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A colorectalis carcinoma több évtizede az onkológiai morbiditás és mortalitás egyik vezető oka. A vastagbélrákos betegek vallási hovatartozása befolyásolhatja a betegség járványtanát, kórlefolyását és gondozását. Járványtani felmérések igazolták, hogy egyes felekezetekhez tartozó egyéneknél (mormonok, hetedik napi adventisták, baptisták, Jehova tanúi) a colorectalis carcinoma kockázata alacsonyabb, mint más felekezeteknél, a zsidóknál viszont magasabb, mint az araboknál. A jelenség hátterében valószínűleg inkább az életmód tényezői, mint maga a hit állhat. A vallási tényezők szerepe észlelhető a szűrővizsgálatokban is, ugyanis az aktív vallási életet élő egyének nagyobb arányban hajlandók részt venni azokban, mint a nem vallásos vagy vallásukat nem gyakorló személyek. Speciális kérdőívekkel kimutatható, hogy az előrehaladott betegségekben szenvedőknél a lelki/vallási gondozás segít a daganattal való megküzdésben, és még a terminális szakban is javíthatja az életminőséget.

Az utóbbi időben a regiszterek értékes adatbázisai lettek a diagnosztikai és terápiás módszerek kiértékelésének. Az első orvosi regisztereket a 20. század elején hozták létre, ezek az onkológiában terjedtek el. A regiszterek létrehozásának módszertanát mind nemzetközileg, mind magyarul kidolgozták. A Transzlációs Medicina Központ honlapján 23 regiszter adatai olvashatók. Egyes regiszterek igen aktívak (akut és krónikus pancreatitis, ERCP, hepatitis), eredményeiket hazai és nemzetközi folyóiratokban közölték, számos regiszter azonban inaktív. A szerző a 10 éves tapasztalata alapján beszámol a Helicobacter pylori kezelésének európai regisztere feltöltésében való részvételéről. A regiszter nemzetközi közleményekben kimutatta az európai eradikációs módszerek heterogén jellegét, a gyógyszerfelírások időbeli tendenciáit és a leggyakoribb hibákat: mindezek beillesztése a gyakorlatba a betegek jobb ellátásához vezethet. Ez azonban egy igen lassú folyamat.

A Helicobacter pylori fertőzés diagnosztikai módszerei a baktérium felfedezése óta folyamatosan fej­lődtek. Az invazív módszerek közül az endoszkópia jelenleg sem mellőzhető a 45-50 év feletti, alarm panaszokkal rendelkező, illetve a vérző betegekben: az utóbbi években bevezetett technikák jelentősen javították a képalkotást, teret engedve a mesterséges intelligenciának is. A szövettan kiegészült az immunhisztokémiával és a fluoreszcens in situ hibridizációval. A leglátványosabb előretörés a genetikai módsze­reknél történt: pontosságuk meghaladja a hagyományos módszerekét. A nem invazív módszerek közül az ureakilégzési és székletantigéntesztek helye felértékelődött mind a fertőzés primer diagnózisában, mind az eradikációs kezelés utáni követésben. Oltóanyag hiányában a szűrés és kezelésre szoruló személyek, betegek köre újabb csoportokkal bővült: a fertőzés prevalenciájának csökkenése elsősorban az aktív eradikációs tevékenységtől várható.

ObjectiveTo evaluate the use, effectiveness and safety ofHelicobacter pyloriempirical rescue therapy in third and subsequent treatment lines in Europe.DesignInternational, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis.ResultsOverall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained ConclusionEmpirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update.Trial registration numberNCT02328131.

To evaluate the use, effectiveness and safety ofInternational, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis.Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed90% of cases. Overall effectiveness remained90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%.Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update.NCT02328131.

A mesterséges intelligencián alapuló vizsgálati módszerek az utóbbi évtizedekben terjedtek el az orvostudományban, így a gasztroenterológiában is. A mesterséges intelligencia előfutárai az ókorban jelentek meg, és szakaszosan fejlődtek az eltelt évszázadok során. A mai értelemben vett mesterséges intelligencia fogalmai (mélytanulás, gépi tanulás, neurális hálózatok, fuzzy logika) az 1950-es évektől alakultak ki. Magyar tudósok számos jelentős elméleti és gyakorlati megoldással járultak hozzá e folyamathoz. A mesterséges intelligencia módszereit egyre szélesebb körben alkalmazzák a gasztroenterológia számos területén (Helicobacter pylori diagnosztika, daganatos betegségek, gyulladásos bélbetegségek, képalkotó módszerek, gyógyszertervezés). Kialakulóban vannak hazai centrumok, ahol a mesterséges intelligencia saját fejlesztésű módszereit alkalmazzák.

A járványok évszázadokig megtizedelték az emberiséget, területenként veszélyeztetve egyes népcsoportok fennmaradását. Az oltások története a 18. század végén kezdődött. A bakteriológia és immunológia lehetővé tette az oltóanyagok laboratóriumi fejlesztését: ehhez a baktériumok, és vírusok inaktivációját és attenuálását használták. Ezzel párhuzamosan országonként különböző és időben változó oltási programok alakultak ki. Utóbb kialakultak a sejttenyészetet és virális vektorokat alkalmazó vakcinák. A genetika fejlődésével a 20-21. században lehetőség nyílt molekuláris genetikai markerek segítségével új típusú oltóanyagok bevezetésére, amelyekkel sikeresen lehetett felvenni a harcot számos emésztőszervi fertőző betegséggel (kolera, rotavírus, hepatitis A- és B-vírus-fertőzés). Minden kutatási erőfeszítés ellenére a tudomány adós maradt néhány közegészségügyileg jelentős fertőzésben az oltóanyaggal: ezek a Helicobacter pylori, a hepatitis C-vírus és a Clostridioides difficile-fertőzés.

Bármily egyszerűnek tűnnek mind a betegek, mind az orvosok és szakasszisztensek számára, a kilégzési tesztek története évszázadokra vezethető vissza. Az első ismeretek a levegő szerepéről és összetételéről az ókorból származnak. A légzés élettani ismeretei és a légzésfunkciós tesztek a 19. század második felében alakultak ki. A mai értelemben vett kilégzési tesztek az alapkutatások és az orvosi technológia fejlődése révén jelentek meg a 20. század második felében: a módszerek kifejlesztésében számos Nobel-díjas tudós vett részt (jelzett izotópos vizsgálatok, kromatográfia, tömegspektrometria és ezek kombinációja, ionszenzitív műszerek, elektronikus orr). Ennek következtében a modern gasztroenterológia olyan pontos kilégzési tesztekkel gyarapodott, amelyek az invazív vizsgálatokat sikeresen helyettesítik és kiegészítik.

Abstract: Introduction and aim: To assess the prevalence of lactase gene promoter C/T13910 phenotypes in patients with lactose intolerance symptoms and to analyze the birth-cohort phenomenon in lactose-intolerant patients. Method: 1266 patients consulted between 2010 and 2017 were enrolled. Five-year cohort periods of patients born before 1939 and after 1995 were defined and the prevalence of C/T13910 phenotypes was calculated. C/T13910 phenotypes were determined by polymerase chain reaction. Results: The prevalence of the CC phenotype was 43.1%, TC was detected in 44.3% and TT in 12.6% of the cases. The prevalence of the CC phenotype showed a non-linear incremental increase in females, from 9.13% in those born before 1939 to 37.7% in those born after 1995. Conclusion: The prevalence of CC phenotype raised incrementally in females, suggesting a gender/hormonal influence. Orv Hetil. 2019; 160(14): 549–554.

The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative 13C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant Hp infections, taking into account the possible predictive role of bacterial density.

Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication., Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection. Here, Kocsmár et al. study clarithromycin resistance and previous macrolide consumption in 4,744 H. pylori-infected patients, shedding light into the sources of primary resistant cases and the role played by prior consumption of macrolides for non-eradication purposes.

Absztrakt

Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells. Here it is transformed enzymatically into fructose-1-phosphate and then, fructose-1,5-diphosphate, which splits further into glyceraldehyde and dihydroxyacetone-phosphate, entering the process of glycolysis, triglyceride and uric acid production. The prevalence of fructose intolerance varies strongly, depending on the method used. The leading symptoms of fructose intolerance are similar, but less severe than those of lactose intolerance. Multiple secondary symptoms can also occur. A symptom-based diagnosis of fructose intolerance is possible, but the gold standard is the H2 breath test, though this is less accurate than in lactose testing. Measuring fructosaemia is costly, cumbersome and not widely used. Fructose intolerance increases intestinal motility and sensitivity, promotes biofilm formation and contributes to the development of gastrooesophageal reflux. Long-term use of fructose fosters the development of dental caries and non-alcoholic steatohepatitis. Its role in carcinogenesis is presently investigated. The cornerstone of dietary management for fructose intolerance is the individual reduction of fructose intake and the FODMAP diet, led by a trained dietetician. The newly introduced xylose-isomerase is efficient in reducing the symptoms of fructose intolerance. Orv. Hetil., 2016, 157(43), 1708–1716.

Introduction: Adult type hypolactasia is the most prevalent carbohydrate malabsorption. Aim: To assess the distribution of lactase gene C/T-13910 polymorphism and the accuracy and concordance of a genetic test and H2 breath test in the diagnosis of adult type hypolactasia. Method: 496 patients with symptoms of lactose intolerance were enrolled in a retrospective study who underwent genetic test using TaqMan polymerase chain reaction and H2 breath test. Results: The prevalence of C/T-13910 genotypes was: CC 48.1%, TC: 40.5%, and TT: 11.4%. When the genetic test was taken as reference, the sensitivity of the breath test was 84.3%, with a specificity of 95.7%, a positive predictive value of 96.7% and negative predictive value of 80.4%. Conversely, the accuracy of genetic test was: sensitivity 96.6%, specificity 80.4%, positive predictive value 84.3% and negative predictive value 95.7%. The concordance value between the two tests (kappa index) was 0.78. The results were discordant in 11.1% of the cases. Conclusions: In symptomatic patients, the lactase non-persistence genotype CC occurred in almost half of the patients. Both the genetic and the breath tests are sufficiently accurate, with good predictive value and they can be used to set up the diagnosis. Discordant results should be carefully interpreted. Orv. Hetil., 2016, 157(25), 1007–1112.

The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10–750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied. Orv. Hetil., 2015, 156(43), 1741–1749.

Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas. Orv. Hetil., 2013, 154, 810–819.

After a short overview of the history of probiotics, the author presents the development of human intestinal microflora based on the newest genetic data and the microbiological features of main probiotics. The indications of probiotic administration have been defined and extended in recent years. The author reviews significant results of probiotic treatment in some gastrointestinal diseases based on meta-analytical data. Probiotics are useful in preventing and treating diarrhoea caused by antibiotics and Clostridium difficile caused diarrhoea. In the treatment of Helicobacter pylori infection, preparations containing certain Lactobacillus,Bifidobacterium strains or Saccaromyces boulardii could enhance by 5–10% the rate of successful eradication and reduce the incidence and severity of the side effects. Some symptoms of irritable bowel syndrome and thus the quality of life can be improved by probiotics. Their beneficial effect in ulcerative colitis was proven, while in Crohn’s disease has not yet been defined. The use of probiotics is not included in guidelines, with the exception of the Maastricht IV/Florence consensus. For each disease it is advisable to use probiotics containing strains only with proven beneficial effect. The efficiency of preparations containing mixed strains has not yet been properly investigated. The author reviews the rare but potentially serious side effects of probiotics. In Hungary, there are many probiotic preparations available which can be purchased in pharmacies without prescription: their use is more empirical than evidence-based. The European Food Safety Authority has recently rejected claims for probiotics to be classed as medicines given the lack of convincing evidence on the effects of probiotics on human health and well-being. Clearly, further research is needed to collect evidence which could be incorporated into the international guidelines. Orv. Hetil., 2013, 154, 294–304.

Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells. Here it is transformed enzymatically into fructose-1-phosphate and then, fructose-1,5-diphosphate, which splits further into glyceraldehyde and dihydroxyacetone-phosphate, entering the process of glycolysis, triglyceride and uric acid production. The prevalence of fructose intolerance varies strongly, depending on the method used. The leading symptoms of fructose intolerance are similar, but less severe than those of lactose intolerance. Multiple secondary symptoms can also occur. A symptom-based diagnosis of fructose intolerance is possible, but the gold standard is the H

Helicobacter pylori, discovered 27 years ago, has remained the most prevalent infectious agent in the world. In the author's hypothesis, the increase of peptic ulcer prevalence in the 19-20th century could be attributable to the extended worldwide use of gastric tubes for secretory testing which led to the iatrogenic transmission of pathogenic strains. Helicobacter pylori outer membrane proteins (OMP), and duodenal ulcer promoting (dupA) proteins were identified as novel virulence factors, leading to the production of pro-inflammatory cytokines, which could be future targets of therapy. There is no ideal first-line eradication of the infection and according to expert's opinion, the efficiency of these regimens has fallen gradually in recent years to unacceptably low levels; however, in the author's opinion this is a multifactorial phenomenon which can not be generalized. As alternative drugs, the efficiency of levofloxacin, furazolidone and rifabutin has been proven by meta-analyses. Sequential and bismuth-free quadruple therapies, although highly efficient, are not yet used on a large scale. The recurrence of the infection is 2.27%/year in developed and of 13.0%/year in developing countries. Spontaneous eradication occurred in 8-20% of the children and 5-11% of adults. The prevalence of clarithromycin resistance is increasing worldwide. In Hungary, it has reached 10.9% in county cities, according to a national survey. In a district of Budapest called Ferencváros, the prevalence between 2005 and 2009 was 16-22%, with no increasing trend. The development of enzymatic inhibitors (urease, carbonic anhydrase and gamma-glutamyl transpeptidase), modified antibiotics and efflux pump inhibitors seem promising ways because these compounds do not lead to resistance; however, none have yet been used in humans.

Az Orvosi Hetilap 1948 és 1989 között az előző időszakhoz képest jelentősen több gasztroenterológiai tárgyú publikációt közölt. Az ismeretek elsősorban angol közvetítéssel kerültek a magyar szakirodalomba. Célkitűzés: Az Orvosi Hetilap ban 1989 és 2008 között megjelent gasztroenterológiai tárgyú publikációk kiértékelése. Módszer: A szerző manuális módszerrel áttekintette a folyóirat 1989 és 2008 közötti évfolyamait. A gasztroenterológiai tárgyú eredeti közleményeket, lapszemléket és könyvismertetéseket azonosította és azokból adatbázist készített. A publikációkat tematikai csoportokba sorolta és arányukat meghatározta. Az eredményeket összehasonlította az 1948 és 1989 közötti időszak publikációs tevékenységével. Részletesen áttekintette a laparoszkópos sebészet, a májátültetés és a genetikai ismeretek recepcióját az Orvosi Hetilap ban. Eredmények: 1989 és 2008 között az Orvosi Hetilap ban 2817 gasztroenterológiai tárgyú dolgozat jelent meg (1067 eredeti közlemény, 1698 folyóirat-referátum, 52 könyvismertetés), ez az összes közlemény 10,1%-a. Az előző korszakhoz képest a gasztroenterológiai tárgyú közlemények száma nem változott (p = 0,82), a folyóirat-referátumok (p = 0,006) és könyvismertetések száma jelentősen csökkent (p = 0,01). 2007-től megjelent az Orvosi Hetilap online változata és a Hungarian Medical Journal . A 1989 és 2008 között legtöbbet a máj (17,8%) és epeutak betegségeivel (4,31%), ezen belül a vírusos hepatitisekkel foglalkoztak (7,0%). Laparoszkópos sebészettel 27 (1,8%), májátültetéssel 39 (2,6%), genetikával 61 (4,0%) közlemény foglalkozott. Százharmincegy szakfolyóiratot szemléztek, a gasztroenterológiai tárgyú folyóirat-referátumok száma az előző időszakhoz képest csökkent (p = 0,006). A referátumok 65,4%-a magfolyóiratokban jelent meg. Az angol nyelvű lapok aránya 62,4%, a lapszemlék 31,5%-a német, 1,69%-a francia forrásból táplálkozik, tehát az angol dominancia erősödött. A könyvismertetések száma 211-ről 52-re csökkent (p = 0,01). A laparoszkópos sebészetben elsősorban a cholecystectomiával szerzett tapasztalatokat ismertették. A májátültetés kérdéskörének fő fóruma az Orvosi Hetilap volt. A 2000-es években az egyetemi centrumokban működő munkacsoportok ismertették az emésztőszervi betegségek genetikai kutatásait. Következtetés: Az utóbbi két évtizedben az Orvosi Hetilap sikerrel látta el hagyományos feladatát a hazai orvosok szakmai tájékoztatásában, emellett fontos szerepet vállalt a kortárs gasztroenterológia új vívmányainak (laparoszkópos sebészet, májátültetés, genetika) ismertetésében.

The editions of Orvosi Hetilap published between 1857 and 1905 covered most of the contemporary aspects of digestive diseases. Most of knowledge was transferred from German, French and English literature. Aim: Evaluation of the papers dealing with the diseases of the gastrointestinal tract published in Orvosi Hetilap between 1905 and 1944. Method: The author manually reviewed the journal volumes published between 1905 and 1944. The original articles, journal and book reviews were identified and classified according to their subject and origin. The rate of publications of the editorial periods (1857 and 1904 vs 1905 and 1944) was statistically compared with that of certain historical periods (World Wars I and II, the years following the Trianon treaty). Results: Between 1905 and 1944, a total of 1101 original articles were publised about the diseases of the gastrointestinal tract, constituting 10.3% of the total publications. The rate of publications was decreased during World Wars I and II and the years following the Trianon treaty. The most studied diseases were that of the stomach and duodenum (21%), while hepatologic studies accounted for 16.4%. The proportion of basic science studies (anatomy, pathology, physiology) decreased to 3%. Endoscopy was studied in only 1.4% of the publications, while gastrointestinal radiology, as a newcomer, achieved a figure of 3.2%. 1695 publications were reviewed from 112 journals, constituting a significant increase as compared to the previous period. 74.6% of the reviews were published in 15 core journals. 57.1% of the journals were German, 19.6% were English/American and 16.9% French, showing the persistence of the major German influence. The number of book reviews slightly decreased from 116 to 95. Peptic ulcers were the most studied disease of the period and several alternative treatments were tried, all of which are now obsolate. Conclusion: The rate of gastroenterologic publications in Orvosi Hetilap increased considerably in 1905–1944, as compared to the prior period. The main sources of knowledge remained the German literature. Diseases of the stomach and duodenum, including peptic ulcers, were studied in most detail. The development of endoscopy was overshadowed by the emergence of radiology.

Introduction: The eradication of Helicobacter pylori infection is of importance in Hungarian health care system. Aims: The aims of the Ph. D. thesis are: 1. The primary, second- and third-line eradication of Helicobacter pylori in outpatient practice; 2. Meta-analysis of the Hungarian and European eradication results; 3. The assessment of the quality of life in functional dyspepsia. Methods: 1. Six primary regimens were evaluated in 3 open, controlled, prospective, single-center trials in duodenal ulcer patients. The regimens given were: a) omeprazole, amoxicillin, metronidazole, n = 48; b) omeprazole, clarithromycin, tinidazole, n = 52; c) pantoprazole, amoxicillin, clarithromycin, n = 48; d) ranitidine bismuth citrate, clarithromycin, n = 51; e) lansoprazole, amoxicillin, clarithromycin, n = 60, and f) ranitidine bismuth citrate, clarithromycin, metronidazole, n = 61 cases). Regimens c) and f) were given in a cross-over manner as second-line treatment in 134 cases. Pantoprazole-based quadruple therapies...

Az Orvosi Hetilap 1857–1905 kozott a gasztroenterologia legtobb korabeli kerdesevel foglakozott. Az ismeretek nemet, francia es angol kozvetitessel kerultek a magyar irodalomba. Celkitűzes: Az Orvosi Hetilap ban 1905–1944 kozott megjelent gasztroenterologiai targyu publikaciok kiertekelese. Modszer: A szerző manualis modszerrel attekintette a folyoirat 1905–1944 kozotti evfolyamait. A gasztroenterologiai targyu eredeti kozlemenyeket, lapszemleket es konyvismerteteseket azonositotta, es azokbol adatbazist keszitett. A publikaciokat tematikai csoportokba sorolta, es aranyukat meghatarozta. Az 1857–1904 es 1905–1944 kozti időszak es egyes tortenelmi korszakok (I. es II. vilaghaboru, trianoni korszak) publikacios tevekenyseget osszehasonlitotta. Eredmenyek: 1904–1944 kozott az Orvosi Hetilap ban 1101 gasztroenterologiai targyu kozlemeny jelent meg, amely az osszes eredeti kozlemeny 10,3%-a, jelentősen tobb az előző időszaknal. A kozlemenyek időrendi megjelenese egyenetlen, az I. es II. vilaghaboru eveiben, illetve a trianoni szerződes utani evekben lenyegesen csokkent. A gyomor es nyombel betegsegeivel a kozlemenyek 21%-a foglalkozik, a hepatologiai targyu kozlemenyek aranya 16,4%, az alaptudomanyoke (anatomiai, patologiai, elettani) 3%-ra csokkent. Endoszkopiaval 21 (1,4%), radiologiaval 48 (3,2%) kozlemeny foglakozott. 112 szakfolyoiratot szemleztek, a gasztroenterologiai targyu folyoirat-referatumok szama 1695, aranya 9,4%, az előző időszakhoz kepest jelentősen novekedett. A referatumok 74,6%-a magfolyoiratokban jelent meg. A nemet folyoiratok aranya 57,1%, a lapszemlek 19,6%-a angol nyelvű, 16,9%-a francia forrasbol taplalkozik. A konyvismertetesek szama 116-rol 95-re csokkent. A fekelybetegseg kezeleseben szamos alternativ, ma mar tulhaladott eljarast alkalmaztak. Megbeszeles: 1905–1944 kozott az eredeti gasztroenterologiai publikaciok szama jelentősen meghaladja az előző időszak teljesitmenyet. Az informaciok forrasa tovabbra is elsősorban a nemet szakirodalom. Az időszakban kiemelkedően a gyomor es nyombel betegsegeivel foglalkoztak a legtobbet; az endoszkopia a radiologia elterjedese miatt hatterbe szorult. | The editions of Orvosi Hetilap published between 1857 and 1905 covered most of the contemporary aspects of digestive diseases. Most of knowledge was transferred from German, French and English literature. Aim: Evaluation of the papers dealing with the diseases of the gastrointestinal tract published in Orvosi Hetilap between 1905 and 1944. Method: The author manually reviewed the journal volumes published between 1905 and 1944. The original articles, journal and book reviews were identified and classified according to their subject and origin. The rate of publications of the editorial periods (1857 and 1904 vs 1905 and 1944) was statistically compared with that of certain historical periods (World Wars I and II, the years following the Trianon treaty). Results: Between 1905 and 1944, a total of 1101 original articles were publised about the diseases of the gastrointestinal tract, constituting 10.3% of the total publications. The rate of publications was decreased during World Wars I and II and the years following the Trianon treaty. The most studied diseases were that of the stomach and duodenum (21%), while hepatologic studies accounted for 16.4%. The proportion of basic science studies (anatomy, pathology, physiology) decreased to 3%. Endoscopy was studied in only 1.4% of the publications, while gastrointestinal radiology, as a newcomer, achieved a figure of 3.2%. 1695 publications were reviewed from 112 journals, constituting a significant increase as compared to the previous period. 74.6% of the reviews were published in 15 core journals. 57.1% of the journals were German, 19.6% were English/American and 16.9% French, showing the persistence of the major German influence. The number of book reviews slightly decreased from 116 to 95. Peptic ulcers were the most studied disease of the period and several alternative treatments were tried, all of which are now obsolate. Conclusion: The rate of gastroenterologic publications in Orvosi Hetilap increased considerably in 1905–1944, as compared to the prior period. The main sources of knowledge remained the German literature. Diseases of the stomach and duodenum, including peptic ulcers, were studied in most detail. The development of endoscopy was overshadowed by the emergence of radiology.

The author summarizes the historical development of our knowledge about functional dyspepsia and overviews the so-called "road to Rome" process. Between 1988 and 2006, expert committees developed using the Delphi method subsequent classifications of functional gastrointestinal disorders (Rome I-III). The Rome III classification reassessed the diagnostic criteria for functional dyspepsia and distinguished new subgroups as the postprandial distress and epigastric pain syndrome. The rationale for the proposed new classification was based on the inadequacy of prior approaches such as the predominant symptom, the results of factor analyses in tertiary care and in the general population, clinical experience and new observations in the peer-reviewed literature. Epidemiologic data suggest that dyspeptic symptoms date back to the 1730s and their prevalence increased markedly subsequently, remaining the commonest diagnosis even in the endoscopic era. The current worldwide prevalence of functional dyspepsia is 7-45%, with large geographic variations. The role of Helicobacter pylori and Salmonella infection as etiologic factors is discussed. Amongst the pathophysiological features, the recent data on the role of phenotypic changes of acid secretion, alterations of fundic accommodation and antro-duodenal motility and gastric emptying, gastric hypersensitivity and hormonal disturbances are presented, but all these abnormalities are present only in a small part of the patients. The possible role of the polymorphism of alpha-adrenoceptor gene was also raised. The treatment of functional dyspepsia led to equivocal results and the high rate of placebo response makes difficult any interpretation. According to the recent meta-analyses, proton pump inhibitors and H 2 -histamine receptor blockers are superior to placebo. In spite of good results, cisapride was withdrawn in 2004. Eradication of Helicobacter pylori can induce sustained remission in a small but significant minority of patients. However, it might prevent further development of peptic ulcer and gastric carcinoma and from public health view, eradication of the infection must be performed by using a test-and-treat or test-and-scope strategy and the benefits and risks of this approach must be discussed with the patient. Each of the above treatments achieves transient symptomatic improvement only and follow-up of dyspeptic patients for 5-7 years showed the benign, but recurrent nature of the disease in 50% of the cases. The aim of the Rome III classification is the identification of pathophysiological changes associated with the new subgroups of functional dyspepsia which will permit their targeted pharmacologic treatment leading to better and cost-efficient results.

Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy.

The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.A szerző az utóbbi 2 év Helicobacter pylori-kutatás eredményeit tekinti át. A genetikusok több mint ezer mikro-RNS közül azonosítottak néhány csoportot, amelyek gyomorrákban vagy rákmegelőző állapotokban túl- vagy alulszabályozottak: ezek lehetnek a jövő markerei vagy terápiás célpontjai. A metaanalízisek 95 közleménnyel gazdagodtak: több dolgozatban kimutatták a Helicobacter pylori és a nyelőcső-, vastagbél-, hasnyálmirigy- és májrák asszociációját, bár a kapcsolat ezek egyikében sem olyan erős, mint a fertőzés és a gyomorrák kapcsolata. Az Epstein–Barr-vírus a gyomorrákok 10%-ában mutatható ki; a fertőzés gyakoriságát normális nyálkahártyában, krónikus gastritisben és peptikus fekélyben jelenleg kutatják. Az eradikációs kezelések eredményei gyakran elégtelenek: néhány módszer kerül bemutatásra, amelyekkel azokat optimalizálni lehet. 2013-ban az Európai Helicobacter Munkacsoport kezdeményezte egy páneurópai regiszter összeállítását: eddig 5792 beteg adatait regisztrálták, kimutatva, hogy több terápiás módszer nem elég hatékony. 2013-ban indult útjára az Egészséges Gyomor Kezdeményezés azzal a céllal, hogy az egészséges egyénekben és gyomorbetegségekben végzett kutatásokat világszerte támogassák, hogy azok mielőbb alkalmazásra kerüljenek. Orv. Hetil., 2015, 156(6), 203–210.

Background: Following standard first-line triple therapies for Helicobacter pylori infection, up to 20% of patients require further eradication. Objective: The aim of this study was to assess the effects of second-line triple therapies and third-line quadruple therapies for the eradication of H pylori. Methods: This 7-week, prospective, crossover, controlled, second- and third-line trial was conducted at the Department of Gastroenterology, Ferencvaros Health Center (Budapest, Hungary). Patients aged 18 to 80 years with duodenal ulcers and an H pylori infection resistant to first-line triple therapy (pantoprazole 40 mg BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID [PAC] given as tablets) received a different triple therapy regimen (ranitidine bismuth citrate 400 mg BID + metronidazole 500 mg BID + clarithromycin 500 mg BID [RBC-MC]) for 7 days (group 1A), and nonresponders after RBC + 2 antimicrobials received the pantoprazole-based regimen (group 1B). After secondary failure, patients were randomized to receive quadruple therapies: pantoprazole, amoxicillin, tetracycline, and either nitrofurantoin or bismuth subsalicylate (groups 2A and 2B). Results: One hundred thirty-four patients were enrolled in the second-line study (56 men, 78 women; mean [SD] age, 51.1 [12.4] years; group 1A, 68 patients; group 1B, 66 patients). Subsequently, 41 (30.6%) of these patients were randomized to receive quadruple therapies. Using intent-to-treat (ITT) analysis, the eradication rates did not differ significantly (60.3% and 65.2% in groups 1A and 1B, respectively; 61.9% and 55.0% in groups 2A and 2B, respectively). Perprotocol eradication rates did not differ significantly (66.1% and 68.3% in groups 1A and 1B, respectively); however, the rates were significantly different in group 2A (66.7%) versus group 2B (55.5%) (P = 0.03).

Peptic ulcer was a rare disease before 1850. The prevalence of peptic ulcer increased gradually in persons born between 1870 and 1900. A similar decay in opposite direction of the prevalence occurred after the 1960-1970s. Although the pathogenesis of peptic ulcer is readily explained by the Helicobacter pylori infection, the bacterium occurred many thousands years ago and followed the migrations of human populations; consequently, its presence does not explain the increase in peptic ulcer prevalence. Gastric tubes for secretory testing were introduced from 1871 and their use was extended gradually in the then growing departments of gastroenterology, becoming a very popular, though unpleasant method. There is circumstantial evidence from the pre-H. pylori era that gastric/enteral infections could be transmitted though contaminated gastric tubes/electrodes. The author's hypothesis is based on the temporary overlap of the increased peptic ulcer prevalence and the extensive use of gastric secretory testing. The use of contaminated gastric tubes in sick persons harbouring pathogenic strains of the bacterium could have led to the transmission of the infection by gastro-oral route to the patients' ward-mates and on, to their family members: years later, new ulcer or dyspeptic patients may have come from such groups. The current decay in peptic ulcer prevalence could be due to the decreased use of secretory testing and implementation of rigorous disinfection rules.

Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future.

Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas.A tumormarkerek olyan géntermékek, amelyek az egyes szervekben kialakuló daganatok jelenlétét, illetve azok sebészeti/gyógyszeres kezelés utáni kórlefolyását jelzik. Felfedezésüket a syngen rágcsálókban kémiai vagy virális úton kiváltott daganatokban leírt tumorspecifikus antigénekből származtatják. A mai klinikai gyakorlatban használt tumorjelzők története az 1940-es években kezdődött: 1944-ben elsőként az alfa-foetoproteint, 1965-ben a karcinoembrionális antigént fedezték fel, azóta palettájuk egyre bővült. Ma már mindegyik pontos szerkezete és genetikája ismert. Egyeseknek funkciója lehet a daganatok növekedésében és a metasztázisok keletkezésében. A tumorjelzők meghatározása végezhető lakossági/kockázati csoportok szűrése céljából, a tumordiagnosztikában, a sebészeti és kemoterápiás kezelés eredményének kiértékelésében, a recidívák kimutatásában és a tumorlokalizációban, de ideális tumorjelző nincs. Izotópokkal jelzett anti-karcinoembrionális antigén ellenanyagnak és E-szelektin-gátló szereknek a jövőben szerepe lehet a vastagbél- és pancreasrák molekuláris sugár- és kemoterápiájában. Orv. Hetil., 2013, 154, 810–819.

The author overviews some aspects of literature data of the past 2 years. Genetic research has dentified polymorphisms of Helicobacter pylori virulence factors and the host which could play a role in the clinical outcome of the infection (peptic ulcer or gastric cancer). So far they have been performed in research centers but with a decrease of costs, they will take their place in diagnosing the diseaes and tailoring the treatment. Antibiotic resistance is still growing in Southern European countries and is decreasing in Belgium and Scandinavia. Currently, the clarithromycin resistance rate is of 17–33% in Budapest and levofloxacin resistance achieved 27%. With careful assessment of former antibiotic use the resistance to certain antibiotics can be avoided and the rates of eradication improved. Immigration is a growing problem worldwide: according to Australian, Canadian and Texan studies, the prevalence of Helicobacter pylori is much higher in the immigrant groups than in the local population. An Italian study showed that the eradication rate of triple therapy is significantly lower in the Eastern European immigrants than in the Italians. A recent research has suggested a link between female/male infertility, habitual abortion and Helicobacter pylori infection. However, there are no published data or personal experience to show whether successful eradication of the virus in these cases is followed by successful pregnancies or not. The author overviews the Maastricht process and analyzes the provisions of the Maastricht IV/Florence consensus, in which the new diagnostic algorithms and indications of eradication therapy are reformulated according to the latest levels of evidence and recommendation grading. According to the “test and treat” strategy, either the urea breath test or the stool monoclonal antigen test are recommended as a non-invasive diagnostic method in primary care. Endoscopy is still recommended in case of alarm symptoms, complicated ulcer, or if there is a suspicion of malignancy or MALT lymphoma. Local resistance to clarithromycin and levofloxacin should be considered in the choice of first-line therapy, in case of levels >15–20% these compounds should not be used. In regions with low resistance rates, classical triple therapy remains the regimen of choice; its alternative is the bismuth-based quadruple therapy. Determining antimicrobial resistance is justified after failed second- or third-line therapies; where available, molecular methods (fluorescence in situ hybridization, polymerase chain reaction) should be used. As second/third line treatments, the sequential, bismuth-based quadruple, concomitant quadruple regimens, hybrid are all possible alternatives. The Hungarian diagnostic and therapeutic approach in practice is different in some aspects from the provisions of the European consensus. Orv. Hetil., 2012, 153, 1407–1418.

Nowadays, the main method for assessing the efficiency of pharmacologic therapies are the randomized controlled trials (RCTs), which are regarded as an objective measure of the biologic response of the patients to a given treatment. However, beside quantifying therapeutic responses, there are many other subjective factors (emotional factors such as depression or anxiety, ability to perform daily activities at the workplace or at home, changes in eating/sleeping, social, familiar, and sexual habits), which are difficult to assess using quantitative methods. Both dyspepsia and quality of life (QoL) are ill-defined terms [1, 2]. Physicians traditionally prefer to use objective methods to diagnose and monitor treatment responses. However, many gastrointestinal diseases have a high symptom burden and enormous health-care costs but little objective evidence of the disease; this is especially true for the large group of functional disorders to which dyspepsia belongs [3, 4].

Studies concerning the eradication of Helicobacter pylori have resulted in a proliferation of meta-analyses. To date, there are 303 meta-analyses cited in PubMed, 113 dealing with the therapy of the infection. A chronological analysis of the results of meta-analyses performed between 1998 and 2010 shows that first-line standard triple therapies achieved eradication rates on an intention-to-treat basis of around 80%; prolonging treatment to 14, but not 10 d should improve the results. The proton pump inhibitors have a similar efficiency, and giving a double dose is more efficient than the standard doses of these drugs. Triple and quadruple therapies proved to be equivalent. Based on meta-analytical data, the decrease in efficiency over time cannot be substantiated: eradication rates < 80% followed from the introduction of triple therapies. As alternatives, ranitidine bismuth citrate-, levofloxacin- or furazolidone-based therapies were shown to obtain the same eradication rates as standard triple regimens. Sequential therapies and quadruple non-bismuth-based therapies were superior to standard triple therapies but their use is limited to certain countries. In the author’s opinion, and from a meta-analytical viewpoint, standard triple therapies cannot yet be considered obsolete. Furthermore, non-inferiority trials are proposed for the future, including assessment of local contemporary antimicrobial resistance profiles and the CagA and CYP2C19 status of the enrolled patients.