The aetiology and clinical relevance of gastric intestinal metaplasia.
Explore the source record for details and available documents.
Gastritis, Atrophic↗
Biomedical subjects
E J Kuipers
Publications and source records attributed to E J Kuipers.
Causes and treatment of recurrent dysphagia after self-expanding metal stent placement for palliation of esophageal carcinoma.
BACKGROUND AND STUDY AIMS: Recurrent dysphagia frequently complicates the palliative treatment of esophageal cancer with self-expanding metal stents. Strategies for repeat interventions and subsequent outcomes have not been adequately reported to date. PATIENTS AND METHODS: A total of 216 patients underwent placement of a self-expanding metal stent (Ultraflex, n = 75; Flamingo Wallstent, n = 71; Z-stent, n = 70) for malignant dysphagia, and were followed up prospectively. The causes of stent-related recurrent dysphagia, the intervals after first stent placement, and the procedures used for repeat intervention and their outcomes were evaluated. RESULTS: Seventy-four episodes of stent-related recurrent dysphagia occurred in 63 patients (29 %), mainly due to tumor overgrowth (n = 30; median 129 days), stent migration (n = 26; median 92 days) and food bolus obstruction (n = 16; median 80 days). Stent migration occurred more frequently ( P = 0.05), whereas tumor overgrowth occurred less frequently ( P = 0.05) with Ultraflex stents in comparison with Flamingo Wallstents and Z-stents. Tumor overgrowth was treated in 25 patients mainly by a second stent (n = 19) and was effective in 23 of the 25 patients (92 %). Five patients received no further treatment. Stent migration was treated by placing a second stent (n = 14), repositioning the migrated stent (n = 7), other treatments (n = 3), or no further treatment (n = 2), and treatment was effective in 20 of 24 (83 %) patients. Food bolus obstruction was treated by endoscopic stent clearance in all patients. Repeat intervention for stent-related recurrent dysphagia improved the dysphagia score from a median of 3 to 1 ( P < 0.001). The median survival period after repeat treatment was 68 days. CONCLUSIONS: Recurrent dysphagia occurs in almost one-third of patients after stent placement. Repeat interventions for stent-related recurrent dysphagia are effective in over 90 % of patients. New innovations in stent design are needed to reduce the risk of stent-related recurrent dysphagia.
Adenocarcinoma↗
Oesophageal cancer incidence and mortality in patients with long-segment Barrett's oesophagus after a mean follow-up of 12.7 years.
BACKGROUND: Data on cancer risk in patients with long-segment Barrett's oesophagus (BO) from older studies are often difficult to interpret, since the definition of BO has evolved from an endoscopical to a histological diagnosis. In this work the diagnoses in the Rotterdam BO cohort on current standards was redefined to obtain more accurate data on cancer risk in patients who had not undergone standard endoscopic surveillance. In addition, it was determined which patient factors present at index endoscopy were associated with neoplastic progression in BO. METHODS: The Rotterdam BO cohort comprises all patients with > or =3 cm BO, diagnosed at endoscopy between 1973 and 1984. In the present study, only patients with intestinal metaplasia were included (n = 105). Follow-up data were obtained by questionnaires and/or interviews with patients or treating physicians. A Kaplan-Meier analysis was used to estimate 20-year risks. RESULTS: The mean length of the BO was 7.1 cm (range: 3-15 cm). Cancer in BO developed in 6/105 (6%) patients, and high-grade dysplasia (HGD) in 5/105 (5%) patients during 1329 patient-years of follow-up, which equals one cancer case per 221 patient-years and one HGD case per 266 patient-years. After a mean follow-up of 12.7 years, 72 (69%) patients had died; only 4 of them died of oesophageal cancer or its treatment. A longer length of BO was associated with an increased risk of progression to HGD or cancer (P < 0.02). Six of 24 patients who ever had low-grade dysplasia progressed to HGD or cancer 2-16 years after a diagnosis of BO. CONCLUSIONS: The annual risk of developing HGD or adenocarcinoma in patients with long-segment BO is 0.83%. Death due to adenocarcinoma is, however, uncommon, even in a cohort of patients with long-segment BO.
Adenocarcinoma↗
Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: a double-blind placebo-controlled study.
BACKGROUND: Ciprofloxacin is effective in perianal Crohn's disease but after treatment discontinuation symptoms reoccur. Infliximab is effective but requires maintenance therapy. AIM: To evaluate the effect of combined ciprofloxacin and infliximab in perianal Crohn's disease. METHODS: A double-blind placebo-controlled study was conducted. Patients were randomly assigned to receive 500-mg ciprofloxacin twice daily or a placebo for 12 weeks. All patients received 5-mg/kg infliximab in week 6, 8 and 12 and were followed for 18 weeks. Primary end-point was clinical response, defined as a 50% or greater reduction from baseline in the number of draining fistulae. Secondary end-points were the change in Perianal Disease Activity Index and hydrogen peroxide enhanced three-dimensional endoanal ultrasonography findings. Analysis was by intention-to-treat. RESULTS: Twenty-four patients were included but two discontinued treatment. At week 18, response was 73% (eight of 11) in the ciprofloxacin group and 39% (five of 13) in the placebo group (P = 0.12). Using logistic regression analysis patients treated with ciprofloxacin tended to respond better (OR = 2.37, CI: 0.94-5.98, P = 0.07). The Perianal Disease Activity Index score only improved (P = 0.008) in the ciprofloxacin group. Three-dimensional endoanal ultrasonography improved in three patients with a clinical response. CONCLUSIONS: A combination of ciprofloxacin and infliximab tended to be more effective than infliximab alone.
Adolescent↗
5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett's oesophagus: a randomised trial.
BACKGROUND: Photochemical and thermal methods are used for ablating Barrett's oesophagus (BO). The aim of this study was to compare 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) with argon plasma coagulation (APC) with respect to complete reversal of BO. METHODS: Patients with BO (32 no dysplasia and eight low grade dysplasia) were randomised to one of three treatments: (a) ALA-PDT as a single dose of 100 J/cm(2) at four hours (PDT100; n = 13); (b) ALA-PDT as a fractionated dose of 20 and 100 J/cm(2) at one and four hours, respectively (PDT20+100; n = 13); or (c) APC at a power setting of 65 W in two sessions (APC; n = 14). If complete elimination of BO was not achieved by the designated treatment, the remaining BO was treated by a maximum of two sessions of APC. RESULTS: Mean endoscopic reduction of BO at six weeks was 51% (range 20-100%) in the PDT100 group, 86% (range 0-100%) in the PDT20+100 group, and 93% (range 40-100%) in the APC group (PDT100 v PDT20+100, p<0.005; PDT100 v APC, p<0.005; and PDT20+100 v APC, NS) with histologically complete ablation in 1/13 (8%) patients in the PDT100 group, 4/12 (33%) in the PDT20+100 group, and 5/14 (36%) in the APC group (NS). Remaining BO was additionally treated with APC in 23/40 (58%) patients. Histological examination at 12 months revealed complete ablation in 9/11 (82%) patients in the PDT100 group, in 9/10 (90%) patients in the PDT20+100 group, and in 8/12 (67%) patients in the APC group (NS). At 12 months, no dysplasia was detected. Side effects (that is, pain (p<0.01), and nausea and vomiting (p<0.05)) and elevated liver transaminases (p<0.01) were more common after PDT than APC therapy. One patient died three days after treatment with PDT, presumably from cardiac arrhythmia. CONCLUSION: APC alone or ALA-PDT in combination with APC can lead to complete reversal of Barrett's epithelium in at least two thirds of patients when administered in multiple treatment sessions. As the goal of treatment should be complete reversal of Barrett's epithelium, we do not recommend these techniques for the prophylactic ablation of BO.
Aged↗
Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial.
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Adult↗
The homeodomain protein CDX2 is an early marker of Barrett's oesophagus.
BACKGROUND: In Barrett's oesophagus (BO), squamous epithelium is replaced by specialised intestinal epithelium (SIE). Transcription factors associated with intestinal differentiation, such as CDX2, may be involved in BO development. AIM: To investigate CDX2 expression in BO, squamous epithelium, and oesophageal adenocarcinoma (ADC). METHODS: CDX2 expression was assessed in 245 samples-167 biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39 patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20 patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2 protein was investigated immunohistochemically in 138 biopsies from 16 patients with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO patients, and when present from ADC. RESULTS: SIE was present in 53/79 biopsies from the columnar lined segment; CDX2 protein was seen in all epithelial cells, but not in biopsies containing only gastric metaplastic epithelium (26/79), or in squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all biopsies with goblet cell specific Muc2 transcription-indicative of SIE. Low Cdx2 mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the squamocolumnar junction of BO patients. CONCLUSION: CDX2 protein/mRNA is strongly associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing squamous epithelium of one third of BO patients, and may precede morphological changes seen in BO. Therefore, pathways that induce Cdx2 transcription in squamous epithelial cells may be important in BO development.
Adenocarcinoma↗
MUC4 is increased in high grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio.
BACKGROUND: Patients with Barrett's oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. AIMS: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. METHODS: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. RESULTS: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. CONCLUSIONS: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.
Adenocarcinoma↗
[Diagnosis and treatment of esophageal cancer in the Netherlands: wide variation in the second line].
OBJECTIVE: To survey the diagnostic procedures and treatment strategies currently employed in hospitals for patients with oesophageal cancer. DESIGN: Questionnaire. METHOD: A questionnaire was sent to all clinicians working in the field of gastroenterology in the Netherlands. This questionnaire focused on clinical preferences regarding diagnostic procedures and treatment strategies for oesophageal cancer. Also, six hypothetical patient vignettes were presented in order to investigate which factors affected choice of treatment, in particular surgical treatment. RESULTS: The response rate was 64% (426/667); 336 questionnaires were relevant to the investigation. Almost 90% of the clinicians treated fewer than 20 patients annually, usually in their own hospital. CT was the most frequently used staging procedure; endoscopic ultrasound was less frequently used (42% used it in less than half the patients). The treatment choice for the patient vignettes varied widely among clinicians. Factors influencing the choice to operate or not were: metastases, loco-regional tumour ingrowth, poor general health, and advanced age with 8, 22, 20, and 53%, respectively, of the clinicians still considering surgery in the presence of one of these factors as opposed to 99% if none of these factors were present. Surgeons opted for operation more often than internists and gastroenterologists. Stent placement was the most frequently chosen method to palliate malignant dysphagia. CONCLUSION: There is a wide variation in the use of diagnostic procedures and treatment strategies for patients with oesophageal cancer in the Netherlands. This stresses the need for scientifically based practice guidelines, taking into account specific patient and tumour characteristics.
Aged↗
[Health Council report on health claims for foods and food supplements].
Explore the source record for details and available documents.
Dietary Supplements↗
[Acute dysphagia: often there is a readily treatable cause].
Three patients, one woman aged 45 years and two men aged 40 and 62 years, presented with acute dysphagia due to oesophageal obstruction by a piece of food. In the woman symptoms of oesophageal perforation developed after the piece of food was removed by rigid endoscopy; she recovered after treatment with a stent, antibiotics and acid inhibitors. The younger man had a stricture of the oesophagus that was dilated. The older man had a Barrett's oesophagus and also oesophagcal adenocarcinoma; he was free of symptoms three years after resection of the oesophagus and the creation of a tubular stomach. In adults, 60% of acute oesophageal obstructions are caused by food impaction, which is associated with a high incidence of secondary pathologic findings in the oesophagus (75-97%). Evaluation of the oesophagus by flexible endoscopy contributes to an adequate diagnosis. Moreover, it can be used to treat the cause of the obstruction. If dilation therapy is started early after detecting a benign stricture in the oesophagus, it reduces the likelihood of recurrence. The detection of early-stage oesophageal malignancies may improve the prognosis of patients with this disorder.
Acute Disease↗
Prospective comparison of hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging of perianal fistulas.
PURPOSE: This study was conducted to determine agreement between hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging in the preoperative assessment of perianal fistulas and to compare these results with the surgical findings. METHODS: Twenty-one patients (aged 26-71 years) with clinical symptoms of a cryptoglandular perianal fistula and a visible external opening underwent preoperative hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography, endoanal magnetic resonance imaging, and surgical exploration. The results were assessed separately by experienced observers blinded as to each other's findings. Each fistula was described with notice of the following characteristics: classification of the primary fistula tract according to Parks (intersphincteric, transsphincteric, extrasphincteric, or suprasphincteric), horseshoe, or not classified; presence of secondary tracts (circular or linear); and location of an internal opening. RESULTS: The median time between hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging was 66 (interquartile range, 21-160) days; the median time between the last study (hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography or endoanal magnetic resonance imaging) and surgery was 154 (interquartile range, 95-189) days. Agreement for the classification of the primary fistula tract was 81 percent for hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and surgery, 90 percent for endoanal magnetic resonance imaging and surgery, and 90 percent for hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging. For secondary tracts, agreement was 67 percent for hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and surgery, 57 percent for endoanal magnetic resonance imaging and surgery, and 71 percent for hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging in case of circular tracts and 76 percent, 81 percent, and 71 percent, respectively, in case of linear tracts. Agreement for the location of an internal opening was 86 percent for hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and surgery, 86 percent for endoanal magnetic resonance imaging and surgery, and 90 percent for hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging. CONCLUSIONS: For evaluation of perianal fistulas, hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging have good agreement, especially for classification of the primary fistula tract and the location of an internal opening. These results also show good agreement compared with surgical findings. Therefore, hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging can both be used as reliable methods for preoperative evaluation of perianal fistulas.
Adult↗
Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects.
BACKGROUND: Several studies have reported inhibitory effects of lactic acid bacteria on bacterial pathogens. AIM: To test whether a drink containing Lactobacillus casei strain Shirota inhibits Helicobacter pylori growth. METHODS: The in vitro growth inhibition of H. pylori was studied when L. casei was added to plates previously inoculated with H. pylori reference strain NCTC 11637. In an intervention study, 14 H. pylori-positive subjects were given Yakult drink (10(8) colony-forming units/mL L. casei) thrice daily during meals for 3 weeks. Six untreated H. pylori-positive subjects served as controls. H. pylori bacterial loads were determined using the 13C-urea breath test, which was performed before and 3 weeks after the start of L. casei supplementation. RESULTS: In vitro, L. casei inhibits H. pylori growth. This effect was stronger with L. casei grown in milk solution than in DeMan-Rogosa-Sharpe medium. No growth inhibition was shown with medium inoculated with lactic acid, Escherichia coli strain DH5alpha or uninoculated medium. Filtration of L. casei culture before incubation with H. pylori completely abolished the inhibitory effect. Urease activity decreased in nine of the 14 (64%) subjects with L. casei supplementation and in two of the six (33%) controls (P = 0.22). CONCLUSIONS: Viable L. casei are required for H. pylori growth inhibition. This does not result from changes in lactic acid concentration. In addition, a slight, but non-significant, trend towards a suppressive effect of L. casei on H. pylori in vivo may exist.
Adult↗
Endoscopic treatment of gastro-oesophageal reflux disease: the new kid on the block.
BACKGROUND: Gastro-oesophageal reflux disease is a common disease entity with approximately 7% of European adults experiencing significant daily symptoms. The impact of reflux disease on the quality of life is considerable. Complications of reflux disease include oesophagitis, stricture, Barrett's and pulmonary symptoms. Most patients can be adequately managed by treatment with a proton-pump inhibitor. However, symptom relapse is common after cessation of therapy, thus many patients are committed to life-long therapy. Until recently, anti-reflux surgery was the single therapeutic alternative. Now, novel endoscopic techniques have become available to treat patients suffering from reflux disease. Application of these techniques is challenging. METHODS: Update on new endoscopic techniques for treatment of reflux discase. RESULTS: Currently available endoscopic techniques include endoscopic suturing, radiofrequency ablation and biopolymer injection. Interventions typically take 30-40 min and can be performed under conscious sedation. First reports describe successful reduction of symptoms. Six months after therapy. reportedly 58%-85% of patients are off proton-pump inhibition. Yet, there are conflicting results on 24-h pH measurement and insufficient data on the mechanism of altered oesophageal motility. Long-term data are not yet available. In our series of over 50 procedures, no serious complications have occurred. CONCLUSIONS: Endoscopic treatment of reflux disease is feasible and safe. Techniques reduce both symptoms and medication use associated with the disease, albeit with an uncertain long-term outcome. As pursuit of this technology is appealing, techniques are being introduced before thorough comparison and evaluation of therapeutic benefit have been completed. Comparative studies between conventional anti-reflux treatment and various luminal anti-reflux therapies are needed and long-term efficacy remains to be established.
Adult↗
Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia.
BACKGROUND: The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the detection of apoptotic cells in tissue sections has facilitated the analysis of the role of apoptosis in the gastritis-atrophy-intestinal metaplasia sequence. METHODS: Archival material from 40 gastric resection specimens with normal mucosa (n = 5), chronic active gastritis (n = 17), or intestinal metaplasia (n = 18) was studied. Immunohistochemistry was performed using antibodies directed against cleaved cytokeratin 18 and active caspase 3. Slides were scored on a 0-3 scale for the presence of apoptotic cells. RESULTS: Normal gastric mucosa contained low numbers of apoptotic cells at the surface epithelium (mean score, 0.20). This number was significantly increased in cases with chronic gastritis (mean score, 1.06) and in those with intestinal metaplasia (mean score, 2.56). Within the intestinal metaplasia cases, 44 different foci of intestinal metaplasia were identified. In 39 of these 44 areas, concentrations of apoptotic cells were seen immediately adjacent to the foci of intestinal metaplasia, but not in the metaplastic epithelium itself. CONCLUSIONS: Apoptosis is uncommon in normal gastric mucosa. Chronic inflammation and intestinal metaplasia are associated with increased apoptosis, but occur mainly at the mucosal surface and not in the deeper layers. These findings do not support the concept that apoptosis underlies the loss of gastric glands and leads to atrophy, but the observed concentration of apoptotic epithelial cells adjacent to foci of intestinal metaplasia could be related to heterogeneity of epithelial damage, causing apoptosis, to which intestinal metaplasia is a response.
Apoptosis↗
Comparative genomic hybridisation as a supportive tool in diagnostic pathology.
AIMS: Patients with multiple tumour localisations pose a particular problem to the pathologist when the traditional combination of clinical data, morphology, and immunohistochemistry does not provide conclusive evidence to differentiate between metastasis or second primary, or does not identify the primary location in cases of metastases and two primary tumours. Because this is crucial to decide on further treatment, molecular techniques are increasingly being used as ancillary tools. METHODS: The value of comparative genomic hybridisation (CGH) to differentiate between metastasis and second primary, or to identify the primary location in cases of metastases and two primary tumours was studied in seven patients. CGH is a cytogenetic technique that allows the analysis of genome wide amplifications, gains, and losses (deletions) in a tumour within a single experiment. The patterns of these chromosomal aberrations at the different tumour localisations were compared. RESULTS: In all seven cases, CGH patterns of gains and losses supported the differentiation between metastasis and second primary, or the identification of the primary location in cases of metastases and two primary tumours. CONCLUSION: The results illustrate the diagnostic value of CGH in patients with multiple tumours.
Adenocarcinoma↗
Genome wide array comparative genomic hybridisation analysis of premalignant lesions of the stomach.
BACKGROUND: Gastric cancer is one of the most frequent malignancies in the world, ranking fifth in the Netherlands as a cause of cancer death. Surgery is the only curative treatment for advanced cases, but results of gastrectomy largely depend on the stage of the disease. A better understanding of the mechanisms of progression from a preneoplastic condition through intraepithelial neoplasia to invasive cancer may provide information relevant to designing focused prevention strategies. METHODS: Because the pattern of chromosomal aberrations in precursors of gastric cancer is unclear, 11 gastric polyps with intraepithelial neoplasia (three hyperplastic polyps and eight adenomas) were analysed by microarray comparative genomic hybridisation to study chromosomal instability in precursors of gastric cancer. RESULTS: Chromosomal aberrations were detected in all specimens. Adenomas showed no more chromosomal aberrations than did the hyperplastic polyps. The most frequent aberrations were gain of 7q36 and 20q12, and loss of 5q14-q21 in the adenomas, and loss of 15q11-14, 1p21-31, and 21q11-21.2 in the hyperplastic polyps. The most frequent chromosomal aberration in common to both types was loss of 9p21.3. CONCLUSION: Hyperplastic polyps showed many chromosomal aberrations, confirming that neoplastic transformation can occur in these lesions. These observations are consistent with the existence of two morphologically and genetically distinct pathways to gastric cancer-the hyperplastic polyp pathway and the (intestinal type) adenoma pathway. The relative contribution of each to gastric carcinogenesis in general, and how they compare to patterns of chromosomal aberrations in the more prevalent flat foci of intraepithelial neoplasia remain to be determined.
Adenoma↗
[The malignant side of chronic inflammatory bowel disease].
Patients with chronic inflammatory bowel disease (IBD) have a higher risk of colorectal carcinoma, and present with this malignancy at a younger age than non-IBD individuals. In three patients, two men aged 20 and 36 years and one woman aged 34 years, colorectal cancer developed at a young age, following a long history of ulcerative colitis. Surveillance for colorectal cancer in IBD patients needs to be performed by regular colonoscopy with extensive biopsy sampling for the detection of dysplasia, regarded by many as predictive for colon carcinoma. Whenever a dysplasia-associated lesion or mass or a highgrade dysplasia is identified, there is a strong indication for colectomy. When low-grade dysplasia is found, the findings should be discussed with the patient and it should be decided whether the patient should resume surveillance or opt for colectomy.
Adenocarcinoma↗