Sedation during endoscopic procedures: a Hellenic Society of Gastroenterology Position Statement.

Administration of sedation by non-anesthesiologists during gastrointestinal endoscopy remains highly controversial in Greece. The aim of this set of 16 position statements prepared by experts in the field on behalf of the Hellenic Society of Gastroenterology is to aid gastroenterologists in their everyday clinical practice and provide evidence for the best use of drugs for the sedation of patients who undergo an endoscopy. The statements address issues such as the level of sedation required, the best drugs used, their mode of action, their side-effects and possible ways to counter their action, and were adopted if at least 80% of all participants agreed upon them.

Comparative Efficacy and Tolerability of Janus Kinase Inhibitor Therapies for Moderate to Severe Crohn's Disease: Α Network Meta-analysis.

BACKGROUND AND AIMS: A number of Janus kinase (JAK) inhibitors (tofacitinib, filgotinib, upadacitinib) have been tested for moderate and severe Crohn's disease (CD) in randomized control trials (RCTs). However, data on their comparative efficacy and tolerability is lacking. We aimed to study their performance comparatively, by means of network meta-analysis (NWM). METHODS: We searched the Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through March 2021 and data was extracted. A bayesian NWM was performed to investigate the efficacy and tolerability of the above JAK inhibitors and to explore their rank order in treating moderate and severe CD patients. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: Four RCTs were entered into this NWM. They included 811 patients totally, randomized to 11 interventions, i.e. placebo, tofacitinib (1mg BID, 5mg BID, 10mg BID, 15mg BID), filgotinib 200 OD and upadacitinib (3 mg BID, 6 mg BID, 12 mg BID, 24 mg BID and 24mg OD). Two upadacitinib doses (6 mg BID and 24 mg BID) and filgotinib 200 OD, performed best as judged by the relevant forest plots, league matrixes, rankograms, SUCRA values (96.7%, 84,6 %and 78,7%, respectively) and the clustered ranking plots for efficacy and tolerability. CONCLUSIONS: Upadacitinib 6 mg BID, upadacitinib 24 mg BID and filgotinib 200 OD performed better as induction therapies in comparison to control therapies. Consequently, these regimens may play a therapeutic role in CD and therefore they merit further evaluation with well-designed RCTs.

Review: Prevention and management of gastric cancer.

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case-control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5-year survival. In an updated meta-analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first-degree relatives of GC patients as well. A meta-analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy.

Hellenic consensus on Helicobacter pylori infection.

The Hellenic Society of Gastroenterology recently organized the "Hellenic consensus on Helicobacter pylori (H. pylori) infection". The aim of this publication is to report the guidelines in order to aid the national gastroenterology community in the management of H. pylori infection. Forty-one delegates from all Greek regions, including gastroenterologists, pathologists, clinical microbiologists, epidemiologists and basic scientists, were invited to this meeting. The participants were allocated to 1 of the 4 main topics of the meeting: i.e., H. pylori diagnosis and association with diseases; H. pylori and gastric cancer; H. pylori and extragastric associated disorders; and H. pylori treatment. The results of each subgroup were submitted to a final consensus vote that included all participants. Relevant data based on international and Greek publications were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. The cutoff level of 70% was considered as acceptance for the final statement. It is hoped that the recommendations and conclusions of this report will guide Greek doctors in their daily practice concerning the management of H. pylori infection.

Review: Gastric cancer-Clinical aspects.

Gastric cancer (GC) was responsible for over 1 000 000 new cases in 2018 and an estimated 783 000 deaths, making it still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Divergent trends for GC incidence were observed in the USA. Incidence rates, particularly for non-cardia GC, were stable or increasing among persons aged <50 years. In an analysis of data from a public hospital database in Hong Kong, treatment of Helicobacter pylori infection was associated with a lower risk of GC, particularly in older subjects who received treatment ≥10 years before. Based on the results of a 16-year endoscopy-based follow-up eradication trial, patients with incomplete-type intestinal metaplasia (IM) should receive endoscopic surveillance upon H. pylori eradication therapy. Updated guidelines on the endoscopic surveillance of preneoplastic conditions of the stomach (MAPS II) have been published. In the RAINFALL trial, the addition of ramucirumab to a backbone chemotherapy as a first-line regimen failed to improve overall survival (OS) of patients with metastatic disease. Also, pembrolizumab did not prolong OS when compared to paclitaxel in the second-line treatment of patients with advanced GC or esophagogastric junction (EGJ) cancer. Trifluridine/tipiracil improved OS by 2.1 months in the third or further treatment line of patients with advanced GC. In a systematic investigation conducted on Chinese patients with GC, CLDN18-ARHGAP26/6 fusion was associated with signet-ring cell content and was prognostic for a worse outcome and predictive for no benefit from oxaliplatin/fluoropyrimidine-based chemotherapy. Organoid cultures represent an appealing model that may be applied for therapy response testing in the near future.

Gastric cancer: epidemiology, prevention, and therapy.

Gastric cancer (GC) is still the third leading cause of cancer death in both sexes worldwide. Helicobacter pylori infection is the most important risk factor for GC and, in spite of the consistent trend of a decreasing incidence, in 2015 approximately 4.4 billion individuals-more than half the world's population-were infected with H. pylori. The birth cohort pattern of decreased H. pylori infection reported in a systematic review contributes to explain the declining GC mortality in Japan. Current trends in estimated annual percentage change of GC incidence foreshadow expected reversals in both falling incidence and male predominance among US non-Hispanic whites. Combining serum pepsinogen 1 and H. pylori serology was shown to be useful for GC risk stratification in a Finnish population. Gastritis staging by operative link on gastritis assessment was confirmed to be reliable in predicting GC risk in a large prospective study. In a randomized trial from South Korea, H. pylori eradication therapy significantly reduced the rates of metachronous GC in patients who received curative endoscopic resection for early GC. A study based on a territory-wide health care database of the Hong Kong Hospital Authority showed that aspirin use is associated with a reduced GC risk. Another study based on the same database showed that proton pump inhibitors increase GC risk, but methodological biases have most likely acted as confounders. Confirmatory data on the role of endoscopic submucosal dissection in patients with early GC have been published. The phase III FLOT4 trial has shown that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) improves the outcome of patients with GC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and 5-fluorouracil). In the phase III ATTRACTION-2 trial, nivolumab was shown to be an effective treatment option with a relative safe profile for heavily pretreated patients with advanced GC.

Gastric cancer - clinical and epidemiological aspects.

Gastric cancer (GC) ranks fifth for cancer incidence and second for cancer deaths. Epidemiological data showed that survivors of Hodgkin's lymphoma and patients with pernicious anemia etiologically linked to autoimmune gastritis are at increased risk of GC. Screening of patients with autoimmune thyroid disease by means of pepsinogen (PG) I and PG I/II detected autoimmune gastritis with oxyntic gastric atrophy in one of four patients and may be recommended for GC prevention purposes. The International Agency for Research on Cancer reported a positive association between consumption of processed meet and increased GC risk. A new GC risk prediction model based on biological markers, age, gender, smoking status, family history of GC, and consumption of highly salted food showed good predictive performance, and might prompt individuals to modify their lifestyle habits, attend regular check-up visits or participate in screening programs. A novel GC classification based on gene expression of primary resected cancers correlated with clinicopathological features. Noncoding RNA for GC screening remains the focus of multiple studies. Patients with early GC undergoing endoscopic resection are more likely to develop metachronous lesions than patients undergoing surgery and endoscopic surveillance is warranted in this special cohort. The addition of gastrectomy to chemotherapy did not improve survival of patients with advanced GC and a single noncurable factor. Apatinib, a novel oral vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, improved the median overall survival of patients with advanced GC and progressive disease after two or more lines of prior chemotherapy of nearly 3 months.

Helicobacter pylori and Gastrointestinal Malignancies.

Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population dependent.

Gastric cancer--epidemiologic and clinical aspects.

Gastric cancer (GC) continues to be an important health threat as the third leading cause of cancer related death in both sexes worldwide. In a recent analysis, the mortality trends for the time period from 1980 till 2011 were significantly downward in all countries, but the declines in the USA, EU and several other major countries were of low magnitude when compared with the past. Furthermore, the relative contribution of cardia cancers compared with noncardia cancers increased among countries with higher GC rates. With respect to preneoplastic changes of the gastric mucosa, a large population-based study suggests that Helicobacter pylori infection and antigastric parietal cell antibodies-mediated autoimmune response might, for the most part, be independent and follow distinct pathways rather than causally related pathways leading to chronic atrophic gastritis. A large prospective, randomized, open-label Korean trial questioned the role of H. pylori eradication for the prevention of metachronous lesions after endoscopic resection of early GC. A review of 1258 Japanese cases undergoing curative endoscopic submucosa dissection for early GC showed that scheduled follow-up endoscopy is mandatory for detecting metachronous lesions at an early stage, where they can be treated by endoscopic resection. Ramucirumab, a vascular endothelial growth factor receptor-2 antagonist, is the first biological treatment that provides survival benefits to patients with advanced GC in progress after first-line chemotherapy. The target agent rilotumumab is currently being evaluated in patients with advanced GC overexpressing the HGF/c-MET signaling pathway. In the near future, ipilimumab and nivolumab, two immunostimulatory monoclonal antibodies with antineoplastic effects, might offer new therapeutic options for patients with advanced GC.

Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.

BACKGROUND: Recent meta-analyses have studied population differences concerning interleukin (IL)-1 gene polymorphisms in gastric carcinogenesis. In addition to the IL-1 gene cluster, candidate genes include those encoding the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The aim of the study was to systematically review the role of TNF-α-238 and TNF-α-308 gene polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by meta-analyzing all relevant studies to look for any differences concerning TNF-α gene polymorphisms in gastric carcinogenesis. METHODS: Extensive English language medical literature searches for human studies were performed up to the end of May 2013, using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using the random-effects model. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test. RESULTS: In seventeen studies, from various countries, the TNF-α-308 and TNF-α-238 frequencies of genotypes G/G, G/A, A/A were examined in gastric cancer patients and controls. For TNF-α-308 frequency overall, the pooled ORs with 95%CI for genotype G/G, A/A and G/A were 0.837 (0.712-0.982), 1.430 (1.064-1.923) and 1.145 (0.973-1.348) with respective P values 0.029, 0.018 and 0.104. Subgroup analyses showed significant results for genotype G/G only in Asians [OR=0.774 (0.610-0.983), P=0.036]. CONCLUSION: In this meta-analysis there was an overall statistically significant increased cancer risk associated with TNF-α-308 G/G and A/A genotypes. Subgroup analyses showed significant results for genotype G/G in Asians, whereas no such significant results were found for Caucasians and Hispanics.

Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis.

AIM: To examine the risk of colorectal neoplasm in acromegalic patients by meta-analyzing all relevant controlled studies. METHODS: Extensive English language medical literature searches for human studies, up to December 2007, were performed using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using either the fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test. RESULTS: For hyperplastic polyps the pooled ORs with 95% CI were 3.557 (2.587-4.891) by fixed effects model and 3.703 (2.565-5.347) by random effects model. The Z test values for overall effect were 7.81 and 6.984, respectively (P < 0.0001). For colon adenomas the pooled ORs with 95% CI were 2.486 (1.908-3.238) (fixed effects model) and 2.537 (1.914-3.364) (random effects model). The Z test values were 6.747 and 6.472, respectively (P < 0.0001). For colon cancer the pooled OR with 95% CI was identical for both fixed and random effects model (OR, 4.351; 95% CI, 1.533-12.354; Z = 2.762, P = 0.006]. There was no significant heterogeneity and no publication bias in all the above meta-analyses. CONCLUSION: Acromegaly is associated with an increased risk of colorectal neoplasm.

The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori infection is a crucial factor in the multistep carcinogenic process of gastric cancer. In this process the gastric mucosa evolves through the stages of acute gastritis, chronic gastritis, gastric atrophy (GA), and intestinal metaplasia (IM) before developing gastric adenocarcinoma. AIMS: The main aim of this study was to systematically review the long-term effects of H. pylori eradication on gastric histology (i.e. effects on GA and IM for both antrum and corpus) by meta-analyzing all relevant studies. METHODS: Extensive English-language medical literature searches for human studies were performed through October 2006, using suitable key words. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using random-effects model. RESULTS: For antrum GA the pooled OR with 95% CI was 0.554 (0.372-0.825), p=0.004. For corpus GA the pooled OR was 0.209 (0.081-0.538), p<0.001. For antrum IM the pooled OR was 0.795 (0.587-1.078), p=0.14. For corpus IM the pooled OR was 0.891 (0.663-1.253), p=0.506. CONCLUSION: The results showed significant improvement of GA, whereas improvement was not shown for IM.

Relationship between Helicobacter pylori infection and esophageal neoplasia: a meta-analysis.

BACKGROUND & AIMS: Helicobacter pylori is an important causative factor in gastric carcinogenesis. However, its role in extragastric gastrointestinal malignancies, such as esophageal cancer, is controversial. The aim of this study was to explore the relationship of H. pylori infection and H. pylori cagA-positive strain with this malignancy by performing meta-analysis of all relevant studies. METHODS: Extensive MEDLINE English language medical literature searches for human studies were performed through February 2007 with suitable keywords. Pooled estimates were obtained by using fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test. RESULTS: In adenocarcinoma patients there were inverse significant relationships with both the H. pylori prevalence (pooled odds ratio [OR], 0.52; 95% confidence interval [CI], 0.37-0.73; P < .001) and the prevalence of H. pylori cagA-positive strain (pooled OR, 0.51; 95% CI, 0.31-0.82; P = .006). Similarly in patients with Barrett's esophagus there were inverse significant relationships (pooled OR, 0.64; 95% CI, 0.43-0.94; P = .025 and pooled OR, 0.39; 95% CI, 0.21-0.76; P = .005, respectively). In patients with squamous cell carcinoma there were no significant relationships with both H. pylori prevalence (pooled OR, 0.85; 95% CI, 0.55-1.33; P = .48) and the prevalence of H. pylori cagA-positive strains (pooled OR, 1.22; 95% CI, 0.7-2.13; P = .48). CONCLUSIONS: The results showed an inverse statistically significant relationship of H. pylori infection with both esophageal adenocarcinoma and Barrett's esophagus, which might suggest a protective role of the infection in these entities. On the contrary, no statistically significant relationship with squamous cell carcinoma was found.

Helicobacter pylori infection in hospital workers over a 5-year period: correlation with demographic and clinical parameters.

BACKGROUND: We aimed to determine whether any of various groups of medical and nonmedical staff in a large acute care hospital were at increased risk of acquiring Helicobacter pylori infection over a 5-year period, and we also aimed to identify risk factors or symptoms related to H. pylori positivity and seroconversion. METHODS: A total number of 437 subjects, aged 36.8 +/- 7.7 years (range, 23-60 years)-employees of our hospital-were tested by immunoassay for serum IgG antibodies against H. pylori. Subjects were assigned to four main groups: (I) nursing staff ( n = 249; aged 34.7 +/- 7 years); (II) administrative and technical staff ( n = 127; aged 39.2 +/- 8.1 years); (III) medical staff ( n = 31; aged 42.4 +/- 4.9 years); and (IV) paramedical staff (blood donor department) ( n = 30; aged 37.6 +/- 8.5 years). Differences in age and educational level between these four groups were statistically highly significant ( P < 0.0001). Each subject completed a questionnaire containing several clinical and demographic parameters. The same cohort of individuals was tested 5 years later. RESULTS: The overall seroprevalence of H. pylori infection was 45.5%, and in each group (I, II, III, and IV) being 48.6%, 44.1%, 41.9%, and 30% respectively. Logistic regression analysis revealed that the risk of infection by H. pylori was significantly higher in group I compared with group II (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.04-3.52; P = 0.037). The H. pylori positivity increased with age: 40.6% for those aged 23-40 years and 57.5% for those aged 41-60 years ( P = 0.001). The level of education was inversely associated with H. pylori infection ( P = 0.001). During the 5-year observation, 59 of 238 (24.8%) subjects initially negative for H. pylori infection became positive, thus giving an annual seroconversion rate of 4.95%. Logistic regression analysis revealed that the seroconversion rate was significantly higher in group I compared with group II (28.1% vs 21.1%; OR, 2.34; 95% CI, 1.08-5.07; P = 0.03). The rate of seroconversion was higher in subjects aged 35-55 years compared with subjects aged 23-34 years (32% vs 17.5%; P= 0.009). Subjects who were positive for H. pylori infection in both examinations had a higher percentage of heartburn ( P = 0.029), regurgitation ( P = 0.023), and nausea ( P= 0.037) compared with those who were negative in both examinations. Differences between those who were continuously negative for H. pylori infection and those who seroconverted during the observation period were not significant. CONCLUSIONS: In this longitudinal study of workers in a large acute care hospital in Greece it was found that nursing staff had a significantly higher risk of infection compared with administrative and technical staff. Age was significantly positively related both to H. pylori infection and to seroconversion. The level of education was strongly related to the prevalence, but not to the incidence of H. pylori infection. The presence of infection over the time was associated with a higher percentage of heartburn, regurgitation, and nausea compared with subjects who were continuously negative for H. pylori infection.