Helicobacter pylori, gastric microbiota and gastric cancer relationship: Unrolling the tangle.

Helicobacter pylori infection (Hp-I) represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors, leading to inflammatory changes, dysbiosis and eventually gastric cancer. The normal gastric microbiota shows diversity, with Proteobacteria [Helicobacter pylori (H. pylori) belongs to this family], Firmicutes, Actinobacteria, Bacteroides and Fusobacteria being the most abundant phyla. Most studies indicate that H. pylori has inhibitory effects on the colonization of other bacteria, harboring a lower diversity of them in the stomach. When comparing the healthy with the diseased stomach, there is a change in the composition of the gastric microbiome with increasing abundance of H. pylori (where present) in the gastritis stage, while as the gastric carcinogenesis cascade progresses to gastric cancer, the oral and intestinal-type pathogenic microbial strains predominate. Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself. Successful H. pylori eradication is suggested to restore gastric microbiota, at least in primary stages. It is more than clear that Hp-I, gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll. Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H. pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.

Prevalence of inflammatory bowel disease in young Greek Army male recruits from 2006 to 2018: a 13-year retrospective study from a tertiary center.

BACKGROUND: The prevalence and incidence of inflammatory bowel diseases (IBDs) vary among countries. Data regarding prevalence of IBD in Greece are limited or outdated. METHODS: We reviewed the medical records of IBD patients from a population of 551,808 Greek Army recruits in a 13-year period (2006-2018). Study population consisted of males 18-37 of age from Northwest, Central Greece (including Attica), Peloponnese, and Aegean Sea Islands. Age, disease distribution, pharmaceutical treatment and IBD-related surgery at the time of patients' admission were recorded. RESULTS: The prevalence of IBD among male recruits during the studied period was 0.15% (839/551 808, 95% confidence interval 0.14-0.16%). Of these, 448 (53.4%) had Crohn's disease (CD) and 391 (46.6%) ulcerative colitis (UC). Although 32.1% of CD patients had been treated with biologics, most often infliximab (60% of them), azathioprine was the most common as monotherapy (27% of patients). Among UC patients, mesalamine was the most often prescribed treatment (64.2%), whereas treatment with biologics as monotherapy or in combination with azathioprine was used in a ratio 1:2 compared to CD patients. A gradual reduction in steroid use was noted from 2006 to 2018, coinciding with the advent and increasing use of biologics. IBD-related surgery had been performed in 8% and 2.8% of CD and UC patients, respectively. CONCLUSION: The prevalence of IBD in Greek male recruits was 0.15% with a slight CD predominance. Remarkable changes in therapeutic trends were noted with an increasing use of biologics and reduced prescription of steroids, especially for CD.

Informed consent in inflammatory bowel disease: a necessity in real-world clinical practice.

In modern medicine, any medical intervention has to be supported by a patient's informed consent. Challenges to this process include the specificity and complexity of medical information being provided, the patient's ability to comprehend the information, the medical uncertainty of the outcomes, and the physician's legal concerns. Important elements of the consent process are respect for the patient's autonomy and self-determination, appropriate disclosure and verification of their understanding, and voluntariness. In inflammatory bowel disease (IBD), pharmaceutical treatment carries significant risks, making discussion and illustration of the treatment critical for decision making. This review aims to emphasize the importance of the informed consent process in routine IBD clinical practice, and suggests an appropriate way of informing patients about the medical treatment on offer. The information that has to be comprehensively presented before consent includes: i) treatment goal; ii) basic characteristics of treatment (route and timetable of drug administration, drug efficacy, adverse events); and iii) consequences of staying untreated. The IBD physician's main concerns must include ensuring not only that the information being provided is detailed and objective, but also that the decision-making process is shared with the patient. Ultimately, the process of obtaining informed consent in real-world clinical practice is undoubtedly of great importance, for both upholding the principles of medical ethics and avoiding legal conflicts.

Evaluation of the Direct Economic Cost per Eradication Treatment Regimen against Helicobacter pylori Infection in Greece: Do National Health Policy-Makers Need to Care?

Helicobacter pylori (Hp) management has undoubtedly resulted in a notable economic burden on healthcare systems globally, including Greece. Its cost has never been estimated so far, especially during the recent 10-year unprecedented financial crisis. Direct medical and procedural costs for one attempt "outpatient" Hp eradication treatment were estimated as the following: (I) first-line regimens: 10 and 14 days standard triple, 10 and 14 days sequential, 10 and 14 days concomitant non-bismuth quadruple, 14 days hybrid, (II) second-line salvage regimens: 10 and 14 days levofloxacin-containing triple regimens. Treatment costs using prototypes and/or generic drugs were calculated. Drug prices were collected and confirmed from two official online medical databases including all medicines approved by the Greek National Organization for Medicines. Regimens based on generics were more affordable than prototypes and those including pantoprazole yielded the lowest prices (mean: 27.84 €). Paradoxically, 10-day concomitant and 14-day hybrid regimens (currently providing good (90-94%) first-line eradication rates in Greece) cost the same (mean: 34.76 €). The expenditures for Hp eradication treatment regimens were estimated thoroughly for the first time in Greece. These data should be taken into account by Public Health policymakers both in Greece and the European Union, aiming for a better and less expensive therapeutic approach.

Plummer-Vinson Syndrome in a Crohn's disease patient.

Plummer Vinson Syndrome (PVS), a rare condition complicating iron deficiency anaemia, manifests as a classic triad of dysphagia, anaemia and oesophageal web. Iron deficiency is the commonest systematic complication of Crohn's disease with only one described case of a Crohn's disease patient combined with PVS in the literature. We present a case of PVS complicating Crohn's disease in a 38-years-old female patient under treatment with the biologic agent Ustekinumab (human interleukin 12/23 monoclonal antibody) suffering from a progressively worsening dysphagia.

Helicobacter pylori eradication regimens in an antibiotic high-resistance European area: A cost-effectiveness analysis.

INTRODUCTION: Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis. AIM: This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period. MATERIALS AND METHODS: Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations. RESULTS: Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively). DISCUSSION: This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I.

Impact of occupational stress on irritable bowel syndrome pathophysiology and potential management in active duty noncombat Greek military personnel: a multicenter prospective survey.

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the gut-brain axis interaction disorders. It has global distribution with varying prevalence and particular financial and psychological consequences. IBS has been associated with stress and anxiety, conditions that are usually prevalent in the army. There are scarce data investigating the impact of IBS on noncombat active duty military without reports of Greek military or stress in the occupational environment. MATERIALS AND METHODS: The main exclusion criteria in our noncombat military multicenter prospective survey were gastrointestinal pathologies, malignancies, hematochezia, recent infections and antibiotics prescription, and pregnancy. Questionnaires included a synthesis of baseline information, lifestyle, and diet, psychological and stress-investigating scales and the IBS diagnosis checklist. Hospital Anxiety and Depression Scale and Rome IV criteria were utilized. RESULTS: Among 1605 participants included finally, the prevalence of IBS was 8% and 131 cases were identified. Women were more vulnerable to IBS, although male sex was prevalent at a ratio of 3.5 : 1 (male:female) in the entire sample. The mean age of all participants was 23.85 years; most of the IBS patients were older than thirty. Abnormal anxiety scores and high levels of occupational stress were related to an IBS diagnosis. DISCUSSION: This prospective multicenter survey showed, for the first time, the potential impact of occupational stress on IBS in active duty noncombat Greek Military personnel. The diagnosis of IBS by questionnaire is a quick, affordable way that can upgrade, by its management, the quality of life and relieve from the military burden. Our results are comparable with previous studies, although large-scale epidemiological studies are required for the confirmation of a possible causative relationship.

Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF.

AIM: To identify factors predicting mucosal healing in ulcerative colitis patients treated with anti-TNFα agents with or without azathioprine. METHODS: In a prospective, multicenter, one-year study biologic naïve patients aged 25-65 years, with corticosteroid-dependent or refractory colitis received combination treatment with anti-TNFα and azathioprine for 6 months followed by anti-TNFα monotherapy. Patients who denied combination therapy or were outside this age range received anti-TNFα monotherapy (controls). Before and at weeks 12 and 54 of treatment the total Mayo score was calculated. Mucosal healing was defined as endoscopic subscore of 0. Mucosal expression of T helper (Th) cell-lineage specific transcription factors (Tbet, Gata3, Rorc, FoxP3) before treatment was also associated with mucosal healing. RESULTS: Of 67 patients, 58 (86.6%) received combination and 9 (13.4%) anti-TNFα monotherapy. Overall 29 (43.3%) patients achieved mucosal healing; rates were higher in patients receiving combination therapy vs. monotherapy (p=0.03) and in azathioprine naïve vs. exposed patients in the combination group (p=0.01). Mucosal healing was associated with lower pre-treatment mucosal expression of transcription factor Th1-Tbet (p<0.05) and higher expression of Th17-Rorc (p<0.05). CONCLUSIONS: Mucosal healing was associated with combination therapy, especially in biologic and azathioprine-naïve patients and pre-treatment mucosal expression of specific Th specific transcripting factors (Tbet and Rorc).

Azathioprine discontinuation earlier than 6 months in Crohn's disease patients started on anti-TNF therapy is associated with loss of response and the need for anti-TNF dose escalation.

OBJECTIVES: A high proportion of Crohn's disease (CD) patients lose response to antitumor necrosis factor (anti-TNF) and therapy needs to be intensified. We aimed to prospectively determine the predictors and frequency of anti-TNF loss of response and therefore the need for dose escalation and de-escalation in CD patients treated with infliximab or adalimumab. METHODS: All patients were anti-TNF naive while concomitant azathioprine was administered for 6 months. In patients initially responding to anti-TNF and subsequently losing clinical response after the first 14 weeks of therapy, dose escalation was scheduled. During the follow-up period and after 1 year of intensified administration, anti-TNF was de-escalated in patients in remission. RESULTS: A total of 161 patients were started on infliximab (n=96) or adalimumab (n=65); however, 29 patients (18.0%) did not respond to therapy and were excluded from further analysis. From the remaining 132 patients (infliximab=77, adalimumab=55), 31 (23.5%) needed a dose escalation for maintenance of remission during a median 28-month follow-up period. Factors associated with loss of response and therefore the need for anti-TNF dose escalation were azathioprine discontinuation earlier than 6 months and smoking. Most patients achieved clinical remission (n=25, 80.6%) without other interventions and among these, 16 patients (64%) were successfully de-escalated to the standard maintenance infliximab or adalimumab dose schedule after 1 year of intensified anti-TNF administration. CONCLUSION: Azathioprine discontinuation earlier than 6 months and smoking in CD patients started on anti-TNF therapy is associated with loss of response and the need for anti-TNF dose escalation.

Long term benefit of one year infliximab administration for the treatment of chronic refractory pouchitis.

BACKGROUND-AIM: The aim of this study is to identify the long term benefit of one year infliximab administration for the treatment of chronic refractory pouchitis following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: Seven patients with chronic refractory pouchitis diagnosed by clinical, endoscopic and histological criteria received infliximab 5 mg/kg at 0, 2, and 6 weeks and thereafter every 2 months for 1 year. Three patients had fistulae (1 pouch-bladder, 2 perianal) and 4 extraintestinal manifestations (2 erythema nodosum, 2 arthralgiae). All patients were refractory to antibiotics and 3 to azathioprine. Crohn's disease was excluded after re-evaluation of the history and small bowel examination with enteroclysis or capsule endoscopy. Clinical response was classified as complete, partial and no response. Fistulae closure was classified as complete, partial and no closure. The pouchitis disease activity index (PDAI) was used as an outcome measure. All patients were followed up for 3 years after discontinuation of infliximab therapy. RESULTS: After 1 year of infliximab administration 5 patients had complete clinical response, 1 partial clinical response and 1 no response, while 2 out of the 3 patients with fistulae had a complete closure. The median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission too. Three years after completion of therapy, all patients with complete clinical response at one year remained in remission. CONCLUSIONS: One year infliximab administration is associated with a long term benefit in patients with chronic refractory pouchitis following IPAA for UC.

One-year infliximab administration for the treatment of chronic refractory pouchitis.

AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis, following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: Seven patients (4 females, 3 males) with chronic refractory pouchitis were included in an open study. Pouchitis was diagnosed by clinical plus endoscopic and histological criteria. Three patients also had fistulae (pouch-bladder in 1 and perianal in 2). Extraintestinal manifestations were also present in 4 patients (erythema nodosum in 2, arthralgiae in 2). All patients were refractory to standard therapy. Crohn's disease was carefully excluded in all patients after re-evaluation of the history and examination of the small bowel with enteroclysis or small bowel capsule endoscopy. Patients received Infliximab 5 mg/kg at 0, 2 and 6 weeks and thereafter every 2 months for 1 year. Clinical response was classified as complete, partial, and no response. Fistulae closure was classified as complete, partial, and no closure. The pouchitis disease activity index (PDAI) was also used as an outcome measure. RESULTS: Clinically, all patients improved. After 1 year of follow-up, 5 of the 7 patients had a complete clinical response, and 2 of the 3 patients with a fistula had complete fistulae closure. At the end of the follow-up period the median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission at the end of the followup period as well. CONCLUSIONS: Our results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated or not by fistulae following IPAA for UC.