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Background Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. Methods A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. Results The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long‐term prognosis and life expectancy are favorable. Conclusions and Inferences A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD., Key summary Current knowledge Functional dyspepsia is one of the most common conditions encountered in clinical practice.There is a lack of guidance for clinicians in guiding diagnosis and treatment of this prevalent condition.No treatments are currently approved for the treatment of functional dyspepsia in Europe. What is new here A Delphi panel consisting of 41 experts from 22 European countries established the level of consensus on 87 statements regarding functional dyspepsia.The statements reaching consensus serve to guide clinicians in recognizing, diagnosing and treating FD in clinical practice.Endoscopy is mandatory for establishing a firm diagnosis of functional dyspepsia D, but in primary care patients without alarm symptoms or risk factors can be managed without endoscopy. Helicobacter pylori status should be determined in every patient with dyspeptic symptoms and H. Pylori positive patients should receive eradication therapy.Proton pump inhibitor‐therapy is considered an effective therapy for FD, but no other treatment approach reached consensus support.

In the below-referenced article,1 the name of one of the authors in the ESNM Gastroparesis Consensus Group was misspelled. D. Kestzhelyi's name should have been listed as D. Keszthelyi. Additionally, Jolien Schol and Lucas Wauters should be listed as co-first authors. We apologize for these errors.

Background and Aims: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. Methods: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. Results: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. Conclusions: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. Conclusions and Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD. © 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.

Background: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. Methods: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. Results: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. Conclusions and Inferences: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis. © 2021 John Wiley & Sons Ltd

Introduction: Antibiotic resistance is the major factor affecting our ability to cure Helicobacter pylori infection. Quadruple therapy is currently recommended ; however, triple therapy with two antibiotics may be sufficient in those patients without clarithromycin resistance. Aims & Methods: To evaluate the effectiveness of the treatments according to the clarithromycin H. pylori resistance in Europe. International multicenter prospective non-interventional European Registry on H. pylori Management (Hp-EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection. Infected adult patients diagnosed with culture registered at AEG-REDCap e- CRF from 2013 to 2019. Per-protocol (PP) analysis was performed based on the presence or absence of clarithromycin bacterial resistance. Results: Overall, 5, 036 patients were included: 1, 747 (35%) were resistant and 3, 289 (65%) sensitive to clarithromycin. The overall eradication rate was higher in clarithromycin-susceptible patients (91% vs. 84% ; p< 0.001). Triple therapy with a PPI, clarithromycin and amoxicillin achieved over 90% eradication rates in clarithromycin- susceptible patients. However, in those with clarithromycin- resistance, optimal effectiveness was only achieved when treated with quadruple therapy with a PPI, clarithromycin, amoxicillin and bismuth. Conclusion: Classic triple therapy with a PPI, clarithromycin and amoxicillin achieves optimal results (>90%) in patients susceptible to clarithromycin. However, when clarithromycin resistance is unknown, quadruple therapy with a PPI, clarithromycin, amoxicillin and bismuth may be a better treatment option.

Introduction: Antibiotic resistance is the major factor affecting our ability to cure Helicobacter pylori infection. Understanding the different H. pylori antibiotic resistances could be the key to improve treatment effectiveness. Aims & Methods: To evaluate the H. pylori antibiotic resistance both prior and after one or several eradication treatments, in order to provide the most appropriate recommendations for the eradication of H. pylori. International multicenter prospective non-interventional European Regis-try on H. pylori Management (Hp- EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection by European gastroenterologists. Infected adult patients diagnosed with culture and with a result of the antibiotic resistance test registered at AEG- REDCap e-CRF from 2013 to 2019. Per-protocol (PP) analysis was performed. The antibiotic bacterial resistances were described by treatment line. Results: A total of 32, 447 patients were included, and culture was performed in 3, 474 (11%). In naïve patients, 21% reported single clarithromycin resistance, and 11% dual (clarithromycin and metronidazole) resistance. Antibiotic resistance increased markedly from the first treatment, reaching over 37% dual resistance in second-line treatment. Conclusion: In Europe, culture testing to determine antibiotic resistance against H. pylori is scarce. H. pylori single clarithromycin resistance remains high (>15%) in all treatment lines, and greater than 20% in naïve patients. Dual or triple resistances are frequent and increase remarkably after the first treatment failure. Resistance to amoxicillin or tetracycline is exceptional.

Introduction: Bacterial antibiotic resistance changes over time based on multiple factors. It is essential to study these trends to apply preventive strategies to help reducing such resistances.Aims & Methods: To conduct a time-trend analysis of the antibiotic resistance to H. pylori infection in the European Registry on H. pylori (Hp-EuReg). International multicenter prospective non- interventional European Registry on H. pylori Management (Hp-EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection by European gastroenterologists. All infected adult patients diagnosed with culture and with a result of the antibiotic resistance test were registered at AEG-REDCap e-CRF from 2013 to 2019.Results: A total of 32, 447 patients were included, and culture was performed in 3, 474 (11%), where 2, 483 näive patients were included for analysis. Resistance to at least one antibiotic was described in 57% of the patients. Resistance to metronidazole (27%) was most frequent, whereas resistance to tetracycline and amoxicillin was below 1%. Clarithromycin resistance remained above 15% throughout the studied years. A significant decrease in the metronidazole resistance rate was observed between 2013 (38%) and 2018 (21%).Conclusion: In naïve patients, resistance to clarithromycin remained above 15% in the period 2013-2019. A progressive decrease in metronidazole resistance was observed. No increasing or decreasing trend was observed in the bacterial resistance to other antibiotics.

Background Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. Aim To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). Methods A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. Results One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera(R); n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. Conclusion In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. Pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/ Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Background/Aims: The aim of the study is detection and evaluation of the abdominal and gastrointestinal; infective foci using Tc-99m-ciprofloxacin (Laboratory for radioactive isotopes, Vinca). Methodology: In total 21 patients with clinical suspicion on abdominal or gastrointestinal infection were investigated. In all the patients, planar liver/spleen scintigraphy was performed. Ciprofloxacin chloride (3.5mg) was mixed with 555MBq of Tc-99m in 3mL of physiological solution and incubated for 20 min. After slow i.v. injection in a cubital vein, dynamic acquisition (1 f/min) was performed during the first 60 min in the position of interest, followed by static acquisition (500 000 imp) anterior and posterior view, abdomen and pelvis after 1 h and 4 h in all patients. When necessary, additional scintigrams were acquired after 24h. In all the patients with negative or equivocal findings of planar scintigraphy, emission computerized tomography (SPECT) was performed (60 positions, 6 degrees). Interpretation was made by three independent observers. Additional data were provided using clinical findings, ultrasonography, computed tomography and magnetic resonance imaging, laboratory analyses, and surgical or microbiological confirmation of infection. Results: There were eleven true-positive findings, seven true negative, two were false negative while one was false positive due to intestinal obstruction. Sensitivity was 79%, specificity 91%, positive predictive value 92%, negative predictive value 77% accuracy 84%. Conclusions: According to our results, scintigraphy with radiolabeled ciprofloxacin is a useful method for detection and assessment of exact localization of abdominal and gastrointestinal infections.

Atomic force microscopy (AFM), a unique tool to investigate drug treatment of cancer cells, was used to analyze the anti-neoplastic activity of adriamycin by comparing DNA structures of non-treated and adriamycin-treated Ehrlich tumor cells. The non-treated cells exhibited a highly branched intact chromatin structure, related to the intensive DNA replication in cancer cells. Images from adriamycin-treated tumor cells showed that the DNA chains were broken and the chromatin structure had been destroyed. Possible explanations for these effects of adriamycin are considered: breakage of hydrogen bonding, oxidation and intercalation effects, as well as the poisoning of topoisomerase enzyme. DNA fractal and multifractal analyses performed in order to evaluate the degree of bond scission, showed that the treated DNA had become more fractal compared to non-treated DNA. DNA izolovana iz Erlihovih tumorskih ćelija je AFM mikroskopijom posmatrana prethodno tretirana adriamicinom i u netretiranom stanju, radi poređenja. AFM mikroskopija pruža mogućnost dobijanja direktne slike izgleda DNA strukture maligne ćelije koja nije tretirana lekom i iste strukture posle delovanja adrijamicina, što daje nove podatke o delovanju citostatika na malignu ćeliju. Netretirane ćelije (viđene AF Mmikroskopijom) su ispoljile netaknutu strukturu hromatina koja odgovara intenzivnoj DNA replikaciji u malignoj ćeliji. Maligne ćelije tretirane adriamicinom su pokazale da su DNA lanci pokidani tj. dalja replikacija je sprečena, što je jedan od osnova aktivnosti citostatika. Multifraktalna analiza AFM mikroskopskih slika tretirane i netretirane DNA je kvantitativno potvrdila zaključke dobijene mikroskopijom jer su grafici AFM slika uzoraka tretiranih adriamicinom pokazali fraktalniju strukturu od AFM slika netretiranih malignih ćelija kod kojih grafik ukazuje na potpuni gubitak fraktalnosti, što je znak prisutnog patološkog procesa u organizmu.

IUBMB 50th Anniversary Symposium, Jul 02-07, 2005, Budapest, Hungary

It is currently unclear whether intestinal metaplasia at the esophagogastric junction and in the distal esophagus represent a continuum of the same underlying disease process, i.e., gastroesophageal reflux, or constitute different entities with a diff e r e n t pathogenesis. Biopsies below the Z line might show specialized epithelium in some patients and the question is whether this is another form of short segment Barrett’s esophagus or whether it is related to a generalized atrophic process of the stomach. Data from recent studies regarding the expression of cytokeratin CK7 and CK20 in intestinal metaplasia (IM) found at the gastroesophageal junction are conflicting. Prompted by these data we undertook the present study: a) to evaluate the expression of CK7 and CK20 in IM of the gastric cardia and to compare the findings with those in patients with Barrett’s esophagus and IM of the gastric corpus and antrum mucosa; and b) to evaluate the immunophenotype of non-intestinalized cardiac mucosa and to compare it with that of normal gastric epithelium. We studied the expression of CK7 and CK20 on biopsy specimens from patients with long-seg m e n t B a r r e t t ’s esophagus (n=17) and surgical resection and biopsy specimens of gastric cardia (n=15), corpus (n=14) and antrum (n=22) from patients with histological evidence of IM. Eighty-four biopsy specimens from 42 patients (antrum n=15, corpus n=20, cardia n=7) without evidence of IM were studied as a control group. We observed an immunophenotype characterised by diffuse moderate to strong CK7 staining on the surface and crypt epithelium combined with strong CK20 staining on the surface and superficial part of the crypts in 94.1% (16/17) of the cases with long-se g m e n t Barrett’s esophagus, but in none of the 36 cases with IM in distal stomach (antrum and corpus). IM in the gastric cardia expressed the immunophenotype seen in IM of the gastric mucosa in 93.3% (14/15) of the cases. On the other hand, normal cardiac epithelium expressed patchy strong CK7 staining on the surface epithelium and on both, superficial and deep parts of the pits combined with patchy strong CK20 staining on the surf a c e epithelium and superficial pits, a feature permitting distinction of the normal cardiac epithelium from those of the normal gastric antrum and corpus epithelium. We conclude that the expression of cy t o keratins 7 and 20 can be used to distinguish the origin of IM of the gastroesophageal junction. The CK7/20 immunophenotype of IM in the gastric cardia closely resembles that of the IM in the gastric antrum and corpus and is different from IM in long-segment Barrett's esophagus. In contrast, the CK7/20 immunophenotype of the cardiac epithelium is different from that of the gastric antrum and corpus mucosa, suggesting that cardiac epithelium might not be a native normal g a s t r i c epithelium but one that is acquired as a consequence of longstanding inflammation. Changing pattern of CK7 and CK20 expression from normal to intestinalized epithelium suggests that IM arising from cardiac epithelium might have distinctive features.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

ObjectiveThe best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.DesignInternational multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed.Results30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%–90%).ConclusionManagement of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.