CONTENTS I NEWS AND CURRENT AFFAIRS THE KYOTO CONFERENCE.............................................................................................215 ŽaloudíkJ. LIGHTS AND SHADOWS OF SCIENCE AND TECHNOLOGY IN TODAY'S SOCIETY.........................................216 Ernst R. R. ABSTRACTS OF SELECTED PAPERS PRESENTED ATTHE XVIth CONFERENCE OF YOUNG PHYSICIANS, ST. ANNE'S FACULTY HOSPITAL IN BRNO, 24 JUNE 2009.....................................................................................278 XXVIth CONFERENCE OF THE CZECH SOCIETY OF HYPERTENSION (ČSH), XVIIIth CONFERENCE OF THE PREVENTIVE CARDIOLOGY WORKING GROUP OF THE CZECH SOCIETY OF CARDIOLOGY (ČKS) AND XlVth CONFERENCE OF THE HEART FAILURE WORKING GROUP OF THE ČKS.......................................284 EDITORIAL............................................................................................................220 Lata J. ■ ORIGINAL RESEARCH HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY................228 Kliment M., Urban O., Fojtík P., Petrášek J., Janík D., Albín A., Liberda M., Šmajstrla V, Kundrátová E., Falt P. ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS................................................................................239 Kajzrlíková I., Vítek P., Chalupa J. FOREKNOWLEDGE AS AN ASSOCIATED FACTOR FOR ADHERENCE TO THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE..................................................................271 Mišejková M., Dujsíková H.,Trumpešová H., Prokopová L., Zbořil V. SCREENING OF COELIAC DISEASE IN OSTEOPOROTIC PATIENTS........................................................274 Fojtík P., Fait P., Kliment M., Urban 0. REVIEW NEW METHODS OF SMALL BOWEL INVESTIGATION....................................................................221 Klímová K. CLINICAL APPLICATION OF ELECTROGASTROGRAPHY.................................................................235 Prokešová J., Dolina J. PRIMARY SCLEROSING CHOLANGITIS - A REVIEW.....................................................................252 Trumpešová H., Mišejková M., Lata J. PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION...................256 Hůlková M., Hosák L. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 213 INTESTINAL MICROFLORA AND BACTERIAL TRANSLOCATION Lata J., Juránková J., Příbramská V. 262 OBSTIPATION AND DIARRHOEA - A COMMON AND SIGNIFICANT PROBLEM IN THE ELDERLY...........................267 Šlapák J., Lata J. ■ CASE REPORT CAPSULE COLONOSCOPY.............................................................................................225 Stibůrek O., Kunovská M., Lata J. ACUTE PANCREATITIS AS A FIRST SYMPTOM OF PANCREATIC CANCER IN A DIFFUSE AUTOIMMUNE PANCREATITIS PATIENTS..............................................................................................................249 Ševčíková A., Novotný I., Hermanová V.,Trna J., Dítě P. ■ INDEX 2009 214 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ NEWS AND CURRENT AFFAIRS From 4 to 6 October 2009, a further world conference of the STS (Science and Technology in Society) forum took place in Kyoto, Japan. The Kyoto Conference had acquired in our country already earlier a mark assigned to it by the media of a mere green action against environmental pollution. Its scope is, however, much wider. With some exaggeration we can say that it is focused against the "pollution" and ballast clogging of a variety of human endeavour fields, especially those of existence. It primarily searches for scientific tools and intellectual alliance to face current risks, whether on a global, supranational, or supraregional scale. It is a gathering of the leading physicists, power engineers, environmentalists, biologists, doctors, science organisers, businessmen, representatives of academic circles as well as of large industrial corporations. The Kyoto Conference is concerned with the main contemporary issues of human society which, apart from environmental protection, sustainable development, new trends in power engineering development, and effective collaboration of non-profit and commercial sectors, also include the less medialised problems of reasonable and available health care and especially education. Education, awareness of the population, knowledge-based society, and the role of scientists in educational processes formed the centrepiece of all specialised topics at the STS forum conference. It is namely becoming apparent that the partial technological successes and a certain advance in the social hierarchy of contemporary populations are paradoxically accompanied by an education deficit, even despite the overwhelming flood of information, which is a sign of the times. The difficult path from information to real knowledge and comprehension of priorities, and from these to wise acting has been designated as being a responsibility of the scientific elite. We have namely, even in countries with sufficient resources, been constantly confronted with unwise, ineffective, and unsustainable acting. Many examples were heard concerning this topic. The elaboration of the "information -knowledge - wisdom" line is an urgent task of not only scientific but also entrepreneurial and political elites. Particular attention was given to the relationship between research and education. The conference completely refused the isolation of the scientific elite from education, ana priori emphasis laid on merely applied research and commercial supervision of science. At the academic level, the scientist has also to teach, the teacher has to be scientifically competent, the research has to be guided by goals higher than just immediately commercial ones. For the citizen of the Czech Republic it is naturally disturbing that the attitudes of significant personalities at the conference, including several Nobel Prize winners, are oftentimes opposite to the contemporary trends set in our country in the interest of commercial control of research, which, however, imply a reduction of free science and education. What is also problematic is the Czech attitude concerning separation of the top-level science and educational experts, which is manifested in a sort of permanent competition between institutes of the Academy of Sciences of the Czech Republic and Czech universities for prestige, performance, and resources. This is considered at least as unwise waste of energy and the real potential of scientific education teams. A variety of inspiring suggestions on methods of education and popularisation of scientific knowledge in the public in establishing a wider scope of erudition in society have sounded at the conference. Especially engaging was the address delivered by Professor Richard Ernst, winner of the Nobel Prize for his discovery of high resolution nuclear magnetic resonance spectroscopy, who with brilliant conciseness and aptness articulated the basic problems of the relationship between science and education as well as the role of academics. Here we bring it to the readers of Scripta Medica with the author's personal consent in the original English version. Prof. MUDr. Jan Žaloudík, CSc. The Dean of the Faculty of Medicine Masaryk University (Translated by L. Červený) http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 215 17 NEWS AND CURRENT AFFAIRS Lights and Shadows of Science and Technology in Today's Society Richard R. Ernst, ETH Zürich, Switzerland I was asked to add a few grains of pepper to the dinner menu by some remarks on the Lights and Shadows of Science and Technology in Today's Society. - Science and technology are neither bright nor dark, neither good nor evil. They function merely as tools; and tools are neutral, capable to all kinds of use and misuse. Obviously, to discuss lights and shadows, we must address the goals and intents for which the tools are used. In my opinion, there is just one relevant goal, namely to serve today's as well as tomorrow's society by all available means. Winning prizes, becoming famous, becoming rich, and having a good life as our bankers in spacious land houses are no respectable goals for science and technology; in contrary, they might even be indicative for excessive selfishness and misuse of societal resources. Fortunately, the infamous bonus disease did not yet infect science. Being researchers, we should not ask primarily for freedom of research. Instead, we should prove by the choice of relevant problems our willingness for behaving responsibly towards society. When we serve those who need moral, scientific, or technological support, a feeling of personal liberty and freedom of mind will follow spontaneously. John D. Rockefeller, Jr. once said: "/ believe that every right implies a responsibility; every opportunity, an obligation; and every possession, a duty." Please remember that research is first of all a means of education, a means of acquiring knowledge. Research is by far the best way of "learning by doing", the best way of experiencing nature by posing incisive questions and answering them by experiments. A well equipped laboratory is infinitely more useful for efficient learning than a fancy lecturing hall. We should never separate research and education! Stand-alone research institutes without educational obligations are for me a luxurious waste of resources. Research can be driven by pure curiosity; but more often, it is from the beginning application-oriented, with a clear goal in mind, trying to satisfy a public need. And as a side-effect, it might even be serving industry. - To use my personal example, I never considered myself being a true scientist but rather an engineer, who made Nuclear Magnetic Resonance to work in a wide variety of exceedingly useful applications. Usefulness was my goal from the beginning and to the very end of my career as a researcher. - NMR and MRI succeeded without much sales promotion; their utility was so plainly obvious. We all know, sales promotion is indispensable merely for selling unnecessary products that better would never had been produced at all. In fact, the promotion of useless gadgets complicates our daily life without any benefit, degrading us to slaves of technology. Examples are plentiful; just watch our children's hypes! Instead of sales promotion, society urgently needs continuing education by providing reliable information, receiving advises for reducing consumption, preserving resources for future generations, and saving our precious time fora life rich in content instead of becoming rich in distraction and idling nonsense. Public teaching is indeed a most important obligation of academic institutions for opening public eyes towards potential future catastrophes, such as global warming, plundering of resources, and overpopulation. How can we teach responsible behavior to the public as long as fraud is still a recurring fact at our universities? The excuse that even researchers are human beings does not help in this situation. Honesty in research and education is more important than all the conveyed specialized knowledge. Much more emphasis than in the past should to be put on aspects of honesty and responsibility in university education. But as long as scientists are driven by competition, by alluring prizes, by the request of long list of publications, and by insane university ranking agencies, no hope is insight. In fact, the academic situation is just a reflection of the prevalent capitalistic free market business model that has last year failed to all extent and lead to a catastrophe on the financial market that required remedies by the otherwise ridiculed Nation States. Personal gain and egoism dominate today our short-sighted business model, following the well-known and, in fact, utterly immoral quotes by Adam Smith. The "invisible hanď'and the stabilizing negative feedback loop of free market economy, unfortunately, are inoperative on a global scale and for longer time spans.-Instead of copying within our academic institutions and think-tanks this irresponsible behavior, it would be more urgent to develop new business models 216 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ NEWS AND CURRENT AFFAIRS and models of behavior based on foresight, ethical principles, and sustainability that lead to what I often call a "responsible market economy"instead of a"free market economy". Certainly, without science and technology, mankind has no future; but with science and technology alone, we will shuffle our own grave for ending prematurely a senseless life as robotic operators. For replenishing our life with meaning and with sense, we need, in addition, very personal passions outside of science and technology; we need a "second leg". We need wisdom for comprehending the dangers lurking along the future pathway, and compassion for relating to our, possibly needy, compatriots and for establishing long-lasting human relations. Remember, science and technology are just tools, as mentioned at the beginning. Their proper usage requires foresight and responsibility, in the sense of the philosopher Hans Jonas who formulated the"lmperative Responsibility": "Actso that the consequences of your actions are compatible with the permanence of genuine human life on Earth."Clearly, his saying boils down to ultimate sustainability. Indeed, sustainability forces us to assume responsibility for the fate of our descen-dents. Let us act invariably as if a sorrowful solicitor of future generations would look over our left shoulder! For example, when we consume too much meat or when we are driving our fuel-wasting SUVs. And for those of you who feel great from time to time, and I hope all of you do, Winston Churchill once remarked: "Responsibility is the price of greatness." Thank you for your kind attention to my Sunday evening sermon! http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 17 90 EDITOR'S OFFICE SCRIPTA MEDICA is indexed in SCRIPTA MEDICA Editor-in-Chief M. Korcová Faculty of Medicine Masaryk University Kamenice 5 CZ-625 00 Brno, Czech Republic Tel.: +420 549 493 998 E-mail: scriptme@med.muni.cz mkorcova@med.muni.cz % muni I PRESS Publisher: Faculty of Medicine, Masaryk University, Brno Periodicity: 4 issues per volume The journal Scripta Medica is printed in 500 copies. ri helbichtiskárna Printed by Tiskárna Helbich, a.s., Brno I me | to | da. Art studio: Metoda, s.r.o., Brno Advertising is accepted in the journal. Further information including rates, specification, etc. is available on request. ISSN 1211-3395 MKČRE4996 Scripta Medica is available free online at http:/www.med. muni.cz/biomedjournal/ EMBASE/Excerpta Medica DIALOG DataStar MEDLINE LEBSCO ProQuest Scopus PubMed Bibliographia Medica Čechoslovaca Online Computer Library Center, Inc. Deutsches Institut für Medizinische Dokumentation und Information Cena: 230,- CZK vč. DPH za 1 číslo; 920,- CZK vč. DPH za 4 čísla celého ročníku (zahrnuje poštovné a balné) Price in EUR -1: EUR 10.00 incl. VAT/1 issue (postage and packing included); EUR 40.00 incl.VAT/4 issues of whole volume Price in EUR - II: EUR 09.00 without VAT/1 issue (postage and packing included); EUR 36.00 without VAT/4 issues of whole volume 8 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ EDITORIAL BOARD Editorial Assistant Jitka Vavrouchová Zdeňka Dohnálková Nataša Honzíkova Martina Kukletová Daniel Schwarz i' Jindřich Vomela International Advisory Board Section Experimental Medicine F. Čiampor, Bratislava, Slovakia K. Javorka, Martin, Slovakia E. Kellerová, Bratislava, Slovakia M. V. Nermut, Herts., South Mimms, UK J. Stingl, Praha, Czech Republic Surgical Medicine J. Dominik, Hradec Králové, Czech Republic S. Haruštiak, Bratislava, Slovakia V. Král, Olomouc, Czech Republic J. Šnajdauf, Praha, Czech Republic Internal Medicine M. Benedeková, Bratislava, Slovakia Z. Pelikán, Breda,The Netherlands J. Rovenský, Piešťany, Slovakia F. Stožický, Plzeň, Czech Republic Foreign Language Editor Ladislav Červený ZdeněkAdam Petr Dubový Hana Hrstková . Jindřich Lokaj ' Jaromír Sláma Editor-in-Chief Marie Korcová Managing Editor Svatopluk Čech Online Presentation Zbyněk Diviš EDITORIAL BOARD Svatopluk Čech PetrGál Roman Janisch Marie Nováková Anna Vašků http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 219 EDITORIAL Ladies and gentlemen, The scientific journal of the Faculty of Medicine of Masaryk University, Scripta Medica, has been published since 1922. In these more than 80 years, tens of gastroenterological papers have been published. Nevertheless, this issue of Scripta Medica is the first in the history to be completely dedicated to gastroenterology and hepatology. It is my great pleasure to present 12 papers, coming mostly from my young colleagues not only from our Department of Internal Medicine and He-patogastroenterology of the Faculty of Medicine of Masaryk University but also from the well-known gastroenterological or hepatological centres in Hradec Králové, Ostrava, and Frýdek-Místek. Gastroenterology and hepatology are parts of medicine which have seen tremendous expansion during the lastyears. The progress in diagnostic procedures and therapeutical possibilities is enormous. I hope that we will be able to present at least part of this progress in this issue of Scripta Medica. In the first paper, Klímová reports on some new methods of investigation of the small bowel, an organ which had been very hard to investigate a few years ago. Balloon enteroscopy and capsule endoscopy are procedures that are of great benefit in the imaging of the small intestine. Stiburek et al. described a brand new use of capsule endoscopy in the investigation of the large intestine. In spite of enthusiasm in this field, the first results are not too optimistic, but technical progress can diminish current difficulties in the future. It seems that some benefit in the investigation of the colon could be reached by improving standard colonoscopy. Kliment et al. described improved visualisation of the colorectal mucosa and increased adenoma detection using high-definition, high-resolution, wide-angle colonoscopy. Electrogastrography is an appealing investigation of the stomach. Prokešová etal. described this completely non-invasive measurement of gastric myo-electrical activity, unfortunately with limited clinical impact. However, even old methods could be effectively used in new indication. Kajzrlíková et al. presents the usefulness of abdominal ultrasound for the detection of hepaticojejunoanas-tomosis-related complications. Ševčíková etal. reports on a relevant case of acute pancreatitis with a short history complicated by invasive ductal pancreatic adenoma - an infrequent but serious issue. Two papers give an account of hepatology. Trumpešová et al. describes a not very frequent but important liver disease - primary sclerosing cholangitis. Hůlková et al. found some very interesting psychiatric aspects of liver encephalopathy. Intestinal microflora and bacterial translocation seem to play a crucial role not only in the above-mentioned liver encephalopathy but also in many other gastroenterological diseases. Lata et al. describes this broad issue. Šlapák et al. defines a growing problem - obstipation and diarrhoea in the elderly population. Even general practitioners have been facing this problem due to the increasing number of seniors in the population. Mišejková et al. describes the important general problem of therapy - adherence to treatment. Limited knowledge or misinformation was the main reason for non-adherence in a group of patients with inflammatory bowel disease. Fojtík et al. focused their paper on a very frequent but underdiagnosed illness - coeliac disease. It is diagnosed very rarely, especially in older age, but it is clear that osteoporosis could be a very important symptom. The year 2009 has started a new epoch of the journal Scripta Medica. I am glad that we have had the opportunity to publish our papers in this year's last issue of Scripta Medica. Prof. MUDr. Jan Lata, CSc Department of Internal Medicine and Hepatogastroenterology, University Hospital Brno and Faculty of Medicine, Masaryk University Brno interní HEPATOGASTRO ENTER0L0GICKÁ KLINIKA BRNO 220 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ REVIEWS NEW METHODS OF SMALL BOWEL INVESTIGATION Klímová K. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Received after revision September 2009 KEYWORDS Capsule endoscopy Intraoperative endoscopy Balloon enteroscopy CORRESPONDING AUTHOR Klímová K. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic ABSTRACT The anatomy of the gastrointestinal tract can be investigated by both invasive and non-invasive methods. Most frequently endoscopy or double-contrast radiological techniques are used. The part of the small intestine between the duodenum and terminal ileum is difficult to reach by standard endoscopy. However, it can be judged by radiological enteroclysis, which has the disadvantage of exposing the patients to X-rays; moreover, it is impossible to examine the pathological findings histologically. New and more accurate enteroscopic (single- and double-balloon including intraoperative) methods and capsule enteroscopy have been coming into wider use. Capsule endoscopy is an endoscopic method that enables to examine the whole small intestine. This technology consists of swallowing a capsule in size of a large vitamin tablet, which is later moved forward by the motility of the gastrointestinal tract distally.The record is then evaluated by a doctor. Intraoperative enteroscopy is still more often substituted by balloon enteroscopy. However, it remains an option when the classical double-balloon enteroscopy did not solve the patient's problems definitely, that is mainly in patients with intestinal adhesions or multiple lesions of small intestine. Balloon enteroscopy is a modern method that is used to examine the whole small intestine, which also enables us to carry out therapeutic efforts when the routine endoscopy was not successful. In some indications it has substituted intraoperative enteroscopy. These three methods are complementary and cannot be replaced by each other. Some authors consider them as the golden standard in the investigation of small intestine. INTRODUCTION Small intestine is the longest part of the gastrointestinal tract starting in the duodenum and ending in the ileocaecal region. The length of the small intestine varies significantly during life (from 200cm in the newborn up to 300 to 600cm http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 221 NEW METHODS OF SMALL BOWEL INVESTIGATION in the adult). Anatomically it can be divided into three parts: duodenum, jejunum, and ileum. The duodenum is approximately 30cm long, the jejunum represents almost one half of the total length of the small intestine. Its mucosa is enlarged by transverse folds and mainly by the presence of minute fingerlike projections known as villi and microvilli. The wall consists of mucosa, submucosa, smooth muscle, and serosa. The mucosa is lined with simple columnar epithelium with brush borders (microvilli). Among the villi there are tubular glands (Lieberkühn glands - glandulae intestinales). Among the enterocytes there are goblet cells which are specialised for the secretion of mucus. The most frequent pathological findings include functional changes, inflammatory bowel disease (Crohn's disease, ulcerative colitis), specific and non-specific enteritis, tumours, obstructions, ischaemias, or malabsorptions. Currently there are different methods that can be used in order to reach fast and correct diagnosis. RADIOLOGY Various radiological methods are used to investigate the small bowel. Of the conventional methods the most important are enteroclysis and ultrasound of the bowels. The main disadvantage of these methods is that they strongly depend on the experience of the doctor who evaluates them. Angiography is used in order to look for abnormalities in the blood vessels; it can also be used to treat acute intestinal bleeding. BLEED SCAN Methods offered by nuclear medicine are not frequently used in gastroenterology. There are two main indications for these investigations: firstly bleeding into the gastrointestinal tract - here it can answer two main questions - the location of the bleeding and the volume of the blood loss, and secondly tumours [1], ENDOSCOPY Endoscopic procedures are irreplaceable as far as early diagnosis is concerned. In an endoscopic procedure, the physician inserts a thin, lighted, camera-tipped tube (endoscope) either through the mouth or rectum inside the body. The patient is sedated before the procedure. During a standard gastroscopy it is usually possible to investigate the proximal part of the duodenum (D1-D3) [2]. Push-enteroscopy is of an excellent diagnostic value as far as the duodenum and the proximal jejunum (94%) are concerned; however, its main disadvantage is the limited reach that dramatically decreases its overall value for investigating lesions in the small bowel (53%) [3].This method is still used in places where the double-balloon technique is not available. The enteroscopes are actively inserted by the endoscopist. Usually it is possible to reach 60-130 cm behind the Treitz ligament at maximum. Compared to the balloon enteroscope it is more difficult to control the push-enteroscope and the value of the investigation is not so high [4]. During the routine colonoscopy we can insert the endoscope retrogradely into the ileum and investigate approximately 30 cm of the terminal ileum. The fundamental advantage of endoscopic methods is the possibility of judging the investigated region of the small intestine visually. Moreover, we can take biopsies or perform therapeutic procedures (polypectomy, APC - argon plasma coagulation or mucosectomy). The value of the optical evaluation can be increased by filtrating the wave lengths of the white light in a new method called Narrow Band Imaging (NBI), which can distinguish between premalignant and malignant lesions. With the contribution of NBI mucosal lesions can also be judged by zooming the endoscope onto the mucosa with conserved sharpness of the image [5]. In local differential diagnostics, chromodiagnostics can also be used. To demonstrate superficial mucosal lesions absorptive dyes (methylene blue) or contrast dyeing (indigocarmine) are used. Most often they are applied through spray catheters to visualise a particular lesion or the mucosa of the whole intestine (panchromoendoscopy) [6]. Chromodiagnostics with zooming onto suspicious lesions have enabled the creation of a so-called pit-pattern classification according to Kudo. The findings on the intestinal mucosa are divided into 5 types."Pit pattern" 1-2 predicts non-tumorous lesions and "pit pattern" 3-5 corresponds with intraepithelial neoplasias (dysplasias or invasive carcinoma) [6]. Another option is represented by "endoscopic microscopy". This includes the confocal microscopy, i.e., non-invasive optical imaging of the mucosa with laser scan of a certain wavelength. It allows us to analyse the mucosa into a depth of 200-500 nm with the reflected light. Another very promising technique is represented by endo-cytoscopy, in which we can magnify the mucosa 1200-fold using standard endoscopy. In combination with chromoen-doscopy you can get a very accurate and detailed picture of the mucosa right during the investigation or you can modify next steps [5], Nowadays new techniques such as enteroscopy and capsule endoscopy have been coming into wider use. These three methods complement each other and follow each other in the investigation algorithm; they cannot be replaced by each other. Some authors consider them as the golden standard for investigation of the small intestine. CAPSULE ENDOSCOPY Capsule endoscopy represents a new diagnostic procedure that was introduced into clinical practice in 2001 and since then its use has developed significantly. It is a highly 222 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ NEW METHODS OF SMALL BOWEL INVESTIGATION specialised minimally invasive endoscopic method designed to investigate the small bowel, oesophagus or colon, which has over the last few years become an important part of the diagnostic algorithm of the examination of the small bowel. In the Czech Republic it has become relatively easy to reach and perform. The diagnostic system includes an endoscopic capsule, a system of antennas, a data recorder, an analyser, and a working station. The endoscopic capsule that the patient swallows enables us to scan the endoscopic picture during its passage through the gastrointestinal tract and its wireless transfer [7], Not only can we investigate the whole small intestine, but also the oesophagus or the colon; however, in these locations it cannot compete with endoscopy. For the patient this method is more than acceptable - they swallow a capsule in the size of a large vitamin tablet, which includes a miniature colour video camera, a light, a battery, and a transmitter. The capsule is later moved distally by the motility of the gastrointestinal tract. It is therefore completely dependent on the quality of the motility of the gastrointestinal tract (it can stay in the stomach for a long time). There is a risk of "saltatory" moving due to increased gut motility together with a change in the patient's position -thus significant pathologies can be missed. Also, we cannot forget the risk of possible transitional covering of the capsule by the content of the bowel or stagnation due to a stricture (which is also a contraindication of this procedure). The price of this method (the capsule itself is worth approximately CZK 15 000) is also fairly high. Important complications are rare. The main disadvantages of this tool are that the camera cannot be controlled and lesions cannot be treated or biopsies taken at the time that they are discovered. In our country capsule endoscopy is used only for investigation of the small intestine on the routine basis. It serves as an additional diagnostic procedure for patients who suffer from unexplained gastrointestinal disorders, such as bleeding, or to evaluate conditions of the small bowel that cause diarrhoea, pain or weight loss, such as Crohn's disease [10], INTRAOPERATIVE ENTEROSCOPY Intraoperative enteroscopy is an endoscopic method that enables the investigation of the whole small intestine, allowing to perform diagnostic (biopsies of mucosa) or therapeutic procedures (electrocoagulation, polypectomy) at one time. Endoscopically unsolvable pathological findings can be solved by the surgeon within seconds - during the same anaesthesia. Its disadvantage is its invasiveness, the necessity of anaesthesia, and laparotomy (laparoscopy) (8,9). It was the first enteroscopic technique brought into practice before balloon enteroscopies. Its main advantage is the possibility of viewing incomparably bigger parts of the small intestine than was allowed by the technique of enteroscopy used until then, introduced maximally with the support of an overtube. Co-operation with the surgeon made it much easier to move the endoscope in the intestinal lumen, to view the anatomical variations of the small intestine in high detail and, in the case of a positive finding, to immediately perform the necessary operative intervention. The disadvantage was the necessity of anaesthesia. Currently, this procedure is being substituted by balloon endoscopy. However, it remains an option when the classical double-balloon enteroscopy did not solve the patient's problems definitely, that is mainly in patients with intestinal adhesions or multiple lesions of the small intestine. BALLOON ENTEROSCOPY Single- or double-balloon enteroscopy is another modern endoscopic method that allows the investigation of a bigger part or even of the whole small intestine. The investigation of the whole small bowel is rarely possible from the oral access; more often it is a combination of oral and aboral access, i.e. a combination of two investigations [8], It enables us to carry out therapeutic procedures in situations when the routine endoscopy has failed. In some indications it has replaced the intraoperation enteroscopy, which remains an irreplaceable method when DBE cannot investigate the whole small intestine [11 ]. Currently there are two systems available: double-balloon -using a system of two balloons insufflated externally. One of them is placed on the overtube and the other is firmly connected with the end of the enteroscope. By alternate insufflation and desufflation of the balloons while moving the enteroscope with the overtube the whole system is pushed inside the lumen of the small bowel distally - ideally as far as the Bauhin's valvula. In case that it is not possible to reach the appropriate position perorally, then the position that had been successfully reached is marked with a special dye and the rest of the bowel is then examined transrectally. The position of the balloon in the end of the enteroscope does not allow its protrusion during the procedure. Single-balloon technology is very similar. The only difference is that at the end of the enteroscope there is no balloon, so the contact between the system and the bowel is kept by the pressure of the endoscope on the intestinal wall. Lately, new modifications have appeared on the market: [1] putting the insufflation balloon directly on the outer surface of the endoscope and inserting the other balloon through the bioptic canal of the enteroscope; [2] a helix placed externally on the enteroscope, which moves the enteroscope distally by its rotation. Both of these systems have been available only for a short time and need to be verified by longer clinical experience. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 223 00 NEW METHODS OF SMALL BOWEL INVESTIGATION CONCLUSION In the past decade, our hospitals and medical centres have been flooded bya greatnumberof new, direct and indirect diagnostic methods. Some of them have become an important part of the routine examination - enteroscopy is the most obvious example of this fact. The development is fast due to the fast development of the technical abilities of video endoscopes and computer technology. The new methods, such as capsule endoscopy, intraoperative enteroscopy and double-balloon enteroscopy, represent a group of complementary investigations, whose value needs to be verified by longer studies. However, they are already considered by some authors as the golden standard in the diagnosis of small bowel abnormalities. REFERENCES 1. Bunganičl, et al. Choroby tenkého čreva [Small bowel diseases]. Prešov: Privarpress, 2005: 71-75. 2. Schulman K, Schwiege K. Capsule endoscopy for small bowel surveillance in hereditary intestinal polyposis and non-polyposis syndromes. Gastrointestinal Endoscopy. Clinic Nam 2004; 14:149-158. 3. Appleyard M, Fireman Z, Glukhovsky A, et al. A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small-bowel lesions. Gastroenterology 2000; 119: 1431-1438. 4. Tacheci I, et al. Kapslová enteroskopie [Capsule enteroscopy]. Hradec Králové: Nucleus, 2008: 259 pp. 5. Beneš Z, Hep A. Význam gastroskopie pro dnešní praxi [Importance of gastroscopy for today's practice]. Med. pro Praxi 2006; 4:197-198. 6. Lukáš M. Idiopatické střevní záněty a kolorektální karcinom. Nové souvislosti a další perspektivy [Inflammatory bowel disease and colorectal carcinoma. New connections and further prospects]. Čes Slov Gastroent Hepat 2006;60[3]: 113-118. 7. Tacheci I, Drastich P, Suchánek Š, et al. Kapslová endosko-pie - standard endoskopického vyšetření tenkého střeva [Capsule endoscopy - standard of small bowel endoscopy]. Čes Slov Gastroent Hepat 2007; 61 [5]: 269-275. 8. Bureš J, Rejchrt S, Široký M, Kopáčova M. Enteroskopie: diagnostické a terapeutické možnosti endoskopického vyšetření tenkého střeva [Enteroscopy: diagnostic and therapeutical possibilities of small bowel endoscopy]. Interní medicína pro praxi 2000; 2: 34-36. 9. Kopáčova M. Dvojbalónová enteroskopie, její možnosti a alternativy [Double-balloon enteroscopy, its possibilities and alternatives]. Čas. Lék. čes. 2009; 148 [2]: 91-96. 10. www.mayoclinic.org/gastrointestinal-bleeding/diagno-sis.html 11. Yamamoto H, Kita H.Sunada K, etal. Endoscopic diagnosis and treatment of small intestinal diseases using the double-balloon enteroscopy. Gastrointestinal Endoscopy 2004; 59: 100. 224 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ CASE REPORT CAPSULE COLONOSCOPY Stiburek O., Kunovská M., Lata J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Received after revision September 2009 KEYWORDS Capsule colonoscopy Indication Strict preparation Recommendations CORRESPONDING AUTHOR Stibůrek 0. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic INTRODUCTION Capsule endoscopy (CE) has already become an integral part of the diagnostic algorithm for small bowel diseases [1 ]. This method is now quite easily available in the Czech Republic and is performed in more than 20 centres. A new method -capsule colonoscopy - has been available since the beginning of 2008. In this paper we present our experience with this method. TERMINOLOGY Based on the type of the capsule, CE is a method designed for the examination of small bowel, large bowel, or oesophagus. The examined patient swallows the capsule and its passage through the gastrointestinal tract (Gl) enables wireless transmission of the endoscopic image. The diagnostic system includes an endoscopic capsule, a sensor system, a data recorder, a real time viewer, and a workstation. In the present days there are similar systems produced by two companies: "Given"and "Olympus" (the Olympus system is designed for small bowel examination only). Technically, an endoscopic capsule consists of a digital camera located in a plastic capsule which is 26 mm long and 11 mm in diameter (31 x 11 mm is the colonic one). The capsule is passively passed through the Gl tract during the examination by peristalsis and records 2 pictures per second (the oesophageal capsule records 14 pictures per second).The data is immediately sent to the sensors (the antenna array) placed on the patient's body and then to the data recorder. The capsule records image data for 8-12 hours, as long as allowed by the batteries'lifespan. Realtime Viewer is a portable computer-like device with special software enabling us to watch the real-time endoscopic image.This is importantfor localising the position of the capsule within the Gl tract. We should use it after 2 hours since the capsule has been swallowed and when the capsule remains in the stomach, it should be removed to the duodenum by the gastroscope. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 225 CAPSULE COLONOSCOPY The workstation is represented by PC with a dock station for the data recorder and the software for data downloading and endoscopic image browsing. The examination of the small bowel takes 8 to 10 hours; the capsule usually leaves the body per vias naturales after 1 to 7 days. Preparation for this examination is quite simple: de-flatulents and fasting with increased fluid intake during the day before the examination [2], The capsule endoscopy of the small intestine is a highly specialised and relatively expensive method. Therefore, in the Czech Republic it remains as the last diagnostic option in case that other endoscopic methods fail to reveal the diagnosis. CAPSULE COLONOSCOPY Since the beginning of 2008 the use of capsule colonoscopy has been approved for commercial use in the Czech Republic. There are some differences between the more common small intestine capsule and the colonic capsule. The colonic one has two cameras, one at each end of the capsule, and is 5 mm longer (with the same diameter). It takes 4 pictures per second - 2 pictures for each camera. The optical system is improved and optimalised. Three minutes after being swallowed the capsule switches to the sleep mode for 105 minutes to save the battery. By the time it turns on again, it should be somewhere in the small intestine. The bowel preparation for the examination is very important and the colon has to be as clean as possible. For the cleaning of the colon and the right course of the examination we use in total 6 litres of electrolyte lavage solution (4 litres before and another 2 litres during the examination) and prokinetics (domperidone is used in our practice) (3,4,5). The capsule has to leave the human body no later than after 11 hours, so a suppository or a retrograde enema could be useful at the end. Based on the next six short case reports, we would like to express our recommendations and comments for capsule colonoscopy. Casel A male, 47 years old, with dyspepsia, occasional diarrhoea, colonoscopy was recommended. He explicitly refused all classic endoscopic methods. After the first 5 hours and 30 minutes the capsule was still retained in the stomach, but he refused gastroscopic relocation into the duodenum. The examination ended incompletely after 11 hours. The recording ended in the colon descendens. A small polyp (about 3mm) was found in the colon ascendens, and the patient was at least persuaded into endoscopic polypectomia. Case 2 A female, 63 years old, with dyspepsia and mild obstipation, type 2 diabetes mellitus, colonoscopy was recommended and refused by her. The bowel prep was poorly tolerated and the patient finally insisted on termination of the examination after 8 hours and 30 minutes. The examination was therefore incomplete and ended in the descending colon. Diabetic impairment of Gl transit could play a role, but the examination was terminated two and a half hours longer. Case 3 A female, 37 years old, with ulcerative colitis. She had a history of very poor toleration of classic coloscopy and therefore had not been examined for more than six years. She tolerated the bowel prep very badly and the examination was incomplete after 11 hours, which is very unfortunate especially in an ulcerative colitis patient. She suffered a cramp attack several hours after the examination, caused by the ion imbalance because of the large (yet standard) amount of the lavage solution. Case 4 A male, 40 years old, obese, with a family history of colorectal carcinoma. He demanded capsule colonoscopy, although the classic one was recommended. After 105 minutes, the capsule started to record already within the colon.There were no records of the caecum. The remaining parts of the colon were without pathology. Case 5 A female, 53 years old, with dyspepsia, to whom colonoscopy was recommended. She underwent several abdominal surgeries and thus had a history of very painful classic colonoscopy. She even refused the procedure under deep analgose-dation. Diverticula and at least 5 polyps were revealed by capsule colonoscopy. After this she underwent coloscopic removal of the polyps in deepanalgosedation. Case 6 A male, 51 years old, with a positive occult bleeding test. He did not follow the guidelines and drank only 3 litres of electrolyte lavage solution before the examination and another 2 litres during the examination, because he felt the preparation was adequate. Therefore we discovered large amounts of faeces, which disabled the examination. Indications for capsule colonoscopy The cases where classic colonoscopy could not be performed (e.g. adhesions after previous abdominal or pelvic operations) should be the main indication. It can also be used in patients who strictly refuse classic colonoscopy. 226 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ADVANTAGES It is a non-invasive examination, without sedatives, intubation, insufflation, no radiation load is involved, and it is painless for the patient. The whole examination is performed by a nurse; the physician evaluates the records later and the record is always fully available. DISADVANTAGES The main disadvantage is the price of the examination. Health insurance companies in the Czech Republic do not cover capsule colonoscopy. The full price has to be paid by the patient (ca. CZK 17500). Non-invasiveness cannot always be considered an advantage. CE is not capable of bioptic sampling and/or therapeutic interventions. A successful CE examination is conditioned by excellent bowel preparation and thus every bowel content residuum decreases the diagnostic yield noticeably. Furthermore, CE is a passive process without the possibility of insufflation, rinsing, and draining. The capsule is not always excreted after 11 hours or is already in the colon after the 105 minutes when it switches on; thereby the examination is often incomplete from one or another side (orthogradely or retrogradely). In most cases classic colonoscopy has to be finally done with the pathological findings. OUR RECOMMENDATIONS 1. The patient's case has to be undoubtedly indicated for colonoscopy. 2. Patients have to be thoroughly informed about all advantages and disadvantages of CE. The recommendation of classic colonoscopy with the possibility of deep analgosedation is the most important part of the protocol. 3. Using the Real Time Viewer is necessary at least once (after two hours since swallowing the capsule) during the examination to demonstrate current position of the capsule (all possible steps have to be taken for the right course of the examination). 4. Most of the patients who want capsule colonoscopy should be persuaded into the classic one because their requirements are associated with lack of information and not with the necessity for CE exam. 5. Strict preparation (colon cleaning) for the examination is essential and cannot be underestimated. Unfortunately, even full compliance of the patient with this intensive bowel cleaning protocol can be insufficient in some cases. 6. Monitoring of patients with IBD (especially with UC) by capsule colonoscopy seems unsuitable because of a relatively large risk of incomplete examination. CAPSULE COLONOSCOPY CONCLUSION Capsule colonoscopy is a modern and sophisticated examination method with its specific indications, but it will probably not reach common use in everyday practice because of its limits and extra price. REFERENCES 1. Tacheci I, Rejchrt S, Drastich P, et al. Capsule endoscopy -initial experiences in the Czech Republic: a retrospective multi-center study. Acta endoscopica 2005; 35[3]: 329-338. 2. Rejchrt S, Drastich P, Kopáčova M, et al. Standard en-doskopického vyšetření tenkého střeva diagnostickou kapslí [Standard capsule endoscopy examination of the small intestine]. Čes Slov Gastroent Hepatol 2004: 58[1]: 24-27. 3. Selby W. Complete small-bowel transit in patients undergoing capsule endoscopy: determining factors and improvement with metoclopramide. Gastrointest Endosc 2005;61:80-85. 4. Dai N, Gubler C, Hengstler P, Meyenberger C, Bauerfeind P. Improved capsule endoscopy after bowel preparation. Gastrointest Endosc 2005; 61: 28-31. 5. Keuchel M, VoderholzerWA, Schenk G, et al. Domperidone shortens gastric transit time of video capsule endoscope. Endoscopy 2003; 35: Al 85. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 227 ORIGINAL RESEARCH HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY Kliment M.\ Urban O.1, Fojtík P.1, Petrášek J.2, Janík D.1, Albín A.1, Liberda M.1, Šmajstrla V.1, Kundrátová E.1, Falt P.1 1 Department of Gastroenterology, Vítkovice Hospital, Ostrava 2 Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague AFFIRMATION Received after revision September 2009 KEYWORDS Colonoscopy High-definition Wide-angle Polyp Flat adenoma The authors of this article do not have any relevant financial relationship with the manufacturer(s) or provider(s) of the commercial products or services that may be discussed herein. ABBREVIATIONS USED HDWAC - high-definition, wide-angle colonoscopy SRSAC - standard-resolution, standard-angle colonoscopy HRSAC - high-resolution, standard-angle colonoscopy CRC - colorectal cancer CCD - charged couple device HG IEN - high-grade intraepithelial neoplasia ABSTRACT H CORRESPONDING AUTHOR Kliment M. Vítkovice Hospital Zalužanského 1192/15 703 84 Ostrava Czech Republic Improved visualisation of colorectal mucosa may increase adenoma detection. The objective of our study was to compare high-definition (1080-line screen), high-resolution (>400 000 pixels), wide-angle (170°) colonoscopy (HDWAC) with standard-resolution (<300 000 pixels), standard-angle (140°) colonoscopy (SRSAC) and high-resolution, standard-angle colonoscopy (HRSAC), both combined with standard-definition (480-line) screen, in terms of adenoma detection. A total of 507 consecutive patients presenting with diagnostic colonoscopy were allocated to undergo either SRSAC (n=254), or HRSAC (n=160), or HDWAC (n=93). The primary outcome parameter was the difference in adenoma detection between the study groups. The mean number of adenoma and flat adenoma detected per patient was higher in HDWAC than in HRSAC and SRSAC groups (adenoma±SD: 0.91 ±1.27 vs 0.63±1.19 vs 0.59±1.15, respectively, P=0.014; flat adenoma: 0.45±0.81 vs 0.28±0.77 vs 0.15±0.51, respectively, P<0.001). 228 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY The proportion of patients with >1 adenoma of any size and >1 adenoma <10mm with advanced histology (containing either high-grade intraepithelial neoplasia or villous morphology) was higher in HDWAC compared with SRSAC and HRSAC groups (any adenoma: 48.4% vs 32.3% vs 34.4%, respectively, P=0.019; adenoma <10mm with advanced histology: 16.1 % vs 7.1 % vs 5.0%, respectively, P=0.005). HDWAC improves adenoma detection when sufficiently long instrument withdrawal time is kept. This is primarily accounted for by increase in the detection of adenomas, including flat adenomas and adenomas with advanced histology, <10mm in size. These findings support the use of HDWAC in clinical practice. INTRODUCTION The interruption of adenoma-carcinoma sequence is the primary end point of colorectal cancer (CRC) screening and colonoscopy is the best tool to achieve this goal. The first studies on incident CRC rates after clearing colonoscopy proved to prevent approximately 80% of CRCs [1,2]. Later studies, however, demonstrated a substantially lower protective effect of colonoscopy [3-5], which may in part be explained by missing adenomas during colonoscopy [6,7], The reasons for missing adenomas are either procedure- (incomplete colonoscopy, fast endoscope withdrawal, ineffective polypectomy) or instrument- (inability to expose mucosa on proximal sides of folds or to detect flat adenomas) related [8], To expose more colorectal mucosa and to detect flat adenomas, several colonoscopic techniques, including wide-angle viewing colonoscopes [9,10], cap-fitted colonoscopy [11], colonoscopy in retroflexion [12], chromoendoscopy [13,14], narrow band imaging [15], and high-definition colonoscopy [16,17], have been studied with mixed results. The studies from Europe [18,19], and US [20] have shown similar prevalence of flat adenomas to that reported in Japan. The miss rate for flat adenomas may be significantly higher than for adenomas of sessile or pedunculated pattern [21]. Since this subgroup of adenomas may carry a higher risk for malignant transformation, especially of depressed type [22], they should not be missed but treated during colonoscopy, which offers efficient and safe therapy [23], Conventional videoendoscopes, equipped with charged couple device (CCD) chips of 100 000 to 300 000 pixels.are referred to as standard-resolution endoscopes. Videoendoscopes equipped with CCD chips of >400 000 pixels are referred to as high-resolution. High-definition endoscopes produce a video signal with 1080 visible horizontal scan lines, whereas a video signal produced by standard-definition endoscopes consists of 480 lines. It is hypothesised that endoscopes with higher image resolution and wider angle view should detect more adenomas, including flat adenomas. Butto date no study has confirmed this hypothesis. In our study, we sought to confirm whether high-definition, wide-angle colonoscopy (HDWAC) detects a higher number of adenomas and flat adenomas compared with standard-resolution, standard-angle colonoscopy (SRSAC), and high-resolution, standard-angle colonoscopy (HRSAC). MATERIALS AND METHODS Patients were eligible if they were aged >18 years and presented with diagnostic colonoscopy. The exclusion criteria were as follows: active gastrointestinal bleeding, inflammatory bowel disease, familial polyposis syndromes, hereditary non-polyposis colorectal cancer, inability to pass the endoscope beyond the sigmoid colon, and inability to give informed consent. The study protocol was approved by the Institutional Review Board and the Ethics Committee at Vítkovice Hospital. The patients were enrolled between November 1,2006 and May 31,2007. Colonoscopies are performed in parallel in 2 suits in our endoscopy unit and the patients are scheduled in 45 minutes' intervals. Cleaning the instrument takes approximately 45 minutes. Depending on the availability of the endoscope, patients presenting with diagnostic colonoscopy were assigned to undergo either SRSAC or HRSAC or HDWAC. In the SRSAC group, three standard-resolution, standard-angle (140°) view videocolonoscopes (Olympus CF Q145, CF Q145L; Olympus Europe, Hamburg, Germany) with a standard-definition 480-line screen were available. In the HRSAC group, colonoscopies were performed with one of the two high-resolution, standard-angle (140°) view videocolonoscopes (Pentax EC 3881 FK, EC-3870 FZK; Pentax Europe, Hamburg, Germany) with a standard-definition 480-line screen. In the HDWAC group, a single high-resolution, wide-angle (170°) view videocolono-scope (Olympus CF HI 180 AL; Olympus Europe, Hamburg, Germany) with a high-definition 1080-line screen was available. Eight endoscopists with previous experience of >200 to >7000 colonoscopies participated in the study, conducted at a single non-university tertiary referral centre. All patients underwent bowel preparation consisting of solid food restriction and drinking either 4L of macrogol or 500mL of magnesium sulphate solution 24 hours prior to colonoscopy. The quality of bowel preparation was graded by the endoscopist as follows: [1] excellent- no solid or liquid residue, [2] good -complete mucosal inspection after suction, [3] fair - greater than 90% mucosal visualisation, [4] poor - less than 90% mucosal visualisation. After caecal intubation the withdrawal time measurement began and was stopped when the endoscope was withdrawn from the anus.The watch was stopped http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 229 HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY Table 1 Demographics, colonoscopy baseline characteristics Parameters SRSAC(n=254) HRSAC (n=160) HDWAC(n=93) Pvalue Patient demographics Mean (SD) age (years) 58.8(14.9) 58.0(15.6) 60.3 (11.6) 0.76 Male gender, N (%) 126 (49.6) 81 (50.6) 51 (54.8) 0.69 Successful caecal intubation, N (%) 244(96.1) 156(97.5) 90 (96.8) 0.73 Mean (SD) withdrawal time (min) 8.8(1.8) 8.6(1.4) 8.6(1.5) 0.89 Indications Bleeding, N (%) 97 (38.2) 55 (34.4) 34 (36.5) 0.84 Change in bowel habits, N (%) 47 (18.5) 37(23.1) 15(16.1) Surveillance, N (%) 41 (16.2) 33 (20.6) 20(21.5) Abdominal pain, N (%) 32 (12.6) 16 (10.0) 12(12.9) Weight loss, N (%) 8(3.1) 5(3.1) 4 (4.3) Others, N (%) 29 (11.4) 14(8.8) 2 (8.7) Bowel preparation Excellent: Good : Fair: Poor 116:76:32:30 84:35:18:23 39:29:14:11 0.46 Table 2 Detection rates of polyps and adenomas - per patient analysis Parameter (±SD) SRSAC(n=254) HRSAC (n=160) HDWAC (n=93) Pvalue Polyps 1.06 (1.62) 1.15(1.61) 1.48(1.69) 0.008 Adenomas 0.59(1.15) 0.63(1.19) 0.91 (1.27) 0.02 Flat adenomas 0.15(0.51) 0.28 (0.77) 0.45(0.81) <0.001 Polypoid adenomas 0.44 (0.97) 0.36 (0.79) 0.44 (0.84) 0.76 Right-sided adenomas 0.27 (0.65) 0.32 (0.77) 0.52 (0.99) 0.04 Left-sided adenomas 0.32 (0.70) 0.30 (0.64) 0.39(0.71) 0.29 for polyp biopsy, polypectomy, and polyp retrieval. According to the international recommendation [24] an attempt was made to keep the extubation time at least 6 minutes in each study group. The morphology and size of each colorectal lesion were recorded. According to the Paris Endoscopic Classification of Superficial Neoplastic Lesions [25] the lesion was endoscopically classified as flat when it did not pass above the closed cups of a biopsy forceps (2.5 mm) (Olympus) placed adjacent to the lesion, whereas lesions passing above were classified as polypoid.The size was measured by placing a fully opened biopsy forceps next to the lesion. All detected lesions were removed by one of several resection techniques except for small lesions in the rectosigmoid which appeared to be hyperplastic, because their pit pattern was determined to be type I or II. The histology of all resected specimens was interpreted by two experienced pathologists using the Vienna Classification [26], The primary outcome measure was the difference in adenoma detection between the study groups.The secondary measures were differences in flat adenoma, adenoma <10mm with advanced histology, defined as either high-grade intraepithelial neoplasia (HG IEN) or villous morphology, right-sided (caecum to splenic flexure), left-sided (splenic flexure to rectum), and multiple adenoma detection between the groups. Statistical analysis We calculated the sample size required to detect a significant improvement of adenoma detection with HDWAC compared 230 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ 00 ■ HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY with SRSAC using the DSTPLAN software (http://linkaqe.rock-efeller.edu/soft). Assuming a 20% prevalence of adenomas in the population, at least 250 patients undergoing SRSAC and 90 patients undergoing HDWAC were required for detection of at least 20% difference in the proportion of patients with adenomas. The calculations were performed at 5% of significance for 80% statistical power. One-way ANOVA, Mann-Whitney or Kruskal-Wallis tests, when appropriate, were used for comparison of continuous variables, and the Fisher exact test was used for comparison of proportions. To assess the role of clinical variables independently influencing the number of diagnosed polyps, stepwise linear regression analysis was used. Goodness-of-fit and co-linearity statistics were assessed for the regression model. The level of significance was set at P<0.05, P values between 0.05 and 0.10 were considered to indicate a statistical trend. All P values were two-sided. Statistical analysis was performed using SPSS version 14.0 (SPSS Inc., Chicago, IL). RESULTS A total of 524 consecutive patients referred for diagnostic colonoscopy fulfilled the inclusion criteria and were enrolled in the study. After exclusion of 17 patients because of either diagnosing IBD or the presence of non-transferable stenosis of rectosigmoid colon, 507 patients (50.9% male) with a mean age of 58.9±14.3 years completed the study protocol. A total of 254 patients were analysed in the SRSAC arm, 160 in the HRSAC, and 93 in the HDWAC arm. Table 1 shows that there was no difference between the study groups in any of the parameters assessed. No complication occurred in any patient included in the study. A total of 592 lesions with a mean size of 6.15±6.43mm (range 1.0-60.0mm) were detected in the entire study population, of which 255 (43.1 %) were hyperplastic polyps, 305 (51.5%) adenomas with low-grade intraepithelial neoplasia, 26 (4.4%) adenomas with HG IEN, 3 (0.5%) intramucosal, and 3 (0.5%) invasive carcinomas. From the total of 331 adenomas, 206 (62.2%) were polypoid and 125 (37.8%) were flat according to the Paris Endoscopic Classification [25]. From the entire study group, at least one adenoma, one flat adenoma, and multiple (>3) adenomas were detected in 182 (35.9 %), 80 (15.8 %), and 35 (6.9%) patients, respectively. Table 2 demonstrates the summary of lesions found in per-patient analysis. The mean rate of adenoma and flatadenoma per patient was significantly higher in HDWAC group compared with the other groups (P=0.02, P<0.001, respectively). The mean number of right-sided adenoma per patient in HDWAC group was almost double that of SRSAC group (P=0.01). In contradiction to right-sided and flat adenomas, there was no difference in the detection of left-sided and polypoid adenomas between the study groups (P=0.29, P=0.76, respectively). The prevalence rates of adenomas and flat adenomas of various size, the prevalence rates of polypoid, right-sided, left-sided adenomas, and adenomas with advanced histology <10mm in size are shown in Table 3. A subgroup analysis of the prevalence of adenomas <10mm showed a statistical trend towards a greater prevalence in the HDWAC group (P=0.07). When this subgroup was restricted to flat adenomas, there was a significantly higher prevalence of flat adenomas <10mm in HDWAC group (P<0.001). The proportion of patients with >1 adenoma <10mm in size with advanced histology was higher in HDWAC than in the other two colonoscopy groups (P=0.005). In a number-needed-to-diagnose analysis, the number of HDWAC needed to detect one additional adenoma patient compared with SRSACand HRSAC would be 6 (with adenoma detection on per-patient basis of 48.4%, 32.3% and 34.4%, respectively). Multivariate analysis with logistic regression found that the type of colonoscopy was the strongest independent predictor for flat adenoma detection. Other variables independently predicting polyp, adenoma and flat adenoma detection are shown in Table 4. DISCUSSION In this study, HDWAC detected more adenomas, flat adenomas, and adenomas with advanced histology <10mm in diameter compared with SRSAC and HRSAC. Our findings are inconsistent with the results of a recently published study of 693 patients [16], which showed no difference in adenoma detection between HDWAC and SRSAC. In this series, however, adenoma prevalence and the mean number of adenomas detected per patient in HDWAC group was 26% and 0.43±0.87, respectively, which is approximately half the prevalence rate and adenoma detection reported in our study. Possible explanations for the difference might be either generally low adenoma prevalence in the population or insufficient quality of colonoscopic procedure performed by endoscopists with low adenoma detection in that study. It is, therefore, possible to speculate whether endoscopists with low adenoma detection would benefit from technical developments in colonoscopic technology, such as increased image resolution or wide-angle view. It is highly probable that rather than endoscopic resolution, the more important factor in attaining high adenoma detection is the operator technique, especially in less experienced endoscopists. Another study compared adenoma detection with high-definition and standard-definition endoscopes (both with 140° angle of view) in a population of 130 patients [17]. Although the mean number of adenomas per patient and the adenoma prevalence were by 30% and 11 % higher in the http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 231 00 HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY Table 3 The prevalence of adenomas categorised according to size, morphology, location, and histology Patients with SRSAC(n=254) HRSAC(n=160) HDWAC (n=93) Pvalue >1 adenoma, N (%) 83 (32.7) 54 (33.7) 45 (48.4) 0.02 <10mm, N(%) 71 (28.0) 50(31.3) 38 (40.9) 0.07 >10mm, N(%) 23(9.1) 13(8.1) 12(12.9) 0.43 >1 flat adenoma, N (%) 27(10.6) 26(16.3) 29(31.2) <0.001 <10mm, N(%) 19(7.5) 22(13.8) 27 (29.0) <0.001 >10mm, N(%) 10 (3.9) 6 (3.8) 6 (6.5) 0.53 >1 polypoid adenoma, N (%) 65 (25.6) 37(23.1) 25 (26.7) 0.77 >1 right-sided adenoma, N (%) 45(17.7) 35(21.9) 28(30.1) 0.04 >1 left-sided adenoma, N (%) 55(21.7) 36 (22.5) 27 (29.0) 0.36 >3 adenomas, N (%) 15(5.9) 11 (6.9) 9 (9.7) 0.47 >1 adenoma <1 Omm with advanced histology, N (%) 18(7.1) 8 (5.0) 15(16.1) 0.005 Table 4 Variables independently influencing the number of diagnosed polyps, adenomas and flat adenomas during endoscopy. As the variable "Examiner" in "All polyps" worsened the good ness-of-fit of the regression model, it was not included in the final model despite its statistical significance All polyps Adenomas Flat adenomas Variables B Pvalue ß Pvalue ß Pvalue Colonoscopy type - 0.05 - 0.07 0.16 <0.001 Age 0.22 <0.001 0.25 <0.001 0.14 0.001 Gender (male vs. female) -0.22 <0.001 -0.24 <0.001 -0.14 0.001 Preparation (4 categories) - 0.67 - 0.21 -0.12 0.007 Examiner (8 categories) - 0.02 - 0.14 - 0.14 Indication (10 categories) - 0.6 - 0.79 - 0.88 ß- standardised coefficient beta high-definition group, the difference was not statistically significant (P=0.20). Two potential effects might have influenced adenoma detection in HDWAC group in our study. Firstly, the wide-angle instrument's capacity to expose more colorectal mucosa might have increased the overall adenoma detection by imaging adenomas on the proximal sides of the folds, predominantly in the right colon, which has a larger diameter with a higher chance for missing adenoma. Secondly, HD imaging might have enabled an increase in the overall adenoma detection by improved resolution of the colonic mucosa and, thereby, imaging subtle mucosal changes between the flat adenoma and the surrounding mucosa. This assumption is supported by the fact thatthe increase in the prevalence of adenomas in HDWAC group was primarily accounted for by increased detection of flat adenomas <10mm in diameter. Improvement in image resolution is not expected to increase the detection of protrusive or large adenomas, but rather of flat and small ones.This is supported by our findings of no difference in the detection of flat adenomas >10mm and polypoid adenomas of any size between the study groups. The studies comparing endoscope withdrawal time and adenoma miss rate between wide-angle (170° or 210°) and standard-angle colonoscopy demonstrated a shortening of endoscope withdrawal time without compromising adenoma detection using a wide-angle instrument [9,10,27], The endoscope withdrawal time did not differ between the groups in our study. Using HDWAC, we detected 0.91 ±1.27 232 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY adenoma per patient, whereas Rexetal [15] reported a detection of 1.8±2.2 adenoma per patient with white-light HDWAC. The quality of bowel preparation and the different experience level of endoscopists participating in our study might have negatively influenced adenoma detection rate. The difference between the endoscopist with the highest and lowest adenoma detection was threefold (data not shown). In one study, however, the variation in adenoma detection was reported to be over tenfold between 12 experienced endoscopists [28], Adenomas with HG IEN or villous morphology carry a higher risk of progression to carcinoma [29]. In our study, a significantly higher proportion of patients with >1 adenoma with advanced histology <1 Omm in size was in the HDWAC group. In contradiction to this, the prevalence of adenomas with advanced histology >10mm did not differ between the study groups (data not shown). The impact of HDWAC on the detection of high-risk adenomas is of clinical importance since missing them may lead to interval CRC development. Although a not statistically significant yet potentially clinically important increase in the number of patients with >3 adenomas was seen in the HDWAC group, since these patients are at high risk for the development of advanced neoplasia during the follow-up [30], There are limitations to our study. As the study was non-randomised and the allocation depended on the availability of the instrument only, selection bias is possible. Nevertheless, the same demographics, colonoscopy indications, and quality of bowel preparation in all groups indicate that the groups were well matched. Different adenoma detection and different numbers of colonoscopies performed by each endoscopist in the study groups were further potentials for biases. On the other hand, our results probably reflect more accurately the true diagnostic yield of the studied technique when performed in the conditions of routine practice. Finally, the colonoscopists were not blinded to which instrument they were using, which might have led to a more precise inspection of the colonic mucosa in the HDWAC group. In conclusion, this study has shown the benefit of HDWAC for colorectal adenoma detection, when a sufficiently long withdrawal interval is kept. The increase in overall adenoma detection was primarily accounted for by the increase in the detection of adenomas, including flat adenomas and adenomas with advanced histology, which were <10mm in size. HDWAC might be useful in decreasing the risk of interval CRC development within a short term after clearing or negative colonoscopy by detecting small neoplastic lesions with advanced histology. These findings support the use of HDWAC in clinical practice, but these results should be interpreted with caution because of the study design and other limitations mentioned. More randomised controlled studies are needed to clearly establish the role of HDWAC in current practice. REFERENCES 1. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993; 329: 1977-81. 2. Citarda F, Tomaselli G, Capocaccia R, Barcherini S, Crespi M. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001; 48: 812-15. 3. Robertson DJ, Greenberg ER, Beach M, et al. Colorectal cancer in patients under close colonoscopic surveillance. Gastroenterology 2005; 129: 34-41. 4. PabbyA,Schoen RE,WeissfeldJL,etal.Analysisofcolorec-tal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61:385-91. 5. Singh H, Turner D, Xue L, Targownik LE, Bernstein CN. Risk of developing colorectal cancer following a negative colonoscopy examination: evidence fora 10-year interval between colonoscopies. JAMA 2006; 295: 2366-73. 6. Rex DK, Cutler CS, Lemmel GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997; 112: 24-28. 7. Rogier E van Gelder, C Yung Nio, Jasper Florie, et al. Computed tomographic colonography compared with colonoscopy in patients at increased risk for colorectal cancer. Gastroenterology 2004; 127:41-48. 8. Rex DK. Colonoscopic withdrawal technique is associated with adenoma miss rates. Gastrointest Endosc 2000; 51: 33-36. 9. Deenadayalu VP, Chadalawada V, Rex DK. 170 degrees wide-angle colonoscope: effect on efficiency and miss rates. Am J Gastroenterol 2004; 99: 2138-42. 10. Rex DK, Chadalawada V, Helper DJ. Wide angle colonoscopy with a prototype instrument: impact on miss rates and efficiency as determined by back-to-back colonoscopies. Am J Gastroenterol 2003; 98: 2000-5. 11. Lee YT, Hui AJ, Wong VW, Hung LC, Sung JJ. Improved colonoscopy success rate with a distally attached mucosectomy cap. Endoscopy 2006; 38: 739-42. 12. Pishvaian AC, Al-Kawas FH. Retroflexion in the colon: a useful and safe technique in the evaluation and resection of sessile polyps during colonoscopy. Am J Gastroenterol 2006; 101:1479-83. 13. Hurlstone DP, Cross SS, Slater R, Sanders DS, Brown S. Detecting diminutive colorectal lesions at colonoscopy: http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 233 HIGH-DEFINITION, WIDE-ANGLE COLONOSCOPY FOR ADENOMA DETECTION - A PROSPECTIVE STUDY a randomised controlled trial of pan-colonic versus targeted chromoscopy. Gut 2004; 53: 376-80. 14. Kiesslich R, von Bergh M, Hahn M, Hermann G, Jung M. Chromoendoscopy with indigocarmine improves the detection of adenomatous and nonadenomatous lesions in the colon. Endoscopy 2001; 33:1001 -6. 15. Rex DK, Helbig CC. High yield of small and flat adenomas with high definition colonoscopes using either white light or narrow band imaging. Gastroenterology 2007; 133:42-47. 16. Pellisé M, Fernández-Esparrach G, Cárdenas A, et al. Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasias randomised controlled trial. Gastroenterology 2008; 135[4]: 1062-68. 17. East JE, Stavrindis M.Thomas-Gibson M, et al. A comparative study of standard vs. high definition colonoscopy for adenoma and hyperplastic polyp detection with optimised withdrawal technique. Aliment Pharmacol Ther 2008; 28[6]: 768-76. 18. Rembacken BJ, Fujii T, Cairns A, et al. Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet 2000; 355:1211-14. 19. Hurlstone DP, Cross SS, Adam I, etal. Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesions of the colorectum: a prospective analysis. Gut 2004; 53: 284-90. 20. Saitoh Y, Waxman I, West AB, et al. Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population. Gastroenterology 2001; 120:1657-65. 21. Heresbach D, BarriozT, Lapalus MG, et al. Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008; 40: 284-90. 22. KudoS, Kashida H.TamuraT, etal. Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer. World J Surg 2000; 24:1081-90. 23. Urban O, Vitek P, Fojtik P, et al. Laterally spreading tumors - experience based on 138 consecutive cases. He-patogastroenterology 2008; 55 (82-83): 351-55. 24. Rex DK, Bond JH, Winawer S, et al. Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: Recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2002; 97:1296-1308. 25. Inoue H, Kashida H, Kudo S, et al. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc 2003; 58: S3-43. 26. Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 2002; 51:130-131. 27. Fatima H, Rex DK, Rohstein R, et al. Cecal insertion and withdrawal times with wide-angle versus standard colonoscopes: a randomised controlled trial. Clin Gastroenterol Hepatol 2008; 6[1 ]: 109-14. 28. Barclay R, Vicari JJ, Johanson JF, et al. Variation in adenoma detection rates and colonoscopic withdrawal times during screening colonoscopy (Abstract). Gastrointest Endosc 2005; 61 :AB107. 29. Eide T. Risk of colorectal cancer in adenoma bearing individuals within a defined population. IntJ Cancer 1986; 38: 173-76. 30. Atkin WS, Morson BC, CuzickJ. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992; 326: 658-62. 234 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ REVIEW CLINICAL APPLICATION OF ELECTROGASTROGRAPHY Prokešová J., Dolina J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Received after revision September 2009 KEYWORDS Electrogastrography Gastric dysrhythmias Gastroparesis Gastric emptying ABSTRACT Electrogastrography (EGG) is a completely non-invasive measurement of the gastric myoelectrical activity from cutaneous Ag\AgCI electrodes placed on the abdominal wall anterior to the stomach. EGG can be recorded from a pair of electrodes for a single or for multiple channels. The advantages of four-channel EGG measurement consist in detailed analysis; it also allows the study of electrical coupling and propagation of gastric slow-wave activity. The study consists of a 45 minutes' preprandial period and a 45 minutes' postprandial period after consumption of a standard meal. In health, the dominant frequency and power reflect the normal basic rhythm of the slow waves, and the contractile activity provoked by food or other stimuli. The peristaltic antral activity that is essential for normal primary gastric function is reflected in EGG as an increase in its dominant power. The impaired myoelectrical activity observed in EGG is associated with disturbed motilityand upper gastrointestinal symptoms, and may be suggestive of delayed gastric emptying. INTRODUCTION CORRESPONDING AUTHOR Prokešová J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic Electrogastrography methods have been used in many clinical studies over the past 80 years. In 1922 Alvarez predicted that electrical abnormalities of the stomach might be related to gastrointestinal symptoms and abnormal gastric function. In 1980 antral dysrhythmias were recorded with mucosal electrodes in a series of patients with unexplained nausea and vomiting. The electrical activity of the stomach can be subdivided into two general categories: electrical control activity (ECA) and electrical response activity (ERA). ECA is characterised by regularly recurring electrical potentials, originating in the gastric pacemaker located in the great curvature of the stomach and sweeping in an annular band with increasing velocity towards the pylorus. ECA is not associated with contraction of the stomach unless coupled with http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 235 CLINICAL APPLICATION OF ELECTROGASTROGRAPHY action potentials, referred to ERA. The usual practice is to record the EGG signal from several cutaneous electrodes and to select the signal with the highest amplitude for further ana lysis (Fourier spectral analysis). The EGG is usually evaluated in terms of changes in EGG amplitude and frequency. Abnormal myoelectrical activity can be detected in many patients with delayed gastric emptying, those who may show abnormally rapid rhythm (tachygastria), abnormally slow rhythm (bradygastria), or no increase in signal amplitude after a meal. Similar changes have been reported in patients with delayed gastric emptying associated with reflux disease or anorexia nervosa, with functional dyspepsia, patients after surgical resections (with Billroth II anastomosis). Another group consists of the so-called pseudo-obstruction - such as scleroderma, amyloidosis, and muscular dystrophies. One of the most common causes of delayed emptying is diabetes, although many diabetics have neuropathy, mainly autonomic neuropathy. The symptoms include bloating, distension, nausea, and vomiting. METHODS Gastric electrical activity was recorded from 4 surface electrodes placed on the upper abdomen. The signal that will be recorded by electrogastrography is very weak and needs to be amplified, filtered, and digitised before it can be stored either online onto a computer or in a separate recording device. In order to obtain an EGG recording with a high signal without any "noise" care must betaken in preparing the skin of the abdomen where percutaneous electrodes should be placed. The places should be cleaned and abraded with some sandy skin preparation jelly in order to reduce the impedance below 10 KQ.To reduce severe motion artefact we use what is called a motion sensor. The most common placement of electrodes for a four-channel recording is shown in Figure 1. Several electrodes are placed along the curvature of the stomach. EGG should be recorded in a quiet room to minimalise the risk for artefacts and the patient needs to stay as quiet as possible to minimalise their movements during the study. The processing of the measurement starts after an overnight fasting; the patient is positioned in a supine or semireclining position. After 45 minutes' fasting recording (preprandial), the 10 minutes'period is followed by a standardised test meal plus drink (including at least 200 kcal of energy; the meal should be mainly solid food) and then a 45 minutes'feed period recording (postprandial). Numerical analysis usually includes transformation of the curve into frequency components using Fourier transforms or a similar technique. Reliable data can be obtained using a recording apparatus set for a frequency range of 0.5 to 9 cpm, and an amplitude of 50 to 500 uV, to encompass a broad range of dysrhythmic patterns. For practical purposes, we will focus on the ambulatory device which we use: Digitrapper EGG; Synectics Medical Inc. INDICATIONS Figure 1 Position of electrodes on the abdomen Ch 1-4: electrodes; R, reference electrode; G, ground Unexplained nausea or vomiting Suspected or confirmed gastroparesis Functional dyspepsia Monitoring pharmacologist therapy ANALYSIS Data collected during the recordings are analysed to obtain major EGG parameters. The clinical application of an EGG measurement consists in the understanding of these parameters and their patterns in different groups: • Dominant frequency: The EGG dominant frequency reflects the frequency of the gastric slow waves (frequency of gastric pacemaker). The recordings obtained from hundreds of human subjects indicate a normal frequency range of 2.5-3.7 cpm. • Dominant power: The dominant power of EGG is associated with the amplitude and regularity of EGG. The absolute value of the power is influenced by a number of factors (e.g., thickness of the abdominal wall, 236 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ CLINICAL APPLICATION OF ELECTROGASTROGRAPHY Figure 2 Spectral analyses of the electrogastrogram (EGG) electrode configuration, recording devices), and thus, only relative changes are considered (e.g., before and after stimulation). • Percentage of normal slow waves: The percentage of the normal slow waves reflects the regularity of EGG. It is defined as the percentage of time during which 2.5-3.7 cpm slow waves are present across the entire recording. • Percentage of gastric dysrhythmias: The percentage of dysrhythmias reflects the time during which 2.5-3.7 cpm slow waves are absent across the entire recording. They are classified according to their peaks in the range of frequency: bradygastria (0.5-2.5 cpm), tachygastria (3.8-9 cpm), and arrhythmia (during which no dominant peak can be identified in the range of 0.5-9 cpm). • Percentage of SW coupling: the percentage of time during which the SW was determined to be coupled. Gastric dysrhythmias have often been reported in patients with motility disorders, but only seldom in normal subjects with no history of gastrointestinal motility diseases. Several studies have shown that EGG can be used to differentiate between normal subjects and patients with gastroparesis (75% of whom have EGG abnormalities). Typical EGG abnormalities in patients with such motility disorders include: - deterioration of EGG after a test meal, which is shown as a decrease in EGG power; - absence of normal slow waves; - gastric dysrhythmias (including bradygastria, tachygastria, and arrhythmia). DISCUSSION Slow waves (SW) determine the frequency and the direction of propagation of the contractions. The corresponding EGG parameter, the dominant frequency, equals that of the internal measurement. In previous studies, Abell et al. and other investigators found that the EGG's dominant frequency is of gastric origin, and matched the gastric slow waves in mucosal tracings. These findings were reproduced in other experiments using serosal and cutaneous electrodes simultaneously. The correlation between gastric contractions and the EGG's dominant power was investigated by internally recording the myoelectrical activity. A postprandial increase in EGG power is often observed and is thought to be attributable to increased slow-wave amplitude and spikes during gastric contractions. The explanation of the postprandial power increase is still debatable. Some investigators think that it reflects the physical distension of the stomach and the subsequent movement of the pacemaker closer to the surface. However, ultrasonographic measurement of the distance between the gastric and abdominal walls, before and after meals, did not support this theory. Gastric contractions remain the main reason for the postprandial power increase. Dysrhythmia is associated with symptomatology and hypo-motility (the existence of hypomotility is proved by simultaneously performing manometry). Gastric dysrhythmia has long been shown to reflect disturbed gastric motility in a variety of states including pregnancy, motion sickness, and diabetic gastroparesis. In the nausea and vomiting associated with pregnancy, dysrhythmic recordings disappear after delivery, along with the symptoms. Experimental induction of motion sickness induces symptoms and dysrhythmia, and diabetic gastroparesis reflects the same association with known hypomotility. Tachygastria (including frequencies from 3.75 to 10.0 cpm) originates mostly from an antral ectopic source with retrograde propagation, whereas bradygastria may be either from a normal or an abnormal source. Tachygastrias are evoked by loss of vagal parasympathetic activity and/or increase in the sympathetic nervous system. An interesting study showed the normalisation of dysrhythmic patterns reflected in EGG, after a prokinetic treatment, with a similar decrease in symptoms. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 237 CLINICAL APPLICATION OF ELECTROGASTROGRAPHY The correlation between gastric emptying and myoelectrical activity has always been of great interest to investigators in the clinical field. Although myoelectrical activity controls motility, there are some factors that affect gastric emptying but cannot be appreciated in EGG, such as pyloric stenosis. Diabetic autonomic neuropathy is considered to be quite a common complication of diabetes mellitus. It usually remains silent for a long time, without clinical signs, and therefore it has been seldom diagnosed and treated. Diabetic autonomic neuropathy significantly rises mortality rates in patients suffering from this disorder. All tissues with autonomic innervation can be affected. Autonomic neuropathy is present in the cardiovascular system as well as in the gastrointestinal and urogenital tracts. It has been suggested that, in patients with diabetes mellitus-based gastric dysrhythmias, it may contribute to disordered gastric motility and dyspeptic symptoms. In diabetic patients studied under euglycemic condition the incidence of dysrhythmias was found to be not higher than in healthy controls. Most commonly, diabetes is associated with gastroparesis. It is defined as a chronic disorder of gastric motility as evidenced by delayed gastric emptying of solid meals. CONCLUSIONS EGG is a non-invasive technique which yields information about the gastric myoelectrical activity. This information is different from that obtained by manometry, barostat studies, and gastric emptying tests. The applications of EGG are in two main areas. The first is assistance in the clinical evaluation and diagnosis of patients with gastric motility disorders. The other is determination of the gastric response to some stimuli (caloric, exogenous or pharmacological). The study of the propagation of the gastric slow wave represented by multichannel recording may provide additional information related to the occurrence of real-time events in different parts of the stomach and the spatial coordination. Multichannel recordings have been somewhat overlooked in the past but certainly have the potential to enhance EGG comprehensibility. Electrogastrography is not only of great clinical significance in diagnosing gastric motor disorders, but may also provide a therapeutic approach. Recently, experiments in gastric pacing (electrical stimulation) have been conducted, including a multicenter study. Promising results have been shown in the improvement of gastric emptying and symptoms in patients with gastroparesis refractory to medical therapy. EGG could be an important screening test in the evaluation of patients with suspected gastroparesis. In the future EGG could be used as a follow-up investigation for monitoring treatment and to assess the relationship between EGG and clinical changes. REFERENCES 1. Alvarez WC. The electrogastrogram and what it shows. JAMA 1922; 78:1116-8. 2. Hamilton JW, Bellahsen B, Reichelderfer M, et al. Human electrogastrograms: comparison of surface and mucosal recordings. Dig Dis Sei 1986; 31: 33-9. 3. Chen JD, Co E, Liang J, et al. Patterns of gastric myoelectrical activity in human subjects of different ages. Am J Physiol 1997; 272: Gl 022-7. 4. Chen J, Vandewalle J, Sansen W, et al. Adaptive spectral analysis of cutaneous electrogastric signals using autoregressive moving average modelling. Med Biol Eng Corn-put 1990; 28: 531-6. 5. Chen JZ, McCallum RW. Electrogastrographic parameters and their clinical significance. In: Chen JZ, McCallum RW, eds. Electrogastrography Principles and Applications. New York: Raven Press, 1994: 45-73. 6. Chen JD, Pan J, Orr WC. Role of sham feeding in postprandial changes of gastric myoelectrical activity. Dig Dis Sei 1996;41:1706-12. 7. Chen J, McCallum RW. Clinical significance of electrogastrography. Motility clinical perspectives in gastroenterology 1993,24: 7-9. 8. Chen JDZ, McCallum RW. Characteristics of the gastric slow wave in the different phases of gastric motility cycles (abstract). Gastroenterology 1991; 100: A428. 9. Di Lorenzo C. EGG like EKG: Are we there yet? J Pediatr Gastroenterol Nutr 2000; 30:134-136. lO.Levanon D, Chen JZ. Electrogastrography: its role in managing gastric disorders. The Lynn Institute for Healthcare Research, Oklahoma City, Oklahoma, U.S. Journal of pediatric gastroenterology and nutrition 1998;27:431-443. 11.Lindberg G, Iwarzon M, Hammarlund B. 24-hour ambulatory electrogastrography in healthy volunteers. Scand J Gastroenterol 1996; 31:658-64. 12.KaihoT, Shimoyama I, Nakajima Y, et al. Gastric and non-gastric signals in electrogastrography. J Auton Nerv Syst 2000; 79:60-6. 13.Smout AJPM, van der Schee EJ, Grashuis J L What is measured in electrogastrography? Dig Dis Sei 1980; 25: 179-87. 238 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ 44 ORIGINAL RESEARCH ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Kajzrlíková I., Vítek P., Chalupa J. Beskydy Gastrocentre, Department of Internal Medicine, Frýdek-Místek Hospital, Frýdek-Místek ABSTRACT Received after revision September 2009 KEYWORDS Hepaticojejunoanastomosis Abdominal ultrasound Complications Stenosis Cholangitis CORRESPONDING AUTHOR Kajzrlíková I. Department of Internal Medicine Frýdek-Místek Hospital El. Krásnohorské 321, 738 18 Frýdek-Místek Czech Republic Hepaticojejunoanastomosis is a surgical replacement of the biliary tract. The most frequent indications for this procedure are biliary duct injuries, other benign biliary tract stenoses, biliary tumours, choledochal cysts, and biliary atresia in children. The main complication of this method is stenosis of the anastomosis. We retrospectively reviewed the cases of eight patients with a history of hepaticojejunoanastomosis for benign disorder with a view to the role of ultrasound examination in their follow-up. All eight patients had hepaticojejunoanastomosis-related complications during the follow-up. Abdominal ultrasound was used as a primary diagnostic modality in the follow-up of all patients. When a complication was suspected, it was followed directly by an invasive therapeutic method (PTD, ERC, drainage); in four patients there were further noninvasive diagnostic tests indicated. Further non-invasive tests did not provide any new information, they only confirmed the ultrasound findings. If the clinical picture, laboratory tests, and ultrasound examination were taken together, we were able to accurately detect complications in all patients. According to our results we can conclude that abdominal ultrasound is an accurate method for the detection of hepa-ticojejunoanastomosis-related complications and should be preferred in the surveillance of these patients. INTRODUCTION Hepaticojejunoanastomosis is a surgical replacement of the biliary tract; it is constructed on the excluded first jejunal loop according to Roux, or in Tondelli's modification, in which the length of the afferent bowel loop is a minimum of 60 cm [1], The anastomosis should be as wide as possible. While constructing the anastomosis, the surgeon should suture the intestinal mucosa with the biliary mucosa with single nonabsorbable stitches. If the biliary pathways are too gracile, a silicon drain (also called "lost drain") can be used for the http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 239 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Table 1 The indications for hepaticojejunoanastomosis and the length of follow-up Patient Indication for hepaticojejunoanastomosis Length of follow-up (years) No. 1 Iatrogenic injury of the common bile duct during laparoscopic cholecystectomy 7 No. 2 Iatrogenic injury of the common bile duct during laparoscopic cholecystectomy 3 No. 3 Distal common bile duct stenosis as a complication of chronic pancreatitis 11 No. 4 Mirizzi's syndrome with duodenal diverticulum 12 No. 5 Iatrogenic injury of the common bile duct during laparoscopic cholecystectomy 6 No. 6 Hepaticolithiasis as a complication of iatrogenic lesion during cholecystectomy 6 No. 7 Treatment of choledochal cyst in childhood 8 No. 8 Iatrogenic injury of the common bile duct during open cholecystectomy 4 Table 2 Complications and final treatment Patients Hospitalisation for cholangitis Stenosis of the anastomosis Other complications Concomitant diseases Final treatment of complications No.l 1 NO Spondylodiscitis Arterial hypertension Intravenous ATB therapy No. 2 3 YES Impacted "lost" drain Operation of herniated intervertebral disc L5-S1 New side-to-side hepaticojejunoanastomosis according to Hepp-Couinaud No. 3 8 YES Chronic pancreatitis Transient PTC/PTD with dilation No. 4 2 NO Thyroid hypofunction Transient PTC/PTD No. 5 4 YES Septic shock with respiratoryfailure Obesity, Paranoid schizophrenia Transient PTC/PTD with dilation No. 6 1 NO Hepaticolithiasis Acute biliary pancreatitis (twice) Intravenous ATB therapy No. 7 2 NO Hepaticolithiasis Chronic pancreatitis Transient PTC/PTD No.8 3 NO Multiple liver abscesses Arterial hypertension. Diabetes mellitus CT with drainage construction of the anastomosis [2, 3]. In these cases the drain is spontaneously passed into the jejunal lumen and subsequently lost in the stools. The most frequent indications for this operation are primarily biliary duct injuries that can occur as a complication of cholecystectomy [4-8], both open (0.2-0.3%) [9, 10] and laparoscopic (0.3-0.8%) [11, 12], followed by other benign biliary tract stenoses [13, 14], some biliary tumours [15, 16], and biliary atresia in children. It is also used in the treatment of choledochal cysts [17-19], mainly types l-IV according to the Todani classification [20], The main complication of this method is stenosis of the anastomosis [21-23]; it can develop in 25% of cases [24]. The stenosis of the anastomosis usually presents as a recurrent cholangitis, cholestasis with development of jaundice and elevation of cholestatic liver enzymes. These stenoses need to be solved by ERC (Endoscopic Retrograde Cholangiography) with dilation and/or a biliary stent placement or PTC/PTD 240 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Table 3 Recommendations for ultrasonographists Hepaticojejunoanastomosis itself Intestinal loop edging to the liver hilus (better view in patient's left side position) Bile ducts Width (normal width of the intrahepatic bile ducts is up to 4 mm) Aerobilia -a sign of anastomosis patency (hyperechoic bodies or spots with just an intimated acoustic shadow) Hepaticolithiasis (hyperechoic bodies with a strong acoustic shadow) Drains if present Liver parenchyma Normal / Cirrhosis, and/or signs of portal hypertension Focal lesions if present Cholangiogenic liver abscess -single/ Hepatocellular carcinoma in cirrhosis Free fluid If present (Percutaneous Transhepatic Cholangiography and Drainage); in a few cases surgical repair is necessary [25], During the follow-up of patients with hepaticojejunoanastomosis we can use clinical examinations, laboratory tests and, finally, imaging methods. Of these, abdominal ultrasound is considered to be the most convenient for its non-invasive-nessand accessibility. We have decided to evaluate the role of ultrasound examination in the follow-up of our group of eight patients with a history of hepaticojejunoanastomosis for benign disorder. We did not include patients with malignant disorders (cho-langiocarcinoma) because of their worse prognosis and survival [26-29]. MATERIALS AND METHODS We retrospectively reviewed the cases of eight patients with a history of hepaticojejunoanastomosis in the surveillance in our gastroenterological outpatient clinic. The main point was the role of abdominal ultrasound in the follow-up of these patients. Our group of patients consisted of two men and six women aged 40-83 years (mean age 57 years).The indications for hepaticojejunoanastomosis and the length of the follow-up of all patients are mentioned in Table 1. In five patients the operation was performed at a tertiary centre with extensive experience in biliary surgery; in three patients the operation was performed in a local hospital.The construction of hepaticojejunoanastomosis during the primary operation was performed in one case only (in a local hospital). We evaluated the position of ultrasound examination in noninvasive imaging methods used in these patients and the accuracy of its findings. RESULTS The complications and final treatment are presented in Table 2. Abdominal ultrasound was used in the follow-up of all eight patients; in all patients it was followed directly by an invasive method (PTD, ERC, drainage), in four patients (No. 5, No. 6, No.7, No.8) there were further non-invasive tests indicated (MRC, CT, choledochoscintigraphy). Further non-invasive tests did not provide any new information, they only confirmed the ultrasound findings (liver abscess confirmed on CT, liver abscess excluded on CT, hepaticojejunoanastomosis with suspected stenosis described on MRC, cholescintigraphy showed prolonged evacuation time and persistent activity in left liver lobe - hepaticolithiasis on ultrasound). If the clinical picture, laboratory tests, and ultrasound examination were taken together, we were able to accurately detect complications in all patients. In our group there was no patient with a non-complicated course. Morbidity was 100%. Stenosis of the anastomosis developed in three patients (37.5%) and was treated by PTC/ http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 241 00 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Figure 1 "Lost"silicon drain in intrahepatic biliary pathway 1 ib-Ů4-flí * OS il it £Ehe a. t ; 1 1)1! CÍ1 (4 1 LmUOH Figure 2 Bowel loop edging to the liver hilus 242 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS ALOKA ii-0i-oe □ B. *D:5i »I&TňUCET + i O. 4 eta - i i i ti! Di9í4i ľlEfríuEE I L K| 3 * 1 t Pftte-1 CLE** MST ftfiCŕi-Ľ *fit*-r uůlvhC m£*T Figure 3 Hepaticojejunoanastomosis: measurementof the width of the intrahepatic bile ducts 1 i n-^—0 4-QE £ÜHc 3.'S s - ^ ^^ i i HIS Q75- 'C41 liu»H Figure 4 Aerobilia as a sign of anastomosis patency http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 243 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Figure 5 Hepaticolithiasis: hyperechoic bodies with a strong acoustic shadow PTD with dilation in two cases (No. 3, No. 5); in patient No. 2 surgical repair was necessary. After a complicated laparoscopic cholecystectomy in 2003 with a common bile duct injury in patient No. 2 solved by follow-up hepaticojejunoanastomosis two days later, the anastomosis was constructed on a silicon ("lost") drain. Since 2006 there had been frequent attacks of cholangitis. On abdominal ultrasound there was a shadow of the silicon drain in the biliary pathways described -impacted"lost"drain, which was the cause of recurrent cholangitis (Figure 1).The ERC and PTC/PTD were not possible, this patient underwent double-balloon ERC (the first double-balloon ERC in the Czech Republic, Faculty Hospital Hradec Králové, December 2006), extraction of the drain was impossible due to a severe stenosis of the anastomosis. The final treatment was a surgical resection of hepaticojejunoanastomosis with the "lost" drain and a construction of the new side-to-side hepaticojejunoanastomosis according to Hepp-Couinaud.The patient is under surveillance, to date with no other complications. In this case the lost drain was only visible on ultrasound and nearly invisible due to its low radiopacity on X-ray examination. The abdominal ultrasound was used as a primary diagnostic modality in each case. It described accurately the impacted drain, hepaticolithiasis, and liver abscesses. In the case of cholangitis, abdominal ultrasound accurately described the width of the biliary pathways (crucial for subsequent PTC/PTD), and it confirmed or excluded the presence of liver abscess. DISCUSSION Physicians performing ultrasonography in patients with hepaticojejunoanastomosis should focus their attention on the anastomosis itself (Figures 2, 3) and also on the detection of possible complications. The width of intrahepatic biliary pathways should be measured and any presence of aerobilia described. An indispensable part of the examination is represented by a careful inspection of liver parenchyma (structure, focal lesion) and the evaluation of portal hypertension signs and free fluid in the abdominal cavity. Recommendations for ultrasonographists are mentioned in Table 3. Abdominal ultrasound in patients with hepaticojejunoanastomosis is an examination with many pitfalls. The lucidity of the subhepatic region could be impaired by the presence of gas and bowel loop adhesions. The examiner must be aware of the presence of foreign bodies, for example drains and clips, and the possibility of other concurrent disease should be counted in. 244 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ 17 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Figure 6 Hepaticolithiasis on a CT scan: intrahepatic biliary duct dilation, coronal (A) and axial (B) images However, abdominal ultrasound remains the only imaging method that we can perform in all patients with hepaticoje-junoanastomosis and the knowledge of the proper examination of these patients is crucial. In the majority of patients we cannot use ERC because of changed anatomy; in some of them the examination has lately become possible due to the so-called double-balloon ERC [30-33], but this method is not widely available except for a few centres. In patients without dilation of the intrahepatic bile ducts PTC/PTD is also an inconvenient imaging method and should not be done only for diagnostic purposes. In all of these patients accurate ultrasound examination can lead us directly to the appropriate therapeutic method selection. There are a fewfindings that the examiner can be encountered with. Frequently aerobilia (Figure 4) is present and is usually considered as a sign of an anastomosis patency. Sometimes it can be confused with hepaticolithiasis (Figure 5), which is also common in these patients. Both aerobilia and hepaticolithiasis portray as hyperechoic bodies along the biliary pathways, but aerobilia has just an intimated acoustic shadow in contrast to hepaticolithiasis, which has a very strong acoustic shadow. Hepaticolithiasis can complicate stenosis of the anastomosis; however, it could also result from a primary disease (i.e. Caroli's disease) [34, 35]. As a prevention of lithiasis ursodeoxycholic acid therapy is recommended [36, 37]. We can also use a CT scan for hepaticolithiasis detection, but CT shows us just the intrahepatic biliary duct dilation, not hepaticolithiasis itself like ultrasound (Figure 6) [38,39], Another typical ultrasound finding is a cholangiogenic liver abscess (Figure 7), both single or multiple [40, 41]. The discovery of a hepatic abscess should always call our attention to possible stenosis of the anastomosis. If the stenosis is left unsolved, subsequently a secondary biliary cirrhosis [42, 43] with its typical ultrasound signs (Figure 8) can develop. Secondary biliary cirrhosis is a very serious complication of hepaticojejunoanastomosis, and it is a respected indication for liver transplantation [44,45], CONCLUSIONS According to our results we can conclude that abdominal ultrasound is an accurate method for the detection of hepa-ticojejunoanastomosis-related complications and should be preferred in the surveillance of these patients. It enables us to directly select an appropriate invasive treatment method. REFERENCES 1. Tondelli P, Ackermann C, Blumgart LH. Biliodigestive anastomoses in benign bile duct diseases. Chirurg 1984; 55: 777-786. 2. Lillemoe KD, Martin SA, Cameron JL, et al. Major bile duct injuries during laparoscopic cholecystectomy. Follow-up after combined surgical and radiologic management. Ann Surg 1997; 225: 459-468; discussion pp. 468-471. 3. Čapov I, Wechsler J, Žák J. Drainage systems in surgery. Brno: IDVPZ, 1998. 4. Skums AV, Nichitailo ME, Shkarban VP, Litvin Al, Ivanitskii Al. Surgical correction of the biliary ducts injury while http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 245 00 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Figure 7 Liver abscess usually portrays as an inhomogeneous lesion; it can be both hyperechoicand hypoechoic performance of laparoscopic cholecystectomy. Klin Khir 2006: 25-29. 5. Galperin El, Kuzovlev NF. Iatrogenic injuries of bile ducts during cholecystectomy. Khirurgiia (Mosk) 1998: 5-7. 6. Ahrendt SA, Pitt HA. Surgical therapy of iatrogenic lesions of biliary tract. World J Surg 2001; 25:1360-1365. 7. Treska V, Skalický T, ŠafránekJ, Kreuzberg B. Injuries to the biliary tract during cholecystectomy. Rozhl Chir 2005; 84: 13-18. 8. Flum DR, Cheadle A, Prela C, Dellinger EP, Chan L. Bile duct injury during cholecystectomy and survival in Medicare beneficiaries. JAMA 2003; 290: 2168-2173. 9. Zeman M,ŠvábJ,etal. Injury of gall bladderandbiliarytract. In: Special surgery. 2nd ed. Prague: Galén, 2004:261-262. 10. Sari YS, Tunali V, Tomaoglu K, et al. Can bile duct injuries be prevented? "A new technique in laparoscopic cholecystectomy". BMC Surg 2005; 5:14. 11. Robertson AJ, Rela M, Karani J, et al. Laparoscopic cholecystectomy injury: an unusual indication for liver transplantation. Transpl Int 1998; 11:449-451. 12. Deziel DJ, Millikan KW, Economou SG, et al. Complications of laparoscopic cholecystectomy: a national survey of 4,292 hospitals and an analysis of 77,604 cases. Am J Surg 1993; 165: 9-14. 13. Lillemoe KD, Pitt HA, Cameron JL Current management of benign bile duct strictures. Adv Surg 1992; 25:119-174. 14. FreyCF, Suzuki M.lsaji S.Treatmentof chronic pancreatitis complicated by obstruction of the common bile duct or duodenum.WorldJSurg 1990; 14:59-69. 15. DvorakJJandikP, Melichar B, et al. Intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas. Hepatogastroenterology 2002; 49: 916-917. 16. Chlapík D. Hepaticojejunal anastomosis in a regional surgical facility. Rozhl Chir 2004; 83: 231-234. 17. Nichitailo ME, Skums AV, Galochka IP. Diagnosis and treatment of cystic transformation of biliary ducts. Klin Khir 2001:22-27. 18. Franko J, Nussbaum ML, Morris JB. Choledochal cyst cho-langiocarcinoma arising from adenoma: case report and a review of the literature. CurrSurg 2006; 63: 281-284. 19. Nasu K, Matsuki S, Kawano Y, et al. Choledochal cyst diagnosed and conservatively treated during pregnancy. Am J Perinatol 2004; 21: 463-468. 20. TodaniT.WatanabeY,NarusueM.Tabuchi K,Okajima K.Congenital bile duct cysts: classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst. Am J Surg 1977; 134:263-269. 246 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ 64 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS Ä C5-OÍ-QE - * ** , , OliHiM 24 Hi 3.f PHR- 1DD"' kŘ m ^^ D17 0*6 ŕ* Figure 8 Ultrasound signs of liver cirrhosis: granular structure of the liver parenchyma, irregular surface of the liver (A), liver parenchyma, ascites (B) http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 247 ABDOMINAL ULTRASOUND ACCURATELY DETECTS COMPLICATIONS IN PATIENTS WITH HEPATICOJEJUNOANASTOMOSIS 21. Walsh RM, Henderson JM, Vogt DP, Brown N. Long-term outcome of biliary reconstruction for bile duct injuries from laparoscopic cholecystectomies. Surgery 2007; 142: 450-456; discussion pp. 456-457. 22. Ihasz M, Regoly-Merei J, Szeberin Z, et al. Laparoscopic cholecystectomy causing injury to biliary tracts. Analysis of the results of 26,440 operations in Hungary. Orv Hetil 1996;137:955-963. 23. Matthews JB, Baer HU, Schweizer WP, et al. Recurrent cholangitis with and without anastomotic stricture after biliary-enteric bypass. Arch Surg 1993; 128: 269-272. 24. Pellegrini CA,Thomas MJ.Way LW. Recurrent biliary stricture. Patterns of recurrence and outcome of surgical therapy. Am J Surg 1984; 147:175-180. 25. Nealon WH, Urrutia F. Long-term follow-up after bilioen-teric anastomosis for benign bile duct stricture. Ann Surg 1996; 223: 639-645; discussion pp. 645-638. 26. Nathan H, PawIikTM, Wolfgang CL, et al.Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg 2007; 11:1488-1496; discussion pp. 1496-1487. 27. Hernandez J, Cowgill SM, Al-Saadi S, et al. An aggressive approach to extrahepatic cholangiocarcinomas is warranted: margin status does not impact survival after resection. Ann Surg Oncol 2008; 15: 807-814. 28. Pitt HA, Nakeeb A, Abrams RA, et al. Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg 1995; 221: 788-797; discussion pp. 797-788. 29. Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg 2008; 248: 84-96. 30. Emmett DS, Mallat DB. Double-balloon ERCP in patients who have undergone Roux-en-Y surgery: a case series. Gastrointest Endosc 2007; 66:1038-1041. 31. Koornstra JJ. Double balloon enteroscopy for endoscopic retrograde cholangiopancreaticography after Roux-en-Y reconstruction: case series and review of the literature. Neth J Med 2008; 66: 275-279. 32. Matsushita M, Shimatani M.Takaoka M, Okazaki K. "Short" double-balloon enteroscope for diagnostic and therapeutic ERCP in patients with altered gastrointestinal anatomy. Am J Gastroenterol 2008; 103: 3218-3219. 33. Maaser C, Lenze F, Bokemeyer M, et al. Double balloon enteroscopy: a useful tool for diagnostic and therapeutic procedures in the pancreaticobiliary system. Am J Gastroenterol 2008; 103:894-900. 34. Joshi RM.Wagle PK, Darbari A, et al. Hepatic resection for benign liver pathology - report of two cases. Indian J Gastroenterol 2002; 21:157-159. 35. Duvnjak M, Supanc V, Virovic L, Tomasic V, Dojcinovic B. Caroli's disease. Acta Med Croatica 2003; 57: 249-252. 36. Gatzen M, Pausch J. Treatment of cholestatic liver diseases. Med Klin (Munich) 2002; 97:152-159. 37. Van de Meeberg PC, van Erpecum KJ, van Berge-Hene-gouwen GP. Therapy with ursodeoxycholic acid in cholestatic liver disease. Scand J Gastroenterol Suppl 1993; 200:15-20. 38. Vetrone G, Ercolani G, Grazi GL, et al. Surgical therapy for hepatolithiasis: a Western experience. World J Surg 2006; 202:306-312. 39. Knorr C, Dimmler A, Hohenberger W. Hepaticolithiasis. Rare benign disease of the intrahepatic bile ducts. Chirurg 2008; 79:481-485. 40. Nychytailo M, Skums AV, Medvetskyi IB, et al. Complex treatment of patients with cholangiogenic hepatic abscess. Klin Khir 2005:17-19. 41. Dull JS, Topa L, Balgha V, Pap A. Non-surgical treatment of biliary liver abscesses: efficacy of endoscopic drainage and local antibiotic lavage with nasobiliary catheter. Gastrointest Endosc 2000; 51: 55-59. 42. Jeng KS, Shih SC, Chiang HJ, Chen BF. Secondary biliary cirrhosis. A limiting factor in the treatment of hepatolithiasis. Arch Surg 1989; 124:1301 -1305. 43. Gangl A. Cholangitis and secondary biliary cirrhosis. Acta Med Austriaca 1983; 10:107-112. 44. Nordin A, Halme L, Makisalo H, Isoniemi H, Hockerstedt K. Management and outcome of major bile duct injuries after laparoscopic cholecystectomy: from therapeutic endoscopy to liver transplantation. LiverTranspl 2002; 8: 1036-1043. 45. LoinazC, Gonzalez EM, Jimenez C, et al. Long-term biliary complications after liver surgery leading to liver transplantation. World J Surg 2001; 25:1260-1263. 248 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ CASE REPORT ACUTE PANCREATITIS AS A FIRST SYMPTOM OF PANCREATIC CANCER IN A DIFFUSE AUTOIMMUNE PANCREATITIS PATIENT Ševčíková A., Novotný I., Hermanová M., Procházka V., Trna J., Dítě P. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno INTRODUCTION Received after revision September 2009 KEYWORDS Hepaticojejunoanastomosis Abdominal ultrasound Complications Stenosis Cholangitis Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis that can be defined as a chronic inflammation of the pancreas due to an autoimmune mechanism showing in most of the cases reversible improvement of pancreatic morphology and function with oral steroid therapy [1]. AIP represents 4% to 6% of all chronic pancreatitis cases [2]. AIP can be divided into two forms - focal and diffuse. The focal form of autoimmune pancreatitis, also called mass-forming pancreatitis, is found in the head of the pancreas in about 80% of all cases; therefore it can be easily misdiagnosed from adenocarcinoma [2, 3]. However, there are no references reporting on the presence of adenocarcinoma in the diffuse form of AIP [4]. We report on a case of a male patient with diffuse form of AIP, with a relatively short history of clinical symptoms, complicated by invasive ductal pancreatic adenocarcinoma with fatal clinical outcome. CASE REPORT CORRESPONDING AUTHOR Ševčíková A. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic A 40-year-old man, complaining of slight pressure pain in the abdomen for several years, was admitted to another local hospital in summer 2005 for painless icterus. The ERCP (endoscopic retrograde cholangiopancreatography) revealed a stenosis (of 2cm in length) of the distal choledochus with prestenotic dilatation. It was solved by duodenobiliary drainage (DBD). Examinations were then completed in autumn 2006 in FHB (Faculty Hospital Brno). MRI (magnetic resonance), CT (computed tomography), and EUS (endoscopic ultrasonography) were performed, showing the typical sausage-like morphology of the pancreas. The level of lgG4 was found to be elevated: 1, 9 (0.07-1.4), the levels of the oncomarkers (CEA, Ca 19-9) were normal (as well as 4 times during the whole follow-up of the patient). A diagnosis of diffuse form of AIP was assumed. Mutational analyses of SPINK, PRSS, and CFTR genes were negative. The patient received corticoids (40 mg http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 249 ACUTE PANCREATITIS AS A FIRST SYMPTOM OF PANCREATIC CANCER IN A DIFFUSE AUTOIMMUNE PANCREATITIS PATIENT per day) for one month, and then in decreased dosage until they were discontinued. In summer 2006 diabetes mellitus was diagnosed with the necessity of intense insulin regime. The findings did not change even after corticoid treatment -that is why EUS-guided fine needle aspiration (FNA) was performed in October 2006. Aspirate preparations contained almost exclusively finely and coarsely granular necrotic debris intermingled with numerous neutrophils. Several sheets of ductal epithelial cells with no signs of dysplasia and some inconspicuous acinar cells were revealed. Even though the performance of FNA was uneventful, a severe acute pancreatitis developed within 3 days, when the patient was again admitted to hospital. Abdominal ultrasound as well as CT showed a formation at the head of the measuring of6x5x4cm and the diagnosis of advanced generalised pancreatic tumour was made. The suggested oncological palliative treatment was not carried out owing to the patient's bad condition. Afterwards, the patient was repeatedly admitted to our clinic and died in March 2007. Autopsy revealed extensive infiltration of the pancreatic head with structures of moderately differentiated ductal adenocarcinoma, spreading into the peripancreatic fatty tissue, with infiltration of omentum, with multiple metastases in vertebral bodies (LI and L3), in the liver and lymph nodes (peripancreatic, in the porta hepatis, and along the abdominal aorta). DISCUSSION Chronic pancreatitis (CP) is usually defined as a progressive process that leads to the destruction of the parenchyma and to exocrine and terminally also endocrine insufficiency [5,6,7,8]. Its incidence in our country - although the data are from the 1980s they are still true - is 7.9 for 100 000 inhabitants per year; the rest of Europe is mostly the same: 7-10 for 100 000 inhabitants per year [9,10,11]. Chronic pancreatitis can be classified from many views; we use theTIGAR-0 classification system of the risk factors associated with CP, which was published in 2002. It divides the patients into groups by aetiology - therefore it is very simple and practical. It can also predict the course of the disease and approximately the risk of pancreatic cancer. The TIGAR-0 means: T for toxic-m eta bo lie, I for idiopathic, G for genetic, A for autoimmune, R for recurrent and severe acute pancreatitis, and O for obstructive form [5]. Autoimmune pancreatitis. The first references on CP in connection with some other autoimmune disease come from the middle part of the last century (1950- Ball connection with ulcerative colitis). There are two basic units: diffuse form (called sausage-like) enlargement of the whole pancreas, with hypervascularisation, segmental or diffuse narrowing of the main pancreatic duct, etc. The focal form - as mentioned before, also called mass-forming pancreatitis, is found in the head of the pancreas in about 80% of all cases. For the typical morphology of the diffuse form, CT, MRCP or EUS can be easily used for the diagnosis. Other important factors to be observed are the set of antibodies (like ASMA, RF, ANA, lgG4, anticarbonyl anhydrase, etc.). Unfortunately, there is none sufficient for the pancreas and there may also be geographical diversity. The inflammatory infiltrate consists mainly of lymphocytes and plasma cells, but it also contains some macrophages and occasionally also neutrophilic and eosinophilic granulocytes. AIP can be also divided into two forms: isolated and associated with other systemic disease (like DM, PSCSS) [12,13]. Acute necrotising pancreatitis does not represent a typical complication of AIP. Clinical symptoms are variable and most commonly include painless jaundice [13], weight loss, and abdominal pain -commonly mild and variable in duration, usually lasting weeks to months. The patients rarely present with acute attacks of pain. Jaundice has been reported in up to 70 %-80% of the patients [2]. In the literature, we have found only few references of acute pancreatitis as a first sign of pancreatic cancer [14,15], Pancreatic cancer is the fourth most common cause of cancer mortality in the USA [16]. Chronic pancreatitis, cigarette smoking, obesity, etc. seem to be the known risk factors for pancreatic cancer; only 5-10% are hereditary in nature. The overall five-year survival rate is 4%. More than one half of the cases have distant metastasis at diagnosis [17]. Diabetes mellitus (DM) has been lately reported as one of the factors directly linked to the origin of the pancreatic carcinoma butthe aetiology connection is not clear [18]. Several studies [19-21 ] consider DM as a risk factor for pancreatic ductal adenocarcinoma due to a long-lasting disease (either for endocrine involvement, or the common risk factors like obesity, smoking, etc.). However, later studies focused on DM, which rises shortly (2-3 years) before the diagnosis of the tumour as an early symptom [22-25].This situation seems to be promising for earlier recognition of pancreatic malignancy. It is recommended to examine patients with atypical DM (occurring in older age, with absence of obesity, quick progression to insulin-therapy, etc.) with the most sensitive methods such as endosonography or MRCP to diagnose asymptomatic ductal adenocarcinoma [18], The explanation of the quick disease progression in our patient is unclear. Little is known about the long-term outcome of AIP and about its malignant potential [26]. The time duration of the disease before the patient was admitted to hospital and the role of corticoids in the progression of the malignancy can be considered. 250 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ACUTE PANCREATITIS AS A FIRST SYMPTOM OF PANCREATIC REFERENCES 1. Kim KP, Kim MH, Kim JC, etal. Diagnostic criteria for autoimmune chronic pancreatitis revisited. World J Gastroenterol 2006;12[16]: 2487-96. 2. Zandieh I, Byrne MF. Autoimmune pancreatitis: a review. World J Gastroenterol 2007; 13(47): 6327-32. 3. Klöppel G, Lüttges J, Sipos B, et al. Autoimmune pancreatitis: pathological findings. JOP J Pancreas 2005; 6(1 suppl): 97-101. 4. Kamisawa T, Egawa N, Nakajima H, et al. Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol 2003; 98[12]: 2694-9. 5. Etemad B.Whitcomb DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology 2001; 120: 682-707. 6. Ciain JE, Pearson PK. Diagnosis of chronic pancreatitis: is a gold standard necessary? Surg Clin North Am 1999; 79: 829-845. 7. Sarles H. Pancreatitis: Symposium of Marseille, 1963. Karger: Basel, 1965. 8. Sarner M. Pancreatitis definitions and classification. In: Go VLW, Di Magno EP, Gardner JD, et al, eds. The pancreas: pathobiology and disease. 2nd ed. Raven: New York, 1993: 575-580. 9. Dite P, Stary K, Novotný I, et al. Incidence od chronic pancreatitis in the Czech Republic. Eur J Gastroenterol Hepatol 2001; 13 [6]: 749-50. 10. Lankisch PG, Assmus D, Pflichthofer D, Maisonneuve P, Lowenfels AB. The burden of pancreatic disease in a well-defined population. Gastroenterology 1998; 114[4]:A24. 11. Copenhagen Pancreatitis Study Group. Copenhagen Pancreatitis Study. An interim report from a prospective epidemiological multicentre study. Scand J Gastroent 1981; 16:305-12. 12. Abraham SC, Leach S,Yeo CJ, etal. Eosinophilic pancreatitis and increased eosinophils in the pancreas. Am J Surg Pathol 2003; 27: 334-42. 13. Okazaki K. Autoimmune pancreatitis: etiology, pathogenesis, clinical findings and treatment. The Japanese experience. JOP J Pancreas (online) 2005; 6(1 suppl): 89-96. 14. Fabre A, Sauvanet A, Flejou JF, et al. Intraductal acinar cell carcinoma of the pancreas.Virchows Arch 2001;438[3]: 312-5. 15. Imamura M,AsahiS,Yamauchi H.TadokoroK,Suzuki H.Minute pancreatic carcinoma with initial symptom of acute pancreatitis. J Hepatobiliary Pancreat Surg 2002; 9[5]: 632-6. 16. Mendieta Zerón H, Garcia Flores JR, Romero Prieto ML. Limitations in improving detection of pancreatic adenocarcinoma. Future Oncol 2009; 5[5]: 657-68. CANCER IN A DIFFUSE AUTOIMMUNE PANCREATITIS PATIENT 17. Freelove R, Walling AD. Pancreatic cancer: diagnosis and management. Am Fam Physician 2006; 73[3]: 485-92. 18. Trna J, Dítě P, Hermanová M, Ševčíková A. Výskyt diabetes mellitus u pacientů s karcinomem slinivky břišní [Diabetes mellitus in patients suffering from pancreatic cancer], Čes Slov Gastroent Hepatol [Czech and Slovak Gastroenterology and Hepatology] 2008; 62 [2]: 69-73. 19. Kessler I. A genetic relationship between diabetes and cancer. Lancet 1970; 1:218. 20. Kessler I.Cancer mortality among diabetics. J Natl Cancer Inst 1970;44:673-686. 21. Ragozzino M, Melton LJ, Chu CP, et al. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chronic Dis 1982; 35: 13-19. 22. Murphy R, Smith FH. Abnormal carbohydrate metabolism in pancreatic cancer. Med Clin North Am 1963; 47:397. 23. Nix GAJJ, Schmitz PJ, Wilson JHP, et al. Carcinoma of the head of the pancreas. Therapeutic implications of endoscopic retrograde pancreatography. Gastroenterology 1984; 87: 37-43. 24. Lin RS, Kessler I. A multifactorial model for pancreatic cancer in man. JAMA 1981; 245:147-152. 25 Moosa AR, Levin B. The diagnosis of early pancreatic cancer: The University of Chicago experience. Cancer 1981; 47:1688. 26. Miura H, Kitamura S, Yamada H. An autopsy case of autoimmune pancreatitis after a 6-year history of steroid therapy accompanied by malignant dissemination of unknown origin. Eur J Gastroenterol Hepatol 2008; 20[9]: 930-4. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 251 REVIEW PRIMARY SCLEROSING CHOLANGITIS Trumpešová H., Mišejková M., Lata J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno ABSTRACT Received after revision September 2009 8-r KEYWORDS Primary sclerosing cholangitis Colitis ulcerosa Cholangiocellular carcinoma Liver transplantation H CORRESPONDING AUTHOR Trumpešová H. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic Primary sclerosing cholangitis (PSC) represents a cholestatic long-waging liver disease, well characterised by inflammation of the bile ducts, which leads to scar formation and narrowing of the ducts over time. The occurrence differs according to geographic conditions. The primary cause of PSC remains unclear. Contemporarily it is supposed to be an autoimmune disease appearing in a field of predisposing gene mutation. The establishment of PSC is based on unique radiological and histological signs in addition to clinical and laboratory signs. The therapy of PSC can be classified from many points of view: specific therapy, the therapy of the complications, pharmacological therapy, endoscope, and surgery. Specific therapy is focused on preventing the progression of the disease. The patients with PSC make up 10% of all transplantation candidates [7]. The results of this type of treatment are really successful, 85% of the patients outlast more than one year. Cholangitis and cholangiocellular carcinoma are included to be the most feared complication. Cholangiocellular carcinoma develops in 7-13% of the patients with PSC [8], most frequently after long-lasting cirrhosis and in combination with colitis ulcerosa. The prognosis of this disease is very poor. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, and the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Definition Primary sclerosing cholangitis (PSC) represents a cholestatic long-waging liver disease, well characterised by inflammation of the bile ducts, which leads to scar formation and narrowing of the ducts over time. As scarring increases, the ducts become blocked. As a result, bile builds up in the liver and damages liver cells. Eventually, scar tissue can spread throughout the liver, causing cirrhosis and liver failure. Epidemiology The occurrence differs according to geographic conditions, oscillating between 8.5 and 13.6 patients/100 000 252 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ PRIMARY SCLEROSING CHOLANGITIS Figure 1 ERCP. Positive findings of alternating areas of stricture and dilated segments of the intrahepatic ducts inhabitants [1]. The memwomen ratio is 2:1. It manifests itself mostly under 40 years of age and the association with other autoimmune diseases is very common, especially with indifferent bowel diseases (IBD). Even in 70% PSC is related to ulcerative colitis; the association with Crohn's disease is lower [2]. The incidence in the group of patients with IBD remains between 2.4 and 7.5 % [1 ]. However, no clear dependence has been established between the duration or the activity of IBD and the occurrence of PSC. The patients sustaining extensive bowel damage suffer more from PSC. Despite this fact the bowel inflammation activity is usually low. Aetiology The primary cause of PSC remains unclear. Contemporarily it is supposed to be an autoimmune disease appearing in a field of predisposing gene mutation [2].The starting torqueses are represented by several toxic or infectious agents entering through the large bowel mucosa [3]. In approximately 75% of PSC patients ANCA (antineutrophil cytoplasm antibodies) is established. Diagnosis The establishment of PSCis based on unique radiological and histological signs in addition to clinical and laboratory signs. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 253 PRIMARY SCLEROSING CHOLANGITIS Figure 2 Needle biopsy. Finding of a fibrous enlargement of portal fields Concerning the clinical signs, most of the patients are asymptomatic at the beginning. The first changes develop after the progression of hepatic malfunction. The patients often complain of tiredness, anorexia, body weight loss, pruritus; later icterus appears. Other clinical signs are connected with hepatic cirrhosis and hepatic failure (ascites, encephalopathy). Laboratory parameters change again in accordance with the clinical course. Anaemia, coagulopathy, and elevation of cholestatic liver enzymes are very common. As already mentioned, ANCA and also ANA, ASMA and anti-ds DNA antibodies are present [3], Radiological diagnostics Endoscopic retrograde cholangiopancreatography remains the golden standard in PSC diagnosis. Cholangiopancreatography (ERCP) shows alternating areas of stricture and dilated segments of the intrahepatic ducts characteristic of the "beaded" appearance (Figure 1). However, a non-invasive MRCP seems to be a promising method; its sensitivity achieves 86%, specificity 77%,and diagnosticaccuracy 88%. With the use of some specific sequences like a RARE the sensitivity and diagnostic accuracy could increase significantly [4], According to localisation, we can distinguish three forms of the disease. The first form is classic, afflicting extra and intrahepatic ducts; the second only afflicts intrahepatic ducts, the last form afflicts only big stem ducts [5], Histological diagnostics Hepatic biopsy should be part of the diagnostic algorithm, because of its importance in a form afflicting small intrahepatic ducts. In this case radiological findings could be inconclusive. Otherwise, hepatic biopsy could be negative in the case of an extrahepatic form. Therefore, both investigations should be performed together. Furthermore, histological investigation could provide histological staging and finally estimate the prognosis of the patient. Microscopically we can find concentric periductal fibrosis, which can lead to the escape of channels (Figure 2). Therefore, this disease belongs to the vanishing bile duct disease. According to the histological findings we can distinguish fourforms of this disease (portal, periportal, septal, and cirrhosis). The typology of the disease is essential for the choice of therapy [6], The major diagnostic criterion is the finding at cholangiography of irregularly distributed multifocal strictures within both the intrahepatic and extrahepatic bile ducts. The most characteristic histological feature of primary sclerosing cholangitis is periductal concentric obliterative fibrosis of small interlobular bile ducts with or without proliferation of bile ducts in portal tracts, but liver biopsy findings alone are infrequently diagnostic. Nevertheless, liver histology remains important to exclude other causes of chronic cholestasis and for the staging the disease. Therapy PSC therapy can be classified from many points of view: specific therapy, the therapy of the complications, pharmacological therapy, endoscope, and surgery. Specific therapy is focused on preventing the progression of the disease. However, presently there does not exist any influential medica-mentous treatment that could stop the progression towards cirrhosis. Neither immunosuppressants nor corticosteroids or cyclosporine A, azathioprine or methotrexate have brought any desirable effect. Finally, the use of ursodeoxycholic acid has brought not only the decrease of cholestatic enzymes, but also the improvement of the prognosis (doses of 20mg/ kg). Furthermore, we can use antibiotics in the therapy of bacterial cholangitis as a complication of PSC. Important stenoses are solvable by ERCP, with implantation of stents, or with a dilatation. However, final resolution of PSC by means of hepatic transplantation could be difficult because of previous surgeries and endoscopies. The patients with PSC make up 10% of all transplantation candidates [7]. The results of this type of treatment are really successful, 85% of the patients outlast more than one year. However, cholangiocarcinoma seems to be an important problem; it develops in between 7 and 13% of the patients [8]. According to several studies the outcome after the transplantation in patients suffering from cholangiocarcinoma is poor and most of them are dying early succumbing to the recurrence of the disease [9]. Therefore, these patients are excluded primarily from the transplantation programme. Mercifully, in the highly selected minority treatment could be successful with a combination of oncology care and transplantation [10,11,12], 254 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ Complications Apart from the above-mentioned cholangitis, cholangiocel-lular carcinoma is the most feared complication. It develops in 7-13% of the patients with PSC [8], most frequently in combination with colitis ulcerosa. Early diagnosis is very difficult because of insufficient sensitivity of needle biopsy and brush cytology. According to several studies, a combination of these methods with the detection of the elevation of on-comarkers (CEA, CA 19-9) and imaging methods could be a useful screening method in the detection of CCA in patients suffering from PSC [13,14]. Most patients with PSC and CCA do not yet have cirrhosis but present with a severe stenosis at the hilum of the liver. The tumour may present as an intrahepatic focal cholangiocellular carcinoma but more often as a ductal infiltrating desmoplas-tic lesion. Treatment with ursodeoxycholic acid may prevent the development of CCA [15], The major challenges of CCA in PSC patients relate to a lack of methods for early diagnosis and the absence of effective treatment. Early diagnosis of CCA in PSC is delayed because its clinical presentation can mimic the benign dominant biliary strictures [16]. Moreover, biliary and serum tests to diagnose the development of CCA in PSC are limiting, although the use of advanced cytological techniques for aneuploidy and chromosomal aberrations is promising in this regard [12], As a result, current therapies do not extend survival with the exception of protocol liver transplantation available to a selected group of patients. Future studies should emphasise the decipherment of the sequence of events transforming the inflammatory changes of the biliary tree to cancer [17]. Only then will chemoprevention, early diagnosis, and therapy of CCA in patients with PSC improve. Prognosis The prognosis of this disease is very poor. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, and the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis [1,2,3], REFERENCES 1. Gordon FD. Primary sclerosing cholangitis. Surg Clin North Am 2008; 88[6]: 1385-407. Review. 2. Tischendorf JJ, Geier A, Trautwein C. Current diagnosis and management of primary sclerosing cholangitis. Liver Transpl 2008; 14[6]: 735-46. Review. 3. Worthington J, Chapman R. Primary sclerosing cholangitis. Orphanet J Rare Disease 2006; 1:41. 4. Silveira MG, Lindor KD, Can J. Primary sclerosing cholangitis. Gastroenterol 2008; 22[8]: 689-98. Review. PRIMARY SCLEROSING CHOLANGITIS 5. Weber C. Magnetic resonance cholangiopancreatography in the diagnosis of primary sclerosing cholangitis. Endoscopy 2008; 40[9]: 739-45. Epub 2008, Aug 12. 6. Chapman R. Hepatobiliary disease. In: Allan RN.: Inflammatory bowel disease. Churchill Livingstone, 1997: 637-646. 7. Worthington J, Chapman R. Primary sclerosing cholangitis. Orphanet J Rare Disease 2006; 1:41. 8. Cripping JS, Lindor KD. Primary sclerosing cholangitis: etiology and immunology. Eur J Gastroenterol Hepatol 1992;4:261-265. 9. Aron JH, Bowlus CL The immunobiology of primary sclerosing cholangitis. Semin Immunopathol 2009, May 26. [Epub ahead of print] 10. Rockville MD, Richmond VA. Annual Report of the U.S. Scientific Registry of Transplant Recipients and the Organ Procurement and Transplantation Network: Transplant Data 1989-1998. (2000, February 21). 11. Lazaridis KN, Gores GJ. Primary sclerosing cholangitis and cholangiocarcinoma. Semin Liver Dis 2006; 26[1]: 42-51. 12. Burak K, Angulo P, Pasha TM, et al. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol 2004; 99: 523-26. 13. Heimbach JK, Haddock MG, Alberts SR, et al. Transplantation for hilar cholangiocarcinoma. Liver Transplantation 2004;10(Suppl2):S65-S68. 14. Charatcharoenwitthaya P, Enders FB, Hailing KC, Lindor KD. Utility of serum tumour markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology 2008; 48[4]: 1106-17. 15. Fevery J, Verslype C, Lai G, Aerts R, Van Steenbergen W. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Dig Dis Sei 2007; 52[11]: 3123-35. Epub 2007, Apr 12 16. Hassoun Z, Gores GJ, Rosen CB. Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma. Surg Oncol Clin N Am 2002;11:909-921. 17. Nashan B, Schlitt HJ,Tusch G, etal. Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation. Hepatology 1996; 23:1105-1 111. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 255 17 I REVIEW_________________________________________________________________________________________ PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION Hůlková M., HosákL. Departmentof Psychiatry, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové ABSTRACT Received after revision September 2009 8-» KEYWORDS Hepatic encephalopathy Hepatitis C Liver transplantation Psychopathology H CORRESPONDING AUTHOR Hůlková M. Department of Psychiatry University Hospital Sokolská 581 500 05 Hradec Králové Czech Republic Psychiatric symptoms often accompany liver disease. The incidence of liver disease has increased recently among psychiatric patients. Hepatic encephalopathy, defined in broad terms as changes in neurological function resulting from liver disease, encompasses a wide range of neuropsychiatric signs and symptoms that are associated with both chronic and acute liver failure. Hepatic encephalopathy is associated with cognitive dysfunction, impairment of the quality of life, and higher incidence of road accidents. The incidence of viral hepatitis C has been increasing worldwide. It can cause general slowing of psychomotor performance, disorientation, depression or hypomania, personality disorders, or sleep disorders. Severe depression can be caused by treatment of hepatitis C with interferon alpha. Paroxetine and Citalopram show the best proven results in a double-blinded placebo-controlled trials of prophylactic treatment for IFN-a-induced depression. Before liver transplantation, anxiety, depression and alexithy-mia are frequent; post-traumatic stress disorder, psychosis and depression (because of survivor guilt) may appear after liver transplantation. In post-transplantation anxiety, women perceive livertransplantationasa psychosocial stressor more than men do. Women also have a worse quality of life after liver transplantation than men. BACKGROUND Most liver diseases are associated with neuropsychiatric symptoms and the incidence of liver disease has increased recently among psychiatric patients [1]. The aim of this article is to highlight the most considerable symptoms of selected liver diseases and their treatment. The authors used the Medline database from 1986 to 2009. Recent summary reports as well as original articles were preferred. To search for information, we used the following keywords: "hepatic AND psych*", 256 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION "liver AND psych*", "hepatic encephalopathy", "hepatitis C AND psych*","liver transplantation AND psych*" (searched in Medline, 20.05.2009). HEPATIC ENCEPHALOPATHY Hepatic encephalopathy, defined in broad terms as changes in neurological function resulting from liver disease, encompasses a wide range of neuropsychiatric signs and symptoms that are associated with both chronic and acute liver failure [2]. Parts of the clinical picture of hepatic encephalopathy are cognitive function impairment (reduced ability to focus, sustain or shift attention, deficit in both short- and long-term memory, impaired visuospatial performance), incoherent speech, slow and short answers, repetition of words, disorientation, depression or hypomania, apathy or overactivity, anxiety, fear, anger, and personality disorders (jocularity, dis-inhibition, irritability). Hallucinations (mostly visual) can be present transiently. The patient may have retrograde amnesia for the hepatic encephalopathy episode. Sensitive, but not specific symptoms are sleep disorders such as insomnia, hypersomnia, or inversion of sleep patterns. As for neurological symptoms, tremor, extrapyramidal rigidity, signs of pyramidal dysfunction, dysarthria, incoordination, impaired handwriting, constructional apraxia, hypoactive reflexes, and ataxia can be present [3], Encephalopathy reaches 1st-4th grades of clinical state, described in the West Haven Criteria scale [4]. Grade 0, the so-called "subclinical" or "minimal hepatic encephalopathy", could be identified only by neuropsychological or neurophys-iological tests [5].The grades conform to consciousness deterioration, from mild somnolence in grade I and somnolence to stupor in grade III to coma in grade 4 (Table 1). Hepatic encephalopathy is a serious complication of liver disease. Even minimal hepatic encephalopathy is associated with impaired quality of life and higher incidence of road accidents [7], The mechanisms involved in hepatic encephalopathy still remain to be defined. Insufficient detoxification of neurotoxic substances in the liver is the most important factor in the aetiopathogenesis of hepatic encephalopathy. The development of oedema and swelling of astrocytes because of quick accumulation of nitrogenous substances and changes in cerebral blood flow is typical of encephalopathy in acute liver failure. Chronic encephalopathy has a more complex mechanism of development. There are changes present in the GABAergic and glutamatergic system and increase of peripheral benzodiazepine receptors. Increased serotonin turnover, raising deposition of manganese in basal ganglia, specific changes in blood-brain barrier permeability, formation of false neurotransmitters from nitrogenous substances which compete with dopamine and norepinephrine, and many other factors are present in the brain of a patient with hepatic encephalopathy [8]. TIPS (transjugular intrahepatic portosystemic shunt) makes a shunt circulation which bypasses the liver. Due to this circulation, the brain is damaged by toxic substances causing hepatic encephalopathy, which has mostly the character of chronic or episodic encephalopathy. Hepatic encephalopathy is treated with the non-absorbable disaccharide lactulose (10-30 ml p. o. ä 8 hours) [9]. It reduces the intestinal production/absorption of ammonia because of its laxative effect, increased incorporation of ammonia into the proteins by colonic bacteria, and interference with uptake of glutamine by intestinal wall [10]. Hepatic encephalopathy can be also treated with rifaximine 400 mg ä 8 hours [11]. Neomycin 1-3 g p. o. ä 6 hours was approved by the FDA (Food and Drug Administration) in the treatment of acute hepatic encephalopathy [12], but this drug is not available in the Czech Republic. The beneficial effects of both rifaximine and neomycin relate to their ability to eliminate urease-pro-ducing organisms from the intestinal tract [9]. L-ornithine-L-aspartate (6g p. o. or in infusion three times a day) [13] or infusion with branched amino acids can support the treatment effect. The benefit of branched amino acids might stem from increased liver regeneration; L-ornithine-L-aspartate has been shown to reduce circulating ammonia levels [10], Albumin dialysis MARS (Molecular Adsorbent Recirculating System) can also improve hepatic encephalopathy [14], The off-label indication is benzodiazepine antagonists (flu-mazenil 0.2 mg slowly i.V., max. 1 mg p. d.), which have short-time duration but great effect [15]. Sodium benzoate binds the ammonium cation, which is then excreted as hippurate into the urine. It can be used as off-label indication, 5 g two times a day [16]. Probiotics seem to be a suitable supplement of the therapy [12]. Manganese chelation and N-methyl d-aspartate (NMDA) antagonists have recently been tested in laboratories [12], HEPATITIS C The prevalence of viral hepatitis C goes up worldwide as well as in the Czech Republic (Figure 1). It has become the most common indication for orthotopic liver transplantation in most Western countries [18]. Infected lymphocytes can cross the blood-brain barrier. After that, the virus starts to replicate in the central nervous system, and neurotoxic cytokines are released from infected cells [1,19], In people with hepatitis C, cognitive dysfunction, mostly attention deficit, and working memory deficit are often present [20]. People infected by hepatitis C frequently have mild depression. The rate of depression is associated with the inflammation activity [21]. Patients with hepatitis C are often drug and alcohol abusers. Interferon therapy is expensive, and http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 257 PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION 1200 -, £ 600 400 at n E 200 0 1998 1999 2000 2001 2002 2003 2004 Years 2005 2006 2007 2008 2009 Figure 1 The prevalence of hepatitis C in the Czech Republic Comment: Coefficient of determination 0.84. Source: SZÚ, 2009 before we start with the therapy, the patient should abstain from addictive substances. We know that abuse of alcohol during interferon alpha treatment is associated with diminished treatment response [22], The interferon therapy has neuropsychiatric side effects, including cognitive impairment, apathy, and medium-serious to serious depression [23]. Nowadays still more authors have been recommending to give antidepressants preventively during INF-alpha treatment [1, 24]. Paroxetine and Citalopram show the best proven results, in a double-blinded, placebo-controlled trials of prophylactic treatment for IFN-a-induced depression [25, 26]. A good result was found with the use of fluoxetine and sertraline [27, 28, 29]. If the patient is nicotine dependent, bupropion could be a suitable choice. Bupropion has also the potential to improve cognitive impairment and psychomotor retardation associated with IFN-a therapy [1, 30]. In case that the patient has marked psychomotoric retardation and no history of abuse, psychostimulants can help to manage fatigue, apathy, and cognitive slowing (modafinil 200mg p. d.) [1]. Atypical antipsychotics are more suitable than mood stabilisers in the management of psychotic, manic, or hypomanic symptoms [31,32,33]. Administration of ribavirin is associated with a higher incidence of insomnia and depression [34]. The treatment of these side effects is similar to the management of IFN-related neuropsychiatric adverse effects. LIVER TRANSPLANTATION Before liver transplantation, anxiety, depression and alexithy-mia are frequent mental problems [35].Trzepaczetal. [36] determined a psychiatric diagnosis in half of 247 livertransplanta-tion candidates (adjustment disorder being the most frequent). In the Czech Republic, abstinence from drugs and alcohol for at least six months is a requirement for patients to be included in the waiting list [37], so some of them require psychiatric treatment for drug dependency.The patient's adherence is also one of the criteria. Liver diseases often cause depression. Depression induces apathy, which is associated with reduced compliance. That is why the treatment of depression is so important when we consider liver transplantation [38], 258 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION Table 1 West Haven Criteria West Haven Criteria Grade Symptoms 1 Mild confusional state Euphoria, anxiety, irritability or depression Attention deficit Slowing in psychomotor performance Sleep disorders II Hypersomnia Lethargy Personality changes Transient disorientation in time and place III Somnolence to stupor Pronounced disorientation Severe memory deficit (retrograde amnesia) Unintelligible speech IV Coma with (IVa) and without (IVb) the reaction to painful stimulus Comment: Sources: Conn 1993, Sherlock 2002 An interesting topic is the psychodynamic aspect of liver transplantation: patients often identify themselves with donors.They give names to the new organ and try to imagine the donor's appearance and what their personal characteristics are like. Sometimes they fear that when a living donor dies they will also die. Storkebaum [39] described one of her patients: she was a lesbian, who rejected the transplantation because she was scared that she might receive a man's liver. In 1973 Basch already described his experiences with patients who had stopped taking their antirejection medication and died, after they had knowledge of the donor and felt repulsion for him or her [40], After transplantation, anxiety, post traumatic stress disorder, psychotic symptoms and depression may appear [35]. Women especially feel unattractive after the transplantation and are afraid whether the partner will accept their'new body' [39]. Women perceive more psychosocial stress with liver transplantation than men do; women also have a worse quality of life after liver transplantation than men [41 ]. Post-transplantation depression can be interpreted as the reaction to the loss of their own organ, which can feel similar to the loss of a family member. It also can be a reaction to the experience of total helplessness and dependence on the doctors'care [39]. Post-transplantation depression can be associated with the survivor guilt'Somebody had to die, so that I can now live'. Psychic problems are often present in people who had the experience of their relative dying after or during major surgery. They can feel guilty because they did not die (Why do I live, when he/she did not?). This so-called 'survivor guilt' was described in the Vietnamese war: soldiers had depression and felt guilty when their friends died but they were alive [42], In preliminary discussions, a psychiatrist or psychologist anticipates these complications, and offers counselling to reduce psychological problems. An important problem is the prevention of the relapse of alcohol abuse after liver transplantation. Gedaly et al. [43] described relapse in 19% of 387 patients with alcohol abuse history. CONCLUSION Patients in the care of hepatologists could profit from a close co-operation between psychiatrists and internal specialists, http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 259 PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION because lots of patients suffer from psychiatric comorbidity. In the Czech Republic, we do not have any consultation - liaison psychiatry as an independent specialisation. The problems of patients hospitalised at somatic wards differ from the care in psychiatric clinics, so this subspecialisation is needed. In more developed countries, this subspecialisation is a common part of psychiatry and we should start to consider this as well. ACKNOWLEDGEMENTS The article has been supported by the grant GAUK No. 73809. REFERENCES 1. Crone CC, Gabriel GM, DiMartini A. An overview of psychiatric issues in liver disease for the consultation - liaison psychiatrist. Psychosomatics 2006; 47:188-205. 2. Haussinger D, Blei AT. Hepatic encephalopathy. In: Rodés J, Benhamou JP, Rizzetto M.Textbook of hepatology: from basic science to clinical practice. 3rd ed. Oxford: University Press, 2007: 728-60. 3. Wiltfang J, Nolte W, Weissenborn K, Kornhuber J, Rüther E. Psychiatric aspects of portal-systemic encephalopathy. Metab Brain Dis 1998; 13: 379-89. 4. Conn HO. Quantifying the severity of hepatic encephalopathy. In: Conn HO, Bircher J, eds. Hepatic encephalopathy: syndromes and therapies. East Lansing (Ml): Medi-Ed Press, 1993:13-26. 5. Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: Final report of the working party at the 11th World Congress of Gastroenterology, Vienna, 1998. Hepatology 2002; 35: 716-21. 6. Sherlock S, Dooley J. Jaterni encefalopatie [Hepatic encephalopathy]. In: Sherlock S, Dooley J. Nemoci jater a žlučových cest [Diseases of the liver and biliary tract], 11th ed. Hradec Králové: Olga Čermáková - nakladatelství, 2002; 93-109. 7. BajajJS. Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol 2008; 14: 3609-15. 8. Felipo V, Butterworth RF. Neurobiology of ammonia. Prog Neurobiol 2002; 67: 259-79. 9. Watanabe A, SakaiT, Sato S, et al. Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy. Hepatology 1997; 26:1410-4. 10. Morgan MY, Blei A, Grüngreiff K, et al. The treatment of hepatic encephalopathy. Metab Brain Dis 2007; 22: 389-405. 11. Mas A, Rodés J, Sunyer L, et al. Compa rison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol 2003; 38: 51-8. 12. Dbouk N, McGuire BM. Hepatic encephalopathy: a review of its pathophysiology and treatment. Curr Treat Options Gastroenterol 2006; 9: 464-74. 13. Oehler G, Kruger-Jansen C, Lambert-Baumann J, Younossi ZM. L-ornithine-L-aspartate improves quality of life in patients with hepatic encephalopathy - treatment in routine clinical practice. Abstract booklet LOLA for the Treatment of Hepatic Encephalopathy-Where Do We Stand in 2008? 43rd Annual Meeting of the European Association for the Study of the Liver, Milan, Italy Satellite Symposium, April 24, 2008:10-1. 14. HassaneinTl.Tofteng F, Brown RS, etal. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 2007; 46:1853-62. 15. Barbaro G, Di Lorenzo G, Soldini M, et al. Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis: an Italian multicenter double-blind, placebo controlled, cross-over study. Hepatology 1998; 28: 374-8. 16. Sushma S, Dasarathy S,Tandon RK, etal. Sodium benzo-ate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology 1992; 16: 138-44. 17. Vybrané infekční nemoci v ČR v letech 1999-2008 -absolutně [Selected infectious diseases in the Czech Republic in 1999 through 2008 - in absolute numbers]. Státní zdravotní ústav, http://www.szu.cz/data/vybrane-infekcni-nemoci-v-cr-v-letech-1998-2007-absolutne 21.5.2009. 18. Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. LiverTranspl 2003; 9: 331-8. 19. Radkowski M, Wilkinson J, Nowicki M, et al. Search for hepatitis C virus negative-strand RNA sequences and analysis of viral sequences in the central nervous system: evidence of replication. J Virol 2002; 76: 600-8. 20. Forton DM, Hamilton G.AIIsopJM, etal. Cerebral immune activation in chronic hepatitis C infection: a magnetic resonance spectroscopy study. J Hepatology 2008; 49: 316-22. 21. Loftis JM, Huckans M, Ruimya S, Hinrichs DJ, Hauser P. Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-lß and tumor necrosis factor-a. Neuroscience Letters 2008; 430: 264-8. 22. National Institutes of Health: National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C. Hepatology 2002; 36 (Suppl): 3-20. 260 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ PSYCHIATRIC ASPECTS OF HEPATIC ENCEPHALOPATHY, HEPATITIS C, AND LIVER TRANSPLANTATION 23. Van Gool AR, Kruit WH, Engels FK, et al. Neuropsychiatric side effects of interferon-alfa therapy. Pharm World Sei 2003;25:11-20. 24. Sockalingam S, Abbey SE. Managing depression during hepatitis C treatment. Can J Psychiatry 2009; 54:614-25. 25. Raison CL, Woolwine BJ, Demetrashvili MF, et al. Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C. Aliment Pharmacol Ther 2007; 25:1163-74. 26. Kraus MR, Schäfer A, Schöttker K, et al. Therapy of interfer-on-induced depression in chronic hepatitis C with Citalopram: a randomised, double-blind, placebo-controlled study. Gut 2008; 57: 531-6. 27. Levenson JL, Fallon HJ. Fluoxetine treatment of depression caused by interferon-a. Am J Gastroenterol 1993; 88: 760-1. 28. Häuser P, Soler R, Reed S, et al. Prophylactic treatment of depression induced by high-dose interferon-a. Psychoso-matics 2000; 41: 439-41. 29. Schramm T, Lawford B, Macdonald G, Cooksley WG. Sertraline treatment of interferon-a-induced depressive disorder. Med J Aust 2000; 173: 359-61. 30. Malek-Ahmadi P, Ghandour E. Bupropion for treatment of interferon-induced depression. Ann Pharmacother 2004; 38:1202-5. 31. lancu I, SverdlikA, Dannon P, Lepkifker E. Bipolar disorder associated with interferon-a treatment. Postgrad Med J 1997;73:834-5. 32. Howes OD, McKenzie KJ. Manic psychosis induced by long term a-interferon treatment for hepatitis C. Int J Psychiat Clin 2000; 4:161-2. 33. Onyike CU, Bonner JO, Lyketsos CG, Treisman GJ. Mania during treatment of chronic hepatitis C with pegylat-ed interferon and ribavirin. Am J Psychiatry 2004; 161: 429-35. 34. Gervais A, Boyer N, Marcellin P. Tolerability of treatments for viral hepatitis. Drug Saf 2001; 24: 375-84. 35. Telles-Correia D, Barbosa A, Barroso E, Monteiro E. Psychiatric approach of liver transplant. Acta Med Port 2006; 19: 165-79. 36. Trzepacz PT, Brenner R, Van Thiel DH. A psychiatric study of 247 liver transplantation candidates. Psychosomatics 1989;30:147-53. 37. ŠperIJ.Taimr P. Desetileté zkušenosti s výběrem kandidátů transplantace jater na čekací listinu [Ten-year experience with selection of candidates for the waiting list for liver transplantation]. Folia Gastroenterol Hepatol 2005; 3 (Suppl1):22-7. 38. Krahn LE, DiMartini A. Psychiatric and psychosocial aspects of liver transplantation. Liver Transpl 2005; 11: 1157-68. 39. Storkebaum S.Transplantation okay - psyche okay? Reflections on psychosomatics in the field of organ transplantation. Acta Gastroenterol Belg 2005; 68: 353-7. 40. Basch SH. The intrapsychic integration of a new organ. Psychoanal Q 1973; 42: 364-84. 41. Blanch J, Sureda B, Flaviá M, et al. Psychosocial adjustment to orthotopic liver transplantation in 266 recipients. LiverTranspl 2004; 10: 228-34. 42. Blacher RS. "It isn't fair": postoperative depression and other manifestations of survivor guilt. Gen Hosp Psychiatry 2000; 22:43-8. 43. Gedaly R, McHugh PP, Johnston TD, et al. Predictors of relapse to alcohol and illicit drugs after liver transplantation for alcoholic liver disease. Transplantation 2008; 86: 1090-5. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 261 REVIEW INTESTINAL MICROFLORA AND BACTERIAL TRANSLOCATION Lata J.1, J u rán ková J.2, Příbramská V.1 Department of Internal Medicine and Hepatogastroenterology1 and Department of Clinical Microbiology2, Faculty Hospital Brno and Faculty of Medicine, Masaryk University, Brno Received after revision September 2009 KEYWORDS Intestinal bacterial overgrowth Bacterial translocation Probiotics Antibiotics ABSTRACT This article presents an overview of the development of the intestinal microflora, its composition and function in individual parts of the gastrointestinal tract, and the role of both internal and external factors. The impact of the intestinal microflora on the immune system is explained as well as potential effects of antibiotics including selective decontamination. Special attention is paid to intestinal overgrowth of bacteria, which may even lead to their translocation into the extraintestinal sites. Besides bacterial factors, unwanted overgrowth is facilitated by the intestinal mucosal and immune systems. H CORRESPONDING AUTHOR Lata J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic The intestine of men is a tube about 10 metres long and its extremely irregular surface is covered with a single layer of epithelial cells, representing an area of approximately 200 m2.The intestine is sterile during foetal development and is first colonised only as the foetus passes through the birth canal. The gut is rapidly colonised after the birth by many microorganisms whose composition varies markedly in the first days of life. Breastfed babies are earlier colonised by those bacterial genera typical of the intestinal microflora of adult humans [1] and e.g. bifidobacteria are less frequent in those who are formula-fed. Preterm infants, babies born by Caesarean section and those hospitalised for a long time have an aberrant composition of the intestinal microflora.Their normal healthy microflora, comprising mainly lactobacilli and bifidobacteria, is replaced by hospital strains, such as potentially pathogenic enterococci, staphylococci, enterobacteria, and others. Major changes in the character of the intestinal ecosystem occur after the baby is no longer breastfed, but the initial intestinal colonisation is crucial for the further development of humans as the present bacteria may modulate gene expression in epithelial cells and thus produce a favourable environment for themselves [2], The intestinal microflora weighs over 1 kg and contains an enormous number of microbes - their amount is more than ten times the number of cells in the human body. The intestinal microbial community comprises over 500 species, of 262 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ INTESTINAL MICROFLORA AND BACTERIAL TRANSLOCATION Table 1 Composition of the human gastrointestinal tract (from Nord and Kager, 1984) Microorganisms Numbers of microorganisms (CFU/1 ml or CFU/1 g) stomach jejunum ileum colon Total bacterial count 0-103 0-105 103-10" 1010-1012 Aerobically growing agents Family Enterobacteriaceae 0-102 0-103 102-107 104-1010 Streptococci 0-103 0-1 o4 102-106 105-1010 Staphylococci 0-102 0-103 102-105 104-l 0" Lactobacilli 0-103 0-1 o4 102-103 106-1010 Yeasts 0-103 0-102 102-104 104-l o6 Anaerobic bacteria Bacteroides rare 0-103 103-107 1010-1012 Bifidobacteria rare 0-1 o4 103-10" 104-10n Peptostreptococci rare 0-103 102-106 1010-1012 Clostridia rare rare 102-104 106-10n Eubacteria rare rare rare 1010-1012 which most have never been cultured and many have not even been identified, and contains both autochthonous or resident bacteria and allochthonous or transient bacteria, i.e. those only passing through the intestine [3].The relationship between the host and the bacteria in the intestinal microflora also plays an important role in postnatal development, intestinal maturation, and development of the mucosal immune system [4], 1. MICROFLORA INTHE INDIVIDUAL PARTS OF THE GIT The normal microflora is an enormously complex ecosystem comprising both aerobic and anaerobic microorganisms. Together with the mucosal immune system, it protects the host's organism from pathogen invasion and plays a positive role in certain metabolic processes [5], In the oral cavity, anaerobes predominate over aerobes in a ratio of about 100:1. Together with saliva and food, oral microorganisms pass through the oesophagus to the stomach. In the oesophagus, the analogical microflora multiplies, especially under pathological conditions, such as in the case of any oesophageal obstruction, both organic and functional. Other contributing factors include severe devastating conditions and immune insufficiency. In such cases, Candida or viral infections are involved, e.g. in Candida or viral oesophagitis. Most microorganisms passing from the oral cavity to the stomach are destroyed by acid gastric juices. Thus, the stomach of healthy individuals is usually sterile, with the transient microflora being mostly gram-positive and aerobic. The concentration of microorganisms is usually less than 103 CFU/1 ml. The most commonly isolated genera are entero-cocci, staphylococci, lactobacilli, and yeasts. The microbial flora of the oral part of the small intestine has a composition similar to that of the stomach and is influenced to a certain extent by pathological conditions of the stomach. In patients with duodenal ulcers or even bleeding ulcers, pyloric obstruction or cancer of stomach, a mixture of aerobes and anaerobes is found. Achlorhydria and bacterial overgrowth are also connected with drugs reducing gastric acidity, e.g. H2 blockers and proton pump inhibitors (PPI). The normal concentration of bacteria is 103~4 CFU/1 ml. Enterobacteria are sometimes present in a concentration of 1025 CFU/1 ml. Microbes increase in number especially in intestinal stasis (intestinal obstruction, blind loop syndrome). In the jejunum, aerobic and gram-positive bacteria prevail. However, coliform and anaerobic bacteria are also present there, even more commonly than in the stomach. I n the distal ileum, gram-negative microorganisms begin to predominate over gram-positive bacteria. The similarity to the large intestinal microflora is due to microorganisms penetrating through the ileocaecal valve (backwash mechanism). The numbers of aerobic and anaerobic microorganisms increase with the distance from the ileocaecal valve. Live bacteria account for about one third of faecal dry matter. The prevailing aerobe is Escherichia coli, which may be isolated in a concentration of 1078 CFU/1 g of stools. Anaerobes are dominated by Bacteroides fragilis and Eubacterium spp. Also frequent are anaerobic gram-positive cocci (Peptostrepto-coccus spp., Peptococcus spp., Clostridium spp.). Additionally, aerobically growing enterococci and various members of the Enterobacteriaceae family are commonly isolated. In the colon, bacteria significantly increase in number orally from an obstruction of any origin. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 263 00 INTESTINAL MICROFLORA AND BACTERIAL TRANSLOCATION 2. FACTORS INFLUENCING COMPOSITION OF THE INTESTINAL MICROFLORA Thecomposition of the intestinal microflora is mostly regulated by saliva (antibacterial activity of lysozyme, lactoferrin and rhodanide), gastric acid (pH) and pepsin, bile containing bile salts and unconjugated bile acids, pancreatic juice (lipase), intestinal motility, and regeneration of intestinal mucosal cells. The microflora has its own regulatory mechanisms (colonisation resistance) that prevent penetration of unwanted organisms and substances and inhibit pathogenic microflora by bactericidal action of short-chain fatty acids and production of hydrogen peroxide or hydrogen sulphide. Important are cellular (intestinal lymphoid tissue.Tand B lymphocytes) and humoral (secretory immunoglobulin A) immune defence mechanisms [6], The intestinal system could be severely affected by ageing and some diseases and their treatment - reduced salivary secretion in Sjogren's syndrome, long-course radiotherapy of the head and neck, after surgery (gastrectomy, vagotomy), biliary obstruction, pancreatic insufficiency, treatment with H2 blockers, proton pump inhibitors, prokinetics, laxatives. Under such circumstances, coliform and potentially pathogenic bacteria grow in number and the risk of salmonella, shigella or Candida infection increases. The external factors influencing the composition of the intestinal microflora include nutrition, treatment, environment, and stress. 3. FUNCTIONS OF THE NORMAL MICROFLORA The intestinal microflora has many important functions: to maintain a microbial barrier against obligate and potential pathogens, to stimulate the intestinal immune system and thus the so-called common mucosal immune system, to reduce bacterial translocation, to affect motility and perfusion of the intestinal wall, and to produce vitamins. The gradual transition from aerobes dominating the upper intestine to anaerobes predominant in the distal portions represents the basic functional and structural changes. In the entire microsystem, aerobes are responsible for the so-called scavenging effect. It means that they, in particular Escherichia coli, consume oxygen in oxidative phosphorylation reactions in energy metabolism. Distally, the redox potential decreases, facilitating the growth of anaerobes, otherwise sensitive to the presence of oxygen due to their enzyme make-up (cata-lase, cytochrome oxidase, superoxide dismutase) insufficient to eliminate superoxide and other oxygen radicals. Thus, the existence of the two groups of microbes is mutually determined as any damage to aerobes apparently leads to subsequent harm to the anaerobic population [7,8]. Impairment of the microsystem of the original intestinal microflora is common in patients with chronic liver disease. Significantly increased numbers of live aerobic gram-positive and gram-negative bacterial species are repeatedly found in the faeces of cirrhotic patients [9], 4. COLONISATION RESISTANCE Colonisation resistance of the gastrointestinal tract is the microbial barrier made of beneficial commensal bacteria in the intestine and preventing pathogens from overgrowing. It acts against both obligate (salmonella, shigella, yersinia, Campylobacter, vibrio, and other species) and potential pathogens (Clostridia, Candidas, etc.) [10]. It also controls the opportunistic microflora (enterobacteria, Pseudomonas, staphylococci, streptococci, etc.). Colonisation resistance is based on growth inhibition and/or killing of foreign microorganisms, competition for substances, vitamins and growth factors, lowering intestinal pH, and direct antagonism of the normal microflora against the obligate and potentially pathogenic microflora [11], 5.THE INTESTINE ANDTHE IMMUNE SYSTEM The present commensal intestinal microflora activates antiinflammatory intestinal systems protecting the intestinal epithelium from inflammation as a reaction to invading pathogens [12], but the intestinal commensals have also a huge regulatory effect on immune responses even outside the intestinal tract [13]. The human organism has mechanical, chemical and immunological barriers which, at the point of contact, protect its internal environment from uncontrolled penetration of antigenic and mitogenic stimuli. The main barriers and contact places involve mucosal surfaces of the digestive, respiratory and genitourinary tracts. The intestinal mucosal immune system provides a barrier against pathogenic microorganisms and immunogens from the diet. The basic features of the mucosal immune system are prevailing IgA antibodies, preferential colonisation of both mucosae and excretory glands by cells originating from intestinal lymph follicles and, finally, polymeric immunoglobulins transported to the secretion through epithelial cells. The gut-associated lymphoid tissue (GALT) is a system that processes information from about 100-200 tons of food per lifetime and is permanently colonised by the normal and, intermittently, non-physiological microflora. The GALT develops mainly in the early postnatal period and is made up of organised lymphoid tissue, free intraepithelial lymphocytes, and lamina propria lymphocytes. The immune reaction in the GIT mucosa produces not only local but also general immune response in other mucosae or 264 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ INTESTINAL MICROFLORA AND BACTERIAL TRANSLOCATION distant organs, the so-called common mucosal immune system. Following their contact with allergens, cells, especially those in the intestinal mucosa, migrate to regional lymph tissue (Peyer's patches, lymph nodes), via the lymphatic system to the bloodstream and from there to all mucosae and endocrine glands (the so-called homing). 6. BACTERIAL TRANSLOCATION The microflora of GIT is continuously affected by many physical, chemical and biological factors. Therefore, it is a constant potential source of diseases of the GITorthe entire organism. Changes may occur in the total number, localisation, representation of genera or species, and in the metabolic activity of microorganisms. The term bacterial translocation was first used in 1979 [14]. Bacterial translocation is defined as either active or passive penetration of living microorganisms and their toxic products through the mucosal epithelial layer to the lamina propria mucosae. From there, microbes migrate to mesenteric lymph nodes and/or extraintestinal sites [14]. Under normal circumstances, these are only small numbers of bacteria readily destroyed by the immune system in the lamina propria mucosae. Translocation is only possible if their numbers are high, up to 108 bacteria in 1 gram of faeces, as reported in the literature [15,16]. According to the clinical significance, there are four degrees of bacterial translocation [17,18]: Degree 0: bacteria and/or their components penetrate the mucosa by various mechanisms: active intracellular penetration, diffusion, absorption, endocytosis, or phagocyted by macrophages. Degree 1: bacteria and/or their components enter the mesenteric lymphatic system and penetrate it centripetally. Degree 2: bacteria and/or their components are already detectable in the systemic circulation and certain organs. They may also pass directly into small intestinal venules and from there into the portal circulation. Part of the bacteria are probably even capable of intracellular passage through the muscularis propria into the peritoneal cavity (this was the reason for adjusting the original 1985 Berg's definition according to which bacterial translocation is a passage of bacteria and/or their components from the intestinal lumen into the lymphatic system with potential systemic penetration into various organs). Degree 3: the organism is systemically overwhelmed by bacteria and/or their components, leading to the septic response. The main mechanisms underlying the translocation are deficient local mucosal immune response, lower phagocytic activity of both macrophages and neutrophils, increased permeability of the intestinal barrier, and the above-mentioned intestinal bacterial overgrowth [15,19]. Bacteria escaping both phagocytosis and destruction by the complement system may even get into the bloodstream. Considering bacteria commonly found in the gastrointestinal tract, only some of them participate frequently in the translocation. The most frequent bacteria are Escherichia coli, Proteus spp., Klebsiella pneumoniae, and other Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, streptococci, and staphylococci - i.e., those causing infections in immunocompromised individuals. Bacterial small-intestinal overgrowth creates conditions favourable for the translocation of the above mentioned bacteria. The factors influencing bacterial translocation may be divided into three groups: bacterial factors, factors of the intestinal wall, and defensive factors (local or systemic). Bacterial factors The presence of commensal microflora is very important for all defence mechanisms [20]. The biological pressure of intestinal microbes is essential for maintaining the mucosal barrier function [21]. Impaired physiological microbial balance (e.g. in acute pancreatitis, liver cirrhosis, or due to morphine administration) results in dysfunction of the mucosal barrier and increased bacterial translocation. Thus, potential pathogens penetrate outside of the intestine. If obligate anaerobic intestinal bacteria outnumber the aerobically growing species by more than 100 to 1, translocation is exceptional [22], Intestinal mucosal barrier factors The primary function of the intestinal mucosal barrier is to maintain the host's integrity by monitoring the contents of the intestinal lumen and protection against invading bacteria and their toxins [20]. Thus, intestinal epithelial cells form an important physical barrier between the intestinal lumen and the human internal environment. Their tight arrangement and fluid secretion represent non-specific protection from bacterial translocation. The function of epithelial cells is supported by other defensive products such as mucus and defensins (small peptides containing cysteine, with high antimicrobial activity). The immune system Specific protection againstthe present antigens is maintained by continuous monitoring of the intestinal contents by the intestinal immune system (GALT) able to distinguish between invasive microorganisms and harmless antigens such as dietary proteins or commensal microorganisms. The primary immunological barrier is a layer of intestinal epithelial cells. In addition to their non-specific barrier function, they are capable of recognising preserved microbial structures by the so-called Toll-like receptors (TLRs). When these are activated by cell-wall lipopolysaccharides of gram-negative bacteria or http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 265 95 INTESTINAL MICROFLORA AND BACTERIAL TRANSLOCATION by lipoteichoic acid of gram-positive pathogens, a process resulting in the inflammatory defence response is initiated [23]. If bacteria break the mucosal line of enterocytes, they encounter macrophages and dendritic cells, currently intensively investigated for their essential role in intestinal immunology. Their task is to monitor the intestinal contents. Their long processes reach the intestinal lumen, passing among tightly connected epithelial cells without breaking the mucosal barrier. The dendrites sample the present bacteria and other antigens and present them to the GALT. This is how continuous communication between the intestinal bacteria and the GALT is maintained [24], The well-balanced gastrointestinal microflora, together with intact structural and immunological barriers, plays an essential role in preventing infectious complications. Therefore, prevention of bacterial overgrowth, promotion of intestinal barriers and modulation of the immune response are promising for prophylactic care and prevention of both early and late infectious complications in severely ill patients. ACKNOWLEDGEMENT Financially supported by the Czech Ministry of Education research grant MSM 6198959223 and IGA MZ ČR NR 9310-3. REFERENCES 1. Mayer L, Shao L. Therapeutic potential of oral tolerance. Nat Rev Immunol 2004; 4(6): 407-419. 2. Saavedra J, Tchernia A. Human studies with probiotics and prebiotics: clinical implications. Br J Nutr 2002; 87: 241-246. 3. Noverr M, Huffnagle G. Does the microbiota regulate immune responses outside the gut? Trends Microb 2004; 12(12): 562-568. 4. Floch MH, Katz J, Conn H. Qualitative and quantitative relationships of the fecal flora in cirrhotic patients with portal systemic encephalopathy and following portocaval anastomosis. Gastroenterology 1970; 59: 70-75. 5. Hooper I, Wong M, Thelin A, et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001; 291(5505): 881-884. 6. Kelly D, Conway S, Aminov R. Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol 2005; 26(6): 326-333. 7. Savage D. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 1977; 31:107-132. 8. Van derWaaij D. The ecology of the human intestine and its consequences for overgrowth by pathogens such as Clostridium difficile. Ann Rev Microbiol 1980; 43: 69-88. 9. Mackie Rl, Shgir A, Gaskins RH. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 1999; 69(5): 2035-2045. 10. Zbořil V. Mikroflóra trávicího traktu - klinické souvislosti [Microflora of the gastrointestinal tract: clinical connections]. Praha: Grada Publishing, 2005. 11. James SP. Gastrointestinal lamina propriaT-cells. Mucosal immunology. San Diego: Academic Press, 1999. 12. Fixa B, Komárkova O. Mikroflóra trávicího ústrojí za fyziologických a některých patologických podmínek [Microflora of the gastrointestinal system under physiological and some pathological conditions]. In: Mařatka Z, ed. Aktuality v gastroenterologii [Latest News in Gastroenterology], Praha: AZ Servis, 1994: 57-82. 13. Backhed F, Ding H.WangT, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sei USA 2004; 101 (44): 19-23. 14. Krčméry V. Manuál antimikrobiálnej chemoterapie [A manual of antimicrobial chemotherapy]. Bratislava: Osveta, 1993. 15. Ramachandran A, Balasubramanian K. Intestinal dysfunction in liver cirrhosis. Its role in spontaneous bacterial peritonitis. J Gastroen Hepatol 2001; 16:607-612. 16. Guarner C, Runyon BR, Young S, etal. Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites. J Hepatol 1997; 26:1372-1378. 17. Luyer MD, Buurman WA, Hadfoune M, Speelmans G, Knol J. Strain-specific effects of probiotics on gut barrier integrity following hemorrhagic shock. Infect Immun 2005; 79(6): 3686-4691. 18. Zbořil V. Fyziologie mikroflóry trávicího traktu [Physiology of the gastrointestinal tract microflora]. Vnitř Lék 2002; 48: 300-403. 19. Macpherson A, UhrT. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 2004;303:1662-1665. 20. Hanson LA, Yolken RH. In: Probiotics, other nutritional factors, and intestinal microflora. Philadelphia: Lippincott-Raven, 1999:18-67. 21. Ersöz G, Aydin A, Erdem S, Yuksel D, Akarca U, Kumanli-oglu K. Intestinal permeability in liver cirrhosis. Eur J Gastroen Hepat 1999; 11 (4): 409. 22. Berg RD. Bacterial translocation from the gastrointestinal tract.Trends Microbiol 1995; 3(4): 149-154. 23. Steffen EK, Berg RD, Deitch EA. Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node. J Infect Dis 1988; 157:1032-1037. 24. Hooper L, Gordon J. Commensal host-bacterial relationships in the gut. Science 2001; 292:1115-1118. 266 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ _______________________________________________________________________________________________REVIEW I OBSTIPATION AND DIARRHOEA - A COMMON AND SIGNIFICANT PROBLEM IN THE ELDERLY Šlapák J., Lata J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno ABSTRACT Received after revision September 2009 8-TT KEYWORDS Elderly Obstipation Diarrhoea Faecal impaction CORRESPONDING AUTHOR Šlapák J. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic Constipation and diarrhoea are common complaints in older people, and many people become gradually more constipated with age. Lack of symptoms is typical of the disease in the elderly. If we are unable to properly evaluate abnormal manifestation and atypical connection and to assign them to the right diagnosis, the consequences can be serious. Constipation is a common complaint in older people, and many people become gradually more constipated with age. Prevention and change in dietary habits are important. Adding fibre and sufficient hydration are helpful. Only then we can use laxatives, especially osmotic or bulk-forming ones. Diarrhoea is a common problem in elderly persons. Worldwide, diarrhoea is the second leading cause of mortality. In the developed world, 85% of its mortality affects the elderly. The main causes of diarrhoea include drugs, thyrotoxicosis, diabetes mellitus, microscopic colitis, diverticulitis, and mesenteric ischaemia. Very important is diarrhoea caused by Clostridium difficile as a result of antibiotic treatment. Rehydration must be maintained to prevent hypotension and organ failure in the often multimorbid patient. False diarrhoea develops in case of faecal impaction and is connected with the development of faecaloma. It is particularly concentrated in the institutionalised or impaired elderly. The clinical consequences may be disabling and occasionally life-threatening. INTRODUCTION Constipation and diarrhoea in the elderly is a common problem. The causes of those conditions are little different from the causes in young age, so we are trying to describe the specifics of those problems in the elderly. Lack of symptoms is typical of the disease in the elderly. If we are unable to properly evaluate abnormal manifestation and atypical connection and to assign them to the right diagnosis, the http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 267 OBSTIPATION AND DIARRHOEA - A COMMON AND SIGNIFICANT PROBLEM IN THE ELDERLY consequences can be much more serious, because the geriatric patient has substantially lower reserves and adaptation mechanisms than the young one. Let us take a closer look at those conditions. DISCUSSION Constipation There is no doubt that constipation appears much more often in older people than in young ones. Constipation is a common complaint in older people, and many people become gradually more constipated with age [1, 2]. Constipation has a significant subjective component, so we must first make clear what the patient means by their constipation complaints. Usually it is less frequent and/or difficult defecation of stools in comparison with the past. Which defecation frequency is normal differs from patient to patient - it varies from once in 3 days to 3 times a day. Pathophysiology: motility problems (inert colon), excessive water absorption (diuretics in medication) or problems with defecation mechanics in the terminal part of the gastrointestinal tract (anorectal outlet obstruction). Motility problems in the elderly can be caused by drugs which are used for another reason (seeTable 1). Table 1 Drugs causing constipation Calcium blockers Codeine and its derivatives Drugs containing calcium Morphine and other opiates Diuretics Antacids containing aluminium Problems with defecation mechanics contain rectal intussusception, prolapsed rectum, and asynergy of pelvic floor muscles. It is important to ask elder women about difficulties during the births, because this can be the initiation factor of defecation problems [1], Constipation can be organic (inflammatory strictures, tumours), secondary (hypothyroidism, diabetes mellitus, drugs), or it can be a specific disease, the so-called functional constipation. Constipation has a significant psychological impact on the afflicted person. It negatively influences their mood and causes depression. Improper usage of laxatives causes a sense of insecurity and limits social activities. Diagnostics: very important is the patient's history. Constipation usually lasts longer and valuable information can be acquired by asking the patient why they decided to attend the doctor (e.g. pain during defecation, rectal bleeding). Pharmacological history is essential as well. During the examination we are searching for other diseases (hypothyroidism). Repeated clinical controls of the patients are necessary to monitor the evolution of the clinical conditions. Do not forget per-rectum examination: some colorectal carcinomas are within the reach of the inspecting finger. We can also measure the transittime of X-ray contrast marks through the gastrointestinal tract. Defecography is best for the evaluation of defecation mechanics problems. Therapy: we must inform the patient in an intelligible way about the physiology of defecation. We must explain to the patient that there is no need of daily defecation. An organism with intact bowels cannot be intoxicated by bowel content. Dietary habits are also important. At first we add sufficient amount of fibre. We usually choose simple natural agents (dried plums, fruit, vegetables). We must take heed of proper hydration (at least 2 litres of fluids per day). If adding fibre is not enough, we add additional fibre in the form of wheat bran (just mix several spoonfuls with yoghurt and drink a lot). If it is possible, increased physical activity is also helpful. The underlying mechanisms regarding the association between physical exercise and constipation are unclear but a favourable effect on colonic motility, decreased blood flow to the gut, biomechanical bouncing of the gut during running, compression of the colon by abdominal musculature, and increased fibre intake as the result of increased energy expenditure have all been reported.The Nurses'Health Study, which followed a cohort of 62,036 women, found that physical activity 2-6 times per week was associated with a 35 per cent lower risk of constipation [3]. Take a look at the patient's medication as well, to check if all drugs used are necessary. Laxatives are usually unavoidable. However, long-term usage of stimulating laxatives is inappropriate. We can use bulk-forming or osmotic laxatives (psyllium, methylcellulose, polyethylene glycol, magnesium salts, lactulose), or glycerine suppositories. Bulk-forming laxatives (psyllium, wheat bran) are not suitable in case of defecation mechanics problems. Osmotic laxatives are more suitable in those cases. Osmotic laxatives soften the stools and by this way augment defecation. Prevention and therapy of the so-called faecaloma are very difficult. It means stagnated stool in the rectum, especially in cachectic immobilised old people. There can even be false diarrhoea with stool incontinence (see below). We can try oil enema or enema with polyethylene glycol [4]. Sometimes stools can be removed from the rectum only via manual extraction. 268 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ OBSTIPATION AND DIARRHOEA - A COMMON AND SIGNIFICANT PROBLEM IN THE ELDERLY Diarrhoea There are similar causes of diarrhoea in the elderly as in younger age. We keep our eyes on the causes appearing in the elderly. Diarrhoea is a common problem in elderly persons. Worldwide, diarrhoea is the second leading cause of mortality. In the developed world, 85% of its mortality affects the elderly [5], In case of acute diarrhoea (up to two weeks) we consider infection, especially in patients living in the community (retirement homes, hospitalised patients). If diarrhoea persists for more than 24 hours, oral rehydration solutions or intravenous fluids must be administered promptly in order to prevent hypotension and organ failure in the often multimorbid patient. Other common factors causing diarrhoea are acute alimentary indigestion and drugs. I n case of chronic diarrhoea, there are several common causes in older age (see Table 2). Table 2 Causes of diarrhoea in the elderly Drugs Thyrotoxicosis Diabetes mellitus Systemic sclerosis Microscopic colitis Mesenteric ischaemia Diverticulitis Colorectal carcinoma Drugs as a cause of diarrhoea Diarrhoea can be a simple adverse effect of a given drug. In the rapidly increasing elderly population, diarrhoea as the result of drug therapy is an important consideration. The elderly consume a disproportionately large number of drugs for multiple acute and chronic diseases. Drugs can compromise both immune and non-immune responses. Ageing decreases the quality and proportion of T cells, which in turn reduces the production of secretory IgA, the primary immune response of the gut. Acid production in the stomach decreases with increasing age and this compromises its vital 'self-sterilising'function, thus increasing the risk of diarrhoea due to viral, bacterial, and protozoal pathogens. Other nonimmune defence mechanisms include the motility of the small intestine and the host-protective commensal bacteria of the colon. Drug-induced hypomotility may result in bacterial overgrowth, deconjugation of bile salts, and diarrhoea. Less commonly, diarrhoea may occur due to hypermotility because of a cholinergic-like syndrome. In the colon the host-protective commensal bacteria provide a powerful defence against pathogens [6], Treatment with broad-spectrum antibiotics can often result in diarrhoea caused by the toxin of Clostridium difficile. Many studies describe thatthis complication afflicts especially old, frail and weakened patients [7]. The symptoms of this serious iatrogenic complication vary in a wide spectrum - from light diarrhoea to fulminant colitis, which threatens the patient's life. Pseudomembranes are a typical finding during endoscopy, but in many times they are missing [7]. A proof of the Clostridium difficile toxin in the stools is the most important part in the diagnostics of this condition. To treat it we can use metronidazole or vancomycin. What is advised is reasonable administration of antibiotics and trying to avoid broad-spectrum antibiotics if possible. In one study Ludlam found that reducing the patient's exposure to injectable third-generation cephalosporins by substituting alternative antibiotics can produce a cost-effective reduction in the incidence of antibiotic-associated diarrhoea [8]. Sometimes, diarrhoea can be caused by fungal overgrowth after antibiotic therapy [9]. Drugs causing diarrhoea are summarised in the following table (seeTable 3). Table 3 Drugs causing diarrhoea Antibiotics Bile acids Theophylline NSAIDs Antacids with magnesium salts Colchicine Laxatives Cytostatics Antisecretory drugs (rare) Hymecromone Statins and fibrates Radiation Though the causes of diarrhoea are diverse, a drug-associated aetiology should always be considered and actively sought and addressed to prevent the complications of dehydration, electrolyte imbalance, and undernutrition. Diseases as a cause of diarrhoea Diabetes mellitus is a frequent cause of diarrhoea in older people. Diarrhoea can afflict patients with type 2 diabetes as well as those with type 1 diabetes. The main symptom is diarrhoea of varying intensity, usually after meals and even during the night. Especially night diarrhoea can end in stool incontinence. There can be present other symptoms of neuropathy (orthostatic hypotension, night sweat, paraesthesia, problems with urination). The cause of chronic diarrhoea in diabetics is vegetative neuropathy of nerve plexuses in the gastrointestinal tract. In some cases diarrhoea is caused by dysmicrobia. If we succeed in cholestyramine therapy, we can assume malabsorption of bile acids. Quite commonly, a test of several therapeutic approaches is done to find the most suitable one. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 269 OBSTIPATION AND DIARRHOEA - A COMMON AND SIGNIFICANT PROBLEM IN THE ELDERLY Hyperthyroidism in the elderly can have only few symptoms; dominating are muscular weakness, weight loss, and diarrhoea. Other causes are similar to those in younger age. Older people are much more threatened by dehydration, electrolyte disruption and nutritional deficit, because the reserves and adaptation mechanisms of older patients are substantially lesser than in young ones. Non-specific inflammatory bowel diseases This category includes ulcerative colitis and Crohn's disease. They both have bimodal age distribution. The first peak appears in adolescents and young adults, the second peak appears between 50-80 years of age. In 15% of the patients colitis develops after 65th year of age [7]. Older people are not protected against chronic bowel inflammations. Typical characteristics are similar to the common picture of the disease.The main symptom is diarrhoea, usually with bleeding. Microscopic colitis (collagenous and lymphocyte) can cause diagnostic problems, because the macroscopic endoscopic finding is normal,and onlya microscopic examination reveals pathology. The dominant symptom is diarrhoea as well, often during the night.This condition is not typical of older age (rather in the middle age) but appears even in the elderly and we must be aware of it. False diarrhoea False diarrhoea develops in the case of faecal impaction and is connected with the development of faecaloma. Faecal impactions occurin both gendersatanyage butare particularly concentrated in the institutionalised or impaired elderly. The clinical consequences may be disabling and occasionally life-threatening. Stools stagnate usually in the rectum and older patients cannot excrete them. Clinical manifestations include faecal incontinence, abdominal distention and pain, anorexia, weight loss, intestinal obstruction, and stercoral ulceration with bleeding or colonic perforation. Chronic irritation causes watery and mucous secretion. This discharge (caused by mucosal irritation) often leaves spontaneously and can look like diarrhoea. Improper antidiarrhoeal treatment worsens this situation even more. The diagnosis begins with recognition of possible faecal impaction and confirmation by digital examination or abdominal radiography. Management consists in disimpaction, colon evacuation,and a maintenance bowel programme to prevent recurrent impactions [10], REFERENCES 1. KalvachZ,ZadákZ,JirákR,Zavázalová H.Sucharda P.Geriatrie a gerontológie [Geriatrics and Gerontology]. Praha: Grada, 2004: 716-718. 2. Schaefer DC, Cheskin LJ. Constipation in the elderly. Amer Fam Physician 1998; 58: 907-914. 3. Dukas L,WillettWC, Giovannucci EL. Association between physical activity, fiber intake, and other lifestyle variables and constipation in a study of women. Amer J Gastroenterology 2003; 98: 1790-1796. 4. Schiller LR. Constipation and fecal incontinence in the elderly. Gastroenterology Clinics of North America 2001; 497-515. 5. Hoffmann JC, Zeitz M. Small bowel disease in the elderly: diarrhoea and malabsorption. Best Pract Res Clin Gastroenterology 2002; 16[1 ]: 17-36. 6. Ratnaike RNJonesTE. Mechanisms of drug-induced diarrhoea in the elderly. Drugs Aging 1998; 13[3]: 245-53. 7. Holt PR. Diarrhea and malabsorption in the elderly. Gastroenterology Clinics of North America 2001; 427-444. 8. Ludlam H, Brown N, Sule O, et al. An antibiotic policy associated with reduced risk of Clostridium difficile-associated diarrhoea. Age Ageing 1999; 28[6]: 578-80. 9. Danna PL, Urban C, Bellin E, Rahal J. Role of Candida in pathogenesis of antibiotic-associated diarrhoea in elderly inpatients. Lancet 1991; 337(8740): 511-4. 10. Wald A. Management and prevention of fecal impaction. Curr Gastroenterol Rep 2008; 10[5]: 499-501. 270 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ORIGINAL RESEARCH FOREKNOWLEDGE AS AN ASSOCIATED FACTOR FOR ADHERENCE TO THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE Mišejková M., Dujsíková H.,Trumpešová H., Prokopová L., Zbořil V. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno ABSTRACT Received after revision September 2009 KEYWORDS Inflammatory bowel disease Adherence to therapy The goal of our essay is to evaluate the privity of patients suffering from inflammatory bowel disease (IBD) with regard to the essence of their disease, risk factors, and present ways of treatment including its side effects. Eighty patients with IBD (58 with Crohn's disease and 22 with ulcerative colitis, 40 males and 40 females) were included in our research and asked to fill in our anonymous questionnaire. It consisted of several parts: diet, possibilities of medicamentous therapy with its side effects, and timing of surgical therapy. In the end they assessed the level of their knowledge and named the resources from which they drew their information. It was concluded that 96% of patients consider themselves sufficiently and correctly cognisant of their disease, but according to our evaluation the real number is lower than 52%. In particular, the knowledge of the side effects of ongoing treatment was found to be inadequate. We assume that limited knowledge or misinformation might participate in the origin and development of non-adherence to therapy. ABBREVIATIONS USED CORRESPONDING AUTHOR Mišejková M. Department of Internal Medicine and Hepatogastroenterology, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno Jihlavská 20,625 00 Brno Czech Republic IBD - inflammatory bowel disease CD-Crohn's disease UC- ulcerative colitis 5-ASA - 5-aminosalicylates INTRODUCTION Inflammatory bowel disease (IBD) refers to two related yet different diseases - Crohn's disease and ulcerative colitis. Both diseases cause chronic inflammation of the intestinal tract, which leads to a variety of symptoms. Crohn's disease may affect any part of the gastrointestinal tract and the inflammation penetrates all layers of the bowel wall. Ulcerative colitis affects the large intestine and the inflammation forms in the http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 271 FOREKNOWLEDGE AS AN ASSOCIATED FACTOR FOR ADHERENCE TO THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE lining of the colon. It may also cause damage to extraintestinal organs -joints, eyes, skin, liver, and lungs. IBD is a lifelong disease with periods of active inflammation in a part of the intestine (relapse) alternating with periods of disease control with mucosal healing of the intestine (remission). The aetiology of IBD remains unknown and is most likely multifactorial. According to a wide range of studies, external agents significantly contribute to IBD manifestation (especially the presence of an infection, eating habits, smoking, hormonal contraception, and psychological pressure). Both diseases reach their spikes in two periods: the first is at the time of puberty and early adulthood and the other between 50-70 years of age. In the Czech Republic there are 3 to 5 out of 100,000 people suffering from Crohn's disease and 3 out of 100,000 suffering from symptomatic ulcerative colitis [1], The therapy of IBD is only symptomatic and may be divided into conservative approach and surgical intervention. The conservative therapy includes medicaments, endoscopic therapy, nutritive and psychological intervention. The main goal of medicamentous therapy is to suppress the inflammation, provoke mucosal healing, and prolong the remission. There are several basic medicament groups used in medicamentous therapy - a suitable group is chosen according to the extent of the damage to the intestinal system and disease activity. 5-Aminosalicylates (5-ASA), immunosuppressives (corticosteroids, azathioprine, methotrexate, cyclosporine) [2] and biological therapy are used. According to the available studies only 40% of all patients are completely adherent to therapy [3]. Most authors agree that adherence is a complex problem. We assume that one of the key factors influencing adherence in patients is the quality of their foreknowledge - in other words understanding the essence of their disease and its cure. METHODS Eighty patients with inflammatory bowel disease participated in the study (40 males and 40 females, 58 patients with Crohn's disease and 22 patients with ulcerative colitis). The average age of the patients was 32 years and the average time of disease duration was 7 years. Thirty-one patients achieved primary education, 44 secondary education, and 5 were university educated. They were asked to fill in an anonymous questionnaire, which was divided into several parts. The first was focused on basic demographic data (age, gender, achieved education, time duration of disease, and current therapy). The second part was devoted to diet. We aimed to find out how important it was for our patients and what kind of food they considered to be inappropriate. The third part was focused on various kinds of therapy. In case of medicamentous therapy we were primarily interested in the patients' knowledge of the side effects of their therapy. They were supposed to describe the side effects they were afraid of. In case of surgical approach we aimed to find out how our patients felt about its timing and asset. We were also interested whether patients sought out complementary medicine and if they considered it beneficial. Finally the patients were asked if they used their medication regularly. In the end the patients assessed the level of their knowledge and named the resources from which they drew their information. RESULTS 1. Diet and its significance for patients with IBD According to our results, 92.5% of women and 75% of men think of eating healthy food as being very important and 91 % of women and 91 % of men really eat it. Alcohol was chosen as the most inappropriate food by both women (95%) and men (100 %), wholemeal pastry by 73% of women and black coffee by 62%. Men chose black coffee in the second place with 62% and grease in the third with 41 %. 2. Conservative IBD therapy Ninety-three per cent of women and 78% of men with CD and 66% of women and 92% of men with UC qualify their disease as incurable. Altogether 82.5% of women and 70% of men with IBD are afraid of the side effects of their medication. Eighty patients were cured with 5-aminosalicylates and corticosteroids. Thirty-nine per cent of women using 5-ASA are not afraid of any side effects, 35.5% are afraid of teratogenic influence, 32% of hepatotoxicity, and 29% of nephrotoxicity. Sixty-three per cent of men are afraid of hepatotoxicity, 33% of nephrotoxicity. Sixty-four per cent of women and 71 % of men using steroids are afraid of osteoporosis, 46% of women and 54% of men of hepatotoxicity. Fifty-nine patients were treated with azathioprine. Altogether 54.5% of women and 39% of men are afraid of haematotoxic-ity, 45.5% of women and 52% of men of hepatotoxicity. Twenty-nine patients were treated with cyclosporine. Forty-four per cent of women are afraid of teratogenic influence, hepatotoxicity and haematotoxicity, 22% of nephrotoxicity. Forty per cent of men using the same cure are afraid of haematotoxicity and nephrotoxicity. Twenty-six patients were treated with methotrexate. Eighty-six per cent of women from this sample are afraid of hepatotoxicity and 71 % of teratogenic influence. Forty per cent of men are afraid of hepatotoxicity; none of them is afraid of any side effects. 272 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ FOREKNOWLEDGE AS AN ASSOCIATED FACTOR FOR ADHERENCETOTHERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE 3. Possibilities of surgical intervention It was concluded that 90% of women and 87.5 % of men consider surgical intervention to be the last resort. 4. Complementary medicine Sixty per cent of female patients and 37.5 % of male ones consider complementary therapy (homeopathy, acupuncture) as beneficial. 5. Regularity of using prescribed medication Altogether 82.5% of female patients and 67.5% of male patients use their medication regularly according to the doctors' recommendation. A total of 12.5% of male patients terminate their treatment when their condition improves. 6. Resources from which our patients drew their information Ninety per cent of men indicated their doctor, 37.5% named booklets they acquired at the doctor's, and 30% mentioned the Internet. Altogether 72.5 % of women indicated their doctor as their resource, 67.5% gained their information from brochures, 50% from their co-patients, and 30% from the Internet. DISCUSSION Several works were published in foreign literature pursuing the topic of non-adherence to medicamentous therapy of IBD. Sewitch and his colleagues determined conscious non-adherence in 36.5 of the patients [4], Lopez San Rom reached 35% [5]. The ways of learning the measure of adherence to therapy are very complicated. D'Inca and his colleagues used the method of anonymous questionnaires and found conscious adherence in 39% of the patients [6]. Červený et al. analysed samples of urine from patients treated with 5-ASA; there was no evidence of 5-ASA in 12.5% of the patients [7], We used the method of anonymous questionnaires in our research with patients of our gastroenterological clinic. However, most of them wished to fill in the form in our presence as they wanted to have the opportunity to discuss the questions. Therefore, we consider the evaluated questions to be very accurate and reflecting the real measure of foreknowledge of our patients. The causes of medication non-adherence are multifactorial. We suppose that the quality of our patients'foreknowledge of their disease is closely linked with their adherence to the therapy. CONCLUSIONS Foreknowledge of patients with IBD concerning the essence of their disease and the possibilities of treatment is inadequate in the present times. While patients considered themselves to be well informed in 95%, 50%oftheiranswers were incorrect. The major group of incorrect information was related to the side effects of ongoing treatment. As they have the deepest influence on non-adherence to therapy, we suggest that the Gastroenterological Society should actively participate in educational programmes and in elaboration of information for patients with IBD. REFERENCES 1. Lukáš M, et al. Idiopatické střevní záněty. Nejistoty, současné znalosti a klinický přístup [Inflammatory bowel disease. Uncertainties, current knowledge, and clinical approach]. Praha: Galén, 1998: 36-38,64-70. 2. Zbořil V, et al. Imunosupresiva v léčbě idiopatických střevních zánětů [Immunosuppressants in the therapy of inflammatory bowel disease]. Praha; Grada Publishing, 2007:18-34. 3. Robinson A. Review article: improving adherence to medication in patients with inflammatory bowel disease. Alimentary Pharmacology and Therapeutics 2008; 27: 9-14. 4. Setwich MJ, Abramhamowicz M, Barkun A, et al. Patient non-adherence to medication in inflammatory bowel disease. Am J Gastroenterol 2003; 98[7]: 1535-1544. 5. Lopez San Roman A, BermejoF, Carrera E, et al. Adherence to treatment in inflammatory bowel disease. Rev Esp En-ferm Dig 2005; 97[4]: 249-257. 6. D'Inca R, Bertomoro P, Mazzocco K, et al. Risk factors for non-adherence to medication in inflammatory bowel disease patients. Alimentary Pharmacology and Therapeutics 2008; 27:166-172. 7. Červený P, Lukáš M, Bortlík M, et al. Non-adherence k medikamentózni léčbě idiopatických střevních zánětů a její nejčastější formy [Non-adherence to medicamentous therapy of inflammatory bowel disease and its most frequent forms]. Čes Slov Gastroenterol Hepatol 2006; 60[5]: 207-212. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 273 ORIGINAL RESEARCH SCREENING OF COELIAC DISEASE IN OSTEOPOROTIC PATIENTS Fojtík P.1, Fait P. \ Kliment M. \ Urban O. \ Novosad P.: 1 Digestive Diseases Centre, Vítkovice Hospital, Ostrava 2 Osteology Centre Mediekos, Zlín INTRODUCTION Received after revision September 2009 KEYWORDS Inflammatory bowel disease Adherence to therapy Coeliac sprue is traditionally understood as a disease related to early age. A certain part of the young population suffers from typical bowel symptoms, which belong to the group of active coeliac syndromes. Looking at the full-scale screening performed in European countries and in the US, we can see that the prevalence of this condition is about 1:100. This means that there are 40 000 to 50 000 people affected by coeliac sprue in the Czech Republic. However, only 15-20% of the patients have been diagnosed and the rest of them remains undiagnosed. The main reason for this is subtle or even missing symptoms in the essential part of the patients (atypical or silent coeliac disease-see Table 1). Osteoporosis is the most frequent atypical manifestation of the disease in adulthood and in the elderly. The treatment is difficult particularly in women with a combination of coeliac disease and postmenopausal osteoporosis. H CORRESPONDING AUTHOR Fojtík P. Digestive Diseases Centre Vítkovice Hospital Zalužanského 1189/14 703 84 Ostrava Czech Republic DEFINITION Coeliac sprue (CS, coeliac disease, gluten-sensitive enteropathy) is a lifelong disease of the digestive tract. There is a strong association with the human leukocyte antigen (HLA) haplotype (DQ2and DQ8),and consumption of gluten-containing cereals is necessary. Gliadin (the alcohol-soluble fraction of gluten), by means of presentation to the helper T cells, initiates an immunologically mediated and inappropriate inflammatory response, which leads to damage of the intestinal mucosa (mostly duodenal and jejunal) resulting in malabsorption. At the same time, a high amount of highly specific antibodies (AtATG - antibodies against tissue transglutaminase) is being generated. EPIDEMIOLOGY On average, the prevalence of coeliac disease in Western countries is supposed to be 1:100. The male-to-female ratio 274 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ SCREENING OF COELIAC DISEASE IN OSTEOPOROTIC PATIENTS r \ ^^ X Figure 1 Atrophie duodenal mucosa ir ^-vT 1 Figure 2 Appearance of atrophic duodenal mucosa after indigocar- mine staining is about 1:2. Coeliac disease has a strong hereditary component. The prevalence ofthe condition in first-degree relatives is approximately 8-18%. Concordance in monozygotic twins approaches 70%. The estimated frequency of coeliac disease in the Czech Republic is 1:200-250. Thus, there live here approximately 40 000 to 50 000 affected people. CLINICAL PRESENTATION The clinical picture of coeliac disease tends to be different depending on the age ofthe patient. The course ofthe disease is also influenced by genetic dispositions, duration of gluten exposure, and the degree of mucosal affection. Coeliac disease is no longer a rare condition affecting mostly children and causing only diarrhoea, weight loss, and anaemia. Its manifestation changes with age, gastrointestinal symptoms weaken, and extraintestinal manifestations play a more important role. The disease is mostly detected between the 30th and 40th year of age, later diagnosis is quite rare. After the 60th year of age, coeliac disease is not considered at all, as there are usually more frequent and urgent conditions to treat. The commonest symptoms that we observe in adulthood are minimal gastrointestinal troubles (flatulence, lack of appetite), fatigue and/or atypical extraintestinal symptoms -primarily osteoporosis with a severity not corresponding to age, anaemia, neurological and psychological disruptions. Glossitis, aphthous stomatitis, skin disorders, alopecia, amenorrhea, infertility, and impotence are less common troubles. Osteopenia and osteoporosis are some of the most serious atypical manifestations ofthe disease in adulthood and in the elderly. Altogether 18-24% of patients suffer from osteopenia, 34% of postmenopausal female patients have osteoporosis in the lumbar area, and 27% in the area ofthe femoral neck. Bone metabolism is mostly disturbed by malabsorption of nutrients with subsequently restricted calcium distribution, by a lower amount of vitamin D, growth hormone, and the insulin-like growth factor 1 (IGF-1). DIAGNOSTICS When considering coeliac disease in adulthood, we base our diagnosis on three factors: 1) Clinical picture as described above. 2) Serological markers - AtTGA (antibodies against tissue transglutaminase) with a sensitivity of 90-98% and a specificity of 95-97%, EMA (antiendomysial antibodies), AGA (an-tigliadin antibodies). Thanks to its high accuracy, good price and availability, AtTGA is the most suitable marker. 3) Biopsy ofthe small intestine mucosa. In common practice it means an endoscopically obtained sample ofthe mucosa of the aboral duodenum. The advanced stages of villous atrophy can be visible during endoscopy with the naked eye. Histologically, mucosal damage is evaluated according to the Marsh classification (stage 0-4), and stage 3 is the most typical for coeliac disease. CLASSIFICATION Because of the high frequency of non-characteristic symptoms coeliac disease is underdiagnosed in most of the http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 275 SCREENING OF COELIAC DISEASE IN OSTEOPOROTIC PATIENTS Figure 3 Normal appearance of duodenal mucosa Figure 4 Normal appearance of duodenal mucosa in water immersion affected people. This supports the concept of the "coeliac iceberg"- the smaller part above the surface represents the active forms of the disease. The essential part of the patients remains under water und thus undiagnosed. Typical form. It represents about 30% of the patients. Serological and histological markers are present, gastrointestinal symptoms dominate. Subclinical (atypical, extraintestinal) form. Serological and histological markers are present. Atypical extraintestinal symptoms (anaemia, osteopathy, neurological and gynaecological symptomatology) prevail. Silent form of CD. Serological and histological markers are present. Clinical symptoms are absent. Some of the patient's relatives can be affected by coeliac disease. Latent form of CD. Specific antibodies are found. Histologically, there is only an increased number of IEA (intraepithelial lymphocytes) without atrophy. Clinical symptoms are missing.These patientsareatriskof developing coeliacdisease in the future. Genetic examination (HLA) is recommended. COMPLICATIONS CAUSED BY CD The most fatal complication of coeliac disease in adulthood and in the elderly is osteoporosis. In female patients osteoporosis associated with coeliac disease often combines with postmenopausal osteoporosis. In the Czech Republic, 15% of menand 33%of women olderthan 50yearsand 39%of men and 47% of women olderthan 70 years suffer from osteoporosis. The clinical importance of osteoporosis consists mainly in its consequences, which are represented by fractures of both axial and appendicular skeleton. The most frequent are compressive fractures of vertebras, femoral neck, and radius. Such complications worsen the quality of life and often lead to its premature end. The mortality of women with a diagnosed fracture of the femoral neck is by 15% higher than that of the other women. This mortality reaches up to 30% in women older than 65 years. Another extraintestinal manifestation in adulthood is anaemia caused by deficiency of iron, folate, pyridoxine, and Table 1 Coeliac disease classification (FH = family history) T IELy/ô = T intraepithelial y/ô lymphocytes CS forms Typical Silent Latent Potential Subclinical Symptoms + -(FH) - often atypical Histology + + T IELy/ô T IELy/ô or- + Serology + + + + or- + 276 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ ■ SCREENING OF COELIAC DISEASE IN OSTEOPOROTIC PATIENTS vitamin BI2. Furthermore, there could be gynaecological (infertility, dysmenorrhoea, abortions), psychological (anxiety, depressions), and neurological symptoms (polyneuropathy, tetany, fatigue, brain atrophy, seizures). The most lethal of them is, fortunately scarce, intestinal lymphoma. TREATMENT AND FOLLOW-UP The treatment of coeliac disease is very simple. The patients have to adhere to a gluten-free diet for life. During the initial 3-6 months the intestinal mucosa is being restored.This process can be supported by substituting vitamins of B group and trace elements. Once the diagnosis is established it is recommended to substitute calcium in doses of 1000 mg per day and vitamin D in doses of 1600 IU per day (e.g. 4 drops of Vigantol per day or 20 drops once a week) in the first year of treatment and then to adapt to the results of densitometry. There are no data concerning the doses of the above-mentioned medication. However, vitamin D seems to play a crucial role. In children the bone mineral density (BMD) is normalised within 3 years of the strict removal of gluten from the diet. On the contrary, in adulthood BMD usually does not reach its original value, especially in patients with secondary hyperparathyroidism in the initial stage. Densitometry is advisable immediately after establishing the diagnosis and then after a year of treatment. Diphosphonates are actually considered as the most suitable medication for the osteoporosis treatment. Strontium preparations seem to be promising as well. SCREENING OF THE TARGET GROUP IN ADULTHOOD AND IN THE ELDERLY In co-operation with an osteology centre in Zlín we examined a serological marker of coeliac disease (AtTGA) in 1409 patients. Thirteen patients were positive and gastroduo-denoscopy with duodenal biopsy followed in all of them. The histology revealed atrophy of the duodenal mucosa of stage III a-b according to the Marsh classification. The total prevalence of coeliac disease in our group was then 1:100. We divided the group into two subgroups: A (younger than 55 years) with the prevalence 1:1.28 and B (older than 55 years) with the prevalence 1:100. None of them had typical bowel symptomatology. Five patients complained of intermittent diarrhoea and eight had occasional abdominal distension. We hereby confirmed the high prevalence of coeliac disease in the population of osteoporotic patients in the Czech Re-public-1:100, which is twice as high as in the common population. However, in patients over 55 the prevalence is 1:28, which means 4 times higher than in the common population. Therefore, it is recommendable to screen all osteopenic and osteoporotic patients younger than 55 years for coeliac disease. Osteoporotic patients older than 55 years should be screened if they do not respond to the treatment adequately or show even minimal intestinal symptomatology. In this way we can improve the prognosis of patients suffering from coeliac disease and associated osteoporosis. REFERENCES 1. Thomson A., et al. WGO-OMEG Practice Guideline: osteoporosis and gastrointestinal diseases. June 2004, www. omge.org/globalguidelines.htm. 2. Bernstein C, Leslie W. American Gastroenterological Association medical position statement: guidelines on osteoporosis in gastrointestinal diseases. Gastroenterology 2003; 124; 791-794. 3. Bernstein C, Leslie W, et al. AGA technical review on osteoporosis in gastrointestinal diseases. Gastroenterology 2003;124:795-841. 4. Štěpán J, Hana V. Osteoporosa u mužů [Osteoporosis in men]. Diabetologie Metabolismus Endokrinologie Výživa 2006; 9 (Suppll): 46-55. 5. DewarD.Ciclitira P. Clinical features and diagnosis of celiac disease. Gastroenterology 2005; 128(Suppl 1): S19-S24. 6. Leslie W.Bernstein C. AGA technical review on osteoporosis in hepatic disorders. Gastroenterology 2003; 125.N.3: 1-41. 7. Leslie W, Bernstein C. American Gastroenterological Association Institute technical review on corticosteroids, im-munomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006; 130: N.3. 8. Lewis N, Scott B. Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease 2007. BSG Guidelines in Gastroenterology; www.bsg.org.uk. 9. Bischoff S, Crowe S. Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives. Gastroenterology 2005; 128:1-36. 10. Sampson HA, Sichere SH. AGA technical review on the evaluation of food allergy in gastrointestinal disorders. Gastroenterology 2001; 120:1026-1040. 11. Di Stefano M. Lactose malabsorption and intolerance and peak bone mass. Gastroenterology 2002; 122: 1793-1799. 12. WGO-OMGE Practise Guideline: Malabsorption, www. omge.org/globalguidelines.htm. http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 277 NEWS AND CURRENT AFFAIRS ABSTRACTS OF SELECTED PAPERS PRESENTED AT THE XVIth CONFERENCE OF YOUNG PHYSICIANS, ST. ANNE'S FACULTY HOSPITAL IN BRNO, 24 JUNE 2009 Z Trávníčková (Department of Clinical Immunology and Allergology, St Anne's Faculty Hospital, Faculty of Medicine, Masaryk University, Brno): Investigation of antibody production after antigen challenge in patients with common variable immunodeficiency (CVID) by ELISPOT Common variable immunodeficiency (CVID) is one of the most common immunodeficiencies. It is characterised by low serum levels of IgG, IgA, normal or low levels of IgM, and impaired antibody response. Despite intensive research the real cause of these diseases and involvement of B cells remain unclear. The goal of the study was to determine the ability of antibody response after vaccination in CVID patients. The use of ELISPOT (enzyme-linked immunosorbent spot) assay permits detection of antibody production on the cellular level. It may detect the antibody response in patients under immunoglobulin substitution. Thirty-seven CVID patients were vaccinated with tetanus toxoid (TAT) and pneumococcal polysaccharide (PCP) vaccine. Fifty healthy individuals were boosted with TAT, ten received pneumococcal polysaccharide vaccine alone, and twenty-one were immunised with both vaccines together. All volunteers were examined before vaccination, on day 7 after vaccination, and 4 to 11 weeks after vaccination by the ELISPOT assay. The median of spot-forming cells (SFC) in healthy volunteers was found to be for tetanus toxoid 9 882 (IgG), 532 (IgA), 0 (IgM), and for pneumococcal polysaccharide 3 870 (IgG), 35 200 (IgA), 10 087 (IgM) SFC/106 B cells. In contrast to this, there was nearly no specific antibody production against protein or polysaccharide antigens in IgG, IgA, and IgM immunoglobulin classes in the CVID patients. If any specific IgG production was detected, most of them (3 patients) belonged to the group smB+21norm (altogether 7 patients) according to the EUROclass classification, while in the remaining groups a response was observed only exceptionally. The ELISPOT technique is a useful functional testforthe detection of specific antibody response in patients under substitution immunoglobulin therapy. Our results may help to better elucidate the antibody production defects in CVID patients. This work was supported by grant No. NR 9035-4 of the Czech Ministry of Health. O. Tichá, M. Štouračová (Department of Clinical Immunology and Allergology, St Anne's Faculty Hospital, Faculty of Medicine, Masaryk University, Brno): Expression of CD38 on the lymphocytes of kidney transplant patients Cytomegalovirus (CMV) infection is a life-threatening complication of patients after solid Organtransplantation. It appears in the first months after transplantation as a consequence of the use of immunosuppression. The study was performed in the Centre of Cardiovascularand Transplant Surgery (Brno, Czech Republic) in the period from December 2002 to April 2008, when 237 patients underwent renal transplantation. The patients were monitored at the time of their hospitalisation 2-3 months after transplantation. The percentage of CD38high cells from Tc lymphocytes estimated by flow cytometry, the titre of anti-CMV IgM antibodies determined by the ELISA method, and the number of CMV copies in peripheral blood using real-time polymerase chain reaction (RT-PCR) were monitored in these patients. Between 31 st and 63rd days after transplantation 12 patients (5%) were diagnosed with CMV infection. These patients had increased percentage of CD38high from CD3+CD8+ T lymphocytes above the arbitrary limit of 20%. Eight of them had an increased level of CD38high above 20% from 3 to 32 days before the CMV infection was diagnosed and antivirotics were administrated. The follow-up of CD38high percentage from CD3+CD8+ lymphocytes seems to be a useful additional diagnostic marker for patients after kidney transplantation. S. Zgažarovď, Z. Trávníčková2 Cist Department of Dermato-venereology. Faculty of Medicine, Masaryk University and St. Anne's Faculty Hospital, Brno, department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St. Anne's Faculty Hospital, Brno): Drug hypersensitivity to tribenoside (Glyvenol) Tribenoside is a semisynthetic sugar derivative. It is widely used as Glyvenol (capsules) and Procto-Glyvenol (cream or suppositories). It is indicated for the treatment of chronic venous insufficiency, haemorrhoids, and arthritis because of high affinity to the vessel wall and a wide spectrum of pharmacological effects including venotonic, antioedemic, fibrin-olysis-promoting, analgesic, antiinflammatory, antiallergic, membrane stabilising, and bactericidal ones. Up to 10% of patients treated with tribenoside can suffer from skin side effects. They usually occur as anaphylaxis, an-gio-oedema, urticaria, and exanthemas (the most common 278 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ 5 maculopapularrash).The pathogenesis of cutaneous adverse drug reactions (CADR) induced by tribenoside is unknown. No universal test for a final diagnosis of CADR with 100% sensitivity and specificity has existed as yet. We evaluated 27 inpatients treated in our Dermatology department for exanthemas induced by tribenoside in the period from October 2005 to August 2008. The patients were investigated to confirm the aetiology of exanthemas. On the basis of history, clinical features and course of disease we supposed a delayed reaction to tribenoside. Twenty-two out of 27 patients were examined using a patch test from in vivo diagnostic methods. In vitro (laboratory) tests were performed in 8 out of 22 patients including the lymphocyte transformation test and the basophil activation test. A positive patch test reaction to tribenoside was seen in 1 out of 22 patients. The basophil activation test gave a positive reaction in 1 out of 8 patients. The lymphocyte transformation test elicited one border-positive reaction. In spite of our study the results in patients with exanthemas exposed to tribenoside prove that immediate as well as delayed hypersensitivity reactions could occur.This finding is in accordance with the clinical picture of exanthemas, which are not uniform, either. H. Škvařilová (Department of Dentistry, St. Anne's Faculty Hospital, Faculty of Medicine, Masaryk University, Brno): The sealing quality of filling materials used in dentistry The aim of this study was evaluation of the sealing qualities of temporary filling materials in the crown part of extracted teeth. The function of a temporary filling material in dentistry is twofold: first, to prevent the saliva with its microorganisms from gaining entrance into the root canal, thus preventing infection; second, to prevent medicaments placed into the pulp chamber from escaping into the oral cavity, thereby preserving the effectiveness of the intracanal medication. Forty extracted teeth, which were fixed in 10% neutral formaldehyde, were examined. Before the experiment the teeth were washed in flowing water for 24 hours. Black's class I and V cavities were prepared. The teeth were filled up with one of the following materials: •Zinc-oxide sulphate cement (Providentin) •Material based on plaster and organic cement (Provimat) •Caviton •Ca vit W •Zinc-oxide eugenol cement (IRM cement) •Glass-ionomer cement (GC Fuji) •Glass-ionomer cement (Ketac Fill plus) •Zinc-oxide eugenol cement (Caryosan) The entire tooth surface, except for a cavity area, was coated with a thick layer of nail polish. After immersing in a solution of methylene blue for 24 hours, the teeth were longitudinally sectioned and fractured, and examined under a stereo magnifying lens under magnification of 10. The results show that the most effective penetration of materials used was noticed with zinc-oxide eugenol (Caryosan) and zinc-oxide sulphate (Providentin) both in the fissure and in the filling material proper. The best results were reached with glass-ionomer cement (GC Fuji) and Caviton. The existing numbers of samples studied do not allow statistical evaluation but show noticeable differences between the materials used. The results of this study serve as a recommendation for the right choice of filling material. J. Nechvátalová, M. Vlkova (Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, St. Anne's Faculty Hospital, Brno):Time-related stability of abnormalities in B lymphocyte subpopulations in patients with common variable immunodeficiency (CVID) Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency disease characterised by a low level of serum immunoglobulins with various degrees of clinical immunodeficiency manifestation. Previous studies have shown various abnormalities in lymphocyte subpopulations; the patients had a reduced number of terminal stages of B-cell development. The presence of these B-lymphocyte abnormalities is the principle of the laboratory classification scheme called EUROclass. The goal of this study was to disclose to what degree these abnormalities were constant. Phenotyping was performed by flow cytometric analysis in 25 patients (aged 46±15 years). We compared representation of certain B-lymphocyte subpopulations in two measurements in the course of 2 to 3 years. Statistical analysis was performed by means of the Wilcoxon signed ranktest. The results showed an increase in the relative number of CD27+ cells ("mature" B lymphocytes) (P=0.008) as well as CD-21iow38iow (p=o.oi2), whereas the lgD+CD27 subpopulation ("immature" B lymphocytes) did not change (P=0.2473). These results may show that lymphocyte subpopulation abnormalities seen in CVID patients are not constant and tend to "normalisation". G. Jamborová', P. NachtigaP, K. Pospěchová2, N. Pospíšilová2, V. Řeháček1, V. Semecký2 (Transfusion Department, University Hospital Hradec Králové, 2Biological and Medical Sciences http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4 / 2009 279 Depa rtment.Facultyof Pharmacy in Hradec, Charles University in Prague, Hradec Králové): MDOC™ effects on acute dermal wound healing in an experimental rat model The occurrence of hard-to-heal wounds is very frequent, especially when associated with other diseases. Moist wound healing is an effective way of even complicated cases of treatment and is represented by various dressing products with appropriate properties. Microdispersed oxidised cellulose (MDOC™), a patent of Alltracel laboratories (Dublin, Ireland), is a random copolymer of polyanhydroglucose and polyanhydroglucuron-ic acid. MDOC™ was identified to be effectively used as a biocompatible and completely absorbable haemostatic agent. This material exhibits low toxicity and is usually administered in powder, spray, gel or textile form. Furthermore, MDOC™ can be employed as a polymeric ion or drug carrier (ATBs). The aim of our study was to investigate the effect of locally applied distinct forms of MDOC™ on acute cutaneous wound healing in an experimental rat model. Male Wistar rats were divided into four tested MDOC™ groups and one control group. A central defect (1 cm in diameter) was made in the paravertebral area and the appropriate amount of MDOC™ tested form (powder, gel, textile, and spray) was implanted in the wound base. Forthe observation of wound contraction several techniques were exploited; in particular gross pathology, light microscopy, and immunohistochemistry technique for the detection of specific marker (TNFRI, CCR2, TGF-ß RH) expression changes in all phases of wound healing. Our results (obtained on days 3,7, and 14 after injury) showed that the application of any MDOC™ form did not lead to any significant differences. The substance under study displayed haemostatic action and localisation of cell infiltrate detectable in the new tissue in the dermis. Additionally, immuno-histochemical analysis did not prove any significant influence of MDOC™, either. The presence of TNFRI, CCR2, and TGF-ß RH was detected in the dermis being expressed by inflammatory cells, by endothelial and epidermal cells in the MDOC™ groups as well as in the control group. Other investigations focusing on specific inflammatory markers (e.g. CD 68, FSP 1) in the wound must be accomplished to clarify precise effects of MDOC™ forms. /. Kajzrlíkovď, P. Vítek', J. Chalupa', A. Hájek2, J. Platoš', J. Kuchař', P. Reha' 0 Beskydy Gastrocentre, Department of Internal Medicine, 2Beskydy Gastrocentre, Department of Surgery, Frýdek-Místek Hospital): THE FAMILY PROJECT - the first experience with direct colonoscopic screening for first-degree relatives of colorectal cancer and advanced adenoma patients The first-degree relatives of patients with colorectal cancer or advanced adenoma havea higherriskof colorectal neoplasia. The primary colonoscopic screening and subsequent follow-up are unambiguously recommended for them. The authors decided to systematically reach out the first-degree relatives in THE FAMILY PROJECT and thus provide adequate screening for this high-risk group. The project was initiated in July 2008 and it has still been running. The patients with colorectal cancer or advanced adenoma are informed in a personal interview and asked for their first-degree relatives'phone numbers. The relatives are contacted and invited to the Project clinic. In accordance with the age and the individual risk of the relatives the colonoscopy is planned.There have been 87 patients with colorectal cancer or advanced adenoma included in the Project until the end of April 2009. Subsequently, 183 first-degree relatives were contacted and out of them 76 (42%) have already visited the Project clinic. Sixty-five first-degree relatives were eligible for colonoscopic screening at the time of attendance, 13 of them have already undergone colonoscopy, 10 of them have already had screening, but the method was not appropriate (FOBT), 42 (65%) of them have not participated in any kind of screening yet. Until the end of April 2009, 43 relatives had undergone colonoscopy within the Project, 17 neoplastic lesions were found and removed, out of them 7 advanced adenomas. The majority of first-degree relatives are either unscreened or screened with an inappropriate method (FOBT). Direct personal counselling of first-degree relatives seems to be effective and can significantly improve compliance of these patients with colonoscopic screening. We have found and removed advanced neoplastic lesions in this group of patients. Complied and revised byl Litzman 280 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ INDEX j FACULTATIS MEDICAE U NIV E RS I TAT IS BRUNENSIS MASARYKIANAE Journal for Biomedical Research PUBLISHED BYTHE FACULTY OF MEDICINE OF MASARYK UNIVERSITY SINCE 1922 Volume 82/2009 CONTENT OF VOLUME 82 1. Hladíková M., Štourač P., Benešová Y, Tschôplová S.: The Promotor Polymorphism of Macrophage Metalloelastasein Multiple Sclerosis....................................................................................................11 2. Vlčková-Moravcová £, Bednařík J.: Painful Sensory Neuropathies in the Elderly..! 6 3. Mičánková Adamová B., VoháňkaS. :The Results and Contribution of Electrophysiological Examination in Patients with Lumbar Spinal Stenosis...............................................................................................38 4. Štourač P., Bednářová 1, Hladíková M., Praksová P, Benešová Y, Kontrová /.: The Value of Intrathecal MRZ Reaction and Oligoclonal IgG Bands for Discrimination between the Primary Progressive and Relapsing Remitting Courses of Multiple Sclerosis.............................................................................................................46 5. Kadaňka Z., Bednařík J.: Spor\dy\ot\c Cervical Myelopathy: What is the Best Approach to Treatment?.....................6 6. Bednařík J., Vondráček P.: Critical Illness Polyneuromyopathy-A Well-known but Still Controversial Entity...............27 7. SloukováE.,OšlejškováH., Šoukalová 1, Masaříková H.: Non-Jewish Child with Canavan Disease..........................52 8. Crha I., Paa'k D., Beharka R., Ventruba P., Žákova J., HuserM., Kubešová B., Pohanka M.: Sperm Banking and Infertility Treatment in Men with Testicular Cancer..............................................................................69 9. Bartáková S., Prachař P., KudrmanJ., Březina V., Podhorná B., Černochová P., Vaněk J., Strecha J:. New Titanium ß-Alloys for Dental Implantologyand their Laboratory-Based Assays of Biocompatibility...........................................76 10. Plánka L, Starý D.,Tůma J., Macháček R., Gál P.: Laparoscopic versus Laparotomie Appendectomy for Generalised Peritonitis in Children................................................................................................83 11. Višňa P., Beitl £, Kočiš J., Vlček M.: Intramedullary Nail Use for Corrective Surgery of Diaphyseal Forearm Fractures........90 12. NovotnýM., KlimeckýP, Pochop J:. Wolf and Helal Metatarsal Osteotomies in Metatarsalgia Treatment.................100 13. Pour L, Kovářová Ĺ, BuchlerT., Adam Z, Penka M., Vorlíček J., Hájek R.: Evaluation of HGF and Endostatin in the Bone Marrow of Patients with Multiple Myeloma and the Effect of Peripheral Blood Admixture.....................................123 14. Yoonis E,., Kukletová M.:Tooth-Colored Dental Restorative Materials in Primary Dentition..............................108 15. VargaG., Paa'k D.: Complete Duplication of the Urinary Bladder and the Urethra in a Woman -a Case Report with a Review of Articles...........................................................................................................115 16. Sothern R. B., Yamamoto T,CornélissenG., TakumiT, Halberg F.: Central and Peripheral Circadian Clock Genes, their Statistical Analysis for Rhythms, and Relationship to Health and Disease.............................................133 17. Yambe T, Shiraishi Y, Saijo Y, Liu /-/., Nitta S., Imachi K, Baba A., Yamaguchi T, Sugawara S., Katahira Y, Ohsawa N., Mibiki Y, Watanabe M., ShibataM., Sato N, Kameyama T,Akino N., MunakataM., HondaM., Yoshizawa M., SugitaN:. Clinical Research on the Accuracy in Determining the Pulse Wave Rising Point..........................................................164 18. Buchtová £ Jiroušek O., Gál P.: Finite Element Model of the Human Head Validated by the Reconstruction of a Real Child Sport Accident.....................................................................................................175 19. F/'amo//'l/.: Treatment of Deep Venous Thrombosis with Continuous Intravenous Infusion of Low-Molecular-Weight Heparin in Children -a Safe and Efficient Alternative to Subcutaneous Application...................................181 20. NeuwirthováJ., SmilekP, Rottenberg 1, Kostřica R., Berkovcová J., Hajdúch M.: Mutations in EGFR Signal Pathway in Correlation with Response to Treatment of Head and Neck Cancers..................................................192 http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA/Volume 82/No. 4/2009 281 21. Dohnalová I., Novotný T, Sišáková M., PoloczekM., Kyselová I., Dostálová L, Floriánová A., Kala P, Toman O., VítP, ŠpinarJ.: QT Dynamicity and Time to Artery Opening in Patients with Myocardial Infarction with ST Elevations.....................197 22. Lukáši., Maňák J., Bednařík 1, Schreiber M.: Regression of Histopathological Myopathic Changes in Patients with Critical Illness Neuromuscular Disorders....................................................................................202 23. Klímová K: New Methods of Small Bowel Investigation...............................................................221 24. StibůrekO., Kunovská M., Lata J.: Capsule Colonoscopy................................................................225 25. KlimentM., Urban O., Fojtík P., Petrášek J., Janík D., Albín A., Liberda M., Šmajstrla V, Kundrátová E., Fait P.: High-definition, Wide-angle Colonoscopy for Adenoma Detection - a Prospective Study.............................................228 26. Prokešová J., Dolina J.: Clinical Application of Electrogastrography....................................................235 27. Kajzrlíková I., VítekP, Chalupa J.: Abdominal Ultrasound Accurately Detection Complications in Patients with Hepaticojejunoanastomosis........................................................................................239 28. ŠevčíkováA., Novotný I., Hermanová M., Trna J., Dítě P.: Acute Pancreatitis as a First Symptom of Pancreatic Cancer in a Diffuse Autoimmune Pancreatitis Patient..........................................................................249 29. Trumpešová H., Mišejková M., Lata J.: Primary Sclerosing Cholangitis..................................................252 30. HůlkováM.,HosákL.: Psychiatric Aspects of Hepatic Encephalopathy, Hepatitis C, and LiverTransplantation...........256 31. Lata 1, Juránková J., Příbramská V.: Intestinal Microflora and Bacterial Translocation....................................262 32. Šlapák J., Lata J.: Obstipation and Diarrhoea - a Common and Significant Problem in the Elderly......................267 33. Mišejková M., Dujsíková H., Trumpešová H., Prokopová Ĺ, Zbořil V.: Foreknowledge as an Associated Factor for Adherence to Therapy in Patients with Inflammatory Bowel Disease................................................................271 34. Fojtík P., Fait P., KlimentM., Urban O.: Screening of Coeliac Disease in Osteoporotic Patients.............................274 ABSTRACTS (Autoreferáty přednášek) 1. R.R.Ernst: Lightsand Shadows of Science and Technology in Today's Society..216 2. Z Trávníčková: Investigation of Antibody Production after Antigen Challenge in Patients with Common Variable Immunodeficiency (CVID) by ELISPOT...............................................................................278 3. O. Tichá, M. Štouračová: Expression of CD38on the Lymphocytes of Kidney Transplant Patients.......................278 4. S. Zgažarová, Z. Trávníčková: Drug Hypersensitivity to Tribenoside (Glyvenol)..278 5. H. Škvařilová: The Sealing Quality of Filling Materials Used in Dentistry................................................279 6. J. Nechvátalová, M. Vlková: Time-related Stability of Abnormalities in B Lymphocyte Subpopulationsin Patients with Common Variable Immunodeficiency (CVID)........................................................................279 7. G. Jamborová, P. Nachtigal, K Pospěchová, N. Pospíšilová, V. Řeháček, V. Semecký: MDOC™ Effects on Acute Dermal Wound Healing in an Experimental Rat Model..............................................................................279 8. /. Kajzrlíková, P. Vítek, J. Chalupa, A. Hájek, J. Platoš, J. Kuchař, P. Reha: The Family Project - the First Experience with Direct Colonoscopic Screening for First-degree Relatives of Colorectal Cancer and Advanced Adenoma Patients.............280 9. M. Souček, P. Svačina: XXVIth Conference of the Czech Society of Hypertension (ČSH), XVIIIth Conference of the Preventive Cardiology Working Group of the Czech Society of Cardiology (ČKS) and XIVth Conference of the Heart Failure Working Group of the ČKS...................................................................................................284 282 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ INDEX Adam Z. 123 AkinoN. 164 Albín A. 228 Baba A. 164 Bartáková S. 76 Bednařík J. 6,16,27,202 Bednářová J. 46 Beharka R. 69 Beitl E. 90 Benešová Y. 11,46 Borkovcová J. 192 Brichtová E. 175 Březina V. 76 BuchlerT. 123 Cornelissen G. 133 Crha 1.69 Černochová P. 76 Dítě P. 249 Dohnalová 1.197 Dolina J.235 Dostálová L. 197 Dujsíková H. 271 Ernst R. R. 216 FaltP.228,274 FiamoliV. 181 Floriánová A. 197 Fojtík P. 228, 274 GálR 83,175 Hajdúch M. 192 Hájek A. Hájek R. 123,280 Halberg F. 133 Hermanová V. 249 Hladíková M. 11,46 Honda M. 164 HosákL 256 Hůlková M. 256 HuserM. 69 Chalupa J.239,280 ImachiK. 164 Jamborová G.279 Janík D. 228 JiroušekO. 175 J u rán ková J. 262 Kadaňka Z. 6 Kajzrlíková 1.239,280 Kala P. 197 KameyamaT. 164 KatahiraY. 164 KlimeckýP. 100 KlimentM.228,274 Klímová K. 221 Kočiš J. 90 Kontrová 1.46 Kostřica R. 192 Kovářová L. 123 Kubešová B. 69 Kudrman J. 76 Kuchař J. 280 Kukletová M. 108 Kundrátová E. 228 Kunovská M. 225 Kyselová 1.197 Lata J. 225, 262,267 Liberda M. 228 LiuH.164 Lukáš Z. 202 Macháček R. 83 MaňákJ. 202 Masaříková H. 52 MibikiY 164 Mičánková Adamová B. 38 Mišejková M. 271 MunakataM. 164 Nachtigal P. 279 NechvátalováJ.279 Neuwirthová J. 192 NittaS. 164 Novosad P. 274 Novotný 1.249 Novotný M. 100 Novotný T. 192 Ohsawa N. 164 Ošlejšková H.52 PacíkD.69,115 PenkaM. 123 Petra šek J. 228 Plánka L 83 PlatošJ.280 Podhorná B. 76 PohankaM. 69 Pochop J. 100 PoloczekM. 197 Pospěchová K. 279 Pospíšilová N. 279 Pour L 123 Prachař P. 76 Praksová P. 46 Procházka V. 249 Prokešová J.235 Prokopová L 271 Příbramská V. 262 Rottenberg J. 192 Reha P. 280 ŘeháčekV.279 Sagawara S. 164 SaijoY 164 Sato N. 164 SemeckýV. 279 ShibataM. 164 ShirashiY. 164 Schreiber M. 202 Slouková E. 52 SmilekP. 192 SothernR. B. 133 Starý D. 83 Stibůrek 0.225 Strecha J. 76 Sugita N. 164 Ševčíková A. 249 ŠišákováM. 197 Škvařilová H. 279 Šlapák J. 267 ŠmajstrlaV. 228 Šoukalová J. 52 ŠpinarJ. 197 ŠtouračP. 11,46 Štouračová M. 278 Ta ku mi T. 133 Tichá O. 278 Toman 0.197 Trávníčková Z. 278 Trna J. 249 Trumpešová H. 271 Tschoplová S. 11 Tůma J. 83 Urban 0.228, 274 VaněkJ. 76 VargaG. 115 Ventruba P.69 Višňa P. 90 Vít P. 197 Vítek P.239, 280 Vlček M. 90 Vlčková-Moravcová E. 16 Vlková M. 279 Voháňka S. 38 Vondráček P. 27 VorlíčekJ. 123 WatanabeM. 164 YamaguchiT. 164 YamamotoT. 133 YambeT. 164 YoonisE. 108 YoshizawaM. 164 Zbořil V. 271 Zgažarová S. 278 Žákova J. 69 http://www.med.muni.cz/biomedjournal/ SCRIPTA MEDICA /Volume 82/No. 4/ 2009 283 I NEWS AND CURRENT AFFAIRS___________________________ XXVIth Conference of the Czech Society of Hypertension (ČSH), XVIIIth Conference of the Preventive Cardiology Working Group of the Czech Society of Cardiology (ČKS) and XIVth Conference of the Heart Failure Working Group oftheCKS Mikulov, October 1 to 3, 2009 A meeting of Czech physicians specialising in the issues of high blood pressure traditionally took place at the beginning of October in the attractive environment of Mikulov Castle. Information useful for clinical practice was exchanged not only among physicians but also, for the fourth year running, among nurses working in this field. Interest in the diagnosis and treatment of hypertension, one of the most frequent cardiovascular diseases, was also confirmed by the participation of a number of foreign experts. It is becoming clear that attaining target blood pressure values in patients remains a topical medical problem even in the 21a century. The introductory block of lectures was opened by Prof. Miroslav Souček, MD, Ph.D., the chairman of the conference organising committee and Prof. Jiří Widimský Jr., MD, Ph.D., the chairman of the Czech Society of Hypertension (ČHS). The results of the joint KOHYBA study were presented at this venue for the first time. Prof. Václav Monhart MD traditionally dedicated his contribution to the level of control of hypertension in patients with chronic renal disease. The group of authors from IKEM (Institute of Clinical and Experimental Medicine), Prague (Burgelová et al) presented the results of the 5-year follow-up of living kidney donors, whose aim was to determine the incidence of hypertension and eventual end-organ complications in these subjects. According to the authors, kidney donation is safe, despite the incidence of Prof. Jiří Widimský jr.. Prof. Miroslav Souček, MD, Ph.D. MD, Ph.D. Mikulov castle - conference venue hypertension (this was 30% at the beginning of follow-up and 52%attheend of follow-up). Jiří CeralMD drew attention in his lecture Malignant Hypertension in the 21st Century to the fact that even in this age, though it remains a rarity, one may face this most serious form of severe hypertension with end-organ damage in clinical practice. Changes on the eye-ground are considered to be diagnostic in such cases. According to the author, today this entity represents one due to "neglected" hypertension, with patients nearly always being guilty of such neglect. Therapeutic success may be achieved today even in this distinctive form of hypertension with the help of available drugs. In the Hot Lines Block dedicated to the BEAUTIFUL study, Prof. JiříVítovec, MD Ph.D. presented in his lecture the results of the sub-analysis of symptomatic patients. This study involved the first evaluation of the effects of the sole decrease of cardiac frequency using ivabradine on the incidence of cardiovascular events in patients with CAD and left ventricular dysfunction. In the next part of this block of lectures. Prof. Jindřich Špinar, MD Ph.D. presented in detail the ONTARIO I and II studies. Both surveys monitored the long-term clinical state of patients receiving various types of ACE inhibitors (ACEi). The first retrospective survey followed the fate of patients who received ACEi during hospitalisation for myocardial infarction (Ml) or later- within one month of the Ml- as part of secondary pharmacological prevention. The second survey similarly followed the fate of a large number of patients with chronic heart failure treated with various ACEi. In Mikulov, the ČSH also introduced the Czech version of the HeartScore9 program - the electronic and interactive version of the SCORE risk tables created and developed for the Czech Republic on the basis of mortality data from ÚZIS (Institute of Health Information and Statistics of the Czech Republic) and data regarding the basic risk factors of cardiovascular disease 284 SCRIPTA MEDICA/Volume 82/No. 4/2009 http://www.med.muni.cz/biomedjournal/ 2428