Use of new, once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis. Is there anything new under the sun?

5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlled-release forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature or, the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations

Recent trends in the epidemiology of inflammatory bowel diseases: up or down?

Inflammatory bowel disease (IBD) is traditionally considered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemiologic studies are needed to better define the burden of illness, explore the mechanism of association with environmental factors, and identify new risk factors

Smoking in inflammatory bowel diseases: Good, bad or ugly?

Smoking is an important environmental factor in inflammatory bowel disease (IBD), having different effects in ulcerative colitis (UC) and Crohn’s disease (CD). A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing Crohn’s disease and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves Crohn’s disease. Data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases

Gene polymorphisms in primary biliary cirrhosis: association with the disease and hepatic osteopathy

Genetic factors have been implicated in the pathogenesis of osteoporosis, a common disorder in primary biliary cirrhosis (PBC). Estrogen receptor-alpha gene (ER-�), vitamin-D-receptor gene (VDR) and IL-1-receptor-antagonist gene (IL-1RN) are all attractive candidates for osteoporosis susceptibility. Furthermore insulin-like growth factor-I (IGF-I) gene microsatellite repeat polymorphism was found to be associated with osteoporosis in some studies and collagen-I�1 (COLIA1) Sp1 s allele was associated with lower bone mineral density (BMD) in one study in PBC. IGF-I treatment restored osteopenia and reduced fibrogenesis in experimental cirrhosis. In this study we summarize our results on polymorphisms of the above genes and bone disease in Hungarian PBC patients. Patients and methods: 70 female patients with PBC were enrolled (age:57.6yrs, range:37-76yrs, each AMA-M2 positive, stage II-IV). 139 age-matched female subjects served as controls (age: 55.9 yrs, range:43-72 yrs). COLIA1 Sp1 and IGF-I microsatellite polymorphisms were determined by PCR in all patients and controls. VDR BsmI, IL-1RN variable-number tandem repeat (VNTR) and ER-� PvuII and XbaI polymorphisms were detected in 33 patients and controls. BMD was measured by dual energy x-ray absorptiometry (Lunar,Prodigy,USA) in lumbar spine (LS) and femoral neck (FN). Results: There was no difference in IGF-I microsatellite repeat polymorphism (192/192=34.2%, 194/192=28.6%, other=37.2%) and COLIA1 Sp1 polymorphism (SS=72.9%, Ss=22.8% and ss=4.3%) and IL-1 VNTR polymorphism between PBC patients and controls, however, the COLIA1 Sp1 s allele was significantly less frequent in patients with PBC (p=0.038). The genotype frequency of VDR BsmI (BB=57.5%, Bb=33.3%, bb=9.1%, p=0.01) and ER-a PvuII (PP=18.2%, Pp=75.6%, pp=6.2%, p=0.03) and XbaI (XX=9.1%, Xx=90.9%, xx=0%, p=0.0003) of the patients was different from that of the control group, with higher frequency of the BB, Pp and Xx genotypes in PBC. Osteoporosis (t score<-2.5) was detected in 22 patients (31.4%). Osteoporotic patients were elder and had longer disease history (p=0.01 for both). An association was found between the IGF-I genotypes and ODM data, the 192/192 genotype was associated with higher FN Z-score compared to other genotypes (p=0.036). Conclusions: In contrast to previous studies the COLIA1 Sp1 s allele was less frequent in patients with PBC, and its presence was not associated with BMD. We confirmed previous findings on higher frequency of VDR BsmI BB genotype in patients with PBC. The ER-α PvuII and XbaI Pp and Xx genotypes were more frequent in PBC patients, while IL-1RN VNTR and IGF-I microsatellite repeat polymorphism was not different. Since IGF-I polymorphism was associated to BMD, it may be hypothesized that not COLIA1 but IGF-I together with other genetic and environmental factors may be involved in the complex regulation of BMD in PBC

Mucocele of the appendix: An unusual cause of lower abdominal pain in a patient with ulcerative colitis

The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examination demonstrated a pericecal cystic mass (11 cm x 3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needle aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patient underwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The patient is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management; however, it is difficult on imaging studies

Relationship between serum calcium and CA 19-9 levels in colorectal cancer

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n=32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25(OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer

A gyulladásos bélbetegségek genetikája (The genetics of inflammatory bowel disease)

A gyulladásos bélbetegségek kialakulásában különböző környezeti tényezők és faktorok (genetikai, epithelialis, immunmechanizmusok és nem immuntényezők) egyaránt szerepet játszanak. A patogenezisben fontos a genetikai tényezők szerepe, a betegség ismereteink szerint poligénes természetű. Úgy tűnik, hogy egyes gének általában a gyulladásos bélbetegségekre való fogékonyságot hordozzák, mások ezen belül a colitis ulcerosára vagy a Crohn-betegségre való hajlamot, illetve a betegség fenotípusát (enyhe vagy súlyos, agresszív, lokalizált vagy kiterjedt stb.) befolyásolják. Ebben az összefoglaló közleményben az elmúlt néhány év genetikai újdonságait foglaljuk össze: a gyulladásos bélbetegségekkel kapcsolatba hozható megismert új kromoszómarészleteket, a NOD2/CARD15, az SLC22A4/A5, illetve a DLG5 szerepét. A genetikai ismeretanyag bővülése egyelőre elsősorban a patogenezis jobb megértését segíti, ez alapul szolgálhat új terápiás támadáspontú gyógyszerek kifejlesztésében. A jövőben elképzelhető, hogy szerepe lesz a diagnózis pontosításában, a betegség lefolyásának pontosabb előrejelzésében. The pathogenesis of inflammatory bowel disease is only partly understood; various environmental and host factors (e.g., genetic, epithelial, immune and non-immune) are involved. It is a multifactorial polygenic disease probably with genetic heterogeneity; some genes confer susceptibility to IBD in general, while others specifically increase the risk of ulcerative colitis or Crohn's disease or affect location (localized or extensive) and/or behaviour (e.g., mild, severe, aggressive). This review presents recent advances in the genetics of inflammatory bowel disease including chromosome segments newly recognized to be involved in inflammatory bowel disease as well as the role of NOD2/CARD15, SLC22A4/A5 and DLG5. The increasing genetic information provides, for the time being, a better understanding of the pathogenesis of the disease thus setting a basis for potential targets for therapeutic intervention. In the future, however, genetics may also help in refining the diagnosis or predicting disease course

A colorectalis daganatok korszerű kezelése (Contemporary therapy of colorectal tumors)

Az elmúlt másfél évtizedben a colorectalis daganatok kemo- és radioterápiája az onkológia sikeres területei közé került. A kezelés alapját évtizedek óta az 5-fluorouracil jelenti, de biomodulátorokkal való kiegészítése, az alkalmazási módszerek továbbfejlesztése (folyamatos infúziós adás, orális szerek) jelentősen javították a hatékonyságot. A nagy változást az irinotecan, illetve az oxaliplatin alkalmazása hozta, amelyek a metasztatizáló vastagbélrákok túlélését háromszorosára, átlagosan 20 hónapra növelték. A prognózis javulásában jelentős része van a metasztázisok hatékonyabb kezelésének is. A Dukes-féle C stádiumú tumorok adjuváns kezelése ma már alapelvként fogalmazható meg, kedvezőtlen prognosztikus tényezők esetén B2 stádiumú tumoroknál is indokolt a kemoterápia. A rectumtumorok prognózisát javítja a neoadjuváns, illetve adjuváns radiokemoterápia. Bár az optimális módszer még nem eldöntött, egyre több adat szól a preoperatív kezelés mellett. A monoterápiával szemben a kettős, hármas, négyszeres kombinációs kezelések hatékonyabbak, és úgy tűnik, hogy az alkalmazás módja, sőt, az egyes szerek sorrendje is lényeges (szekvenciális kezelés). Nemcsak a jövő, hanem lassan a jelen szereit is jelentik az új biológiai szerek, így az epidermális növekedési faktor receptor elleni antitest, a cetuximab, valamint a vascularis endothelialis növekedési faktor elleni monoklonális antitest, a bevacizumab, amelyek az eddigi adatok szerint tovább javítják a citosztatikus kezelésre már nem reagáló betegek esélyeit. Az új szerek alkalmazásának magas áruk szab korlátot.\ud Chemo-radiotherapy of colorectal tumours has become a successful field in oncology. The cornerstone of the treatment has remained the 5-FU containing regimes, however the improvement of administration protocols (e.g. continuous infusion, oral administration) and the addition of biomodulating agents has improved efficacy considerably. The recent availability of newer agents, like irinotecan and oxaliplatin has significantly improved survival of advanced (metastatic) colorectal cancer, extending up to 20 months average survival, also being a consequence of the more aggressive treatment of hepatic and lung metastases. The adjuvant chemotherapy of Dukes’ C tumours has become standard, while the treatment of high-risk B2 tumours is also recommended. Neoadjuvant/adjuvant chemo-radiotherapy improves the prognosis of rectal tumours, however the optimal regime has not yet been determined. The combination of two or more agents is superior to monotherapy and the route and sequence of administration may also influence efficacy. The biological agents of the near future including cetuximab (directed against epidermal growth factor receptor) and bevacizumab (a monoclonal antibody to vascular endothelial growth factor) may further improve survival in poor prognosis patients. The use of the new drugs is limited at the moment by their high costs