Search

Colorectal cancer is one of the most common cancers in the Netherlands, where it is now the second most commonly-occurring cancer in terms of both incidence (10,000 new cases each year) and mortality rate (4,400 each year). - In 40% of all cases the disease is diagnosed at a late stage, which is associated with a poor outcome. - Research has shown that screening of the general population for colorectal cancer by means of the faecal occult blood test (FOBT) results in a reduction in mortality of approximately 16%. Whether endoscopic screening will result in a greater reduction in the mortality rate is currently under investigation. - This year, the first pilot study on implementation of screening for colorectal cancer using two different types of FOBT will start in the Netherlands.

Gastro-oesophageal reflux disease is a chronic disorder. The most important therapeutic measure is long-term pharmacological acid inhibition. Anti-reflux surgery plays a role in cases where pharmacological treatment fails. A new development is endoluminal treatment for reflux disorders. The various methods used are based on one of the following principles: radiofrequency ablation, gastroplication and implantation of a bulking agent. Short-term results with endoluminal treatment are not very positive and longer-term results have been disappointing so far. Results from randomised studies are still largely unavailable. Longer follow-up and controlled randomised studies are needed before a well-founded judgment can be made regarding the place of endoluminal treatment in the therapeutic armamentarium.

10-15% of patients with ulcerative colitis experience a severe episode of colonic inflammation that does not respond to mesalazine and oral corticosteroids. These patients require hospitalisation and treatment with intravenous corticosteroids. However, 25% of these patients do not respond to treatment. In these cases, intravenous cyclosporin is effective. Infliximab, an antibody against tumour necrosis factor alpha, is also beneficial. With these new treatment options, the colectomy rate in the acute phase has declined to about 35%. Other new therapies are under investigation in phase 2 and 3 trials. Surgery remains an important treatment option. Patients, gastroenterologists and surgeons should be involved in the clinical decision-making process.

This year, the Nobel Prize in Physiology or Medicine was awarded to the Australian doctors Marshall and Warren for their discovery and further identification of the stomach bacterium Helicobacter pylori. Thanks to their confidence in their own observations, we are now able to cure people with peptic-ulcer disease and low-grade gastric lymphoma and are potentially able to prevent gastric cancer.

Statins are widely prescribed as lipid-lowering agents in the primary and secondary prevention of cardiovascular disease. They are increasingly associated with potential chemopreventive effects with respect to cancer. A recent case-control study reported a 47% relative reduction in the risk of colorectal cancer associated with statin use after adjustment for other known risk factors. There is evidence of an inhibitory effect of statins on colorectal carcinogenesis from in vitro studies, animal experiments, and observational and epidemiological reports in humans. Although statins seem promising as chemopreventive agents, it is still too early to recommend their use against colorectal cancer outside the context of clinical trials.

Objective: To determine whether an investigation of microsatellite instability (MSI) in patients with colorectal carcinoma that have been selected by the pathologist could increase the number of detected families with hereditary non-polyposis colorectal carcinoma (HNPCC)., Design: Prospective inventory., Method: Pathologists selected patients with a newly diagnosed colorectal carcinoma for MSI analysis of their tumour tissue if they met one of the following four criteria: (a) colorectal carcinoma diagnosed below 50 years of age; (b) a second colorectal carcinoma; (c) a combination of colorectal carcinoma and another HNPCC-related cancer; (d) colorectal adenoma with high-grade dysplasia diagnosed below 40 years of age. Patients with a positive MSI-test were referred to a clinical geneticist. The new strategy was introduced and explored in 5 hospitals for a period of to months., Results: The new strategy was adopted and implemented successfully by pathologists and surgeons and accepted with satisfaction by the patients. Of the 55 patients included, 10 had a positive MSI-test. In 8/10 patients, DNA-mutation analysis was started by the clinical geneticist and 3 germline mutations in the MSH2-gene were detected. In 2 of 3 families with a pathogenic mutation, the family history alone did not fulfil the clinical criteria for HNPCC., Conclusion: Selection by the pathologist for MSI investigation was feasible in daily practice and identified more HNPCC patients than selection based on family history alone.

Coeliac disease is a common disorder, but most persons with coeliac disease remain undetected because they have only mild aspecific symptoms or are free of symptoms. For a definitive diagnosis small bowel biopsies showing partial or (sub)total villous atrophy are required. The presence of anti-endomysium and/or anti-tissue-transglutaminase antibodies in serum is strongly predictive for coeliac disease. In case of clear clinical suspicion the most straightforward way to diagnose or exclude coeliac disease is by taking endoscopic biopsies from the distal duodenum. When the suspicion is low, determination of the above mentioned antibodies as a first step suffices. At present there are insufficient reasons to initiate population-wide screening for coeliac disease by means of serological testing or individual screening by taking duodenal biopsies during each gastroscopy.

Acetylsalicylic acid was recently shown to inhibit the development of colorectal adenomas in subjects with a moderately increased risk for colorectal cancer. The mechanisms by which acetylsalicylic acid and other NSAIDs, including COX-2 inhibitors, exert this effect include: inhibition of COX-2, induction of apoptosis and induction of the P21 protein that controls the development of crypt cells. For the majority of the population, a healthy lifestyle and healthy eating habits are the best means of preventing colorectal cancer. In addition, population-wide screening should be encouraged. For people with an increased risk of colorectal cancer, acetylsalicylic acid only has a partial effect and therefore endoscopic surveillance is still indicated. Sulindac or celecoxib may be useful for patients with familial adenomatous polyposis and in particular for inhibiting the development of rectal adenomas after subtotal colectomy with ileorectal anastomosis. However, in these cases endoscopic surveillance is also still necessary.

An improved understanding of the pathogenesis of inflammatory bowel disease (IBD) has led to the development of new drugs such as infliximab and insights into the modes of action of commonly used drugs such as azathioprine and methotrexate. These drugs act, at least in part, by inducing apoptosis of activated T-cells, which are an important phenomenon in the aberrant mucosal immune response in Crohn's disease. Gene therapy directed towards delivering anti-inflammatory proteins such as interleukin 10 (IL-10) to the inflamed mucosa is another new means of correcting the balance between the proinflammatory and anti-inflammatory cytokines in IBD. Gene-therapeutic manipulation of T-cells or bacteria to make them selectively deliver IL-10 to the gut mucosa has been successfully described in experimental models of IBD. Although interleukin-10-based gene therapy for Crohn's disease is an attractive option, safety aspects concerning the gene transfection method and questions about the efficacy of interleukin-10 in Crohn's disease in particular, prevent its application in the near future.

The definition of 'irritable bowel syndrome' (IBS) as given by the Dutch College of General Practitioners' standard may be too broad to define IBS. Coeliac disease should be added to the differential diagnosis of IBS. Attention should be given to subjects with an increased familial risk of colorectal cancer. Based on the results of thorough investigations, the role of disturbed motility, visceral hyperalgesia, modified cerebrovisceral perception, induction by infectious diseases and contributing psychological factors should be recognised as pathophysiologically relevant for IBS. When treating patients, making a positive diagnosis of IBS, explaining possible pathophysiological factors and exploring contributing factors is much more important than simply giving reassurance. Medical therapy is of limited value, but may relieve symptoms in selected patients.

A 34-year-old man from Nigeria who had resided permanently in the Netherlands for five years had experienced fever, upper abdominal pain and weight loss for several months. He did not give the impression of being ill. A CT scan gave cause to suspect pancreatitis. An HIV test gave a positive result. Puncture of the accumulated fluid around the pancreas led to the diagnosis 'tuberculosis' (infection by Mycobacterium tuberculosis). Once the patient had made a good recovery with antituberculosis therapy, antiretroviral therapy was initiated, whereupon the number of CD4+ cells in the blood increased. Extrapulmonal tuberculosis is not unusual in HIV seropositive patients from countries with a high prevalence of tuberculosis. However, in such patients isolated tuberculosis of the pancreas is unusual and has not previously been described in the Netherlands. The diagnosis can be established following a CT guided puncture; tuberculosis is instantly suspected if the Ziehl-Neelsen stains are positive and the diagnosis can then be confirmed by a polymerase chain reaction (PCR) analysis and by culturing. Anti-retroviral therapy is withheld until response to anti-tuberculosis treatment is satisfactory.

Individuals with one first-degree relative with colorectal cancer diagnosed before age 45 years and those with two first-degree relatives with colorectal cancer run a significantly increased risk (relative risk: 4-6) of developing colorectal cancer. Based on calculation of the mortality due to colorectal cancer for the age group 50-70 years (which is higher than the mortality due to breast cancer) surveillance may be justified, e.g. by colonoscopy at 5-year intervals from the age of 45-50. The total number of people in the Netherlands in this high risk group is estimated at 10,000. The authors conclude that prospective studies are needed to assess the cost-effectiveness of such a programme.