[Show abstract][Hide abstract] ABSTRACT: Coeliac disease (CD) is an autoimmune disorder which leads to chronic inflammation of the gut. Furthermore, CD is associated with upper gastrointestinal malignancies, particularly lymphoma of the small intestine. Besides lymphoma, an increased frequency of associated small bowel carcinoma has been described. Here we report the case of a 70-year-old male suffering from CD who was treated with a gluten-free diet presenting with complaints of nausea, vomiting and weight loss of about 8 kg in two months. He underwent esophagogastroduodenoscopy, which identified distention of the stomach and duodenum and in the pars horizontalis a distinct obstruction was suggestive. However, histopathological examination showed a normal mucosal membrane. Additionally, a computed tomography scan of the abdomen was performed which showed an expanded stomach and duodenum up to the ligament of Treitz. During an explorative laparotomy a small tumor was palpated near the ligament of Treitz. Subsequently, a duodenal segment resection was performed. After surgery, the patient recovered well and left our hospital in good condition.
Case Reports in Gastroenterology 10/2010; 4(3):416-420. DOI:10.1159/000313547
[Show abstract][Hide abstract] ABSTRACT: To assess the prevalence and location of advanced neoplasia in patients undergoing colonoscopy, and to compare the yield per indication.
In a multicenter colonoscopy survey (n = 18 hospitals) in the Amsterdam area (Northern Holland), data of all colonoscopies performed during a three month period in 2005 were analyzed. The location and the histological features of all colonic neoplasia were recorded. The prevalence and the distribution of advanced colorectal neoplasia and differences in yield between indication clusters were evaluated. Advanced neoplasm was defined as adenoma > 10 mm in size, with > 25% villous features or with high-grade dysplasia or cancer.
A total of 4623 eligible patients underwent a total colonoscopy. The prevalence of advanced neoplasia was 13%, with 281 (6%) adenocarcinomas and 342 (7%) advanced adenomas. Sixty-seven percent and 33% of advanced neoplasia were located in the distal and proximal colon, respectively. Of all patients with right-sided advanced neoplasia (n = 228), 51% had a normal distal colon, whereas 27% had a synchronous distal adenoma. Ten percent of all colonoscopies were performed in asymptomatic patients, 7% of whom had advanced neoplasia. In the respective procedure indication clusters, the prevalence of right-sided advanced neoplasia ranged from 11%-57%.
One out of every 7-8 colonoscopies yielded an advanced colorectal neoplasm. Colonoscopy is warranted for the evaluation of both symptomatic and asymptomatic patients.
World Journal of Gastroenterology 03/2009; 15(9):1085-92. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sample handling can have a profound effect on serum protein profiles, challenging results obtained with archived sera under non-standardized sample collection. Here, we evaluate the influence of variations in sample handling on previous serum protein profiles for colorectal cancer (CRC) (Engwegen et al., World J. Gastroenterol. 2006, 12, 1536-1544). Sera were prospectively obtained from individuals with an indication for colonoscopy (n = 150: 65 controls, 52 adenomatous polyps, 29 CRC, 4 unknown), as well as from normal volunteers (n = 8). Protein profiles were acquired by SELDI-TOF MS on CM10 chips at pH 5. We assessed the influence of Storage temperature, type of collection tube, coagulation temperature and freeze-thaw cycles on the serum protein profile. Several peptides occurred only in samples stored at -20 degrees C, indicating proteolytic degradation during storage. One was a previous CRC biomarker candidate, an N-terminal albumin fragment (m/z 3087), and two others complement C3f and a fragment thereof (m/z 2022 and 1863). Overall differences in protein profiles were also seen for different collection tubes, coagulation temperature and freeze-thaw cycles. However, three of five of our previously defined CRC biomarker candidates are stable to variations in the sample handling protocol, justifying their further validation in prospective studies.
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation-time of flight mass spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP). Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52) and CRC (n = 47) were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM). We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups.
[Show abstract][Hide abstract] ABSTRACT: To prospectively evaluate participants' experience and preference of magnetic resonance (MR) colonography with limited bowel preparation compared with full-preparation colonoscopy in participants at increased risk for colorectal cancer.
This study had institutional review board approval; all participants gave written informed consent. In this multicenter study, consecutive participants undergoing conventional colonoscopy because of a personal or family history of colorectal cancer or adenomatous polyps underwent MR colonography 2 weeks prior to colonoscopy. They all followed a low-fiber diet and were given lactulose and an oral contrast agent (fecal tagging with gadolinium) 2 days before colonography. Before imaging, spasmolytics were administered intravenously, and a water-gadolinium chelate mixture was administered rectally for distention of the colon. Breath-hold T1- and T2-weighted sequences were performed in the prone and supine positions. Participant experience in terms of, for example, pain and burden was determined by using a five-point scale and was evaluated with a Wilcoxon signed rank test; participant preference was determined by using a seven-point scale and was evaluated with the chi2 statistic after dichotomizing.
Two hundred nine participants (77 women, 132 men; mean age, 58 years; range, 23-84 years) were included. One hundred forty-eight participants received sedatives (midazolam) and/or analgesics (fentanyl) during colonoscopy. Participants rated the MR colonography bowel preparation as less burdensome (P<.001) compared with the colonoscopy bowel preparation (10% and 71% of participants rated the respective examinations moderately to extremely burdensome). Participants also experienced less pain at MR colonography (P<.001) and found MR colonography less burdensome (P<.001). Immediately after both examinations, 69% of participants preferred MR colonography, 22% preferred colonoscopy, and 9% were indifferent (P<.001, 69% vs 22%). After 5 weeks, 65% preferred MR colonography and 26% preferred colonoscopy (P<.001).
Participants preferred MR colonography without extensive cleansing to colonoscopy immediately after both examinations and 5 weeks later. Experience of the bowel preparation and of the procedure was rated better.
[Show abstract][Hide abstract] ABSTRACT: To prospectively evaluate the diagnostic performance of magnetic resonance (MR) colonography by using limited bowel preparation in patients with polyps of 10 mm or larger in diameter in a population at increased risk for colorectal cancer, with optical colonoscopy as the reference standard.
The institutional review boards of all three hospitals approved the study. All patients provided written informed consent. In this multicenter study, patients undergoing colonoscopy because of a personal or family history of colorectal cancer or adenomatous polyps were included. Two blinded observers independently evaluated T1- and T2-weighted MR colonographic images obtained with limited bowel preparation (bright-lumen fecal tagging) for the presence of polyps. The limited bowel preparation consisted of a low-fiber diet, with ingestion of lactulose and an oral gadolinium-based contrast agent (with all three major meals) starting 48 hours prior to imaging. Results were verified with colonoscopic outcomes. Patient sensitivity, patient specificity, polyp sensitivity, and interobserver agreement for lesions of 10 mm or larger were calculated for both observers individually and combined.
Two hundred patients (mean age, 58 years; 128 male patients) were included; 41 patients had coexistent symptoms. At colonoscopy, 12 patients had 22 polyps of 10 mm or larger. Per-patient sensitivity was 58% (seven of 12) for observer 1, 67% (eight of 12) for observer 2, and 75% (nine of 12) for both observers combined for polyps of 10 mm or larger. Per-patient specificity was 95% (178 of 188) for observer 1, 97% (183 of 188) for observer 2, and 93% (175 of 188) for both observers combined. Per-polyp sensitivity was 55% (12 of 22) for observer 1, 50% (11 of 22) for observer 2, and 77% (17 of 22) for both observers combined. Interobserver agreement was 93% for identification of patients with lesions of 10 mm or larger.
In patients at increased risk for colorectal cancer, specificity of MR colonography by using limited bowel preparation was high, but sensitivity was modest.
[Show abstract][Hide abstract] ABSTRACT: To prospectively evaluate short- and midterm patient preference of computed tomographic (CT) colonography relative to colonoscopy in patients at increased risk for colorectal cancer and to elucidate determinants of preference.
Consecutive patients at increased risk for colorectal cancer underwent CT colonography prior to scheduled colonoscopy. Patient experience and preference were assessed both directly after the examinations and 5 weeks after the examinations. Differences in pain, embarrassment, discomfort, and preference were assessed with the Wilcoxon signed rank sum test or a binomial test. Potential determinants of preference were investigated with logistic regression analyses.
Data for 249 patients were included. Fewer patients experienced severe or extreme pain during CT colonography (seven [3%] of 245) than during colonoscopy (81 [34%] of 241) (P < .001). Directly after both examinations, 168 (71%) of 236 patients preferred CT colonography; 5 weeks later, 141 (61%) of 233 patients preferred CT colonography (P < .001). Initially, a painful colonoscopy examination (odds ratio, 0.17; 95% confidence interval [CI]: 0.08, 0.38) was a determinant of CT colonography preference. Similarly, a painful (odds ratio, 3.70; 95% CI: 1.54, 8.92) or an embarrassing (odds ratio, 4.46; 95% CI: 1.18, 16.88) CT colonography examination was a determinant of colonoscopy preference. After 5 weeks, the presence of polyps emerged as a determinant of colonoscopy preference (odds ratio, 1.94; 95% CI: 1.02, 3.70), while the role of experiences waned.
Patients preferred CT colonography to colonoscopy; however, this preference decreased in time, while outcome considerations gradually replaced temporary experiences of inconvenience.
[Show abstract][Hide abstract] ABSTRACT: To date, computed tomographic (CT) colonography has been compared with an imperfect test, colonoscopy, and has been mainly assessed in patients with positive screening test results or symptoms. Therefore, the available data may not apply to screening of patients with a personal or family history of colorectal polyps or cancer (increased risk). We prospectively investigated the ability of CT colonography to identify individuals with large (>or=10 mm) colorectal polyps in consecutive patients at increased risk for colorectal cancer.
A total of 249 consecutive patients at increased risk for colorectal cancer underwent CT colonography before colonoscopy. Two reviewers interpreted CT colonography examinations independently. Sensitivity, specificity, and predictive values were determined after meticulous matching of CT colonography with colonoscopy. Unexplained large false-positive findings were verified with a second-look colonoscopy.
In total, 31 patients (12%) had 48 large polyps at colonoscopy. This included 8 patients with 8 large polyps that were overlooked initially and detected at the second-look colonoscopy. In 6 of 8 patients, the missed polyp was the only large lesion. With CT colonography, 84% of patients (26/31) with large polyp(s) were identified, paired for a specificity of 92% (200-201/218). Positive and negative predictive values were 59%-60% (26/43-44) and 98% (200-201/205-206), respectively. CT colonography detected 75%-77% (36-37/48) of large polyps, with 9 of the missed lesions being flat.
CT colonography and colonoscopy have a similar ability to identify individuals with large polyps in patients at increased risk for colorectal cancer. The large proportion of missed flat lesions warrants further study.
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori gastritis may progress to glandular atrophy and intestinal metaplasia, conditions that predispose to gastric cancer. Profound suppression of gastric acid is associated with increased severity of H pylori gastritis. This prospective randomised study aimed to investigate whether H pylori eradication can influence gastritis and its sequelae during long term omeprazole therapy for gastro-oesophageal reflux disease (GORD).
A total of 231 H pylori positive GORD patients who had been treated for > or =12 months with omeprazole maintenance therapy (OM) were randomised to either continuation of OM (OM only; n = 120) or OM plus a one week course of omeprazole, amoxycillin, and clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy sampling as well as symptom evaluation were performed at baseline and after one and two years. Gastritis was assessed according to the Sydney classification system for activity, inflammation, atrophy, intestinal metaplasia, and H pylori density.
Corpus gastritis activity at entry was moderate or severe in 50% and 55% of the OM only and OM triple groups, respectively. In the OM triple group, H pylori was eradicated in 90 (88%) patients, and activity and inflammation decreased substantially in both the antrum and corpus (p<0.001, baseline v two years). Atrophic gastritis also improved in the corpus (p<0.001) but not in the antrum. In the 83 OM only patients with continuing infection, there was no change in antral and corpus gastritis activity or atrophy, but inflammation increased (p<0.01). H pylori eradication did not alter the dose of omeprazole required, or reflux symptoms.
Most H pylori positive GORD patients have a corpus predominant pangastritis during omeprazole maintenance therapy. Eradication of H pylori eliminates gastric mucosal inflammation and induces regression of corpus glandular atrophy. H pylori eradication did not worsen reflux disease or lead to a need for increased omeprazole maintenance dose. We therefore recommend eradication of H pylori in GORD patients receiving long term acid suppression.
[Show abstract][Hide abstract] ABSTRACT: The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re-bleeding. The haemostatic mechanisms that may influence the re-bleeding of ulcers are largely unknown.
We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity.
Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D-Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes.
Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24-h ranitidine infusion.
Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.
[Show abstract][Hide abstract] ABSTRACT: We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis.
To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes.
In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months.
In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p<or =0.0001). The decrease in active and chronic inflammation in the corpus differed significantly compared with the persistently H pylori positive group (both p=0.001). For atrophy scores, no significant differences were observed between H pylori eradicated and persistently H pylori positive patients within one year of follow up. No changes were observed in the H pylori negative control group (n=26).
H pylori eradication prevents the increase in corpus gastritis associated with profound acid suppressive therapy. Longer follow up is needed to determine if H pylori eradication prevents the development of atrophic gastritis.
[Show abstract][Hide abstract] ABSTRACT: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years).
Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus.
In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients.
Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND
We have previously observed that profound acid suppressive therapy inHelicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis.AIMTo investigate ifH pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes.PATIENTS/METHODS
In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months.RESULTSIn the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in theH pylori positive group that becameH pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p⩽0.0001). The decrease in active and chronic inflammation in the corpus differed significantly compared with the persistentlyH pylori positive group (both p=0.001). For atrophy scores, no significant differences were observed betweenH pylori eradicated and persistentlyH pylori positive patients within one year of follow up. No changes were observed in the H pylori negative control group (n=26).CONCLUSIONSH pylori eradication prevents the increase in corpus gastritis associated with profound acid suppressive therapy. Longer follow up is needed to determine if H pylori eradication prevents the development of atrophic gastritis.
Gut 01/2000; 46(5):615-621. DOI:10.1136/gut.46.5.615 · 13.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Omeprazole maintenance therapy for gastro-oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori-infected patients and with a decreased absorption of protein-bound, but not of unbound cobalamin.
: To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy.
Forty-nine H. pylori-positive GERD patients were treated with omeprazole for a mean (+/- s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow-up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow-up for histopathological scoring according to the updated Sydney classification.
At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow-up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow-up. During follow-up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136-716) vs. (T1) 341 (136-839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156-716) at latest follow-up (P < 0.01).
The development of atrophic gastritis during omeprazole treatment in H. pylori-positive GERD patients is associated with a decrease of serum vitamin B12 levels.
[Show abstract][Hide abstract] ABSTRACT: Patients with reflux esophagitis suffer from a chronic condition that may cause considerable discomfort because of recurrent symptoms and diminished quality of life. This study was designed to evaluate acute and long-term treatment comparing standard doses of omeprazole and high-dose ranitidine.
Patients with endoscopically verified symptomatic esophagitis grade I or II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice daily for 4-8 wk. Patients who were symptom free were randomized to maintenance treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients were seen every 3 months or at symptomatic relapse.
The percentage of asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively, for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients treated initially, 277 were asymptomatic, of whom 263 entered the maintenance study. The estimated proportion of patients in remission after 12 months of maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001).
Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half the standard dose is more effective than ranitidine in a standard dose in keeping patients in remission for a period of 12 months.
The American Journal of Gastroenterology 04/1999; 94(4):931-6. DOI:10.1111/j.1572-0241.1999.989_l.x · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several scoring systems have been developed to predict the risk of rebleeding or death in patients with upper gastrointestinal bleeding (UGIB). These risk scoring systems have not been validated in a new patient population outside the clinical context of the original study.
To assess internal and external validity of a simple risk scoring system recently developed by Rockall and coworkers.
Calibration and discrimination were assessed as measures of validity of the scoring system. Internal validity was assessed using an independent, but similar patient sample studied by Rockall and coworkers, after developing the scoring system (Rockall's validation sample). External validity was assessed using patients admitted to several hospitals in Amsterdam (Vreeburg's validation sample). Calibration was evaluated by a chi2 goodness of fit test, and discrimination was evaluated by calculating the area under the receiver operating characteristic (ROC) curve.
Calibration indicated a poor fit in both validation samples for the prediction of rebleeding (p<0.0001, Vreeburg; p=0.007, Rockall), but a better fit for the prediction of mortality in both validation samples (p=0.2, Vreeburg; p=0.3, Rockall). The areas under the ROC curves were rather low in both validation samples for the prediction of rebleeding (0.61, Vreeburg; 0.70, Rockall), but higher for the prediction of mortality (0.73, Vreeburg; 0.81, Rockall).
The risk scoring system developed by Rockall and coworkers is a clinically useful scoring system for stratifying patients with acute UGIB into high and low risk categories for mortality. For the prediction of rebleeding, however, the performance of this scoring system was unsatisfactory.
Gut 04/1999; 44(3):331-5. DOI:10.1136/gut.44.3.331 · 13.32 Impact Factor