Eosinophilic Gastrointestinal Diseases

Eozinofili su potentne stanice imunosnog sustava koje znatno pridonose održavanju homeostaze intestinalne barijere. Brojna dosadašnja istraživanja pokazala su da imaju važnu ulogu u patogenezi nekih poremećaja probavnog trakta. Eozinofilne gastrointestinalne bolesti (EGIB) heterogena su skupina kliničkih poremećaja. Cilj je ovoga preglednog članka sažeti rezultate literature o patofiziološkoj ulozi eozinofila u zdravoj sluznici probavnog trakta i kod pojedinih gastrointestinalnih poremećaja te prikazati nove spoznaje vezane za pristup bolesnicima s ovim poremećajima.Eosinophils substantially contribute to homeostatic maintenance of intestinal barrier function against luminal bacteria. These cells are now recognized to have key functions in the pathogenesis of several gastrointestinal disorders. Eosinophilic gastrointestinal diseases are an increasingly common heterogeneous group of intestinal diseases. The purpose of this review is to summarize a growing literature defining the pathophysiological role of eosinophils in healthy intestine and in some gastrointestinal disorders, and present the latest knowledge about the care of patients with eosinophilic gastrointestinal diseases

Terminal ileum resection as a trigger for strongyloides stercoralis hyperinfection and ensuing serial sepsis in a 37-year-old patient with complicated Crohnʼs disease: a case report

The nematode Strongyloides stercoralis, outside the tropics and subtropics present in small endemic foci, can cause an infection after direct skin contact with contaminated soil containing infective filariform larvae and, rarely, after intimate interhuman contact or after transplantation of an infected solid organ. Following skin penetration, migration, and maturation through several stages, a small number of invasive filariform larvae can develop anew in the gut lumen, perpetuating new cycles of penetration, tissue migration, and reproduction, without leaving the host. In a state of immunosuppression, autoinfection can progress to life-threatening hyperinfection and/or infection disseminated through virtually any organ. In developed countries, the most frequently recognized risk for severe hyperinfection is corticosteroid therapy, but this has been also described in malnourished, alcoholic, cancer, and transplant patients. Due to the frequent need for immunosuppressive therapy, patients suffering from inflammatory bowel disease (IBD) are susceptible to develop overwhelming strongyloidiasis. Strongyloidiasis can be easily overlooked in clinical settings, and in many European regions there is poor insight into the epidemiological burden of this disease. We present a case of S. stercoralis hyperinfection that triggered 3 successive episodes of sepsis caused by pathogens of the gut flora in a young patient suffering from stenotic form of Crohn's disease. S. stercoralis hyperinfection occurred in the corticosteroid-free period, shortly after resection of the terminal ileum, which was probably the trigger for the overwhelming course. The patient was successfully treated with 10-day albendazole therapy

Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn’s disease: a retrospective casecontrol study

Aim To analyze the distribution of SLC6A4 gene polymorphisms in Crohn’s disease (CD) patients and their association with the disease. Methods We evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis.Results CD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively; P = 0.154) and age (41.3 ± 12.8 years vs 41.7 ± 8.8 years, respectively, P = 0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P = 0.003 and P = 0.002, respectively) and between the corresponding female subgroups (P = 0.004 and P = 0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P = 0.013, age- and sexadjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29-0.86; women: P = 0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/ rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P = 0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes. Conclusion STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis

Opportunistic screening for colorectal cancer in high-risk patients in family medicine practices in the Republic of Croatia

Colorectal cancer is a malignant neoplasm which has an increasing incidence and represents a global public health problem. The majority of patients are diagnosed after the age of 50, and the risk of developing it over lifetime is 5%. Development of preventive, diagnostic and treatment methods has resulted in a significant reduction in mortality and other negative clinical outcomes. Precisely because of the efficient method of prevention and early detection of this disease, numerous countries, including Croatia, have organized national colorectal cancer screening and monitoring programs. However, these programs are primarily organized for the population with the usual, i.e. average risk of developing colorectal cancer. High-risk groups include persons with endoscopically detected and removed colon polyps, persons surgically treated for colon cancer, persons with a positive family history of colorectal cancer, persons with inflammatory bowel diseases, individuals and families with hereditary disorders or genetic mutations that increase the risk of this disease several fold, persons with acromegaly, and patients who have undergone ureterosigmoidostomy. Recommendations for the detection and monitoring of high-risk groups are often not defined clearly, and some of the existing ones are based mostly on scarce scientific evidence. It is commonly accepted that screening in high-risk groups should start at an earlier age, with shorter intervals between follow-ups. The basic diagnostic method for screening and monitoring in these patient groups is endoscopic monitoring, or colonoscopy. The aim of this review paper is to present the characteristics of the abovementioned risk groups and provide clear screening recommendations

ENDOSCOPIC MUCOSAL RESECTION OF SESSILE POLYPOID COLORECTAL LESIONS: A TWO-YEAR RETROSPECTIVE STUDY, TECHNIQUE DESCRIPTION, INDICATIONS AND COMPLICATIONS

Uvod: Endoskopska mukozna resekcija (EMR) terapijska je metoda resekcije premalignih lezija i intramukoznih karcinoma probavne cijevi. Do sada nisu objavljeni podaci o EMR-u u Hrvatskoj. Materijali i metode: Pacijenti uključeni u retrospektivnu analizu liječeni su u Kliničkome bolničkom centru Zagreb od prosinca 2006. do prosinca 2008. g. Za izvođenje EMR-a upotrebljavana je strip metoda s pomoću submukozne injekcije adrenalina (razrjeđenje s fiziološkom otopinom 1:5.000–10.000). Rezultati: EMR sesilnih polipoidnih lezija debelog crijeva izvedena je u 95 pacijenata. Najčešća lokalizacija lezija bio je rektum (52 pacijenta – 54,7%), a najčešća veličina bila je između 16 i 25 mm (43 pacijenta – 45%). U 75 pacijenata učinjena je en-bloc, a u ostalih piecemeal resekcija. Neposredno nakon EMR-a krvarenje je nastupilo kod 5 pacijenata (5,3%). Najčešća patohistološka dijagnoza bila je vilotubularni adenom (67 pacijenata – 70%). U 6 pacijenata (6,3%) verificiran je invazivni, a u 20 pacijenata (21%) intramukozni karcinom. Na kontrolnoj endoskopiji nije nađen recidiv lezije u 73 (77%) pacijenata. Kirurški zahvat bio je potreban kod 6 pacijenata zbog dijagnoze invazivnog karcinoma. Zaključak: EMR je sigurna i pouzdana metoda odstranjenja premalignih lezija i intramukoznih karcinoma debelog crijeva s malim rizikom od teških komplikacija i prihvatljivim postotkom rezidua osnovne lezije.Introduction: Endoscopic mucosal resection (EMR) is a therapeutic method for removal of sesile premalignant lesions and intramucosal carcinoma of the gastrointestinal tract. No reports on EMR data in Croatia have been published yet. Matherials and methods: All patients included in the study were managed at the University Hospital Centre Zagreb between December 2006 and December 2008. EMR was performed using strip technique with submucosal injection of epinephrine (dilution with saline 1:5000–10000). Results: EMR of sessile polypoid colorectal lesions was performed in 95 patients. The most common localisation of the disease was rectum (52 pts – 54.7%). In most patient size of the lesion was between 16–25 mm (43 pts – 45%). En-bloc resection was performed in 75 patients and piecemeal resection in the rest. Bleeding occurred immediately during the EMR in 5 pts (5.3%). Patohistological diagnosis revealed tubulovillous adenoma in 67 pts (70%). Invasive carcinoma was observed in 6 pts (6.3%) and intramucosal carcinoma in 20 pts (21%). On follow up, 73 pts (77%) did not show and sign of disease recurrence. Surgery was needed in 6 pts (6.3%) due to the diagnosis of invasive carcinoma. Conclusion: EMR is safe and reliable method with low risk of serious complications and acceptable recurrence rate

Gut microbiota in mucosa and feces of newly diagnosed, treatment-naïve adult inflammatory bowel disease and irritable bowel syndrome patients

The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease

Metabolic Liver Diseases

Najčešće nasljedne metaboličke bolesti jetre jesu Wilsonova bolest (WB), hemokromatoza i nedostatak alfa- -1-antitripsina. WB je autosomno-recesivno nasljedni poremećaj metabolizma bakra koji dovodi do patološkog nakupljanja bakra u mnogim tkivima i organima s njihovom posljedičnom jetrenom, neurološkom i/ili psihijatrijskom disfunkcijom. Hemokromatoza je najčešća genska bolest bjelačke populacije u sjevernoeuropskim zemljama. Prezasićenost organizma željezom često je klinički neprepoznata te se hemokromatoza dijagnosticira tek u vrlo uznapredovalim fazama bolesti. Neliječene WB i hemokromatoza uvijek su smrtonosne bolesti. S druge strane, rano dijagnosticiranje i adekvatna terapija, uključivo izbjegavanje hrane koja sadržava povišene količine bakra/željeza, odnosno terapija penicilaminom/terapijska venepunkcija, omogućava da ovi bolesnici mogu živjeti potpuno normalan životni vijek. Upravo stoga je obiteljski probir kod članova uže obitelji bolesnika s nasljednom metaboličkom bolesti jetre obvezatan. Nedostatak alfa-1-antitripsina najčešći je nasljedni jetreni poremećaj u djetinjstvu. Iako ne postoji učinkovita farmakološka terapija ovog poremećaja, ohrabruju rezultati moguće ciljane genske terapije.The most common metabolic liver diseases are Wilson’s disease (WD), hemochromatosis and alpha-1 antitrypsin defi ciency. WD is an autosomal recessive disorder of copper metabolism leading to its accumulation in the body which results in a number of possible hepatic, neurological and psychiatric sequelae. Hemochromatosis is the most common genetic disease in white persons of northern European descent. The features of iron overload are often unrecognized and diagnosed only in the setting of advanced disesae. If left untreated, WD and hemochromatosis are a fatal conditions. On the other hand, patients detected early and treated with copper/iron reduction therapy, including penicillamine/phlebotomy, can have a normal life expectancy. Given the genetic basis of the condition it is vital that counselling and screening of the patient’s fi rst-degree relatives be carried out. Alpha-1 antitrypsin defi ciency is the most common metabolic liver disesae in childhood. There is currently no specifi c treatment for alpha-1 antitrypsin defi ciency, although researchers are exploring different techniques of possible gene therapy