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  • 1. Vol. 9, Issue 2, 2004 WORLD GASTROENTEROLOGY NEWS ISSN 1567 7753 Modern Management of Echinococcosis Does the COX-1/COX-2 Concept Still Hold? GI Medicine on the Frontiers: Iran WGO/OMGE-OMED Training Centers PU LL OUT WGO/OMGE Position Statement : Colorectal Cancer Screening and Surveillance Global Guidelines for the 21st Century Official Newsletter of the World Gastroenterology Organisation (OMGE / WGO) and the World Organisation of Digestive Endoscopy (OMED)
  • 2. WGO/OMGE and OMED Supporters of WGN© 2004WGO/OMGE – OMED / Marathon InternationalAll rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner.No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, through negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical science, the Publisher recommends that independent verification of diagnoses and drug dosages should be made.The World Gastroenterology Newsletter is published by Marathon International B.V. in association with WGO/OMGE and OMED. Marathon International.Printed in the Netherlands
  • 3. CONTENTSEDITORIAL BOARD EDITORIAL 5 Message from the Editor-in-Chief — Jerry WayeEDITOR-IN-CHIEF Impact of Screening on Surgery and Early Detection of Gastrointestinal CancerJ.D. Waye (USA) — Alberto MontoriSENIOR EDITORS CONGRESS NEWS 9M. Classen (Germany) A Memorable Experience Awaits You at the WCOG 2005, Montreal!A. Montori (Italy) — Hugh ChaunMANAGING EDITOR SCIENTIFIC NEWS 11B. Barbieri (Germany) Role of Genetic Factors in the Pathogenesis of Alcoholic Liver Disease — J. Petrasek, M. Jirsa, J. Sperl, F. Stickel, D. Schuppan, J. SpicakPUBLISHER Modern Management of Echinococcosis — Hans G. SchipperK. Foley (The Netherlands) Critical Appraisal of Laparoscopic Bile Duct Exploration — Bertrand Millat Does the COX-1/COX-2 Concept Still Hold? — Christopher HawkeyEDITORIAL COMMITTEE Molecular Biology for the Gastroenterologist — Peter FerenciH. D. Allescher (Germany)H. Cohen (Uruguay) GASTROINTESTINAL MEDICINE ON THE FRONTIERS 23G. Costamagna (Italy) Upper Gastrointestinal Cancer in Iran — A. Pourshams, R. MalekzadehM. Crespi (Italy)Angelita Habr-Gama (Brazil) E D U C AT I O N A N D T R A I N I N G 27M.J.G. Farthing (UK) OMGE/OMED Training Centers — Jim ToouliM. Rizzetto (Italy) The European Endoscopy Training Center in Rome — Guido CostamagnaT. Rösch (Germany)Esmat A. Sheba (Egypt) DIGESTIVE CANCER AWARENESS C AM PAIG N 33C. Tzeuton (Cameroon) Digestive Cancer Series: Taxonomy for Neoplastic Lesions of the Digestive MucosaC. Yurdaydin (Turkey) — René LambertQi-lian Zhang (China) International Digestive Cancer Alliance Meeting during Digestive Disease Week 2004 — Sidney J. Winawer, Meinhard Classen, Paul RozenINTERNET SECTION EDITORS OMED Colorectal Cancer Screening Committee — Paul Rozen, Sidney J. WinawerJ. Krabshuis (France) Ten Rules for Cancer Prevention — Attilio Giacosa, Massimo Crespi OA. Grassi (Italy) WGO/OMGE INSIGHT 41INTERNET SITES Treasurer’s Report — J.E. Geenenwww.worldgastroenterology.org Global Guidelines for the 21st Century – Focus on “Evidence” or Focus on “Need”?www.omed.org ASNEMGE–WGO/OMGE European School of Gastroenterology LaunchedEDITORIAL OFFICE ADDRESS OBITUARY 45Medconnect Elbio Zeballos — Henry CohenBruennsteinstrasse 1081541 Munich GASTROENTEROLOGY ON THE INTERNET 47Germany PubMed/Medline: What Every Gastroenterologist Needs to KnowTel.: + 49 89 4141 92 40 — Justus KrabshuisFax: + 49 89 4141 92 45E-mail: Medconnect@medc.de NEWS FROM THE INDUSTRY 51PUBLISHING/ADVERTISINGADDRESSMarathon InternationalWesterdijk 1R1621 LC HoornThe NetherlandsTel.: +31 229 211 980Fax: +31 229 211 241 3
  • 4. EDITORIALMessage from the Editor-in-Chief Jerry WayeThe major European Conference for Gastroenterol- and the OMED cancer screen-ogy, UEGW, is right around the corner. It will be held ing committee continues itsin Prague, Czech Republic from 25 to 29 September, multidisciplinary activities. Our2004. The topics and presentations are outstanding, special insert in this issue isand you will miss out on a great educational opportu- concerned with colorectal can-nity if you do not attend. Start preparing now for the cer screening as a part of thequadrennial meeting of the World Congress of Gastro- Digestive Cancer Awarenessenterology which will be held in Montreal next year Campaign. There is a specialfrom September 10–14, 2005. Be sure to make time in report on mucosal neoplasticyour schedule to include this exceptional international nomenclature.conference. Mark your calendars, make hotel arrange- In this age of informationments, and secure the air flights since thousands of explosion, our resident librar-doctors will flock to this gem of a city in affordable ian presents special pointersCanada to learn, to meet friends, to be updated, to on extracting information fromsocialize, and to have all of the progress in the entire Pub-Med. This issue also inau-field of gastroenterology over the past 4 years detailed gurates a new series of articles on “Gastroenterologyby the world’s leading experts. There will be unprec- on the Frontier”. The first article in this series is fromedented hours of live endoscopy broadcast daily to the Iran, where special problems and cancers are encoun-convention facility. tered. I request anyone who knows of “frontier-style” Since this issue precedes UEGW, we have high- gastroenterology be in touch with WGN so that we maylighted several of the presentations at the combined track down the broad variety of gastroenterology that isEAGE, ISDS, EDS and EAES Postgraduate Course to be being practiced outside of the mainstream of medicine.held on September 25 and 26, 2004. ■ OMGE/WGO and OMED are continuing their inter- Jerome D. Waye, MDnational leadership in all fields of gastroenterology, Clinical Professor of Medicineand especially in training and education. New learn- Mt. Sinai Medical Centering centers are being established and certified. IDCA New York, USAcontinues its focus on worldwide digestive cancers, E-mail: Jdwaye@aol.comThe city of Prague, venue of UEGW 2004. . 5
  • 5. EDITORIAL Message from the Senior Editor Impact on Surgery of Screening and Early Detection of Gastrointestinal Cancer Alberto Montori I n the last two decades, gastroenterologists have be aware of current devel- been focusing their efforts on the screening and early opments in their own and detection of gastrointestinal cancers, with considerable other fields, maintaining their success. Discussions at the meetings of the Combined enthusiasm and commitment Screening Committee of the Organisation Mondiale and fully participating in every d’Endoscopie Digestive (OMED) and the International aspect of patient care. As Digestive Cancer Alliance (IDCA) have been making a teachers, they should prepare valuable contribution to answering the following ques- students for the profession in tions: the best possible way, and as ● Which areas of screening require quality assurance? surgeons they should try to cure patients by prevention ● What methodology should be used? and early detection, as well as by radical intervention ● What further action is required? when necessary. All of this can be achieved with com- ● What impact have the screening campaigns had bined efforts based on a multidisciplinary approach. on surgeons’ performance and on the outcome for I conclude with the old maxim: the competent sur- patients? geon knows how to operate; the good surgeon knows The work of the OMED Screening Committee, chaired when to operate; and the best surgeon knows when by Paul Rozen, in collaboration with the International not to operate. Digestive Cancer Alliance (IDCA) chaired by Meinhard ■ Classen and Sidney Winawer, is sure to be helpful in defining appropriate current indications for oncologic Alberto Montori, M.D., F.A.C.S., OMED Senior Editor surgery. Surgeons today need to be directly involved Chairman and Professor of Surgery, “La Sapienza” University in the screening process, accepting that in the future, Viale Regina Elena 324 their role in decision-making for the patient will extend 00161 Rome, Italy well beyond the operating room. Surgeons need to E-mail: alberto.montori@uniroma1.it Information about advertising World Gastroenterology News is currently distributed twice a year to 48 000 gastroenterologists worldwide. If you would like information about advertising in this publication please contact Marathon International, Westerdijk 1R, 1621 LC Hoorn, The Netherlands, tel.: +31 229 211 980, fax: +31 229 211 241 For information regarding editorial content, please contact Bridget Barbieri at Medconnect, Bruennsteinstrasse 10, 81541 Munich, Germany, Association Management Company tel: +49 89 4141 92 40 or telefax: +49 89 4141 92 45, e-mail: Medconnect@medc.de 7
  • 6. VISIT our stand at UEGW Prague VISIT our stand atto enjoy pancakes and maple syrup to enjoy pancakesA TASTE OF CANADA: A TASTE OF CANADA:OUR UNIQUE MAPLE SYRUP OUR UNIQUE MAPLE SYRUPIn Canadian forests, the maple is considered aavaluable In Canadian forests, the maple is considered valuabletree. ItIt is harvestedfor its hard, resilient wood and, tree. is harvested for its hard, resilient wood and,mainly in Quebec, for its sap from which aa mainly in Quebec, for its sap from whichdelicious syrup is obtained. delicious syrup is obtained.The collection of the sap, followed by its The collection of the sap, followed by itstransformation into syrup by boiling, is aa transformation into syrup by boiling, isvery old custom inherited from native very old custom inherited from nativeIndians who were the first to Indians who were the first torecognize itit asaasource of recognize as source of energy and nutrition. In earlyenergy and nutrition. In early spring, they would piercespring, they would piercethe tree trunk with aa the tree trunk withtomahawk, placing aa tomahawk, placing wood chip under thewood chip under the hole to channelhole to channel the maple waterthe maple waterinto aa bark into bark receptacle.receptacle. SEPTEMBER 10-14, SEPTEMBER 10-14, 2005 Your Your meeting meeting place in 2005 place in 2005
  • 7. CONGRESS NEWSA Memorable Experience Awaits You At the2005 WCOG, Montreal!Hugh Chaun, Co-chair, Press & Congress News Canadian Organizing Committee, 2005 WCOGThe meeting in Montreal 10–14 esis and approaches to treatment; B OW E L D I S E AS E , organized by YaleSeptember, 2005 promises to be I N F EC TIO N AN D T H E G I T R ACT will University, to be held in Stowe, Ver-a milestone in the history of the include a global perspective of the mont, U.S.A.World Congress of Gastroenter- GI complications of AIDS. The meeting will offer an excel-ology. It will embrace a unique The GASTROINTESTINAL SURGICAL lent opportunity to enjoy theprogram that will address the PROGRAM will discuss controversies splendours of MO NT R E AL , a uniqueexpanding horizons of global goals in the management of inflam- North-American city with a richin Gastroenterology in the 21st matory bowel disease, recent European heritage, vibrant, con-century. 2005 WCOG will be an advances in anorectal disorders, temporary, multicultural, safe, easilyevent not to be missed, and Can- oesophageal surgery, surgery for accessible, and most affordable. Itsada eagerly anticipates welcoming obesity, and frontiers of transplan- many restaurants are recognized asall gastroenterologists, hepatolo- tation. some of the best in this continent,gists, pediatric gastroenterologists, You can also attend PO STG R AD U - and September is the ideal monthand gastrointestinal surgeons, ATE COU R S ES of your choice over weather-wise to be in Montreal.pathologists, basic scientists, and the week-end prior to the main Montreal is the home of theGI nurse assistants and research scientific congress. These will O S L E R L I B R ARY , Canada’s nationalassistants world-wide to Montreal. include the AGA Course on E V I - library for the history of medi-Of the many outstanding aspects DEN C E-BAS E D G AST R O E NT E R O L- cine. McGill University was theof the program in Montreal that OGY : Translating the Evidence into alma mater of S I R W I L L I AM O S LERwill enrich your educational and Practice; I NT E R ACT I V E CO U RS E O N (1848–1919), Canada’s most illus-personal experiences, the following U P P ER A N D LOW ER I N T EST I NA L D I S - trious physician, often regarded asare just a few highlights. EASE A N D L I V E R D I S E AS E , organized the greatest physician of the past T H R EE F U L L DAYS OF LIVE by the Sociedad Interamericana century. He wrote more than 1500E N D OSCOPY transmits directly de Endoscopia Digestiva and the papers and books, many on gas-from Toronto and Hong Kong that Interamerican Society of Gastroen- trointestinal disorders. He referredwill demonstrate state-of-the-art terology; E M E R G I NG T ECH NO LO G I ES to DYS P E PS I A as “the besettingtechniques in diagnostic and thera- A N D C U R R E NT P R ACT I CE I N D I G ES - malady”. He postulated that “morepeutic endoscopy by experts from TIVE EN D O SCO PY , presentation en people are killed by over-eatingaround the world. français, organized jointly by the and drinking than by the sword…” The SCI ENT I F IC P R OGR A M which Association de Gastroenterologie Although the sword is history, notwill deliver CU R R EN T EVI DEN C E et d’Endoscopie du Quebec and much has changed in this regard inand CUT T I NG -EDGE R ESEA RC H the Société Française d’Endoscopie the last hundred years!applicable to clinical practice by Digestive; F R O NT I E R S I N M I N I MA L LY As a further invitation to all ourworld-renowned speakers, on all I N VASIVE T H E R AP I ES F O R D I G EST I V E colleagues in every continent toimportant topics of gastroenterol- DISEASES: E V I D E NCE AN D T ECH- come and share an unforgettableogy and hepatology world-wide. N IQ U ES , organized by the Canadian experience in Montreal in Sep-These days will include C A N C ER OF Surgeon Forum; and I NT EST I NAL tember, 2005, it is appropriate toTH E G I T R ACT , its global epidemiol- FA I LU R E, F U NCT I O N F O O D S AN D G I reflect on one of William Osler’sogy, genetic environmental issues; DISEASE AN D H E ALT H , organized sayings – “Medicine is the onlyA B D OM I NAL PAI N , its international by the Canadian Society for Clini- world-wide profession, followingperspective, mechanisms of pain cal Nutrition. In addition, there will everywhere the same methods,generation, and new drug thera- be a post-meeting conference on actuated by the same ambitionspies; H EPATOLOGY , with presenta- CON TROVE R S I ES I N T H E D I AG NO S I S and pursuing the same ends.”tion of new concepts in pathogen- A N D TH E R APY O F I N F L AM MATO RY ■ 9
  • 8. SCIENTIFIC NEWSRole of Genetic Factors in the Pathogenesis ofAlcoholic Liver DiseaseJ. Petrasek, M. Jirsa, J. Sperl, F. Stickel, D. Schuppan, J. SpicakNote: This paper will be presented at large studies, bythe core meeting of the UEGW in Hrubec et al. and Julius SpicakPrague, September 2004. Reed et al., showing that genetic factorsBackground contribute about Excessive alcohol intake leads to 50% of all the riskliver disease, which can range from variables for devel-simple steatosis to steatohepatitis, opment of end-fibrosis, and/or cirrhosis. While organ damage.steatosis develops in most regular The epidemio-drinkers, the vast majority do not logical data havedevelop more severe liver dam- stimulated investi-age; the reasons for this are largely gations based on a Jan Petrasekunknown, but may include both “candidate gene”environmental and genetic factors. strategy to search Earlier data from retrospec- for genes and polymorphisms tively. Chronic ingestion of largertive epidemiological studies are involved in a predisposition to amounts of ethanol induces theconflicting, raising doubts over alcohol-induced liver damage. The microsomal cytochrome P450 2E1the relationship between alcohol projects are based on the prin- (CYP2E1) system, which convertsconsumption and the risk of liver ciple of allelic association studies, ethanol to acetaldehyde. CYP2E1disease. In contrast, recent pro- comparing relative distributions of activity may increase up to 10-fold,spective studies provide evidence genotypes between patients with thereby increasing the amount offor both a threshold effect and a alcoholic liver disease and drinkers toxic acetaldehyde and reactivedose–response relationship, sug- (control individuals) without liver oxygen species. Both ADH andgesting that the minimum alcohol disease. Unfortunately, associations ALDH reduce the beta oxidationquantity that confers a measur- between single gene variants and rate and induce lipid accumula-able risk of developing alcoholic alcohol-induced liver damage need tion. The resulting hepatic steatosiscirrhosis is 30 g ethanol per day to be judged with caution, due to increases the risk of lipid peroxi-and that the cumulative lifetime the polygenic background of alco- dation, which is an independentalcohol intake leading to cirrhosis holic liver disease. risk factor for the developmentis 100 kg of pure ethanol. In addi- of severe forms of alcoholic livertion, men and women who con- Candidate Genes for a disease.sume more than 80 g/d of ethanol Predisposition to Alcoholic Liver Numerous functional polymor-have an equal risk for cirrhosis. Disease phisms in genes encoding ALD,According to these data, less than Genes encoding enzymes ALDH and CYP2E1 have been5% of heavy drinkers develop cir- in ethanol metabolism. Differ- studied. According to in-vitro stud-rhosis, which contrasts with the ences in ethanol metabolism and ies, the presence of the ADH1B*2previously published incidence rate elimination are, in part, genetically and ALD1C*1 allele increases theof 20%. determined. Two major degrada- catalytic activity of alcohol dehy- tion systems catalyze ethanol drogenase, resulting in higherEvidence for a Genetic elimination. Low blood levels of acetaldehyde production, but thesePredisposition to Advanced ethanol are degraded by alco- findings could not be reproducedForms of Alcoholic Liver Disease hol dehydrogenase (ADH) and in subsequent studies. ALDH2*2 The most compelling evidence subsequently by aldehyde dehy- polymorphism, present in 50% offor a genetic predisposition to alco- drogenase (ALDH), producing the Asian population, reduces theholic liver disease comes from two acetaldehyde and acetate, respec- rate of acetaldehyde breakdown 11
  • 9. SCIENTIFIC NEWS by aldehyde dehydrogenase and experimental studies, polymor- functional differences that could elevates the serum level of acetal- phisms within the TGF-E gene possibly lead to biological effects. dehyde, causing flushing, tremor, could have an impact on TGF-E However, so far, most of the poly- and sweating and thus discourag- expression and thus influence morphisms tested have not been ing individuals from further alcohol the risk of alcoholic liver disease. shown to have any significance in drinking. However, no association with liver human studies. Genes affecting endotoxin- fibrosis has been proved in alco- Future studies should aim derived inflammation in alco- holic liver disease. to identify a panel of candidate holic liver disease. According to genetic variations. Identifying both in-vitro and in-vivo studies, Conclusions and Perspectives these would make it possible to it is postulated that ethanol acti- In summary, genetic factors clarify the pathogenic pathways of vates Kupffer cells by promoting may explain the broad spectrum of chronic liver disease and contribute leakage of bacterial lipopolysac- interindividual responses to chronic to new approaches to prevention charide (endotoxin) from the ethanol exposure. In the previous and treatment strategies. intestine into the portal circulation. 15 years, it has been suggested ■ Activated Kupffer cells produce that numerous candidate genes Corresponding Author large amounts of tumor necrosis and polymorphisms may act as Professor Julius Spicák factor-alpha (TNF-D) and other genetic factors capable of predis- Clinic of Hepatogastroenterology proinflammatory cytokines such posing ethanol-exposed individu- Institute of Clinical & Experimental Medicine as interleukin-1 (IL-1) and IL-6. als to chronic forms of alcoholic Vídenská 1958/9 Key organelles in inducing hepa- liver disease. In-vitro studies of the 14021 Praha 4 Krc tocyte necrosis and apoptosis are candidate genes proved that some Czech Republic the mitochondria. Chronic ethanol of these polymorphisms involve E-mail: julius.spicak@medicon.cz exposure promotes mitochondrial oxidative stress, decreases adenos- ine triphosphate (ATP) synthesis, and initiates apoptosis. Numer- Modern Management ous allelic variants of the TNF-D gene have a direct impact on of Echinococcosis TNF-D expression and on the tis- Hans G. Schipper sue concentration of TNF-D. Single nucleotide polymorphisms at posi- tions -308, -238 result in increased Introduction multilocularis TNF-D synthesis, while polymor- Echinococcosis is a zoonotic occurs in phism -863 decreases TNF-D gene infection transmitted by dogs in fewer areas. expression. Despite the importance livestock-raising areas that inciden- Echinococcus of these experimentally proved tally affects humans. Worldwide, multilocularis findings, none of these polymor- infection with the larval stage of causes a slowly phisms convincingly influence the the dog tapeworm Echinococcus progressive liver necrosis that risk of alcoholic liver disease. granulosus is the one that occurs tends to metastasize and behave Genes involved in hepatic most frequently. This relatively like a malignant disease. Colder fibrogenesis. Activation of stellate benign parasitic disease is char- climates and mountain and forest cells is the crucial event initiating acterized by slowly growing cysts, areas inhabited by foxes are the hepatic fibrogenesis. Activation of most commonly in the liver and primary risk areas for acquiring these cells is induced by several less frequently in lungs and rarely alveolar echinococcosis. Infection mechanisms, the most important elsewhere in the body. Develop- with Echinococcus vogeli (the jag- being transforming growth factor- ing countries with poor hygiene in uar tapeworm) and Echinococcus beta (TGF-E), which is secreted by which sheep and cattle are raised oligarthrus (the puma tapeworm) numerous cell types. Activated stel- are high-risk areas for acquiring is rare and occurs only in South late cells transform into contractile cystic echinococcosis. America. myofibroblasts, which synthesize Infection with the larvae of This paper will focus on cystic excess collagen. According to the fox tapeworm Echinococcus echinococcosis of the liver, the 12
  • 10. SCIENTIFIC NEWSmost relevant type of echinococco-sis in the world.Pathogenesis and Etiology Dogs are the definitive hostof Echinococcus granulosusand harbor the tapeworm inthe small intestine. Sheep andcattle are intermediate hostsand become feco-orally infectedby Echinococcus eggs shed intothe environment in the feces ofinfected dogs. Echinococcus eggshatch in the intestinal mucosa ofthe intermediate host and trans-form into oncospheres, whichpenetrate the bowel wall. Viathe portal circulation, the liver isreached, in which slowly expand-ing cysts develop. The intermediatehost responds to the presence ofthe parasitic cyst by surroundingit with fibrous tissue. This com- Figure 1. Ultrasound showing a univesicular cyst with a “double membrane” and oneplex of parasitic cyst plus fibrous daughter cyst.capsule is called an Echinococcuscyst or hydatid cyst. The parasite’s tralia, New Zealand, and northern ing bile ducts, especially whenlife-cycle is closed when dogs are Europe. endoscopic retrograde cholangio-infected by viable cyst-containing pancreatography (ERCP) has beenorgans from slaughtered livestock. Diagnosis performed. Rupture into the biliaryIn the intestine of the dog, proto- The diagnosis is based on (1) tree typically occurs in larger cystsscoleces develop into adult tape- history and geography; (2) imag- containing multiple daughter cysts.worms. ing; and (3) serology. Parasitology Less threatening complications are Humans are dead-end of cystic contents confirms the related to the mass effect of thehosts who become infected by diagnosis. Most cysts occur in the cyst, and include compression ofEchinococcus eggs feco-orally. liver (52–77%), and they are found the bile ducts and portal or hepaticChildren playing with infected dogs less frequently in the lungs (8.5– veins. This may result in obstructivemay become infected early in life. 44%) or elsewhere in the body jaundice, postobstructive cholangi- (15–19%). tis, and impaired blood flow in theEpidemiology portal and hepatic veins. Treatment Echinococcosis is prevalent Complications is primarily directed at resolvingthroughout the world. High preva- Anaphylactic shock, cyst infec- the mass effect, by percutaneouslence rates are found in parts of tion, and rupture into the biliary tree or surgical intervention.southern and eastern Europe, the are the most severe complications.former USSR, Middle East, northern Anaphylactic shock due to Imagingand eastern Africa, north-western spontaneous or traumatic cyst Ultrasonography is the pre-Kenya (Turkana), southern Sudan, rupture, or during surgery, is a rare ferred diagnostic tool for hepaticEthiopia, Eritrea, north-western and and severe complication. Seeding hydatid cysts. It is easily available,eastern China, and South America. of cyst contents into the perito- cost-effective, and is used to clas-Sporadic infections occur in North neal cavity is a serious secondary sify cysts and assess their viabilityAmerica, the south-western United complication of cyst rupture. Cysts (Figure 1).States, Central America, northern may become infected following Computed tomography (CT) isSouth America, South Africa, Aus- bacteremia or via communicat- usually the next step after an ultra- 13
  • 11. SCIENTIFIC NEWS sound diagnosis has been made. age of anteriorly located cysts has Which treatment is best? The main purpose is to visualize been introduced as a new surgical Compared with surgery, PAIR plus the relation between the hydatid technique. This technique is limited chemotherapy is associated with cyst and the surrounding liver tis- to laparoscopically accessible cysts, greater clinical and parasitologic sue, bile ducts, and portal and mainly those located anteriorly in efficacy; lower rates of morbidity, hepatic veins, and to identify its the liver. mortality, and disease recurrence; segmental location. Medical treatment. Benzimid- and shorter hospital stays. azole carbamates (mebendazole Serology and albendazole) are anthelmin- Conclusion Enzyme-linked immunosorbent thic drugs that kill the parasite Modern management of echi- assay (ELISA) is used as a screen- by impairing its glucose uptake. nococcosis requires the availability ing test and immunoelectrophore- Albendazole is the drug of choice, of all three treatment options sis as a confirmation test. Serology due to its better absorption and – medical treatment, percutane- may be negative in 10–15% of better clinical results. Continu- ous treatment, and surgery. Surgery cases, especially in well encapsu- ous daily treatment for a 3-month is no longer the treatment of first lated cysts and pulmonary cysts. period is usually prescribed, with choice for hepatic echinococcosis. a 74% success rate; relapses may In patients with univesicular cysts, Treatment be seen in 25% of patients, usually albendazole monotherapy is the The ultimate goal of treatment within 2 years of treatment. first choice. PAIR is indicated when is to eliminate the germinal layer, In clinical practice, albenda- pain is intractable or albendazole although the hydatid cyst itself and zole should be administered at a fails. Percutaneous treatment with its mass effect on the surrounding dosage of 10 mg/kg, twice daily, a combination of alcohol and poli- liver tissue are the eye-catchers. combined with a meal (breakfast docanol may be used, but not in Currently, three treatment options and dinner) and preferably not cases associated with cystobiliary are available: (1) surgery; (2) co-administered with drugs that fistulas. Surgery is the first choice medical treatment; and (3) percu- reduce gastric acidity. only when: (1) expertise in percu- taneous treatment. Since the early Percutaneous treatment. In taneous treatment is not available; 1990s, a new method of percuta- PAIR, the cyst is punctured under (2) percutaneous treatment can- neous intervention has been used ultrasound guidance; the cyst fluid not be safely undertaken; and (3) to treat uncomplicated hydatid is subtotally aspirated; 95% alco- significant extrahepatic extension cysts with drainable contents. The hol or hypertonic saline is injected; of the cyst is associated with a high technique is known as puncture– and scolecidal agents are reaspi- risk of perforation or precludes aspiration–injection–reaspiration rated after 10 min. After intracystic adequate percutaneous treatment; (PAIR). PAIR-derived techniques injection of scolecidal agents, and (4) in case of a rupture into were later also introduced to treat both the germinal layer and the the peritoneal cavity. complicated hydatid cysts and cysts protoscoleces become instanta- ■ containing nondrainable material. neously nonviable. Success with Surgery. The core principles PAIR is defined as detachment of Hans Gijsbert Schipper, MD of hydatid surgery are firstly, total the endocyst, rupture of daughter Dept. of Internal Medicine, Division of Infectious Diseases, removing all infectious parts of a cysts, and no evidence of viable Tropical Medicine and AIDS, cyst; and secondly, avoiding intra- proto-scoleces on microscopy of Academic Medical Center, abdominal spillage of the cyst the cyst fluid. Meibergdreef 9, contents. Radical surgical resection New developments. A sim- 1105 AZ Amsterdam, (liver resection, pericystectomy, plified method of PAIR using a The Netherlands E-mail: h.g.schipper@amc.uva.nl and cystectomy) is the best way of mixture of 95% alcohol and 1% preventing intra-abdominal spill- polidocanol (lauromacrogol 400, Note: This paper will be presented at age. The hydatid cyst is entirely aethoxysclerol) has also proved to the EAGE Postgraduate Course during removed and opening the hydatid be safe and effective. Polidocanol the forthcoming UEGW in Prague, cyst is avoided. Complication and was chosen as the sclerosing agent September 2004. The full-length version including refer- recurrence rates are low. to destroy the germinal layer of the ences is available in the online version Recent developments. Laparo- cyst and to enhance the sclerosing of World Gastroenterology News scopic (peri-)cystectomy or drain- effect of alcohol. (www.worldgastroenterology.org). 14
  • 12. SCIENTIFIC NEWSCritical Appraisal ofLaparoscopic Bile Duct Exploration Bertrand MillatLaparoscopic exploration of the was unsuccessful in 27 patients and enormouscommon bile duct (CBD) is carried (19.6%), most often because of costs of bile ductout for the diagnosis or the treat- failure to intubate the cystic duct. injuries have toment of CBD stones. CBD stones Unsuspected cystic or CBD stones be taken intodemonstrated by laparoscopic were diagnosed by IOC in three of account whenintraoperative cholangiography 138 patients. evaluating the cost-effectiveness(IOC) or laparoscopic ultrasonog- Cystic duct cholangiography of IOC. The rate of bile duct inju-raphy (LUS) are extracted either is clearly better than cholecysto- ries associated with laparoscopicthrough the cystic duct or through cholangiography, and fluoroscopic cholecystectomy is approximatelycholedochotomy. An alternative imaging should be the standard for 0.6%, and this can be reduced withfor the treatment of CBD stones is IOC. Until now, no specific clinically IOC. In all cases associated with anto perform an endoscopic sphinc- significant complications directly increased risk of CBD injury, andterotomy either before, during, or attributable to laparoscopic IOC particularly during a physician’s firstafter laparoscopic cholecystectomy. have been reported. Expected suc- 20–30 cases of laparoscopic cho-The aim of this review is to evalu- cess rates for laparoscopic IOC are lecystectomy, IOC should be man-ate these different techniques. in the range of 90–100%. Inability datory. Ability to perform an IOC, to cannulate a narrow cystic duct not just removing the gallbladder,Intraoperative Cholangiography is the main cause of failure. The should be one of the requirements(IOC) success rate is higher in a group for adequate training in laparo- Two prospective randomized with selective indications for IOC scopic biliary surgery.studies have assessed the value in comparison with a group with-of routine IOC during laparoscopic out such indications – 98% versus Laparoscopic Ultrasonographycholecystectomy. In the first pro- 93%, respectively. (LUS)spective trial, by Soper and Dun- In addition to screening for Several studies of LUS havenigan [1], relevant information was potential asymptomatic CBD been published suggesting thatobtained in eight of 56 patients, stones, the second important attri- LUS is superior to IOC. LUS is per-and it altered the intraoperative bute of IOC is that it provides ade- formed with a higher success rate,management in four. In the sec- quate definition of the ductal anat- in a shorter time, and with betterond trial, by Nies et al. [2], IOC omy. The disastrous consequences specificity, but with less precision with regard to the delineation of the biliary tree anatomy. LUS isTable 1. Criteria for routine intraoperative cholangiography of little, if any, help in diagnosing Preoperative factors or preventing bile duct injuries, Endoscopic retrograde cholangiography ± sphincterotomy whereas IOC is better than LUS for Ultrasound findings delineating the entire biliary tree, from the intrahepatic tree to the Common bile duct size over 6 mm pancreatic portion of the CBD. Choledocholithiasis LUS is operator-dependent, and History of jaundice or pancreatitis there is evidently a learning curve Elevated bilirubin, alkaline phosphatase, transaminases – 20–40 examinations, which may Intraoperative factors be difficult to obtain in small-vol- Unclear anatomy ume centers in which the 10% prevalence of CBD stones means Conversion to open cholecystectomy that the learning curve may take Dilated cystic duct over 4 mm 1–2 years to complete. 15
  • 13. SCIENTIFIC NEWS Laparoscopic Extraction of Data gathered from randomized during laparoscopy. In other cases, Common Bile Duct Stones trials have demonstrated that ES, the available data do not allow any Once stones have been as an additional procedure to sur- formal conclusions regarding the detected during laparoscopic IOC, gery, does not improve the clinical choice between advanced laparo- laparoscopic extraction of them results in patients who are fit for scopic biliary explorations and post- is a logical extension of the pro- primary single-stage surgical treat- operative ES. In a decision analysis cedure. Laparoscopic exploration ment, whether performed laparo- by Erickson and Carlson [3], assess- of the CBD can be performed scopically or not. Severe cholangitis ing different approaches to using either through the cystic duct or by is an unquestionable indication endoscopic retrograde cholangiog- laparoscopic choledochotomy, and for urgent endoscopic drainage, raphy (ERC) in patients undergo- both procedures are feasible and regardless of whether or not the ing laparoscopic cholecystectomy, safe. Endoscopic sphincterotomy CBD can be cleared of associated postoperative ERC was associated (ES) is commonly offered preop- stones. with lower costs and less morbid- eratively as the alternative to sur- All surgeons undertaking lapa- ity, but laparoscopic CBD explora- gery for CBD stones. ES is indicated roscopic cholecystectomy must tion was not included in the study in patients with severe cholangitis be able to perform an IOC. When design. Finally before embarking on for urgent drainage of infected IOC demonstrates CBD stones, a more invasive laparoscopic CBD bile, and in patients with retained appropriate treatment is decided exploration policy for small stones stones after cholecystectomy. In on according to the available equip- that cannot be retrieved using the open conventional surgery, con- ment and skills. Transcystic clear- transcystic approach, surgeons trolled studies have not shown that ance of CBD stones may be suc- must remember that asymptom- ES, performed either prior to sur- cessful. In the case of large stones atic migration does exist, even if gery or in patients with gallbladder (more than 20 mm in diameter) the definitive fate of small CBD in situ, was superior to single-step or other potential difficulties as stones is not at present known. surgical management. The conclu- regards postoperative ES, such as a The potential safety afforded by sions reached in these randomized periampullary diverticulum, conver- temporary biliary drainage still has trials have not been extrapolated to sion to open surgery is indicated to be balanced with its unavoidable laparoscopic biliary surgery. when the stone cannot be removed morbidity. Does the COX-1/COX-2 Concept Still Hold? Christopher Hawkey R ecognition erosions that ultimately deepen to The COX-1/COX-2 hypothesis that nonsteroi- become ulcers as a consequence was that drugs that inhibit COX-2 dal anti-inflam- of acid peptic attack. Subsequently, would have the same therapeutic matory drugs it has become clear that prosta- activity as NSAIDs, but without (NSAIDs) were glandin synthesis derives from two their adverse effects. inhibitors of distinct but similar cyclooxygenase prostaglandin enzymes. The constitutive cyclo- Therapeutic Activity synthesis was oxygenase – cyclooxygenase-1 Numerous clinical trials have critical to understanding both their (COX-1) – is expressed in many tis- shown that COX-2 inhibitors relieve therapeutic activity and gastroin- sues, including the gastrointestinal pain and inflammation in arthritis testinal pathology. In the stomach tract. The inducible cyclooxygen- in a dose-dependent fashion, with and duodenum, inhibition of pros- ase – cyclooxygenase-2 (COX-2) maximum effects that are usu- taglandin synthesis undermines –becomes highly expressed under ally not significantly different from defensive mechanisms such as the influence of many factors such those of NSAIDs. Thus, although mucosal blood flow and mucus as cytokines and growth factors some have suggested – contrary and bicarbonate secretion, and in tissue injury, inflammation, and to the COX-1/COX-2 hypothesis leads to the development of micro- malignant transformation. – that COX-1 may contribute to 16
  • 14. SCIENTIFIC NEWSReferences but not all, studies, the levels of Cancer[1] Soper NJ, Dunnegan DL. Routine ulceration have been similar to Since COX-2 is induced in gastro- versus selective intra-operative chol- those observed with a placebo. intestinal cancers, a development angiography during laparoscopic In outcome studies, the incidence of the COX-1/COX-2 hypothesis cholecystectomy. World J Surg 1992; 16: 1133–40. of clinically significant ulcers or predicts that COX-2 inhibitors may[2] Nies C, Bauknecht F, Groth C, et al. ulcer complications is reduced in prevent or reverse gastrointestinal Intraoperative Cholangiographie als comparison with NSAIDs. In most malignancy without harmful effects Routinemethod? Eine prospektive, studies, the reduction has been on normal mucosa. This has been kontrollierte, randomisierte Studie. Chirurg 1997; 68: 892–7. between 50% and 60% rather shown in animal studies and in[3] Erickson RA, Carlson B. The role of than the 75–85% that might be genetic models in humans. How- endoscopic retrograde cholangio- inferred from the fourfold to five- ever, aspirin is also effective, but is pancreatography in patients with fold increase in ulcer complications a COX-1 inhibitor. Understanding laparoscopic cholecystectomies. Gas- caused by NSAIDs. the way in which aspirin prevents troenterology 1995; 109: 252–63. ■ or reverses premalignant and Dyspepsia malignant processes in the gastro-Bertrand Millat, MD The original COX-1/COX-2 intestinal tract will contribute to ourDept. of Visceral Surgery, hypothesis did not relate to dys- understanding of oncogenesis.Saint Eloi University Hospital, pepsia. Nevertheless, high levels80, avenue Augustin Fliche,34295 Montpellier cedex 5, of dyspepsia with NSAIDs are suf- Practical PrescribingFrance ficiently general that this may be a The COX-1/COX-2 hypothesisE-mail: b-millat@chu-montpellier.fr class-based (and therefore mecha- does not discount the influence nism-based) effect. This argument of additional factors, and in fact SCIENTIFIC NEWSNote: This paper will be presented atthe EAGE Postgraduate Course during is reinforced by data from COX-2 acknowledges that NSAID ulcersthe forthcoming UEGW in Prague, inhibitors, which quite consistently have prostaglandin-dependentSeptember 2004. appear to be associated with levels and acid peptic-dependent com-The full-length version including refer- of dyspepsia that are greater than ponents. This would lead one toences is available in the online versionof World Gastroenterology News those with a placebo but lower hypothesize that acid suppression(www.worldgastroenterology.org). than those with NSAIDs. and COX-2 inhibitor substitution might be complementary strategies Thrombotic Events in preventing ulcer disease. Recent When patients present with data show that acid suppression NSAID-associated ulcer bleed- very effectively reduces ulcer devel- ing, it may be because the NSAID opment and dyspepsia in patients causes ulcer formation or impairs receiving COX-2 inhibitors who are hemostasis, leading to bleeding. at high risk of these two gastroin-symptoms in arthritis, this effect Equally, since vascular prostacyclin testinal problems.does not appear to be sufficiently is recognized to be largely derived ■great to have a measurable clinical from the COX-2 enzyme, it is pos- Professor C.J. Hawkeyimpact. sible that COX-2 inhibitors could Division of Gastroenterology induce thrombosis. This issue came University HospitalToxicity of COX-2 Inhibitors and to a head in the Vioxx Gastrointes- School of Medical and SurgicalNSAIDs tinal Outcomes Research (VIGOR) Sciences NG7 2UH Nottingham Remarkably, acute studies have study, in which patients receiving United Kingdomshown that even at very high naproxen were reported to have E-mail: cj.hawkey@nottingham.ac.ukdoses (up to ten times the thera- fewer thrombotic cardiovascularpeutic dosage), COX-2 inhibitors events than those receiving rofe- Note: This paper will be presented at the EAGE Postgraduate Course during thecause no demonstrable muco- coxib. This could be attributed forthcoming UEGW in Prague, Septembersal injury in healthy volunteers. either to a harmful effect of rofe- 2004.Medium-term endoscopy stud- coxib or of naproxen. Recent data The full-length version including refer-ies in patients show substantial suggest that the latter is the domi- ences is available in the online version ofreductions in ulceration in com- nant factor, although the former World Gastroenterology Newsparison with NSAIDs. In some, may not be absent. (www.worldgastroenterology.org). 17
  • 15. for your precious momentsdetails are everything Gastroscopes Duodenoscopes Colonoscopes Enteroscopes Sigmoidoscopes Zoom Colono- and Gastroscopes Ultrasound-Endoscopes Intubation-Endoscopes Bronchoscopes Naso-Pharyngo-Laryngoscopes Cystoscopes UreteroscopesMany consider the new Pentax 70K/80K series to be the best video system Choledocho-Nephroscopesavailable. Superior and patented hygiene features, enlarged instrument chan-nels and our world class Digital Signal Processing (DSP) technology are justsome of the reasons why. Contact Pentax for a new perspective on your next Cholangio-Pancreaticoscopesendoscopic procedure: Telephone + 49 - 40 - 5 61 92 · 0; Fax +49-40-5604213;E-mail: medical@pentax.de or Internet: www.pentax-endoscopy.com Autofluorescence-Bronchoscopy Cholangio-Pancreaticoscopes Autofluorescence-Bronchoscopy
  • 16. SCIENTIFIC NEWS Molecular Biology for the Gastroenterologist Peter Ferenci An increasing number of diseases a result of a mutation, molecular forms of a gene of the digestive organs are being genetics describes variations in or a genetic recognized as having a genetic the base sequence of the genes. marker are background (Table 1). The era of These changes are not always referred to as genetics began with the obser- associated with impaired func- alleles. In other vations by Gregor Mendel that tions of the gene product, and do instances, allelic changes in the color of flowers and not necessarily imply the presence variants may reflect mutations in the shape of their seeds followed of phenotypic disease. It is these a gene that clearly alter its function. a clear pattern over the years. The fundamental differences from phe- What is a mutation? A muta- fundamental rules of inheritance notype-based genetics that define tion is a base sequence that differs that he established were thus the role of molecular genetics in from the wild type in a patient based on easily recognizable signs. clinical medicine. who presents with a phenotypic His work preceded the discovery disorder. The sequence is never that DNA is the carrier of genetic Definitions observed in healthy individuals. information. A few basic definitions are The functional consequences An observed trait is referred to needed to clarify the implications of a mutation are manifold. Muta- as a phenotype; the genetic infor- of molecular genetics. tions can be broadly classified as mation defining the phenotype is What constitutes a normal either gain-of-function mutations called the genotype. As advances gene? A normal gene is defined by or loss-of-function mutations. were made in understanding the the base sequence that is observed Gain-of-function mutations are functioning of DNA, phenotypic in the majority of healthy individu- typically dominant. Inactivating genetics was replaced by molecu- als in a given population, and it mutations are usually recessive, lar genetics. In contrast to phe- is known as the wild type. Base and an affected individual is homo- notypic genetics, which assumes variations in the wild-type gene in zygous or compound heterozygous that gene products are either fully healthy individuals are termed DNA (i.e., carrying two different mutant functional or devoid of function as polymorphisms. These alternative alleles) for the disease-causing mutations. Mutations may result in the complete absence of geneTable 1. Selected genetic diseases in gastroenterology and hepatology. products (“null” mutations), or in proteins devoid of any function. Diseases Gene symbol Cholestatic liver diseases Such mutations are associated with Byler disease, Summerskill–Walshe syndrome FIC1 (now ATP8B1) severe diseases occurring at birth or Progressive familial intrahepatic cholestasis 2 ABCB11 in early childhood. Other mutations Progressive familial intrahepatic cholestasis -3 ABCB4 result in less pronounced functional Dubin–Johnson syndrome ABCB2 (now TAP1) consequences and milder disease Hepatic storage diseases that presents later in life. A change Wilson’s disease ATP7B in a single amino acid may affect Hemochromatosis HFE the tertiary structure, the assembly, Colon cancer inactivation, secretion, or conforma- Familial polyposis coli APC tional stability of the gene product. Hereditary nonpolyposis colon cancer MSH2, MLH1 Peutz–Jeghers syndrome STK11 Tools for Molecular-Genetic Idiopathic pancreatitis Analysis Cystic fibrosis CFTR Molecular genetics requires Hereditary pancreatitis Trypsinogen, SPINK the visualization of differences in Crohn’s disease NOD2 (now CARD15) the DNA sequence. DNA polymor- 19
  • 17. SCIENTIFIC NEWS phisms in coding regions (exons) or variable number of times (known mutations. The simplest approach noncoding regions of the genes are as tandem-repeat sequences or takes advantage of the base- inherited in accordance with the microsatellites). sequence specificity of restriction Mendelian rules. The value of highly There are several methods of endonucleases. A mutation will variable DNA sequences as genetic assessing variations in the DNA prevent the enzyme from cutting markers rests on straightforward sequence. Restriction fragment at that point in the sequence; principles. Every person carries two length polymorphism (RFLP) conversely, a mutation may result copies of each chromosome, except analysis detects variations in the in the creation of a new enzyme- for the sex chromosomes. To be size of DNA fragments obtained recognition site and lead to cutting useful for analyzing the transmis- after digestion with restriction where it normally should not occur. sion of the two chromosomes in a enzymes. The pattern of digestion is indica- family, the DNA copies at the poly- Direct mutation analysis. tive of the presence or absence of morphic site in the person under Direct sequencing. New technolo- a particular mutation. The specific- study have be different in the two gies allow automated sequence ity of the PCR reaction itself allows chromosomes. The chromosomal analysis of large portions of a gene direct detection of mutations. sites at which the DNA sequences to detect point mutations, dele- can have many alternative forms tions, inversions, and other changes Interpretation of Test Results are thus ideal sites for genetic in the nucleotide sequence. How- Molecular-genetic analysis can markers. In the human genome, ever, direct sequencing of the yield three possible findings: the the sites that have the properties whole sequence does not yet play a individual being tested can be a most favorable for such extensive role in clinical medicine. homozygous carrier of the muta- variation include a repetition of Polymerase chain reaction tion, a heterozygous carrier of it, or the same short DNA sequence a (PCR)-based detection of known does not carry the mutation at all. Journal Publishing Partners Blackwell Publishing is proud to sponsor The American Journal of Gastroenterology Lecture The use of Anesthesia in Endoscopy- A Critical Examination Attend the debate on November 1, 2004 from 2:40 to 3:20 p.m. at the 69th Annual Scientific Meeting of the American College of Gastroenterology in Orlando, Florida To register for the annual meeting, visit www.acg.gi.orgAs the world’s largest independent society publisher, Blackwellpublishes over 700 journals with more than 550 academic andprofessional societies. We partner with leading societies to advanceknowledge in Gastroenterology, Hepatology and Endoscopy. BOOKS: JOURNALS: Phone: 1-800-216-2522 • Fax: 802-864-7626 Phone: 1-800-835-6770 • Fax: 781-388-8232 e-mail: books@bos.blackwellpublishing.com e-mail: subscrip@bos.blackwellpublishing.com 20 www.blackwellgastroenterology.com
  • 18. SCIENTIFIC NEWS Homozygous mutation carrier. affected cells. This loss of heterozy- that limit the use of genetic testsGenotypic diagnosis in a healthy gosity is assumed to be an impor- for population screening. Firstly,individual raises the question of tant event in carcinogenesis. screening is only appropriate if awhether person being tested will Individuals not carrying the validated treatment is availableever develop the disease. In most mutation. A negative finding does for asymptomatic individuals.hereditary diseases, the penetrance not exclude phenotypic disease, Secondly, other screening strate-of a disease is not complete. since other mutations of the gene gies may be more cost-effective Heterozygous mutation car- may be present. In addition, gene or straightforward than mutationrier. Compound heterozygotes defects may be due to mutation of analysis. For colorectal screening,carry two different disease-causing other genes. DNA-based mutation analysis isgenes. In most inherited diseases, not capable of replacing endos-multiple different mutations of the Target Populations for Molecular- copy, as a colonoscopy examina-affected gene are present (more Genetic Testing tion is needed whether or not athan 800 in cystic fibrosis, for Patients with symptomatic mutation is present. In addition,example). The problem is to dif- phenotypic disease. In patients the development of cancer can beferentiate a “true” heterozygote with hereditary diseases, DNA prevented by endoscopic polypec-(carrying a wild-type allele) from a analysis strengthens the final diag- tomy. Endoscopy combined withcompound heterozygote. The most nosis. In diseases that have only a testing for fecal occult blood willimportant question is whether few mutations (such as HFE-asso- therefore continue to be the stan-the individual being tested is (and ciated hemochromatosis), muta- dard approach for the foreseeablewill remain) free of a disease or tion analysis can replace invasive future.not. According to Mendelian rules, diagnostic tests. In patients with a Disease association studies.individuals carrying a wild-type and transferrin saturation index > 45%, The rapid growth of human genet-a disease-causing gene with auto- testing for common HFE mutations ics is creating countless opportuni-somal-recessive inheritance (true allows a direct diagnosis of heredi- ties for studies of disease associa-heterozygotes) are healthy. This tary hemochromatosis. tion. Given the number of poten-statement is only valid if the other Mutation analysis is important tially identifiable genetic markersgene not carrying the mutation is for differentiating between various and the multitude of clinicalalso functionally intact. The gene genetic diseases with similar phe- outcomes to which these may bethat does not have an established notypic symptoms, as in patients linked, the testing and validationmutation may have a different (dis- with primary findings of iron over- of statistical hypotheses in geneticease-causing) one. Unfortunately, loading. At least four independent epidemiology is a challenge on anthis is not an exception, but a gen- genetic diseases are now known to unprecedented scale.eral rule. result in the accumulation of iron ■ Haploinsufficiency. Mutation in in various organs.a single allele can result in a situa- Family screening. Mutation Prof. Peter Ferenci, M.D. Dept. of Internal Medicine IV,tion in which one normal allele is analysis is the state-of-the-art Gastroenterology and Hepatology,not sufficient for a normal pheno- approach for screening the family University of Vienna Generaltype. This phenomenon applies, for of index patients and can replace Hospital,example, to the expression of rate- other diagnostic tests to identify Waehringer Guertel 18–20,limiting enzymes in heme synthesis individuals at risk of developing the A-1090 Vienna, Austriathat cause the porphyrias. Mutation disease. A negative test result in a Tel. +43-1-40400-4741,in a single allele can also result in relative of a patient with a disease- fax +43-1-40400-4735loss of function due to a dominant- related mutation indicates a low E-mail: peter.ferenci@akh-wien.ac.atnegative effect. risk of the disease. Loss of heterozygosity. Individu- Population screening. Muta- Note: This paper will be presented at the EAGE Postgraduate Course during theals with a normal and an abnormal tion analysis has not yet been forthcoming UEGW in Prague, Septembergene without any apparent disease tested for detecting presymptom- 2004.may undergo somatic mutations of atic disease in the general popula- The full-length version including refer-the normal gene later in life. Such tion. Apart from the difficulties in ences is available in the online version ofevents may result in overt dysfunc- interpreting test results mentioned, World Gastroenterology Newstion of the gene product in the there are also several factors (www.worldgastroenterology.org). 21
  • 19. Absolute control. The new double-balloon method for examining the entire small intestine. A leap forward — the new double-balloon endoscope allows endoscopy of the entire small intestine to be performed for the first time with all diagnostic and therapeutic resources. Examine the whole area without surgery, and with optimum image quality and maximum comfort — for both doctor and patient. Fujinon. To see more is to know more.www.fujinon.de Medical TV CCTV Machine Vision Binoculars FUJINON (EUROPE) GMBH, HALSKESTRASSE 4, 47877 WILLICH, GERMANY TEL.: +49 (0) 21 54/9 24-0, FAX: +49 (0) 21 54/9 24-2 90, www.fujinon.de FUJI PHOTO OPTICAL CO. LTD., 1-324 UETAKE, KITAKU, SAITAMA-CITY, SAITAMA 331-9624, JAPAN TEL.: +81 (0) 48/6 68/21 52, FAX: +81 (0) 48/6 51/85 17, www.fujinon.co.jp
  • 20. GASTROINTESTINAL MEDICINE ON THE FRONTIERS Upper Gastrointestinal Cancer in Iran A. Pourshams, R. Malekzadeh Background After cardiovascular disease and accidents, cancer is the third most frequent cause of death in Iran, with its population of 69 million. Iran is bounded by the Persian Gulf in the south and Turkey and Iraq on the west. The Caspian Sea, Armenia and Turkmenistan lie on the northern border, and on the east are Afghani- stan and Pakistan (Figure 1). There are major regional varia- tions within Iran in the incidence of different types of cancer, related to differences in ethnicity, lifestyle, environment, climate, and living conditions. Because of the high risk of esophageal and gastric cancer in A. Pourshams (right) and J.D. Waye (Editor-in-Chief WGN). northern Iran, several studies have been carried out to evaluate the part of the area. About 40% of Ira- is Turkish and also speaks Farsi, the population at risk. nians are Turks who have both the official Iranian language, in addi- Carrying out research in the power and resources needed for tion to their mother tongue. western part of the Caspian Sea development (large cities, multiple Acceptance of medical research area is much easier than in the universities and businesses). There among the general population has east. The people who live in the was no problem in finding physi- always been high in Ardabil. In western part are ethnically Turkish, cians and paramedical personnel 1968, the first cancer registry pro- and are more educated and better to work for the Ardabil studies, gram was launched on the basis of off than the residents in the eastern since almost everybody in Ardabil a collaborative agreement between the Health Institutes of the Univer- Figure 1. Map of Iran sity of Tehran and the International Agency for Research on Cancer Armenia Turkmenistan (IARC) in order to study esophageal Caspian cancer in the area of the Caspian Ardabil Sea ■ Gonbad littoral, from Ardabil province in the Turkey Gilan Golestan west to Golestan province in the Mazandaran east. Studies conducted at that time ■ Tehran Afganistan calculated the annual age-adjusted incidence rate of esophageal cancer (mainly esophageal squamous-cell Iraq cancer) to be over 100 per 100 000 in the Gonbad district in Golestan Pakistan province – among the highest rates Kerman in the world. A subsequent collab- orative case–control study revealed a pattern of very low consumption Persian Gulf of fresh fruit and vegetables in north-eastern Iran. 23
  • 21. GASTROINTESTINAL MEDICINE ON THE FRONTIERS The situation in the north-east d) Gonbad does not have units for gastrointestinal malignancy in Iran. part of the country, near Turkmeni- chemotherapy or radiotherapy, Ardabil has the highest incidence of stan, is considerably different from and does not have specialist gastric adenocarcinoma. According that in the west (Ardabil). Most cancer surgery units, so that to an active cancer surveillance pro- Turkmen live in northern Golestan cancer patients need to travel to gram conducted in Ardabil (1996– province, and they constitute less other provinces. Unfortunately, 1999), gastric adenocarcinoma rep- than 2% of the population of Iran. there are no flights or fast trains resents 31% of all malignancies in In their appearance (especially between Gonbad and Tehran the region, with incidences of 49.1 their eyes), ethnicity, and social or other provinces that do have and 25.4 per 100 000 per year for habits, they are different from cancer care facilities. men and women, respectively. Half Persians (who make up 50–55% e) Some of the roads are unpaved of these gastric cancers are located of Iranians). The main traditional in the Gonbad district. in the cardia. In 2000, upper endo- occupation of Turkmen has been in f) The weather is not tolerable dur- scopic screening was carried out in animal husbandry. They tradition- ing the summer in the Gonbad 1011 randomly selected rural and ally lived in temporary houses and district (very hot and humid), urban residents of Ardabil, with tents in the hills, mountains, and and there is a risk of huge mean age of 53 years. Urease test- plains in the border region between floods every spring. ing or histology for Helicobacter Iran and Turkmenistan, and they The initial collaborative studies pylori was positive in 89% of those had several disputes with the cen- stopped at the time of the politi- tested, and 95% had chronic gas- tral governments before taking up cal changes that took place in Iran tritis. H. pylori, which is known to obligatory permanent residence in in 1978. Recently, The Digestive contribute to the development of north-eastern Iran about 70 years Disease Research Center (DDRC) gastric adenocarcinoma, is com- ago. Because of the differences in at Tehran’s University of Medical mon in Ardabil. No dysplasia or cultures, Turkmen have not had Sciences, the IARC, and the United esophageal cancer was found in strong relationships with the Per- States National Cancer Institute a recent population-based study sians (intermarriage, for example) have started studying upper gastro- with chromoendoscopy screening until the last few years. intestinal cancers in the northern program in 504 asymptomatic ran- There were many problems in Iranian plain again. The Turkmen domly selected adults in Ardabil. conducting the studies in the north- were resistant to endoscopy when North-east. Case–control study. eastern Turkman area, including: the case–control study started in A referral clinic for upper gastroin- a) The fact that more than 90% of 2002. To motivate them to par- testinal diseases was established women and about 50% of men ticipate in the studies, the DDRC by the DDRC in Golestan province over 40 years of age in the vil- established a very well-equipped in August 2001. Among the initial lages are illiterate and cannot endoscopy unit in Gonbad 3 years 682 patients seen at the clinic, 370 speak Farsi, so that gathering ago (with the latest video endo- were confirmed histologically as data is possible only through scopes from Olympus and Pen- having cancer, including 60% with face-to-face interviews together tax), along with a gastrointestinal esophageal squamous-cell cancer, with Turkmen interpreters. pathology laboratory, providing 6% with esophageal adenocarci- b) Finding enough educated Turk- free diagnosis, treatment, and noma, 16% with gastric cardia ade- men able to assist in the studies management of all patients with nocarcinoma, and 16% with non- is a major problem; Persians upper gastrointestinal cancer. This cardia gastric adenocarcinoma. The cannot speak the Turkmen lan- included payment for surgery, proportional occurrence of these guage and are not a suitable chemoradiotherapy, dilation pro- four main upper gastrointestinal substitute. cedures, and stenting. Once the cancers was similar to that seen in c) Most Turkmen are aware that results were seen, acceptance of Linxian, China, another area with survival in those with esopha- the treatment improved rapidly. a high incidence of esophageal geal cancer is poor, and did not squamous-cell cancer, and was initially accept any interven- Recent Studies on Upper markedly different from the current tion for people with the signs Gastrointestinal Cancers in proportions in Western countries. and symptoms of esophageal Northern Iran Negligible alcohol consumption cancer; however, acceptance is North-west. Gastric adeno- and cigarette smoking in these improving. carcinoma is the most common patients suggest that the high rates 24
  • 22. GASTROINTESTINAL MEDICINE ON THE FRONTIERS of esophageal squamous-cell can- organ is similar in all areas of the geal carcinoma. However, none cer seen in north-eastern Iran are Caspian littoral, but quite different of these four alleles had a high associated with other risk factors. from that found in the central part enough prevalence in Turkmen to Cohort study. In 2002, a cohort of Iran. explain the high rates of the disease study was initiated in Gonbad dis- Ecological studies. A study was in that group. Three of the four trict to evaluate the genetic and carried out to assess the hypoth- alleles were less frequent among environmental risk factors of upper esis that the high rates of esopha- Turkmen than in some Asian popu- gastrointestinal cancers, mainly geal carcinoma in Golestan and lations with lower risks of esopha- esophageal carcinoma. A total the high rates of gastric cancer in geal cancer. The authors concluded of 1359 (704 rural, 645 urban) Ardabil may be partly attributable that it is unlikely that variations in inhabitants aged between 35 and to selenium deficiency. The find- these polymorphic genes are major 80 were selected randomly and ings suggest that selenium defi- contributors to the high incidence invited to participate in the study. ciency is not a major contributor to of esophageal carcinoma among An active follow-up examination the high incidence of esophageal Turkmen in Iran. was carried out after 12 months. cancer seen in north-eastern Iran, Because P53 mutations are the Cigarette smoking and opium although it may play a role in the most frequent mutations in cancer, and alcohol use were reported high incidence of gastric cancer in and may provide clues on the etio- by13.8%, 10.3%, and 3.7%, respec- Ardabil province. logical mechanisms of esophageal tively. The mean temperature of Genetic studies. The frequen- squamous-cell cancer, P53 was ingested tea was 57.4ºC. Two sub- cies of polymorphisms in 10 genes analyzed in pathology samples jects developed esophageal squa- that have been hypothesized to from 98 Iranians with esophageal mous-cell cancer. The data show have a role in the risk of esophageal squamous-cell cancer, and muta- that the incidence of esophageal carcinoma were compared among tions in 50% of the patients were carcinoma is still high in the region, three Iranian ethnic groups with found. The P53 mutation pattern but that the pattern of causes of highly varying rates of the disease. in Iran was significantly different death is similar to that in other These three groups included high- from that observed in esophageal parts of Iran. risk Turkmen, medium-risk Turks, squamous-cell cancer in high- Active surveillance. Although and low-risk Zoroastrian Persians. incidence areas of China and Iran’s National Cancer Registry Compared to Zoroastrians, Turk- Western Europe. These results are program is still in its initial stages, men had a higher frequency of four consistent with the hypothesis that the DDRC carried out active surveil- alleles that are thought to favor car- several factors are involved in P53 lance for cancers in the Caspian cinogenesis (CYP1A1 m1, CYP1A1 mutagenesis in Iran, including a littoral and Kerman province (in m2, CYP2A6*9, and ADH2*1); background of chronic inflamma- the center of the country) in 1999 these results were consistent with tory stress, as was shown by Crespi (Table 1). The data show that the an influence of these allele variants and colleagues in the 1970s. cancer burden relative to each on the population risk of esopha- Ongoing Studies Case studies on esophagealTable 1. The relative frequency of cancers by province (1999–2002). and gastric cancers are ongoing in Ardabil Gilan Mazandaran Golestan Kerman Ardabil and Golestan provinces. Stomach Stomach Stomach Esophagus Breast A cancer registry in the northern 31.4% 19.0% 16.3% 31.0% 10.2% plain has been initiated by the Esophagus Breast Esophagus Stomach Stomach DDRC, and reports will soon be 13.1% 9.9% 12.9% 16.8% 8.8% forthcoming. Colorectal Colorectal Breast Breast Colorectal ■ 4.8% 9.2% 9.6% 8.8% 6.7% Lung Esophagus Colorectal Colorectal Blood Corresponding Author: 4.7% 8.7% 7.1% 5.3% 5.6% A. Pourshams, M.D. Blood Bladder Blood Bladder Lung Digestive Disease Research Center 4.4% 7.9% 5.3% 3.4% 5.0% Tehran University of Medical Sciences, Tehran Other cancers Other cancers Other cancers Other cancers Other cancers Iran 41.6% 45.3% 48.8% 44.7% 63.7% E-mail: pourshams@ams.ac.ir 25
  • 23. EDUCATION AND TR AINING involvement. Professor Segal brought his ideas regarding the training center concept to the early meetings of the newly formed combined Education and Training Committee. These ideas merged with those being developed by the chairs and committee members through other contacts, and as a result the committee took on the ● ● ● Rabat Cairo task of enlarging and expanding Karachi Morocco Egypt Pakistan the training center concept. The WGO/OMGE executive embraced ● the ideas with enthusiasm and La Paz/Bolivia ● ● there then evolved guidelines for Santiago Soweto setting up centers in areas of the Chile South Africa world where it was felt a need existed, where trusted colleagues ●Spread of WGO/OMGE-OMED endorsed Training Centers around the world. (● Center for advanced would be our local representatives,endoscopic training.) and where we would be wel- comed, but also where our limited WGO/OMGE-OMED Training budget might provide a nidus for attracting further funds that would Centers make the centers viable in the long term. An underlying principle has Jim Toouli (Co-Chairman, Joint Education and Training Committee) been the development of centers in association with the local gov- The Organisation Mondiale de There are two types of train- ernment authorities and relevant Gastro-Entérologie/World Gastro- ing center. The first type, of which gastroenterology groups (e.g., the enterology Organization (OMGE/ there are five, are situated in the local gastroenterology society). In WGO), along with its partner orga- vicinity of developing countries, addition, each of the centers has a nization, the Organisation Mon- and their major aim is to train gas- designated member of the WGO/ diale d’Endoscopie Digestive/World troenterologists in the developing OMGE executive assigned to over- Organization of Digestive Endos- world. The second type, of which see negotiations with the relevant copy (OMED), has developed train- there is only one at this stage, is authorities, as well as two mem- ing centers in different regions of aimed at providing more advanced bers of the Education and Training the world with the aim of deliver- training in gastroenterology. Committee who plan its activities. ing education and training in all The centers have evolved gradu- (One of these two is usually the aspects of gastroenterology. These ally, with most of the activity hap- director of the center, who is co- centers have been developed pening in the last 2–5 years. The opted on to the education commit- over the last few years, bringing first center was inaugurated in tee as a full member.) together the ideas of numerous Soweto, South Africa, and was sup- Five centers have now devel- people who have served on the ported initially by the Munich Gas- oped, including Soweto. They are executive and/or education com- troenterology Foundation through all different, but have the common mittees of the organizations and Professor Meinhard Classen. The aim of bringing education and our colleagues in many parts of center was the “brainchild” of training in gastroenterology to our the world. They reflect the major Professors Issy Segal and Classen, colleagues in the developing world. mission of the organizations, and the former also became its Apart from Soweto, the other which is to foster the progress of first Director. The World Organiza- four centers are situated in Rabat our profession through educa- tion of Gastroenterology became (Morocco), Karachi (Pakistan), tion and training with a global associated with the Soweto center Cairo (Egypt), and La Paz (Bolivia). perspective. as a result of Professor Classen’s The centers in Morocco, Pakistan, 27
  • 24. E D U C AT I O N A N D T R A I N I N G and Egypt are functioning and have the center has been placed in a the world (e.g., Afghanistan). The taught a number of trainees on a renovated ward of the main teach- center in Karachi can serve as the variety of topics. The La Paz center ing hospital in Rabat. An ambitious medium for disseminating valu- will be inaugurated early in 2005. program has evolved, and already able programs from any of our Each of the centers has developed a number of workshops have other centers or any departments differently from the others and taken place. In addition to our in the world that may wish to their initial activities have been own involvement, our colleagues contribute to the overall program. quite diverse. from ASNEMGE (the European/ A curriculum is being established, In Soweto, trainees come from Mediterranean Gastroenterology and we believe that the future the surrounding countries and Association – Association des potential of this resource will be include gastroenterology nurses, Sociétés Nationales Européennes enormous. family practitioners receiving basic et Mediterranéennes de Gastroen- The Cairo center is the most training, and physicians obtaining térologie) have provided financial recent to be inaugurated and is specialist training in gastroenter- support. It is planned that trainees a joint venture with the Egyptian ology. Soweto aims to reach out from the French-speaking countries Ministries of Higher Education and to the developing countries in of Africa will be trained at this cen- Health and the Theodor Bilharz sub-Saharan Africa, where there ter by our colleagues from Rabat, Institute in Cairo. In addition, the is a large need for training in along with international colleagues involvement of the African and gastroenterology. The activities who will visit periodically to pro- Middle East Association of Gas- of the Soweto center have been vide a global perspective. troenterology (AMAGE) has been embraced by the South African The Karachi center has devel- important in setting up this facility. Gastroenterology Society, and as oped in partnership with the Aga The opening ceremony and the a result, much-needed support is Khan University and its department opening meeting were highlighted provided for the center’s educa- of gastroenterology. The depart- in the last issue of WGN. With tional activities by our South Afri- ment and university are highly aims similar to those of the other can colleagues. developed institutions with pro- centers, this center is targeting the The Rabat Center has evolved grams at the cutting edge of medi- training needs of our colleagues in to address the needs of Franco- cine. The aims here are to develop the Middle East and in particular phone Africa. In conjunction with an electronic web-based teaching the Arab world. The first training the Moroccan Ministry of Health, program that may be deliver- program appropriately focused able to more remote regions of on the assessment and manage- ment of portal hypertension and View of Baragwanath hospital (the largest in the southern hemisphere) in Soweto, South Africa. 28
  • 25. E D U C AT I O N A N D T R A I N I N Gattracted trainees from the MiddleEast and throughout Africa. It is the aim of the educationcommittee, which oversees thecenters’ activities, that – whilealways recognizing the diversity ofthe various centers – a commonbasic philosophy should evolve forall of the centers. A subcommitteehas therefore been charged withdeveloping this philosophy andthe necessary guidelines for imple-menting it. Our vision for thesetraining centers is that they willbecome centers of major influencein the training of colleagues in thedeveloping world. As finances per-mit, we would hope to expand thenumbers to other regions of theworld. The second type of center aims The team at the Soweto Center with representatives of WGO/OMGE and AMAGE.to address areas of excellence ingastroenterology and will be rec-ognized for providing training at whether their center may qualify Whilst there is no direct financialthe cutting edge of our specialty. for this prestigious designation. support from the biomedical indus-However, in keeping with the phi- The members of the executives try for any of the centers, it is thelosophy of an internationally rec- of the WGO/OMGE and OMED, as income that is derived from theognized center of excellence, these well as the committee members industry’s support for the Worldcenters need to be able to offer of the combined education and Congresses that is used to under-hands-on experience for trainees training committee, have great pin these important educationalfrom all countries. aspirations for the potential of the endeavors. With the anticipated The first of these centers to be various training centers. We antici- success of the next World Congressrecognized is a center of excellence pate that they will become the in Montreal next year, we hopein delivering of endoscopic training focus of many of the activities of to not only expand the activitiesand is to be designated The WGO/ our societies and have a significant at the existing centers but alsoOMGE-OMED Advanced Center in impact in leading the training and to expand the number of centersEndoscopy Training. The first center maintenance of standards in gas- around the world.recognized is in Santiago, Chile, troenterology on a global basis. On ■and will be inaugurated in August. behalf of the organizations, I invite James Toouli, MDIt is hoped that other centers, not input from the wider gastroen- Co-Chairman, WGO/OMGE-OMEDonly in endoscopy but also in the terology community on how best Education and Training Committeeother areas of gastroenterology to advance our vision for these Flinders Medical Centre,(e.g., hepatology, luminal gastro- centers. In so doing, I also wish to Department of General and Digestiveenterology, gastrointestinal surgery, acknowledge the support provided Surgery, Bedford Park,liver transplantation, minimal- to the organizations by our indus- SA 5042, Adelaide,access surgery) will be recognized. try partners, without whom none AustraliaWe invite colleagues to consider of this activity would be possible. E-mail: Jim.Toouli@Flinders.Edu.Au 29
  • 26. E D U C AT I O N A N D T R A I N I N G The European Endoscopy Training Center in Rome Guido Costamagna The European Endoscopy Train- The EETC is located in ing Center (EETC; www.eetc.it) – a the center of the univer- comprehensive center exclusively sity campus, close to the devoted to education and train- animal laboratory, in a ing in gastrointestinal endoscopy, fully renovated building based at the Catholic University (Figure 1) on two floors, School of Medicine in Rome, Italy with an area of approxi- – has now completed its first year. mately 500 square The EETC is at present the only per- meters. The heart of the Prof. Costamagna teaching EETC trainees manent establishment of its kind in EETC is on the basement Europe. The idea of creating a cen- level, where there is an operating hospital to allow live display of ter in Rome for teaching gastroin- room (Figure 2) with five worksta- endoscopic procedures conducted testinal endoscopy developed out tions fully equipped with state-of- by local staff or by invited guest of long-term experience in training the-art Olympus video endoscopes teachers. The center includes a activities over the past 15–20 years and Erbe electrosurgical generators small library and meeting room at the well-established Digestive with argon plasma coagulation and another room equipped with Endoscopy Unit in Rome’s Gemelli (APC), where trainees can carry out four personal computer worksta- University Hospital. Between 1987 a variety of therapeutic endoscopic tions for electronic interactive and 2003, nearly 200 endosco- procedures on animal models, with teaching, as well as a Simbionix pists (111 from Italy, 16 from other appropriate guidance from tutors. electronic simulator for upper and European countries, and 52 from Various endoscopic procedures lower gastrointestinal endoscopy outside Europe) attended train- can be carried out in the isolated and ERCP (Figure 3). Uniquely, the ing courses ranging from a month swine upper or lower gastrointesti- EETC includes facilities in which (observation) to a year (hands-on) nal tract using the Erlangen model every step in the teaching process at the unit. The EETC project was – including polypectomy, muco- that should precede hands-on successfully implemented thanks sectomy, hemostatic procedures, experience with patients can be to collaboration between the APC treatments, self-expandable replicated. Catholic University in Rome and metal stent insertion, antireflux Other facilities associated with five leading industrial companies procedures, and sphincterotomy. the center include a low-cost involved in gastrointestinal endos- The EETC is also fully certified and hotel on campus and a nearby copy: Bard, Boston Scientific, Erbe authorized to use live animals apartment that can accommodate Elektromedizin, Olympus, and under general anesthesia for spe- foreign trainees free of charge for Wilson-Cook. cial procedures. The presence of periods of up to a year, thanks a veterinary doctor specialized in to a Wilson-Cook educational animal care ensures that all ethical grant. requirements are fully respected. The EETC started its activities The development of other models in July 2003. During the past year, for teaching gastrointestinal endos- there have been 34 courses last- copy is also being currently investi- ing 2–4 days, including hands-on gated at the EETC. sessions, with more than 500 par- On the first floor, there is an ticipating physicians. A further six auditorium for 20–25 people, with courses for nurses at the hospital, up-to-date audiovisual equipment on preoperative and postoperative and a permanent link to an endos- assessment of patients undergoing copy suite at Gemelli University therapeutic gastrointestinal endos- 30
  • 27. E D U C AT I O N A N D T R A I N I N Gcopy, were also given by the unit’s apy, and treatment of acute and ter for the European Society of Gas-endoscopy nurses. New courses chronic pancreatitis. trointestinal Endoscopy (ESGE) andbeing prepared include capsule The EETC has been already rec- is currently applying for similar rec-endoscopy, esophageal endother- ognized as an official training cen- ognition by the OMED-WGO/OMGE Education and Training Committee and by the gastroenterology branch1 of the Union Européenne des Médecins Spécialistes/European Union of Medical Specialists (UEMS). All of the staff at the EETC are looking forward to expanding the center’s activities further and welcoming physicians from all over the world. ■ Guido Costamagna, M.D., F.A.C.G. Scientific Director of the EETC, Professor of Surgery Policlinico A. Gemelli Unità Operativa di Endoscopia Digestiva L. go A. Gemelli 82 00168 Rome Italy E-mail: gcostamagna@rm.unicatt.it3 Figure 1. Newly renovated premises of the EETC. Figure 2. The operating room features five fully equipped endoscopic worksta- tions. Figure 3. Trainees have the opportunity to work on personal computer worksta- tions for electronic interactive teaching as well as a computer simulator. 31
  • 28. DIGESTIVE CANCER AWARENESS CAMPAIGN The International Digestive Cancer Alliance Digestive Cancer Series (Co-Editors: Sidney Winawer and Meinhard Classen) Taxonomy for Neoplastic Lesions of the Digestive Mucosa René Lambert Taxonomy: “the systematic Table 1. Macroscopic classification of neoplasia in the gastrointestinal mucosa (Paris distinguishing, ordering, and naming Consensus Classification). of type groups within a subject field” Superficial cancer (Merriam–Webster 3rd Unabridged Type 0 Superficial protruding or nonprotruding lesions Dictionary, 2003). Advanced cancer Type 1 Protruding carcinoma, attached with a wide base Type 2 Ulcerated carcinoma with sharp and raised margins Superficial versus Advanced Type 3 Ulcerated carcinoma without definite limits Neoplastic Lesions Type 4 Nonulcerated, diffusely infiltrating carcinoma ,Q GLJHVWLYH HQGRVFRS QHRSODV Type 5 Unclassifiable advanced carcinoma WLF OHVLRQV DUH FDOOHG superficial ZKHQ WKHLU DSSHDUDQFH VXJJHVWV WKDW WKH GHSWK LV UHVWULFWHG WR WKH affects the choice of treatment Large neoplasms are readily PXFRVD RI WKH VXEPXFRVD RU between three options: doing identified by endoscopy, but the advanced ZKHQ LQYROYHPHQW RI nothing, for a nonneoplastic lesion; most important aspect of cancer WKH PXFXODULV SURSULD LV VXVSHFWHG carrying out endoscopic mucosec- prevention is the observation and 7KH FODVVL¿FDWLRQ DV VXSHU¿FLDO tomy; or referring the patient for classification of superficial lesions. RU DGYDQFHG ZLOO EH FRQ¿UPHG RU radical surgery. Endoscopy can discover “super- HYHQWXDOO XQFRQ¿UPHG
  • 29. E WKH ficial” neoplastic lesions by identify- SDWKRORJLVW The Paris Classification of Gross ing a slight elevation or depression, Morphology discolored areas, or irregularities in The Relevance of Classifications In 1926, Borrmann classified the vascular network. Various dyes The secondary prevention of the gross morphology of gastric can be applied to the lesions to gastrointestinal cancer relies on cancer into types 1, 2, 3, and 4 enhance their surface characteris- detecting superficial neoplasia at relative to protrusion, excavation, tics, and endoscopic magnification a presymptomatic stage. At this or infiltration. The same categories is opening up new perspectives stage, the probability of a complete were later adopted in Japan for for analyzing the surface (e.g., the cure is very high. Endoscopy is the the esophagus and the large intes- pit pattern in the large intestine) gold standard for detection: pro- tine, and a type 5 was added for and the capillary network, as seen truding or excavated lesions are unclassifiable advanced cancer. The through the trans- easily found, because they alter the Japanese experts also added type lucent unstained surface contours. Nonprotruding 0 for the endoscopic description of epithelium. lesions may be suspected on the superficial lesions – i.e., the precur- The endo- basis of changes in color or in the sors of advanced cancer (Table 1). scopic description network of superficial capillaries. Based on these descriptions, a of “superficial” The endoscopic appearance or consensus Paris classification was neoplastic lesions morphology of superficial lesions published in December 2003. (type 0) is based 33
  • 30. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G N Table 2. Subtypes of type 0 superficial the risk of invasion is greater and is are slightly elevated (IIa), with a neoplastic lesions (Paris Consensus relatively independent of the size. A very low risk of progression to can- Classification). suspicion of deep invasion can be cer. On the other hand, depressed further confirmed if the lesion fails (IIc) lesions are significant precur- Protruding to lift after injection of saline into sors of advanced cancer, in spite of Pedunculated Ip the submucosa. Types that com- being rare (no more than 5% of all Sessile Is bine the IIa and IIc patterns share superficial neoplastic lesions). Nonprotruding the same prognosis as depressed Slightly elevated IIa Completely flat IIb lesions. The Vienna Histopathological Slightly depressed IIc There are wide variations Classification Elevated and depressed IIa + IIc along the gastrointestinal tract in There is worldwide agreement IIc + IIa the relative proportions of each among pathologists in the inter- Excavated subtype of superficial neoplastic pretation (diagnosis, histological Ulcer III lesion that are observed. Overall, pattern, grading of differentiation) the nonprotruding subtypes are of invasive gastrointestinal cancer. more frequent, reaching 84% in On the other hand, there has been on three criteria: size; morphology the esophagus (squamous epithe- wide variation in the classification (Table 2); and location in the gas- lium), 97% in the distal stomach, of superficial neoplastic lesions: trointestinal tract. Type 0 is divided and 50% in the large intestine. in Western countries, a polypoid into categories: protruding lesions Depressed (IIc) lesions are fre- neoplastic lesion of the columnar are termed 0-I and divided into quent in the squamous epithelium epithelium in the gastrointestinal two subtypes, pedunculated (Ip) of the esophagus (45%), but rela- tract is called “adenoma,” and a or sessile (Is). Nonprotruding and tively rare in Barrett’s esophagus flat neoplastic area is called “dys- nonexcavated lesions are termed or at the esophagogastric junction, plasia.” In Asian countries, these 0-II, and these are divided into and are very frequent (78%) in the lesions are referred to as polypoid, three subtypes: slightly elevated distal stomach. In the large intes- flat, and depressed adenomas. (IIa), completely flat (IIb), or tine, most nonprotruding lesions Similarly, noninvasive lesions with slightly depressed (IIc). The distinc- tion between small sessile protrud- ing lesions (Is) and slightly ele- Table 3. Histological classification of superficial neoplastic lesions in the esophagus, stomach, and large intestine (revised Vienna Classification). vated nonprotruding lesions (IIa) can be made more easily by plac- Group 1 Negative for intramucosal (or intraepithelial) neoplasia ing a closed forceps biopsy device Group 2 Indefinite for intramucosal (or intraepithelial) neoplasia (2.5 mm in diameter) next to the Group 3 Low-grade intramucosal (or intraepithelial) neoplasia lesion and using it as a calibrating (this is equivalent to adenoma or dysplasia) gauge. The lesion is called IIa when Group 4 High-grade intramucosal neoplasia its elevation is less than the diam- 4-1 Adenoma/dysplasia eter of the forceps (< 2.5 mm) 4-2 Noninvasive carcinoma and Is when it is more elevated 4-3 Suspicious for invasive carcinoma than the forceps. Excavated lesions 4-4 Intramucosal carcinoma with invasion of the lamina propria (ulcers) are classified as 0-III. Group 5 Submucosal carcinoma The morphologic classification of superficial lesions has a prog- Table 4. Staging of superficial tumors in the TNM classification. nostic value at all sites, and the risk of invasion Esophagus Stage 0 Tis N0 M0 into the submu- Squamous-cell cancer Stage I T1 N0 M0 cosa varies with Adenocarcinoma Stage IIb T1 N1 M0 the subtype. Stomach Stage 0 Tis N0 M0 Depressed 0-IIc Carcinoma Stage IA T1 N0 M0 lesions deserve Stage IB T1 N1 M0 special atten- Colon and rectum Stage 0 Tis N0 M0 tion, because Carcinoma Stage I T1 N0 M0 34
  • 31. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G Nhigh-grade intraepithelial neopla- sion into the lamina propria. In the behavior of the tumor (2 for benign,sia have been called intramucosal esophagus and stomach, intramu- 3 for malignant). An adenocarci-carcinoma in Japan, but high-grade cosal lesions are Tis (noninvasive) noma in the esophagus, stomach,dysplasia in Western countries. or T1m (invasive). In the large or large intestine would be classi- Most of the divergence in intestine, all intramucosal lesions fied with the code 81140/3.semantics has now disappeared (invasive or noninvasive) are Tis,with the adoption of the Vienna because there is no risk of lym- An Inseparable Couple: theconsensus classification, which phatic propagation. Clinician and the Pathologistapplies to both squamous and Superficial malignant lesions Assessment of invasion into thecolumnar epithelium. In the Vienna are classified into stages I or II, but submucosa based on surgical speci-classification (Table 3), the term Tis lesions are always classified mens is easy, as the full thickness of“intraepithelial neoplasia” replaces as stage 0. Advanced tumors are the gastrointestinal wall is availableboth of the terms “adenoma” and classified into stages I to IV. When for examination. A semiquantitative“dysplasia.” Noninvasive neoplastic the tumor is staged clinically, each evaluation into superficial invasionlesions are classified as low-grade component has to be defined as (sm1) or deep invasion (sm2) isor high-grade intraepithelial neo- clinical or pathological. For exam- frequently used. In specimens fromplasia. Noninvasive intramucosal ple, after an endoscopic mucosec- endoscopic mucosectomy, thecarcinoma, also called “carcinoma tomy, pT1, cN0, cM0 means that submucosa is not complete, and ain situ,” is in group 4-2; invasive the primary tumor is confirmed at quantitative micrometric measureintramucosal carcinoma is in group histology and that positive lymph of the depth of invasion from the4-4. Lesions termed “intramucosal nodes and metastases were absent lower limit of the muscularis muco-carcinoma” in the East and “high- clinically. When the classification is sae is preferred. Japanese patholo-grade dysplasia” in the West have based on postoperative findings, gists have established empiricaltherefore now become subdivi- it is called pTNM. The TNM classi- cut-off limits for the legitimacy ofsions of the same group. Carci- fication used in cancer registries is endoscope treatment: 200 µ in thenoma invading the submucosa also used for clinical trials in cancer esophagus, 500 µ in the stomachis in group 5 of the classification. treatment. and 1000 µ in the large bowel.Confirmed superficial neoplastic This micrometric measure actuallylesions are therefore classified into The WHO Classification of deserves generalization for compar-groups 3, 4, or 5. Neoplastic Lesions ing outcomes after either surgical or The WHO International Classifi- endoscopic treatment. AssessmentThe TNM Classification cation of Diseases (ICD) includes a of the completeness of a resec- Tumor staging for cancer reg- specific classification for oncology tion often requires input from theistries uses the TNM classification (ICD-0). The double coding system, clinician, which can be combined(Table 4). The TNM applies only to for topography and morphology, is with the microscopic view from thecases that have been microscopi- also used in tumor registries, and it pathologist.cally confirmed as malignant and describes premalignant and malig- ■combines categories selected in nant lesions.the T (tumor), N (nodes), and M The coding for topography is René Lambert, MD(metastases) components in all based on four alphanumeric sym- International Agency for Research onstages. bols – the first three refer to the Cancer, 150, cours Albert Thomas, Advanced carcinomas are clas- viscera (C15, esophagus; C16, 69372 Lyon cedex 08,sified as T2 (invasion of the mus- stomach; C18, colon; C20, rectum), Francecularis propria), T3 (invasion of and the fourth is for the subsite. An E-mail: Lambert@iarc.frthe serosa), or T4 (invasion into adenocarcinoma is coded C15.5 inadjacent structures). Superficial the lower third of esophagus, C16.3malignant lesions are classified as in the gastric antrum, and C18.7 inT1m or T1sm. For carcinomas, an the sigmoid, with the fourth digit“in situ” category (Tis) is used for indicating the visceral sector.high-grade intramucosal neoplasia The coding for histology has sixwhen there is no invasion of the numbers – the first five for the typebasal membrane – i.e., no inva- of carcinoma, and the sixth for the 35
  • 32. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G N International Digestive Cancer Alliance Meeting during Digestive Disease Week 2004 Sidney J. Winawer, Meinhard Classen, Paul Rozen In the four years since the launching of the Interna- Presentations of various pilot and screening pro- tional Digestive Cancer Alliance (IDCA) in Rome in grams on CRC already established were made by May 2000, many meetings have been held around the professors Finlay Macrae (Australia); Benjamin Wong world and others are being planned. A tradition has (Hong Kong); Robert J.C. Steele (United Kingdom); been established of holding an annual meeting dur- Julius Spicak (Czech Republic); Dai Ming Fan (China); ing the Digestive Disease Week (DDW) conference in Roque Sáenz (Chile); and Urs Marbet (Switzerland). the United States, taking advantage of the presence of CRC is on the rise in Australia, where pilot programs many American and international members. The IDCA using immunochemical tests have been initiated. To meeting held during Digestive Disease Week (DDW) date, 38 228 people have taken part in these, and in New Orleans (Sunday 16 May 2004) was opened 95% of those with positive findings (8.7–12.5% of by a brief review of the evolution of IDCA and its mis- those screened), have been referred for colonoscopy. sion and activities since inception. The meeting was In Hong Kong, CRC is also on the increase, but so especially exciting; being attended by 97 invited IDCA far the government has not been willing to initiate members from 36 countries and representation of a screening program. The IDCA has agreed to help Industry. develop a prevention model with outcomes that will help make a positive case for prevention to the health National Colorectal Cancer Screening Programs: authorities there. Large-scale pilot studies have already Successful Strategies for Unique Challenges and been started in the United Kingdom, using guaiac- Barriers – Key Lessons based fecal occult blood testing (FOBT) to detect The aims of the meeting were: firstly, to present early-stage cancer, but several issues still need to be successful strategies and key lessons from several clarified in connection with compliance, improve- national programs; secondly, to communicate infor- ments in the test, pathology, and surgery. Eastern mation to members about expertise, outcome models, Europe has many programs in progress, almost all and the resources available to assist national screen- using FOBT, except for Poland, where a large colonos- ing programs; thirdly, to review the relative benefits copy screening trial is in progress involving approxi- of primary and secondary colorectal cancer (CRC) mately 40 centers throughout the country. China has prevention; and fourthly, to initiate a discussion on been studying various approaches to CRC screening, gastric cancer, its epidemiology and potential for including guaiac-based FOBT immunochemical test- prevention. ing and exfoliative cytology. The incidence of CRC has been rising very rapidly in Chile, doubling in the last 5 years and rising 83% in the last 20 years. There are many problems there in attempting to initiate a screening program, including costs and colonoscopy capacity. There is currently no national screening program in Switzerland, although they are studying population preferences for flexible sigmoidoscopy, FOBT, and colonoscopy, as well as the quality of the examinations, acceptance, and the outcome of each examination. International Assistance to National Screening Programs: Expertise, Outcome Models, Resources The second phase of the meeting provided a forum for presenting the resources available through inter- national organizations involved in the prevention of 36
  • 33. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G N colorectal cancer. Presentations Screening Network that will focus on universal out- were made by Professors René come measures and quality indicators for screening Lambert (International Agency programs. An inaugural meeting was held in London for Research on Cancer), Ann in 2004. Zauber (IDCA), Carolyn Aldigé The European Society of Gastrointestinal Endos- (Cancer Research and Preven- copy (ESGE) has mounted several initiatives, includ- tion Foundation), Robert Smith ing meetings, journals, and training programs, and (Union Internationale Contre together with the United European Gastroenterology le Cancer/American Cancer Federation (UEGF) it has recently published a review Society), Marion Nadel (Centers of CRC screening (Endoscopy 2004; 36: 348–66). Thefor Disease Control, USA), Anthony Axon (European UEGF Public Affairs Committee has recently completedSociety of Gastrointestinal Endoscopy), Christa Maar a European survey of colorectal cancer prevention(Burda Foundation), Colm O’Morain (United European practices. It was quite clear that both in Europe andGastroenterology Federation Public Affairs Commit- the United States, the media and role models are criti-tee), and Mark Pochapin (Weill Medical College, Cornell cal for achieving increased public awareness. ManyUniversity, Monahan Center, New York). It was clear barriers to screening perceived by the public canthat considerable resources are available internationally be broken down through active involvement by thethat can be helpful to the national programs. The Inter- media, and screening awareness and screening activi-national Agency for Research on Cancer (IARC), with ties can be increased.its new Director, Professor Peter Boyle, has a stronginterest in cancer prevention worldwide. The IARC Relative Benefits of Primary and Secondaryhas substantial resource materials available, includ- Colorectal Cancer Preventioning the Globocan program (http://www-dep.iarc.fr/ The IDCA meeting concluded with a review by Pro-globocan/globocan.html), which provides the latest fessor Graeme Young (Australia) of the relative bene-data on cancer incidence, mortality, and other statistics fits of primary and secondary prevention of CRC, and aworldwide. review by Professor Richard Hunt (Canada) of the epi- The IDCA model is to use the Globocan data in its demiology and potential for preventing gastric cancer.mathematical model, as well as country-specific addi- The IDCA considered it important to include these top-tional data to help IDCA members in each country ics in the meeting, to emphasize both primary preven-make the case for cancer prevention to health min- tion and the importance of other cancers in addition toisters, and then help organize awareness meetings, CRC. The IDCA has a strong interest in primary preven-followed by pilot campaigns. The Cancer Research tion as well as screening and has a broad interest inand Prevention Foundation (CRPF) has developed a all types of digestive cancers in addition to colorectalnumber of creative methods of increasing CRC aware- cancer. The latter two aspects are to be included inness, including the “Dialogue for Action” meeting that the next IDCA campaign, concerned with reducing thewas replicated recently in Berlin, “remember to be burden of gastric cancer through Helicobacter pyloriscreened” bracelets, the Colossal Colon model tour eradication in a model project in China. A workgroup,in U.S. cities, developing partner groups to promote conference, and protocol are currently being plannedscreening, and having the U.S. Congress designate for October 2004 in China.March as CRC Awareness Month. The American Can- The meeting closed with a brief summary of futurecer Society (ACS) has developed a round table that IDCA activities, including active involvement in China,brings together many disciplines from the profes- meetings in Brazil and Rome, and the World Congresssional and lay community to work together on CRC in Montreal in 2005.prevention, and is working closely with the Union ■Internationale Contre le Cancer (UICC). A world con-gress on cancer prevention is being planned. The Corresponding AuthorCenters for Disease Control (CDC) have initiated Professor Sidney J. Winawerseveral campaigns in the USA, including “Screen for Co-Chair IDCALife” (http://www.cdc.gov/cancer/screenforlife) Memorial Sloan Kettering Cancer Center 1275 York St.and “Call to Action” (http://www.cdc.gov/cancer/ NY 10021 New Yorkcolorctl/calltoaction) and has recently supported, USAalong with the ACS, an International Colorectal Cancer E-mail: winawers@mskcc.org 37
  • 34. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G N OMED Colorectal Cancer Session 3 (Chaired by Dr. M. Classen, Germany, and Dr. M. Screening Committee Meeting Korman, Australia) This session addressed endo- Paul Rozen, Sidney J. Winawer scopic screening programs. Dr. R.S. Bresalier (USA) updated the U.S. Flexible Sigmoidoscopy PLCO The annual meeting of the specificity than office-developed screening trial. Three to 5 years after Colorectal Cancer Screening guaiac FOBTs. Dr. G. Castiglione flexible sigmoidoscopy, 3.1% of the Committee of the Organisation (Italy) uses the latex agglutination patients had distal neoplasia after Mondiale d’Endoscopie Digestive/ test (OC-SENSOR). Biennial one- a negative baseline examination. World Organization of Digestive day testing increased screenee Advanced distal adenoma, male Endoscopy (OMED/WGO) was held compliance, the overall positivity sex, and age over 70 were risk fac- jointly with the International Diges- was 5%, and the predictive positive tors for advanced proximal neopla- tive Cancer Alliance (IDCA) during rate for significant neoplasia was sia. Nonphysicians had performed Digestive Disease Week in New 29%. Dr. H. Saito (Japan) com- 70% of the 56 000 examinations. Orleans on 15 May 2004. pared HemSp with the automated Dr. W. Schmiegal (Germany) MagStream Sp. The sensitivities of addressed the issue of quality con- Session 1 (Chaired by Dr. M. both tests were 90% for CRC, but trol in Germany’s national colonos- Crespi, Italy, and Dr. J. Mandel, MagStream’s specificity was signifi- copy screening program, including USA) cantly lower. The automated FOBT 320 000 examinations. Total colo- This session addressed colorec- is convenient, but its specificity noscopy was achieved in 98.8% of tal cancer (CRC) epidemiology and needs improvement. Dr. G.P. Young the examinations, 18% of which screening modeling. Dr. Mandel (Australia) compared InSure (an were without sedation. Adenomas reported a declining CRC incidence automated immunochemical test) were found in 30% of cases and and mortality in the white popula- and the guaiac, office-developed cancers (Dukes A and B) in 0.54%. tion in the United States. Dr. R. HemoccultSensa test. InSure has Dr. M. Crespi (Italy) noted that Italy Lambert (France) reviewed Interna- simplified sample collection, which provides free screening colonos- tional Agency for Research on Can- improved compliance; predictive copy, but there is no centralized cer (IARC) data on the high and ris- positive rates and specificities data management and because ing CRC incidence and mortality in for neoplasia were similar. Two- of low uptake, a public awareness “Westernizing” and “aging” coun- day InSure, with 96% specificity, campaign has now been initiated. tries. Dr. A. Zauber (USA) discussed detected 100% of CRCs and 60– Dr. J. Regula (Poland) stated that CRC screening modeling using the 70% of adenomas. Dr. D. Ahlquist Poland now has a national single- MISCAN model, and reported that (USA) reviewed fecal DNA test- colonoscopy screening program flexible sigmoidoscopy with fecal ing; this requires collection, rapid with recruitment by general practi- occult blood testing (FOBT) saved transfer to a central laboratory, and tioners. A total of 30 000 persons more life-years with lowest costs. freezing. A colonoscopy-controlled participated, 77% without seda- comparison showed a sensitivity of tion; 90% of the examinations Session 2 (Chaired by Dr. P. 51.6% and a specificity of 94.4% were completed to the cecum, and Rozen, Israel, and Dr. J. Terdiman, for invasive CRC, and a sensitivity significant neoplasia was detected USA) of 15.1% for advanced adenomas. in 5.1% of cases. Dr. D. Lieberman This session considered nonen- Dr. J.H. Bond (USA) reviewed com- (USA) observed that the Medicare doscopic screening methodologies. puted-tomographic colonography; program allows screening colo- Automated quan- the best results were from an noscopy every 10 years; quality titative immuno- experienced single institution. The and resource availability is being chemical FOBTs limitations of this method are its evaluated. Interval lesions occurred for fecal hemo- long learning curve, radiation expo- 3–5 years after baseline neoplasia, globin, without sure, costs, availability, a decreased cancer in 0.7–1.1% of cases, and dietary restric- sensitivity for lesions smaller than advanced neoplasia in 6–11% tions, should 1 cm, and the inability to take – underlining the importance of provide better biopsies or carry out polypectomy. high-quality examinations. 38
  • 35. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G NSession 4: Panel Discussions able. In conclusion, it was agreed is acceptable and is needed when(Chaired by Dr. S.J. Winawer, USA) that both population screening and public health policy has not yet The first panel session case-finding have their place. included population CRC screening.addressed the question of interval A full report is also to be pub-neoplasia, occurring during surveil- Conclusions lished and will be available fromlance of the colon. Dr. D.O. Faigel This annual meeting allowed an the authors or OMED.(USA) noted that “new” findings international exchange of experi- ■could represent polyps that were ence and ideas on how to performmissed initially due to inadequate and promote CRC screening. It Corresponding Author Prof. Paul Rozen, Chairman,preparation and examination. Dr. emphasized the development and OMED Screening CommitteeR. Lambert (France) stated that promotion of high-quality screen- Dept. of Gastroenterology,with the low sensitivity of the ing methodologies. Modeling will Tel Aviv Medical Center,guaiac test, biennial FOBTs can be help decide on appropriate screen- 6 Weizmann Street,false-negative for CRC, especially ing policies for diverse settings. Tel Aviv 64239, Israelas some CRCs start as flat adeno- Population CRC screening should Tel.: +972-3-6974869mas. Dr. J. Mandel (USA) observed be promoted and integrated into Fax: +972-3-6974622that FOBTs have to be prepared in public health policy. Case-finding E-mail: rozen@tasmc.health.gov.iladequate numbers and repeatedly.Dr. Y. Sano (Japan) reported thatafter polypectomy, 7% of patientswere found to have advanced Ten Rules for Cancerlesions at the follow-up examina-tion; 34% were flat lesions and 5% Preventionwere depressed. The panel’s con- Attilio Giacosa, Massimo Crespi (United European Gastroenterologyclusions were that the use of sensi- Federation Public Affairs Committee)tive FOBTs should be promoted, aswell as good bowel preparation, Colorectal cancer (CRC) is the Diets high in calories tend tohigh-quality and complete colono- leading cancer in nonsmokers be high in fat (especially animalscopic examinations, and follow-up (of both sexes) in North America, fat) and refined carbohydrates, butadjusted to the quality of the initial Australasia, and western Europe. low in fiber and vegetable intake.examination and findings. The major risk factors for CRC The consequent glycemic overload The second panel session are genetic and dietary. Evidence produces a compensatory increasefocused on “population CRC regarding genetic polymorphisms, in blood insulin and insulin-likescreening and/or case-finding.” Dr. which may influence the metabo- growth factors, which in turn areM. Crespi (Italy) stated that many lism of nutrients, is thought to be thought to stimulate colorectal cellcountries have no population CRC important in the etiology of CRC turnover and increase the suscepti-screening, and case finding should and colorectal adenomatous pol- bility of cells to malignant transfor-therefore be supported. Dr. R.J. yps. At present, the strongest evi- mation.Steele (UK) reported that a United dence of gene–nutrient interaction Most vegetables are inverselyKingdom national FOBT screening in relation to CRC is for folate and associated with CRC risk. Aprogram will probably be intro- genetic variants associated with dif- reduced risk has been particularlyduced, but he considered that this ferences in metabolism of folate. In associated with raw, green, anddid not negate case-finding. Dr. B. European studies, significant trends cruciferous vegetables, but less soWong (Hong Kong) observed that have been found for increased CRC for fruit consumption. Among mac-there is a high incidence of CRC in risk proportional to the intake of ronutrients, a highHong Kong, but that screening is bread and pasta, cakes and des- intake of starchnot a public health priority, so that serts, and refined sugar. Regard- and saturated fatcase-finding is therefore encour- less of the specific food source appears to lead toaged there. Dr. G.P. Young (Austra- of calories, caloric excess and its an increased risk.lia) considered that a national CRC consequences can be regarded as High intakes ofscreening program is best, but that a well-established risk factor for polyunsaturatedcase finding should also be avail- colorectal cancer. fatty acids (chiefly 39
  • 36. D I G E ST I V E C A N C E R AWA R E N E S S C A M PA I G N derived from olive oil and seed oils) show a marginal inverse asso- ciation with CRC. While fish con- sumption has been thought to be inversely associated with CRC risk, the correlation with meat intake is still debated. While excess weight is associ- ated with increased CRC risk (more so in men than women), physical exercise is inversely correlated to colon cancer. In addition, the body mass index (BMI) is directly associ- ated with colon adenomas (with a stronger association for larger ade- nomas). Analysis of the available observations shows that increasing levels of physical activity are associ- ated with an approximately 40% reduction in the risk of colon can- cer, independent of BMI. Taking all this into consideration, the Public Affairs Committee of the United European Gastroenterology Federation (UEGF) has developed “Ten Rules” on healthy diet and lifestyle for preventing colorectal UEGF Ten Rules for Healthy Lifestyle cancer. These guidelines, which and Cancer Prevention have been widely distributed through the national gastroenterol- ogy societies, also apply to other ● Maintain a high level of physical exercise: at least 30 minutes a day types of cancer (e.g., prostate, of vigorous activity are suggested (but the type of activity can vary breast) and degenerative diseases with age). in general. ● Avoid excess weight, preferably by increasing physical activity. ■ ● Eat plenty of fiber-rich food and whole grains and less food con- taining sugars and products with white flour. Corresponding Author ● Aim to eat at least five portions a day of fruits and vegetables. Prof. Massimo Crespi ● Moderate the intake of animal fat (i.e., dairy fat and fatty meat) by “Regina Elena” National Cancer Institute choosing light dairy products and removing visible fat from meat Viale Regina Elena 291 and skin from chicken. Fat derived from “added fat” during cooking 00161 Rome, Italy can be replaced by vegetable oils and possibly extra-virgin olive oil. E-mail: mcrespi@uni.net ● Remember that fish and beans are attractive alternatives to meat. Fish oil is also good for preventing some other types of cancer (such as breast cancer) and cardiovascular diseases. ● Drink plenty of water. For alcoholic beverages, have less than two glasses a day of wine or beer. ● The selection and storage of food are very important: look mainly for local and seasonal fresh or frozen food. ● Healthy cooking requires lowering the amounts of added cooking oils and fats, using low temperatures and short cooking times. ● Whatever you do, do not smoke! 40
  • 37. WGO/OMGE INSIGHTTreasurer’s ReportJ.E. GeenenThe Organisation Mondiale de $624,702.39. Funds received from is $1 million, and the budget forGastro-Entérologie/World Gastro- members’ dues amounted to 2005 is projected as $1.1 million.enterology Organization (OMGE/ $61,125.94; funds received from Hopefully we will be able to con-WGO) had a very busy year. We the biomedical industry, mainly tinue to support all of our educa-successfully launched another from our Concordat members, tional programs.training center in Cairo, Egypt. With amounted to $280,000. Incomethis facility, we now have four func- from interest and dividends totaled Concordat Contribution Updatetioning centers, with another two $173,616.70; refund on consult- The annual Concordat contribu-planned to open in 2005. ing fee amounted to $6.673,75 tions have been raised to $30,000 The “Train the Trainers” pro- and gain on investments was per member company. The currentgram is continuing to be a suc- $103,286.00. members are:cessful endeavor for WGO/OMGE. WGO/OMGE’s total expenses for ● AstraZenecaThe feedback received from the 2003 were $837,411.76. The ● Boston Scientificprogram held in New Zealand in expenses have been broken down ● Altana2003 shows that WGO/OMGE is into three categories: meetings; ● Fujinonfulfilling its aim of ensuring that educational activities; and sup- ● Janssenendoscopists from all parts of the porting services. Meeting expenses ● Olympusworld are able to participate, learn, totaled $295,238.02. Educational ● Pentaxand take their new-found knowl- activities, which include preparing ● Takedaedge and skills back to their own guidelines and publications, run- ● Novartiscountries. ning training centers, the Train the ● Axcan Plans for the next World Con- Trainers course, and expenses forgress of Gastroenterology (WCOG), the partner societies OMED and WGO/OMGE thanks the Concordatto be held on 10–14 September IDCA, totaled $330,900.90. Sup- members for their ongoing sup-2005 in Montreal, are progress- porting service expenses totaled port.ing well, and it is anticipated that $211,272.84. Supporting services ■the event will meet or exceed our include Medconnect, administra-expectations. tive services, professional fees, and Joseph E. Geenen, M.D., The above are a few examples Marathon publications. WGO/OMGE Treasurerof our accomplishments since The difference between Suite 1030,2003. The finances for managing expenses and revenue was 2801 W. Kinnickinnic River Parkway, Milwaukee,these initiatives (as well as many $202,709.37. WI 53215, USAothers) are outlined below. Total expenses are continu- Fax: +414-908-6504 Total revenue for 2003 was ing to increase. The 2004 budget E-mail: giconsults@aol.com 5HIXQG  &RQVXOWLQJ )HH  ²  <HDU (QG 7RWDO ([SHQVH ²  *DLQ RQ ,QYHVWPHQWV 6XSSRUWLQJ 6HUYLFHV 0HHWLQJV  ²   ²  0HPEHUV XHV  ²   ²  &RQFRUGDW  ²  (GXFDWLRQ LYLGHQGV,QWHUHVWV  ²   ²  7RWDO 5HYHQXH  Figure 1. WGO/OMGE 2003 Total Expense Comparison. Figure 2. WGO/OMGE 2003 Components of Revenue. 41
  • 38. WGO/OMGE INSIGHT An Invitation to a Special Symposium Global Guidelines for the 21st century – Focus on “Evidence” or Focus on “Need”?*/2%$/ *8,(/,1(6 When the World Congress of Gastro- the limited resources in the developing world. Is itIRU WKH VW FHQWXU enterology (WCOG) opens in Montreal necessary and ethical, therefore, to recommend and in September 2005, the Organisation implement “minimum” guidelines? Mondiale de Gastro-Entérologie/World Gastroenterol- ● How can we improve on the implementation of ogy Organization (OMGE/WGO) will be able to look guidelines? Is it reasonable to expect that global back at 4 years of successful publication of guidelines. guidelines can change health policy? Almost twenty guidelines will have been produced by ● Should the biomedical industry be involved in the then, and the guidelines are being quickly translated into guideline-making process? If so, in what ways? French, Spanish, Russian, Chinese, and Arabic – in line ● Is the evidence-based approach always desirable or with WGO/OMGE’s global commitments. But are global feasible? guidelines truly possible? Do they have to be based These questions will serve as the framework for the strictly on evidence, or should they also take local needs symposium, which will take the form of a half-day meet- and available resources into account? ing with an invited faculty. Special invitations to attend WGO/OMGE’s unique global position makes devel- the conference will be extended to all 93 member societ- oping guidelines a special challenge. In addition to the ies of the World Gastroenterology Organization and all challenges experienced by all guideline developers – for the collaborating organizations. example, the complex issues involved in methodological The core team of renowned gastroenterologists who rigor, including a strictly evidence-based approach with will chair the five symposium sessions is: Prof. M. Fried graded recommendations whenever possible – WGO/ (Switzerland, Chair); Prof. E. Quigley (Ireland); Prof. OMGE is faced with unique challenges involved in pro- G.N.J. Tytgat (The Netherlands); Prof. M. Farthing (United duction, dissemination, and implementation. No other Kingdom); Prof. R. Hunt (Canada); and Prof. D. Bjorkman body involved in gastroenterology has WGO/OMGE’s (United States). Each session will feature one advocate global commitments, and no one else needs to take into and one opponent of a motion. These chaired sessions account the gap between resource-poor and resource- and a subsequent round-table discussion will then form rich regions in the same way. the basis for an WGO/OMGE position statement. For For WGO/OMGE, the quality of guidelines cannot be a full program with details of all the speakers for and based strictly on issues of evidence alone. Sometimes against each motion, and the names of the moderators there is no evidence base, and even when there is evi- and commentators, please consult the symposium web dence, it may require the use of equipment and tech- site (www.worldgastroenterology.org). nologies that are not available throughout the world. The This unique consensus conference will bring together gap between resource-poor and resource-rich regions is key leaders involved in producing, disseminating, imple- expanding, rather than narrowing. The increasing sophis- menting clinical guidelines. Much can be learned from tication of medical technology saves extra lives in the other medical disciplines, as well as from organizations highly resourced West, but the use of intermediate tech- whose task it is to monitor implementation and assess nology and the provision of better infrastructure could needs. With a strong belief in professional solidarity, and save millions of lives in the rest of the world. Should mindful of its global commitment to the 93 national gas- these differences in resources be taken into account troenterology societies affiliated to it, WGO/OMGE hopes when guidelines are being compiled? to ensure it will continue to represent gastroenterologists As no one else has addressed these issues systemati- in every part of the world. cally from a medical and clinical point of view, WGO/ ■ OMGE has decided to call upon experts throughout the world to participate in a unique symposium as part of Global Guidelines Conference Core Team Chair: Prof. Michael Fried WCOG 2005 (www.wcog2005.org), focusing on the fol- WGO/OMGE Executive Secretariat lowing five questions: C/o Medconnect, Bruennsteinstr. 10, ● Are global guidelines desirable and feasible? 81541 Munich, Germany ● Most clinical guidelines do not take into account E-mail: omge@omge.org 43
  • 39. WGO/OMGE INSIGHT ASNEMGE–WGO/OMGE European School of Gastroenterology Launched In a joint venture, the Association the Erlangen EASIE model; liver work with faculty members at this des Sociétés Nationales Euro- disease; how to write a scientific level. péennes et Mediterranéennes de paper) was limited to a maximum The European School of Gastro- Gastroentérologie (ASNEMGE) and of 10 participants. enterology will be repeated in the Organisation Mondiale de Gastro- With Professor G. Tytgat first half of June 2005 and will be Entérologie/World Gastroenterol- (WGO, Amsterdam) and Profes- announced both by ASNEMGE and ogy Organization (OMGE/WGO) sor P. Ferenci (ASNEMGE, Vienna) OMGE/WGO through the national held the first European School of as chairmen, the faculty included societies. Participants will be Gastroenterology in Dubrovnik, Professors R. Caprili (Rome), selected by ASNEMGE and OMGE/ Croatia, on 11–13 June 2004. M. Carneiro de Moura (Lisbon), WGO. The event involved a new edu- C. Gasche (Vienna), J. Hochberger The organizers and participants cational approach, combining (Hildesheim), R. Hultcrantz (Stock- are grateful to Altana Pharma for state-of-the-art lectures (covering holm), L. Greiner (Wuppertal), their generous support for this high- gastroesophageal reflux disease, K. McColl (Glasgow), F. Megraud level educational event (with six malabsorption, inflammatory (Bordeaux), H. Mönnikes (Ber- Council on Medical Education cred- bowel diseases, chronic liver dis- lin), R. Stockbrügger (Maastricht), its), and to Doris Möstl (ASNEMGE) eases, and colon cancer screening) B. Vucelic (Zagreb), and C. Yur- and Heike Dietrich (ALTANA) for in the morning with practical train- daydin (Ankara). The participants their organizational support and ing in the afternoon. Each of the were young gastroenterologists Boris Vucelic for his invaluable work courses given (abdominal ultraso- from 12 European countries, as the local organizer. nography; endoscopy training with enjoying a unique opportunity to ■ Participants and faculty of the launch of the ASNEMGE– WGO/OMGE European School of Gastroenterology. 44
  • 40. OBITUARY Elbio Zeballos Henry Cohen was able to organize the Pan-American Congress in October 2003, at which he was elected to act as Honorary President, allowing his pupils to chair the meeting under his guidance. In the scientific field, he played an active role in the development of diagnostic lapa- roscopy. His interest in celiac disease brought him prominence as a recognized expert on the subject, and shortly before his death, the World Gastroenterology Organization acknowledged his expertise by appointing him as a coordina-Elbio Zeballos (left) with tor for international guidelines on the condi-colleague and friend Henry Cohen. tion. In addition to being a natural teacher and educator, he also published and contributed to dozens of scientific papers. His last work,P rofessor Elbio Zeballos died of heart failure in Montevideo in April 2004 at the age of 61.The Uruguayan gastroenterology community has Semiología Gastroenterológica, is already a classic in the field. As a keen scholar and his- torian, he was the author of several papers onlost a respected leader, as well as an outstand- the development of gastroenterology in Uruguaying scholar, physician, and teacher. and South America. Dr. Zeballos was known among his peers In addition to his professional achievements,for his thoughtfulness and calmness, and for he was also interested in art and was himselfhis friendly approach. He was always willing to an outstanding painter. His paintings mergedexpress encouragement and provide valuable aesthetic sensitivity with a fine sense of humor,advice to those around him, and he never failed delicate irony, and tremendous creativity.to express his convictions and defend his prin- His life-long companion Rosario and fam-ciples when necessary. He was deeply commit- ily were, above all, the most important focusted to the university’s medical school and served of his life, and he was proud to see both of hisfor 12 years as head of the Gastroenterology children becoming successful members of theDepartment in Montevideo’s Hospital de Clíni- medical profession themselves.cas. His outstanding teaching and unique style ■were widely recognized. He served as Secretary-General of theNational Academy of Medicine and as Presidentof the Uruguayan Society of Gastroenterology(1984 to 1986), completing his final term withan extremely successful national conference.As President of the most important associationfor the specialty in the Americas, the AsociaciónInteramericana de Gastroenterologia (AIGE) in1999 to 2001, he led major advances for thesociety and for gastroenterology in the region. Itwas thanks to his exceptional work that Uruguay 45
  • 41. GASTROENTEROLOGY ON THE INTERNET PubMed/Medline: What Every Gastroenterologist Needs to Know Justus Krabshuis Earlier this year, I asked an eminent New York You can modify your current search by adding or gastroenterologist/endoscopist a few short questions eliminating terms in the query box or in Details. If you about the average U.S. gastroenterologist’s awareness applied Limits, the check box next to Limits will be of PubMed/Medline. It’s one man’s view, admittedly marked, and a listing of your limit selections will be – but surely his answers below are not far from the displayed. To turn off the existing limits, click on the truth? check box to remove the check before running your • Do gastroenterologists use PubMed? Yes. next search. • Do gastroenterologists use MeSH? I doubt that It is very useful to be able to limit the search to most use MeSH. “title” and to “time.” • Do gastroenterologists use Boolean logic in Example: searches? Most know about it, but are not sure 1 Type “how to find the evidence you need” in the how to do it. query box. • Do they use the Preview/Index features? I don’t 2 Click on “Limits” on the Features bar. think so. 3 Select “Title” from the drop-down menu that starts • Do they combine free text and indexing? Definitely with “All fields.” not. 4 Click “Go” • Are they aware of the limitations of MeSH (e.g., The four hits together provide you with a small com- creation date issues; indexing policies)? Definitely prehensive vade-mecum for searching Medline. not. • Are they aware of the limitations of Medline vis- Searching for Journals à-vis other databases in terms of currency, scope, PubMed (www.pubmed.org) is a service provided and coverage? Not at all. by the U.S. National Library of Medicine (NLM) and Let’s assume the above views are true, and let’s also includes over 14 million citations for biomedical assume that it matters. articles. You can search by the full journal title – e.g., Searching PubMed molecular biology of the cell; the Medline abbrevia- PubMed searching is easy: just enter search terms tion – e.g., mol biol cell; the International Standard in the query box and press the Enter key, or click Go. Serial Number (ISSN) – e.g., 1059-1524; or the variant The Features bar directly underneath the query box title as it appears in the NLM catalog. See the Journals provides access to additional search options. The Database there for the full journal titles. PubMed query box and Features bar are available from Example: every screen, so you don’t need to return to the home 1 Click on “Journals database” in the left-hand bar. page to enter a new search. 2 Type in “gastroenterology” in the search box, and You can enter one or more terms (e.g., “gastro- click “go” esophageal reflux disease”) in the query box, and 3 From the 41 journals with titles including the word PubMed automatically combines (ANDs) significant “gastroenterology,” click the journal you are inter- terms together using automatic term mapping. The ested in – e.g., “China national journal of new terms are searched in various fields of the citation. If gastroenterology = Chung-kuo hsin hsiao hua ping your search includes the Boolean operators AND, OR, hsueh tsa chih.” NOT, they have to be in upper case: Gerd OR Gord Searching for Books Gerd AND children Did you know you can search ‘books’ in PubMed/ Gerd NOT animals Medline? Books on the “Bookshelf” are also linked to Once you click Go, PubMed will display your search terms in PubMed abstracts: when viewing an abstract, results. The query box displays your search terms as select the “Books” link to see phrases within the you entered them. abstract hyperlinked to book sections. Click on ‘books’ 47
  • 42. GASTROENTEROLOGY ON TH E I NTERN ET in the drop-down menu just to the left of the search • Use the [au] search tag if the author name is box, as illustrated below. Then type in your search also a subject term – e.g., moran a [au]. The – e.g. “Endoscopic Retrograde Cholangiopancreatog- unqualified phrase, moran a, will search as “moran raphy” and click “Go.” Note the 138 items in the HSTAT A”[Substance Name] OR moran a [Text Word]. book series. So, you want to search for articles written by Professor J.D. Waye , the Editor of WGN. Example: 1 Waye JD 2 Click “go” Searching for a Topic – GERD or GORD? The key problem here is how to make sure you find all relevant articles about gastro-(o)esophageal reflux disease – unless you only want key articles such as reviews, perhaps . If you search for “gord” you will not find “gerd,” and vice versa. But if all articles dealing with “gerd” and “gord” are indexed with the term “GERD,” then you will find all articles about gas- troesophageal reflux disease, whatever the spelling Searching for Articles and description used by the author, if you search for Looking for an article? Use the “Single citation articles indexed with the indexing term “GERD.” matcher”! Try and remember as many details of the This is the first of three reasons why you should article as possible. use: indexing. The second reason has to do with what Example: is called “explosion.” If you search for “proton-pump Let’s say you remember that Professor Jerry Waye inhibitors” (PPIs), you will only find articles where wrote an article about colonoscopy – you can’t remem- these words occur together – usually adjacent to each ber the journal or the title, but you do remember that other in that order. But surely you want to find litera- the word “painless” was in the title. This is easy … go ture dealing with ‘esomeprazole’ (drugs are usually to “Single citation matcher” in the left-hand naviga- indexed with their INN generic name – so Nexium is tion bar. Fill in as many details as you can remember indexed as “esomeprazole,” for example – yet another – e.g., the author name, WAYE J, and fill in the word you reason for using indexing ) and other PPIs. In other remember, e.g. “painless”; click “Search” and voilà! words, you need an indexing system that assigns “nar- rower” terms like esomeprazole to broader terms such Searching for Authors as “proton-pump inhibitors.” This indexing system is To search by an author’s name, enter the name in called Medical Subject Headings (MeSH). Find MeSH the format of last name plus initials (with no punctua- terms by clicking on “MeSH Database” in the left-hand tion) – e.g., Waye JD, Tytgat GN. PubMed automatically side bar. Then maybe spend a few moments viewing truncates the author’s name to account for varying the animated tutorial – this will pay off later. initials and designations such as “Jr.” or “2nd.” A name entered using this format will prompt a search in the Clinical Queries author field. If only the author’s last name is entered, PubMed/Medline does provide some help by offer- PubMed searches the name in All Fields, except ing a choice between “clinical queries” and “systematic when the author name is found in the MeSH transla- reviews” – the two poles of the study-type evidence tion table (e.g., Yang will search as Yin-Yang [MeSH] continuum. If you click “clinical queries” in the left- or Yang [Text Word].) To search for an author in the hand bar, you can choose between the options below: author field when only the last name is available, Category: therapy – diagnosis – etiology – prognosis qualify the author name with the author search field Emphasis: sensitive search (broad) – specific search tag [au] – e.g., tytgat [au]. (narrow) Note: If you click “systematic reviews,” it limits retrieval • Use double quotes around the author’s name with to articles indexed with the MeSH term “systematic the author search field tag [au] to turn off the auto- reviews” and/or indexed with “systematic review” as a matic truncation, e.g., “smith j” [au]. document type. 48
  • 43. GASTROENTEROLOGY ON TH E I NTERN ET Example: 7 WGO/OMGE’s “Ask a Librarian” desk:1 Click “Clinical Queries” in the left-hand bar on the www.omge.org; click on “global guidelines” and home page under “PubMed Services.” then on “Ask a librarian” in the left-hand navigation2 Mark : “Systematic Reviews.” bar.3 Type “dysphagia” in the subject search box at the ■ bottom of the screen.4 Click “Go” Drs Justus H. Krabshuis Highland DataAnd sure enough – the Cochrane Reviews come rolling ‘Les Charleix’out. 24390 Tourtoirac , FranceComplex Evidence-Based Searches E-mail: justus.krabshuis@highland-data.com You are a very busy clinician; instead of masteringthe intricacies of deep thesaurus- driven evidence-based multifile searches, why not invest some timeinstead in telling a research librarian what you want,and then get him or her to do the job. Physicians arephysicians and not knowledge managers. Finally, remember that WGO/OMGE runs a free helpdesk for “remote” gastroenterologists searching forclinical or research information. E-mail WGO/OMGE’s“Ask a Librarian” service at www.omge.org. Happy searching – and thanks to the American tax-payer for providing us all with PubMed.References and Further Reading1 PubMed/Medline: www.pubmed.org2 Where to get help/NLM Publications on PubMed: • PubMed Help Manual • Tutorial • NLM PubMed Training Manuals • NLM Technical Bulletin- Articles about PubMed3 Evidence-based emergency medicine. How to find evidence when you need it, part1: databases, search programs, and strategies: Corrall CJ, Wyer PC, Zick LS, Bockrath CR. Ann Emerg Med 2002; 39: 302–6.4 How to find evidence when you need it, part 2: a clinician’s guide to Medline: the basics: Gallagher PE, Allen TY, Wyer PC. Ann Emerg Med 2002; 39: 436–40.5 How to find evidence when you need it, part 3: a clinician’s guide to Medline: tricks and special skills. Gallagher PE, Allen TY, Wyer PC. Ann Emerg Med 2002; 39: 547–51.6 How to find evidence when you need it, part 4: Matching clinical questions to appropriate data- bases: Wyer PC, Allen TY, Corrall CJ. Ann Emerg Med 2003; 42: 136–49. 49
  • 44. NEWS FROM THE INDUSTRY symptomatic healing. ReQuest™ Pantoprazole the PPI of Choice ALTANA was recently validated in erosive In clinical studies, pantoprazole GERD and in GERD patients [1–3]. has been shown to provide fast, Pharma sustained, and excellent daytime Pantoprazole: Fast, Sustained and night-time symptom reliefGERD is More than Just Symptomatic Relief – which, combined with high heal-Heartburn The first study using ReQuest™ ing rates, makes pantoprazole the Gastroesophageal reflux disease to evaluate the time to symptom ideal PPI for treating the overall(GERD) has a highly heteroge- relief was conducted by Mönnikes spectrum of symptomatic GERD.neous symptom profile, character- et al. in symptomatic patients withized by numerous abdominal and endoscopy-negative reflux disease Referenceschest symptoms. Although heart- who received either pantoprazole [1] Bardhan KD, Stanghellini) V, Arm-burn and acid regurgitation are fre- 20 mg or esomeprazole 20 mg for strong D, Berghöfer P, Gatz G, Mönnikes H. Evaluation of GERDquently defined as the most promi- 28 days. The results showed rapid symptoms during therapy, Part 1:nent symptoms, it is acknowledged and sustained relief of a wide range Development of the new GERDthat GERD is also associated with of GERD symptoms, and estab- questionnaire ReQuestTM. Digestionextraesophageal manifestations lished that pantoprazole 20 mg is 2004; 69: 229–37.– respiratory complaints, as well as at least as effective as esomepra- [2] Monnikes H, Bardhan KD, Stang- hellini V, Berghöfer P, Bethke TD,dyspepsia. zole 20 mg with regard to the time Armstrong D. Evaluation of GERD needed to achieve initial and sus- symptoms during therapy, PartGERD Symptom Assessment tained symptom relief [4]. II. Psychometric Evaluation and– ReQuest™ Leads the Way Validation of the New Questionnaire ReQuestTM in Erosive GERD. Diges- The measurement of GERD Proton-Pump Inhibitors (PPIs) are tion 2004; 67: 238–44.symptoms has traditionally relied Equipotent on a Milligram-for- [3] Bardhan KD, Stanghellini V, Arm-on a variety of symptom scales Milligram Basis strong D, Berghofer P, Gatz G, Mon-that are not GERD-specific. In addi- The results of the study by nikes H. International validation oftion, there is a lack of standardiza- Mönnikes et al. confirm those of ReQuestTM in patients with endos- copy negative gastroesophagealtion in defining and assessing the previous studies showing that pan- reflux disease. Aliment Pharmacolbroader symptom spectrum. This toprazole and esomeprazole are Ther 2004, in press.limits the scope for changing to therapeutically equivalent at a dos- [4] Mönnikes H, Bardhan KD, Pfaffen-alternative treatment options that age of 40 mg in patients with ero- berger B, Gatz G, Hein J, Stanghellini V. Pantoprazole 20 mg is at least asmight be more suitable to treat the sive GERD (Los Angeles grades B/C) effective as esomeprazole 20 mg forcondition. Consequently, there is with regard to healing of esopha- first and sustained symptom reliefa pressing need for a tool capable geal lesions (88% patients healed in patients with endoscopic-nega-of assessing symptoms accurately in each group), and that pantopra- tive gastroesophageal reflux diseaseand evaluating the daily treatment zole provides significantly faster (ENGERD) [abstract]. Gut 2003; 52 (Suppl VI): A127.response in patients with GERD. first-time relief from daytime and [5] Gillessen A, Beil W, Modlin IM, Gatz ALTANA Pharma is leading the night-time GERD-related symptoms G, Hole U. 40 mg pantoprazole andfield in developing ReQuest™ – a than esomeprazole (approximately 40 mg esomeprazole are equivalentstate-of-the-art reflux question- 2 days earlier) [5,6] In addition, pan- in the healing of esophageal lesionsnaire. It is a brief and reliable toprazole 40 mg and esomeprazole and relief from gastroesophageal reflux disease-related symptoms. Jpatient-administered symptom 40 mg have an equivalent effect on Clin Gastroenterol 2004; 38: 332–40.scale, sensitive and specific for intraesophageal pH in patients with [6] Scholten T, Gatz G, Hole U. Once-GERD, that can precisely define symptomatic GERD [7]. daily pantoprazole 40 mg and 51
  • 45. NEWS FROM THE INDUSTRY esomeprazole 40 mg have equiva- reflux disease. Eur J Gastroenterol by the assistant, lent overall efficacy in relieving Hepatol 2003; 15: 791–9. until the distal GERD-related symptoms. Aliment end of the scope Pharmacol Ther 2003; 18: 587– Contact details: 94. Silke Horbach reaches the liga- [7] Simon B, Muller P, Pascu O, Gatz ALTANA Pharma AG ment of Treitz. G, Sander P, Huber R, et al. Intra- Byk-Gulden-Str. 2 At this point, oesophageal pH profiles and phar- 78467 Konstanz the overtube macokinetics of pantoprazole and E-mail: esomeprazole: a crossover study in silke.horbach@altanapharma.com tip is fixed in a patients with gastro-oesophageal Url: www.altanapharma.com stable position in the duode- num, so that reaches the stomach, the overtube the scope can Fujinon is advanced along the endoscope advance further The anterograde route. until the tip of the overtube reaches without becom- the stomach. With the overtube ing looped again being held by an assistant to pre- in the stomach. vent it from being withdrawn, the After the balloon scope is then inserted further until it at the tip of the reaches the descending duodenum. scope has been The balloon on the endoscope is inflated and fixed then inflated so that it maintains a in a stable posi- stable position within the intestinal tion in the intes- lumen. The overtube is advanced tine, the balloon along the endoscope until the on the overtube overtube tip enters the duodenum. tip is deflated so The balloon on the overtube is then that the overtube inflated to hold a stable position in can be advanced The retrograde route. the intestine. With both balloons again along the inflated, the endoscope is gently scope, up to withdrawn together with the over- the balloon at the distal end. The tube to straighten it. The balloon on overtube balloon is then inflated the endoscope tip is then deflated, again and fixed in a stable position The double balloon enteroscope. and the endoscope is advanced in the intestine, and the scope bal- along the overtube, which is held loon is deflated so that the scope In collaboration with Dr. H. Yama- moto, Jichi Medical School, Japan, Fujinon has now developed a new double-balloon enteroscope (DBE) system that allows detailed exami- nation and treatment throughout the whole small intestine. The Principle The two balloons (the tip of an enteroscope and an overtube). The examination procedure Scheme: Dr. A. May, Wiesbaden,Germany starts with the insertion of an enteroscope, which has a balloon attached to its tip, into a sliding overtube that has another balloon attached to the tip of the tube. The endoscope is first inserted into the stomach with both bal- loons deflated. When the scope Double Balloon Enteroscopy Method. 52
  • 46. NEWS FROM THE INDUSTRYcan advance. These procedures are Contact details: that the device tip has reached therepeated so that the balloons can Fujinon (Europe) GmbH distal end of the scope, and the Halskestrasse 4,be advanced and alternately fixed Olympus V-System ERCP Scope 47877 Willich, Germanyin stable positions in deeper and Tel.: +49-(0)2154/924-0 elevator can be lowered. Whendeeper locations. If complex loops Fax: +49-(0)2154/924-290 withdrawing the device from theform, the overtube can be gently Url: www.fujinon.de scope, the same marking indicateswithdrawn together with the scope Fuji Photo Optical Co. Ltd. when to raise the elevator to lock 1-324 Uetake, Kitaku,with both of the balloons inflated. Saitama-City, Saitama 331-9624, Japan the guidewire. Tel.: +81-(0)48/668/2152 Fax: +81-(0)48/651/8517 Url: www.fujinon.co.jp frustrating. With the new Linear- Olympus GuideV™, unwanted movement is a thing of the past. Olympus V-Sys- tem scopes feature a revolutionary V-Groove in the V-Scope forceps elevator that allows LinearGuideV™A Revolutionary System that to be securely locked in place with-Simplifies and Enhances the out any special attachment whenEfficiency of Therapeutic ERCP extended 13 cm from the distal end The Olympus V-System is a com- of the scope. Approaching the biliaryplete system that integrates endo- or pancreatic ducts via the papilla C-Hook. Now endoscopistsscopes and endotherapy devices. can be accomplished quickly and have the option to manipulateThe revolutionary design simplifies easily without worrying about the guidewires and devices. Theand improves the efficiency of guidewire slippage. convenient C-Hook allows thetherapeutic endoscopic retrograde device handle to be attached tocholangiopancreatography (ERCP). the endoscope’s control section,With an array of unique features, the so that it is within easy reach forOlympus V-System allows either the the endoscopist. With the devicephysician or the assistant to manip- handle immediately to hand, theulate the guidewire. It also makes endoscopist can maneuver theit easier to exchange catheters and guidewire, inject contrast media,enhances cannulation capability. and manipulate the handle – while still keeping hold of the scope con- trol section. Unique Features of Endotherapy Products in the Olympus V- System V-Marking. This indicates when to raise and lower the V-Groove forceps elevator in the Olympus V-System ERCP Scope elevator. TheThe Innovative OLYMPUS V- exclusive V-Marking is located onSystem Design Lets You Proceed the proximal side of the sheath.with Confidence and Efficiency When this marking reaches the V-Sheath – device control by When a guidewire slips out instrument channel port on the the endoscopist or the assistant.of position, it can be extremely scope’s control section, it indicates The C-Hook gives the endoscopist 53
  • 47. NEWS FROM THE INDUSTRY complete control of the device, but pist or the assistant to control the • FlowerBasket V™ (retrieval bas- device control can also be passed device. ket) to the assistant if preferred. The Procedure for replacing devices • TetraCatch V™ (retrieval basket) unique device design allows the with the Olympus V-System: • Multi3V™ (triple-lumen extrac- guidewire sheath and injection 1. Confirm the position of the V- tion balloon) sheath/handle to be separated. Marking on the V-System Endo- • StarTip V™ (cannulas) The V-Sheath, with a forked sheath therapy accessory. • X-Press V™ (cannulas) design, allows either the endosco- 2. When the V-Marking is com- • Biliary Stent on QuickPlace pletely visible above the V™ (biliary stent and insertion instrument channel port the device) guidewire may be locked in the • DoubleLayer™ Stent V on Quick- V-Groove. PlaceV™ (biliary stent and inser- 3. Completely remove the device tion device) leaving the guidewire in place. – And more new products will be launched in the future. Olympus V System Product Line- Up Contact details: • V-System ERCP Scope Sales and Marketing Dept. • LinearGuideV™ (guidewire) Medical Systems Group • CleverCut 3V™ (triple-lumen OLYMPUS CORPORATION Shinjuku Monolith sphincterotome) 3-1 Nishi-Shinjuku 2-chome • CleverCut 2V™ (double-lumen Shinjuku-ku, Tokyo, 163-0914 sphincterotome) Japan onds, allowing a patient to take the with a variety of administration Takeda medication with or without water. options suitable for children and The tablet is strawberry-flavored. teenagers. The availability of the Lansoprazole: Wide Range of Patients simply place the tablet on drug to help this larger group Indications and Administration the tongue and allow it to disin- of patients further reinforces its Options tegrate until the particles can be leadership position in the PPI Eighteen years of clinical swallowed. LFDT is bioequivalent market. Use of lansoprazole in experience and availability in 98 to lansoprazole capsules and has patients aged 1–17 is supported countries throughout the world identical indications and recom- by evidence from adequate and have shown that lansoprazole is mended dosages (approved indica- well-controlled studies of lanso- effective and well-tolerated in the tions vary from country to country). prazole in adults, and additional management of acid-related disor- For children and elderly or other clinical, pharmacokinetic, phar- ders. The range of indications and patients who have difficulty in swal- macodynamic and safety studies modes of administration for lanso- lowing tablets, two other ways of have been conducted in pediatric prazole are continuing to expand administering the drug – via either patients (Figure 1). (approved indications vary from an oral syringe or a nasogastric tube country to country; please refer to – are available in the United States. New Intravenous Administration local prescribing information for all Option for Lansoprazole formulations mentioned here). Now Approved for Treatment of Lansoprazole injection has been Acid Reflux Disease in Children approved for the treatment of Lansoprazole Fast-Disintegrating Aged 1–17 erosive esophagitis in hospitalized Tablet (LFDT): First and Only Lansoprazole is now available patients in the United States. When Orally Disintregating PPI in the United States for short-term patients are unable to take oral LFDT is an easy-to-take tablet treatment of symptomatic gastro- formulations, intravenous injection that has been micro-engineered so esophageal reflux disease (GERD) of lansoprazole is indicated as an that it disintegrates quickly in the in children aged 1–17 years and alternative for short-term treatment mouth, usually in less than 60 sec- in those with erosive esophagitis, (up to 7 days) of all grades of ero- 54
  • 48. NEWS FROM THE INDUSTRY complications. Clini- matory drugs, cyclo-oxygenase-2- $OO DGROHVFHQWV Q 
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  • 51. to balance the risks, chronic anti-inflammatory therapy. 0HGLDQ 3HUFHQWDJH RI 7LPH benefits, and costs of Aliment Pharmacol Ther 2004;19: NSAIDs, COX-2 inhibi- 197–208. tors, and prophylactic [4] Graham DY, Agrawal NM, Campbell PPIs. Clinically detailed, DR, Haber MM, Collis C, Lukasik NL,et al. Ulcer prevention in long- evidence-based, and term users of nonsteroidal anti- economically sensitive inflammatory drugs: results of a dou- 3UHWUHDWPHQW )LUVW  :HHNV )LUVW  ZHHNV guidelines can help ble-blind, randomized, multicenter, rationalize decision- active- and placebo-controlled study 6WDWLVWLFDOO VLJQLILFDQW IURP SUHWUHDWPHQW DW S  of misoprostol vs lansoprazole. making involving dif- NSAID-Associated Gastric UlcerFigure 1. Median percentage of days with symptoms of ferent NSAID treatment Prevention Study Group. Arch Interngastroesophageal reflux [1]. strategies in patients Med 2002;162:169–75. TAP data on with varying degrees file. of gastrointestinal and Visit our homepage: cardiovascular risk (Fig- www.takeda.co.jp/index-e.html  ure 2). (Lansoprazole 3DWLHQWV 5HPDLQLQJ 8OFHU )UHH  is the only PPI in the  United States that is Takeda Satellite Symposium
  • 52.  indicated for healing and Booth at the 12th United  0LVRSURVWRO  J 4, /DQVRSUD]ROH  PJ 4 and reducing the risk European Gastroenterology /DQVRSUD]ROH  PJ 4 3ODFHER of recurrence of gas- Week (UEGW), Prague, 2004:      tric ulcers associated “Experience or evidence? XUDWLRQ 2I 7KHUDS :HHNV
  • 53. with NSAIDs in chronic New Challenges in  SDWLHQWV + SORULQHJDWLYH ORQJWHUP WUDGLWLRQDO 16$, XVHUV NSAID users, and Acid-Related Disorders” 3   ODQVRSUD]ROH PLVRSURVWRO YV SODFHER the indications have Time and date:Figure 2. Ulcer prevention in long-term users of traditional been approved world- Tuesday 28 September 2004,NSAIDs: comparison of lansoprazole, misoprostol, and placebo [4]. wide [3]). 18:00 h. Venue: sive esophagitis in the U.S., and it References Congress Hall, Congress will become available worldwide [1] Fiedorek S, Tolia V, Huang B, Stolle Center. J, Lee C, et al. Gastroenterology (Table 1). Panel: 2004;126 (Suppl 2): 509. [2] Kovacs TO. Intravenous (IV) and oral Prof. James W. Freston NSAID Ulcers Lansoprazole are equivalent in sup- (chairman), The risk of gastrointestinal pressing stimulated acid output in Prof. Jean P. Galmiche, events induced by nonsteroidal patients with erosive esophagitis. Prof. Chris Hawkey, Presented at DDW, Orlando 2003. anti-inflammatory drugs (NSAIDs) is Prof. Brendan Delaney, [3] Dubois RW, Melmed GY, Henning JM, two to four times greater in patients Laine L. Guidelines for the appropri- Prof. Fabio Baldi. with a history of ulcer disease or ate use of non-steroidal anti-inflam- Table 1. Antisecretory effect of intravenous lansoprazole 30 mg and oral lansoprazole 30 mg in patients with erosive esophagitis [2]. Parameter Lansoprazole delayed- Intravenous Intravenous release capsules (oral) lansoprazole placebo Maximal acid output (mEq/h; 7.16 7.64 † 26.90 ** median, interquartile range) (4.65, 10.05) (4.47, 10.29) (22.02, 30.37) Basal acid output (mEq/h; 0.77 0.51 3.19 * median, interquartile range) (0.24, 1.66) (0.09, 1.35) (1.87, 8.94) * Significantly different from intravenous lansoprazole at P = 0.005. ** Significantly different from intravenous lansoprazole at P < 0.001. † Equivalent to oral lansoprazole: significant at P < 0.04 for rejecting the hypothesis that intravenous lansoprazole is inferior to oral lansoprazole (Wilcoxon’s signed-rank test). 55