological type according to Lauren. The majority of these studies have focused on advanced gastric carcinomas whereas data on c-erbB-2 overexpression in early gastric carcinomas, especially of Caucasian origin, are relatively sparse. We therefore examined a series of Caucasian early gastric carcinomas to assess overall c-erbB-2 overexpression and to correlate c-erbB-2 overexpression, if any, with the type of growth pattern and the Lauren type. METHODS AND RESULTS: Forty-five paraffin-embedded gastrectomy specimens from early carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia and dysplasia. The Lauren type and the type of growth pattern were reassessed for all early carcinomas. c-erbB-2 overexpression was assessed with monoclonal antibody 3B5 and polyclonal antibody A485. Complete absence of c-erbB-2 overexpression was observed in chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. Moreover, c-erbB-2 overexpression was found absent in both intestinal-type (n = 20) and diffuse-type early gastric carcinomas (n = 25), irrespective of growth type. CONCLUSIONS: c-erbB-2 overexpression does not play a role in the progression from normal to neoplastic gastric mucosa and should be considered as a late event in gastric carcinogenesis. Moreover, c-erbB-2 overexpression does not discriminate between intestinal and diffuse type early gastric carcinomas of Caucasian origin. Finally, it appears that mechanisms other than c-erbB-2 overexpression underlie the reported differences in biological behaviour of early gastric carcinomas with different types of growth pattern.

Gastric Mucosa

Colonic pseudo-obstruction due to beta2-microglobulin amyloidosis after long-term haemodialysis.

Beta2-microglobulin (A beta2M) amyloidosis is a relatively new secondary amyloidosis associated with renal failure and haemo- and peritoneal dialysis. Although beta2-microglobulin depositions are systemic, clinical manifestations are limited to articular and para-articular disease in most cases. A very limited number of patients have been reported with extra-articular manifestations including those of the gastrointestinal tract. We report on a patient who was treated with haemodialysis for 23 years and developed colonic pseudo-obstruction due to A beta2M amyloidosis.

Aged

CT before and after ERCP: detection of pancreatic pseudotumor, asymptomatic retroperitoneal perforation, and duodenal diverticulum.

BACKGROUND: A prospective study was done to investigate the occurrence of morphologic changes after ERCP that present as pancreatic pseudotumor on CT scan. Fifty-eight patients underwent CT before and after ERCP. In addition, post-ERCP complications and the value of routinely obtained CT before ERCP were assessed. RESULTS: Thirty-nine patients could be fully analyzed; 12 underwent a papillotomy (group 1). Pseudotumor of the pancreatic head was demonstrated on CT after ERCP in them (17%). No changes were seen in the 27 patients who underwent diagnostic ERCP (group 2) (p = 0.048). Asymptomatic retroperitoneal perforation after papillotomy was diagnosed in 3 patients (13%). Routinely obtained CT scans before ERCP defined a specific etiology of the biliary obstruction in 12% of patients not suggested by ultrasound. Duodenal diverticulum was found in 4 patients, resulting in a sensitivity of 36% and a specificity of 100% for CT. Oral contrast (600 ml) administered a few hours before endoscopy never hampered the endoscopist. CONCLUSION: Pancreatic pseudotumor on CT after ERCP occurred only when papillotomy was performed. CT remains a valuable diagnostic tool after diagnostic ERCP. Asymptomatic perforation may occur following ERCP with papillotomy. Routinely obtained CT before ERCP was not profitable for the endoscopist in more than 80% of our patients.

Cholangiopancreatography, Endoscopic Retrograde

Preliminary experience with a new ultraviolet-cured expandable plastic endoprosthesis in the management of malignant esophageal strictures.

BACKGROUND AND STUDY AIMS: Different types of expandable metal stent are currently available for the palliative treatment of malignant esophageal strictures. To overcome some of the disadvantages involved in the design of metal mesh stents, we designed a balloon-expanded plastic endoprosthesis, which is hardened by irradiation with ultraviolet light after deployment. We present here our preliminary results. PATIENTS AND METHODS: From April 1995 to January 1996, four patients with unresectable esophageal malignancies were treated with this stent. Insertion of the stent was the only palliative procedure carried out. The patients were followed up until death. RESULTS: Stent placement was successful in all patients, and no procedure-related complications occurred. Dysphagia was reduced from an average score of 2.6 to 1.0. Early complications included retrosternal pain of limited duration in one patient. One patient died 72 hours after uncomplicated stent placement, due to cardiac arrhythmia. Late complications were limited to tumor overgrowth in two patients, after a mean of 104 days. The stent patency rate averaged 92 days. CONCLUSIONS: In patients with a malignant esophageal stricture, this newly developed expandable endoprosthesis is effective in relieving dysphagia. The deployment of the stent is easy and safe. The endoprosthesis has potential advantage over current expandable metal mesh stents.

Aged

Lansoprazole 30 mg versus omeprazole 40 mg in the treatment of reflux oesophagitis grade II, III and IVa (a Dutch multicentre trial). Dutch Study Group.

OBJECTIVES: To compare the efficacy and safety of lansoprazole 30 mg daily (LAN30) and omeprazole 40 mg daily (OME40) in the treatment of moderate (Savary-Miller grade II) as well as severe reflux oesophagitis (grade III/IVa). DESIGN: A double-blind, randomized, multicentre study, involving 211 patients at 29 Dutch hospitals. METHODS: Healing was assessed by endoscopy, performed on admission, after 4 weeks and after 8 weeks if the patient was not healed after 4 weeks. Symptom relief was determined by symptom assessments at the same time points. Safety was evaluated by determining the incidence of adverse events. RESULTS: There was no significant difference in intention-to-treat (ITT) healing rates after 4 weeks (LAN30 87.5%, OME40 80.6%; 95% CI (-4.0; +17.8)) and in the ITT overall healing (LAN30 96.1%, OME40 93.1%; 95% CI (-4.2; +10.2)) rates between the LAN30 and the OME40 group. Relief of reflux-related symptoms at 4 weeks as well as 8 weeks did not differ significantly between the treatment groups. No difference in the incidence of adverse events was observed between the groups. CONCLUSION: Treatment of patients with reflux oesophagitis grade II, III or IVa with LAN30 was as effective as with OME40 with respect to healing as well as symptom relief.

2-Pyridinylmethylsulfinylbenzimidazoles

Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis. Dutch Pentasa Study Group.

OBJECTIVE: To investigate a possible dose-effect relationship with two dosages of oral slow-release mesalazine in patients with quiescent ulcerative colitis. METHOD: One hundred and sixty-nine patients with ulcerative colitis in remission were treated with either 1.5 or 3.0 g/day mesalazine for 1 year or until relapse into active colitis. RESULTS: Fewer of the 3.0 g dose group relapsed than of the 1.5 g dose group (33 compared with 46%). This difference failed to reach statistical significance (P = 0.057). A significant relationship between age and relapse rate was established. No dose-related adverse events were found. Three serious drug-related adverse events were, however, reported. All of the serious adverse reactions resolved after the medication was discontinued. CONCLUSION: There is a trend for high doses of oral mesalazine to be more effective in prevention of relapse of ulcerative colitis. These higher doses are not associated with a higher incidence of adverse reactions.

Administration, Oral

Chronology of p53 protein accumulation in gastric carcinogenesis.

p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early carcinomas were examined for the presence of chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type and the type of growth pattern were reassessed for all early carcinomas. p53 Protein accumulation was examined using the monoclonal antibody DO-7. Complete absence of p53 protein accumulation was observed in normal gastric mucosa, chronic atrophic gastritis, and intestinal metaplasia, irrespective of subtype. In gastric dysplasia (one mild, two moderate, and one severe), only severe dysplasia was p53 positive. Intestinal type (n = 20) and diffuse type early gastric carcinomas (n = 25) were p53 positive in 70% and 52% of cases, respectively. Both tumour types differed significantly in the percentage of p53 positive tumour cells per tumour (p < 0.01) and in staining intensity (p < 0.05). No significant difference in p53 protein accumulation was found between early carcinomas with different types of growth pattern. It is concluded that p53 protein accumulation--usually reflecting missense p53 gene mutation--seems to be a late event in gastric carcinogenesis. Moreover, it is suggested that missense p53 gene mutation occurs in a final pathway common to both intestinal and diffuse type of early gastric carcinoma. Finally, the types of growth pattern do not seem to differ in p53 protein accumulation.

Cell Transformation, Neoplastic

Absence of ras gene mutations in early gastric carcinomas.

The aims of this study were to assess the prevalence and type of activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes in a series of early gastric carcinomas in white patients and to correlate these ras gene mutations, if any, with the histological type (Lauren classification), the type of growth pattern, and with the Helicobacter pylori status. Haematoxylin and eosin and Giemsa stained sections from 45 formalin fixed, paraffin wax embedded early gastric carcinomas were used to assess the Lauren type, the type of growth pattern, and the antral H pylori status. DNA was extracted according to standard procedures. Mutations at codon 12 of the Ki-ras gene were examined with a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) method and dot blot hybridisation with allele-specific 32P-labelled oligodeoxynucleotide (ASO) probes. All other ras genes were analysed with specific PCR amplification and dot blot hybridisation with ASO probes. Mutations were detected by overnight autoradiography at -70 degrees C. Some 20 intestinal-type and 25 diffuse-type early gastric carcinomas were seen. According to growth pattern, there were 24 small mucosal type early gastric carcinomas, five superficial spreading type early gastric carcinomas, and 16 penetrating type early gastric carcinomas (four penetrating A type, 12 penetrating B type). H pylori was found in the antral mucosa of 28 early gastric carcinomas (62%). Activating ras gene mutations were not found. It was discovered that activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes do not play a part in the development of early gastric carcinomas in white subjects, irrespective of Lauren type. Moreover, differences in biological behaviour between early carcinomas with different types of growth pattern are not related to these ras gene mutations. Finally, H pylori positive and H pylori negative gastric carcinomas cannot be discriminated on the basis of ras gene mutational analysis.

Base Sequence

Esophageal dysfunction as a cause of angina pectoris ("linked angina"): does it exist?

PURPOSE: The differentiation between cardiac and esophageal causes of retrosternal chest pain is notoriously difficult. Theoretically, cardiac and esophageal causes may coexist. It has also been reported that gastroesophageal reflux and esophageal motor abnormalities may elicit myocardial ischemia and chest pain, a phenomenon called linked angina pectoris. The aim of this study was to assess the incidence of esophageal abnormalities as a cause of retrosternal chest pain in patients with previously documented coronary artery disease. PATIENTS AND METHODS: Thirty consecutive patients were studied, all of whom had undergone coronary arteriography. The patients were studied after they were admitted to the coronary care unit with an attack of typical chest pain. On electrocardiograms (ECGs) taken during pain, 15 patients (group I) had new signs of ischemia; the other 15 patients (group II) did not. In none of the patients were cardiac enzymes elevated. As soon as possible, but within 2 hours after admission, combined 24-hour recording of esophageal pressure and pH was performed. During chest pain, 12-lead ECG recording was carried out. RESULTS: In group I, all 15 patients experienced one or more pain episodes during admission, 25 of which were associated with ischemic electrocardiographic changes. The other two episodes were reflux-related. Only one of the 25 ischemia-associated pain episodes was also reflux-related, ie, it was preceded by a reflux episode. In group II, 19 chest pain episodes occurred in 11 patients. None of these was associated with electrocardiographic changes, but 8 were associated with reflux (42%) and 8 with abnormal esophageal motility (42%). CONCLUSION: Linked angina is a rare phenomenon.

Aged

Does color vision deficiency in the endoscopist influence the accuracy of endoscopic diagnosis? An anonymous study with Dutch gastrointestinal endoscopists.

Colors play a major role in the endoscopic diagnosis of many gastrointestinal conditions. Gastrointestinal endoscopists in the Netherlands are predominantly male (> 90%), and from population data it is to be expected that approximately 8% will have a color vision deficiency. The present study was designed to assess the prevalence of color vision deficiencies amongst Dutch gastrointestinal endoscopists and to determine whether color vision deficiency affects an endoscopist's diagnostic skill. One hundred and thirty-nine gastroenterologists and physicians of internal medicine took an F2 color vision test and assessed nine videofragments of endoscopies. Color vision deficiencies were detected in 8% of Dutch gastrointestinal endoscopists. In one out of the nine video excerpts of endoscopies, a statistically significant difference was detected between test subjects with and without a color vision deficiency. However, this video excerpt showed a green pea, which could not be mistaken for a polyp at polypectomy. The study therefore does not show any effect of color vision deficiencies on endoscopic skills, nor does it show any deviant prevalence of color vision deficiencies amongst Dutch gastrointestinal endoscopists.

Adult

Helicobacter pylori and early gastric cancer.

The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered.

Adenocarcinoma

Efficacy of famotidine 20 mg twice a day versus 40 mg twice a day in the treatment of erosive or ulcerative reflux esophagitis.

Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day) were evaluated in a double-blind, randomized multicenter study in 474 symptomatic patients with erosive ulcerative reflux esophagitis. A total of 238 patients were treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinner-time. Relief of symptoms was significant in all patients after six and 12 weeks and not different in both treatment groups. Overall endoscopic healing was significantly better in the famotidine 40 mg twice a day group compared with 20 mg twice a day at week 6 (58% versus 43%; P < 0.05) and at week 12 (76% versus 67%; P < 0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a day in those patients not healed after 12 weeks did not result in further symptom relief or in significantly better overall healing. The differences in efficacy of these two doses were more pronounced with increasing severity of esophagitis. Analyzed by grade of esophagitis at entrance, healing was significantly better with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades III and IV, and at week 24 for grade IV esophagitis. The results show that in the treatment of erosive/ulcerative reflux patients famotidine 40 mg twice a day is more effective and achieves faster healing than famotidine 20 mg twice a day.

Adolescent

Serum antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease are mainly associated with ulcerative colitis. A correlation study between perinuclear antineutrophil cytoplasmic autoantibodies and clinical parameters, medical, and surgical treatment.

Perinuclear antineutrophil cytoplasmic antibodies have recently been demonstrated in the sera of patients with inflammatory bowel disease. Three hundred and sixty six sera obtained from 120 patients with ulcerative colitis, 105 patients suffering from Crohn's disease and 49 non-inflammatory bowel disease controls were tested in two laboratories, using an indirect immunofluorescence assay. In addition, a fixed-neutrophil enzyme linked immunoadsorbent assay (ELISA) was evaluated in one of the two laboratories. The results in the immunofluorescence test showed a high degree of correlation between the two laboratories (Kappa coefficient = 0.8). Ninety five of the 120 (79%) ulcerative colitis patients had a positive test whereas only 14 of the 105 (13%) patients with Crohn's disease were positive. Sera from four patients suffering from primary sclerosing cholangitis were positive as well as four of the 45 control sera (9%). The sensitivity of the perinuclear antineutrophil cytoplasmic antibody immunofluorescence test for the diagnosis of ulcerative colitis was 0.75 with a specificity of 0.88 and a positive predictive value of 0.88 (all sera). In the ELISA technique 37 of 94 ulcerative colitis sera and one of the 68 Crohn's disease sera were positive. In the control group only one of the patients suffering from primary sclerosing cholangitis reacted positively (32 non-inflammatory bowel disease sera tested). The ELISA technique had a high specificity (0.97), but a low sensitivity (0.39). There was no relation of perinuclear antineutrophil cytoplasmic antibodies in ulcerative colitis patients or in Crohn's disease patients with disease activity, duration of illness, localisation, extent of disease, previous bowel operations or medical treatment. The clinical significance of perinuclear antineutrophil cytoplasmic antibody positive and negative subsets in both groups of patients thus remains unexplained. Our study confirms that determination of serum antineutrophil cytoplasmatic antibodies in patients with inflammatory bowel disease may differentiate ulcerative colitis from Crohn's disease. Further immunological studies are needed to explain the absence of these antibodies in a subset of ulcerative colitis patients and their role in the pathogenesis of the disease.

Adult

Acute noncardiac chest pain in a coronary care unit. Evaluation by 24-hour pressure and pH recording of the esophagus.

Twenty-four-hour recording of esophageal pressure and pH was performed successfully in 41 patients admitted to the coronary care unit of a general hospital who had an episode of acute, prolonged retrosternal chest pain and who were initially suspected of suffering from coronary artery disease (severe angina pectoris, myocardial infarction), but in whom the pain was subsequently shown not to be of cardiac origin. The recordings were analyzed with fully automated techniques. A pain episode was considered to be related to abnormal esophageal motility when contraction amplitudes or durations in the pain episode exceeded the patient's upper limit of normal (97.5th percentile) or when the proportion of abnormal propagated contractions (simultaneous, nontransmitted) in the pain episode was significantly increased (chi 2 test). Thirty patients (73%) had one or more pain episodes (in total 63 pain episodes) during the 24-hour recording. Forty-three percent of the pain episodes was related to abnormal motility and 30% to reflux, and 27% was not related to esophageal function disturbance. Using the criterium that the symptom index had to be greater than or equal to 75%, it was found that the pain was related to reflux in 13 patients (43%) and to motor abnormalities in 10 patients (33%). It is concluded that in the majority of patients acutely admitted with noncardiac chest pain, esophageal motor abnormalities and reflux can be shown to be the likely cause of the symptoms.

Acute Disease

Intestinal metaplasia and Helicobacter pylori: an endoscopic bioptic study of the gastric antrum.

To study the relationship between intestinal metaplasia and Helicobacter pylori infection, 2274 gastroscopic antral biopsies taken from 533 patients were examined. Overall, intestinal metaplasia was found in 135 patients (25.3%) and H pylori in 289 patients (54.2%). The prevalence of intestinal metaplasia and H pylori was age related, being more common in patients greater than or equal to 50 years compared with patients less than 50 years (intestinal metaplasia, p less than 0.001 and H pylori, p less than 0.05). Intestinal metaplasia was found more often in H pylori positive patients compared with H pylori negative patients (33.9% v 15.2%, p less than 0.001). The mean age of intestinal metaplasia positive patients who were also H pylori positive was 64 (13.3) years, whereas the mean age of intestinal metaplasia positive patients who were H pylori negative was 72 (14.7) years (p less than 0.005). The extent of intestinal metaplasia was not statistically different in the latter two groups. Although our data do not prove a causal relationship between H pylori infection and the histogenesis of intestinal metaplasia it is suggested that H pylori infection is an important factor in the development of intestinal metaplasia, which is generally recognised as a precursor lesion of intestinal type gastric carcinoma.

Adult

Subtypes of intestinal metaplasia and Helicobacter pylori.

To determine whether there is a relationship between the presence of H pylori and the various subtypes of intestinal metaplasia in the gastric antrum, 2274 antral gastroscopic biopsies from 533 patients were examined. H pylori was found in 289 patients. Intestinal metaplasia in general was found in 135 patients. Type I intestinal metaplasia was found in 133 patients (98.5%), type II in 106 patients (78.5%) and type III in 21 patients (15.6%). Ninety eight of these 135 patients (72.6%) were H pylori positive and 37 patients (27.4%) were H pylori negative. No statistically significant difference was found in the prevalence of type I and II intestinal metaplasia between the intestinal metaplasia positive and H pylori positive and intestinal metaplasia negative and H pylori negative patients. Type III intestinal metaplasia was found less often in the intestinal metaplasia positive and H pylori positive patients (11.2%) as compared with intestinal metaplasia positive and H pylori negative patients (27%) (p less than 0.05). In contrast with type I and II intestinal metaplasia type III intestinal metaplasia was found more often in moderate/severe intestinal metaplasia than in mild intestinal metaplasia (p less than 0.02). Within the group of patients with moderate/severe intestinal metaplasia, type III was found less often in the H pylori positive patients (p less than 0.05). We suggest that the gastric milieu for H pylori is less appropriate in type III intestinal metaplasia positive patients. As type III intestinal metaplasia might be regarded as a marker of possibly increased gastric cancer risk, the lower prevalence of H pylori in these type III intestinal metaplasia positive patients might be the result of severe changes in mucosal architecture.

Adult