Small bowel lesions in patients with iron deficiency anaemia without overt bleeding: a multicentre study.

The diagnostic work-up in iron deficiency anaemia (IDA) patients can be challenging when bleedings or malabsorption are not clinically manifest. Lesions on the small bowel mucosa may cause IDA. We evaluated the prevalence of lesions on the small bowel mucosa detected at Videocapsule Endoscopy (VCE) in IDA patients following negative upper and lower endoscopies. Clinical and endoscopic data collected in 5 centres were retrieved. Lesions with a high bleeding potential (P2) were computed, and predictive factors investigated at multivariate analysis. By considering data of 230 patients, the endoscopic examination detected a total of 96 (41.7%; 95% CI: 35.4-48.1) P2 lesions on the small bowel mucosa, including 4 (1.7%) cancers. The use of non-steroidal anti-inflammatory drugs was found to be the only associated factor at both univariate (OR: 5.7, 95% CI: 2.4-13.4; P <0.001) and multivariate (OR: 2.8; 95% CI: 1.7-3.9, P <0.01) analyses. Present study showed that evaluation of small bowel mucosa with VCE allows to disclose a potential cause of IDA in near half patients. The cooperation between haematologists and gastroenterologists in the diagnostic work-up may be useful.

Diagnostic Yield of Small Bowel Videocapsule Endoscopy in Patients with Iron Deficiency Anemia. A Systematic Review and meta-analysis.

BACKGROUND AND AIM: Gastrointestinal (GI) bleeding or malabsorption represents the most frequent aetiologies of iron deficiency anemia (IDA). The cause of IDA remains undetermined in ~10% to 20% of patients undergoing upper and lower GI endoscopies. In this scenario, a small bowel examination with videocapsule endoscopy (VCE) is recommended. We performed a systematic review with meta-analysis to evaluate the diagnostic yield of VCE in patients with IDA without overt bleeding, assessing the prevalence of either any lesion or lesions at high potential of bleeding. MATERIALS AND METHODS: A computerized literature search was performed using relevant keywords to identify all the pertinent articles published until March 2023. RESULTS: Twelve studies with a total of 1703 IDA patients (Males: 47%; age range: 19-92 y) were included in this systematic review. The diagnostic yield of VCE for overall lesions in the small bowel was 61% (95% CI=44-77; 95 CI=97.2-98.1; I2=97.7%). When analyzing only small bowel lesions likely responsible of IDA, the diagnostic yield was 40% (95% CI=27-53; 95% CI=95.3-97; I2=96.3%). CONCLUSION: VCE plays a relevant role in the diagnostic work-up of patients with IDA without overt bleeding with a satisfactory diagnostic yield.

Efficacy of Helicobater pylori eradication in patients with diffuse large B-cell lymphoma of the stomach: A systematic review.

OBJECTIVES: The role of Helicobater pylori eradication in the treatment of high-grade diffuse large B-cell lymphoma (DLBCL) of the stomach is unclear. METHODS: We performed a systematic review and meta-analysis of currently available data. DLBCL-remission rate after eradication therapy, post-remission maintenance, and response rate in the case of additional oncological therapy were extracted. RESULTS: By considering data of seven studies, the DLBCL remission was achieved in 81 (53.3%; 95% CI = 45.3-61.2) out of 152 H. pylori eradicated patients. The regression rate did not differ between pure DLCBL and DLCBL with MALT component, between stage I and stage II disease, and between Caucasians and Asians. Disease regression was maintained in all patients after at a median of 63 months (range: 46-29) follow-up. In those non-responders, DLBLC remission after additional chemo-immunotherapy was achieved in 63 (98.4%; 95% CI = 95.4-100) out of 64 patients. CONCLUSIONS: Data this systematic review suggest considering H. pylori eradication as first-line therapy to treat infected patients with early-stage, high-grade gastric lymphoma.

Role of MIC levels of resistance to clarithromycin and metronidazole in Helicobacter pylori eradication.

OBJECTIVES: Antimicrobial resistance to clarithromycin and metronidazole significantly affects the cure rate of standard therapies for Helicobacter pylori infection. We tested whether different MIC levels of resistance to these antibiotics play a role in therapeutic efficacy. METHODS: This was a post hoc analysis of data from a therapeutic trial in which patients with antibiotic susceptibility testing (Etest) received first-line sequential therapy. The level of antibiotic resistance was classified according to MIC values into low (MIC from >0.5 to ≤8 for clarithromycin, and from >8 to ≤32 for metronidazole) and high (MIC from >8 to 256 mg/L for clarithromycin, and from >32 to 256 mg/L for metronidazole). RESULTS: Data from 1006 patients were included. There were 520 (51.7%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains and 206 (20.5%) with clarithromycin-resistant and metronidazole-resistant strains. In the presence of double resistance, the cure rate was still high (38/41, 92.7%) when MIC levels were low and it was reduced (94/112, 83.9%) only when MIC levels of both antibiotics were high. The cure rates did not significantly differ between patients with single antibiotic-resistant strains, irrespective of MIC values, and those with susceptible strains. CONCLUSIONS: We found that MIC levels of resistance to either clarithromycin or metronidazole play a role in H. pylori therapy outcome and that bacterial resistance becomes relevant in vivo when clarithromycin-resistant and metronidazole-resistant strains have high MIC values for at least one of these antibiotics.

Weight loss and decubitus duodenal ulcer in Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion.

Apparently, unexplained weight loss is a common symptom experienced by patients affected by Parkinson's disease, especially in those treated by levodopa-carbidopa infusion gel (LCIG) with a poor control of dyskinesias. Weight loss is considered part of gastrointestinal dysfunction seen in patients affected by Parkinson's disease, along with gastroparesis and reduced bowel peristalsis. In patients treated with LCIG, weight loss needs to be accurately evaluated, because of possible underlying life-threatening adverse events, like duodenum decubitus ulcer.

Eradication therapy in Helicobacter pylori-negative, gastric low-grade mucosa-associated lymphoid tissue lymphoma patients: a systematic review.

AIM: To assess the remission rate of gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma after an eradication therapy in Helicobacter pylori-negative patients. METHODS: We performed a systematic review with pooled analysis of published studies. Data were analyzed according to: (1) number of H. pylori-negative patients treated with only eradication therapy; (2) number of patients in whom the complete lymphoma remission was achieved; and (3) the method used to exclude H. pylori infection. RESULTS: Overall, 11 studies with 110 patients met the inclusion criteria for this pooled analysis. H. pylori infection was excluded in all studies with at least 3 different diagnostic tests. Eradication therapy achieved a complete lymphoma regression in 17 (15.5%; 95% confidence interval, 8.7-22.2) patients. CONCLUSIONS: Eradication therapy is successful in a small but distinct subgroup of H. pylori-negative patients with low-grade mucosa-associated lymphoid tissue lymphoma. On the basis of the generally indolent behavior of this neoplasia, before resorting to aggressive, costly, and potentially more toxic oncologic therapies, it would seem reasonable to attempt eradication therapy in all patients, irrespective of their H. pylori status.

Endoscopic Submucosal Dissection for Subepithelial Tumor Treatment in the Upper Digestive Tract: A Western, Multicenter Study.

Background/Aims: Endoscopic submucosal dissection (ESD) has been proposed for removal of gastrointestinal subepithelial tumors (GI-SETs), but data are still scanty. This study aimed to report a case series from a western country. Patients and Methods: Data of patients with upper GI-SETs suitable for ESD removal observed in 4 centers were retrospectively reviewed. Before endoscopic procedure, the lesion was characterized by endosonographic evaluation, histology, and CT scan. The en bloc resection and the R0 resection rates were calculated, as well as incidence of complications, and the 1-year follow-up was reported. Results: Data of 84 patients with esophageal (N = 13), gastric (N = 61), and duodenal (N = 10) GI-SETs were collected. The mean diameter of lesions was 26 mm (range: 12-110 mm). There were 17 gastrointestinal stromal tumors, 12 neuroendocrine tumors, 35 leiomyomas, 18 lipomas, and 2 hamartomas. En bloc and R0 resection were achieved in 83 (98.8%) and in 80 (95.2%) patients, respectively. Overall, a complication occurred in 11 (13.1%) patients, including bleeding (N = 7) and perforation (N = 4). Endoscopic approach was successful in all bleedings, but 1 patient who required radiological embolization, and in 2 perforations, while surgery was performed in the other patients. Overall, a surgical approach was eventually needed in 5 (5.9%), including 3 in whom R0 resection failed and 2 with perforation. Conclusions: Our study found that ESD may be an effective and safe alternative to surgical intervention for both benign and localized malignant GI-SETs.

Introdução/objetivos: A dissecção endoscópica da submucosa (ESD) tem sido proposta para a exérese de tumores subepiteliais gastrointestinais (GI-SETs), embora a literatura seja escassa. Este estudo teve como objetivo reportar uma série de casos de um país ocidental. Métodos: Coorte retrospectiva incluindo doentes com SETs do tubo digestivo superior submetidos a ESD em 4 centros (1 ano de follow-up). Antes do procedimento, a lesão foi caracterizada por ecoendoscopia, histologia e tomografia computadorizada. Foram avaliadas as taxas de ressecção em bloco e R0, bem como a incidência de complicações. Resultados: Incluídos 84 doentes com GI-SETs esofágicos (N = 13), gástricos (N = 61) e duodenais (N = 10). O diâmetro médio das lesões foi de 26 mm (intervalo 12­110 mm) ­ 17 tumores do estroma gastrointestinal, 12 tumores neuroendócrinos, 35 leiomiomas, 18 lipomas e 2 hamartomas. A resseção foi em bloco e R0 em 83 (98.8%) e em 80 (95.2%) doentes, respectivamente. Globalmente, ocorreram complicações em 11 (13.1%) doentes, incluindo hemorragia (N = 7) e perfuração (N = 4). A terapêutica endoscópica foi eficaz em todas as hemorragias exceto em 1 doente que necessitou de embolização radiológica e em 2 perfurações (submetidas a cirurgia). No geral, a abordagem cirúrgica foi necessária em 5 (5.9%) ­ 3 doentes com resseção R1 e 2 com perfuração. Conclusões: A ESD pode ser uma alternativa eficaz e segura à intervenção cirúrgica para GI-SETs benignos e malignos localizados.

Upper Gastrointestinal Endoscopy Quality in Italy: A Nationwide Study.

BACKGROUND AND AIMS: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy. METHODS: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated. RESULTS: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers. CONCLUSIONS: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.

Quality performance measures in upper gastrointestinal endoscopy for lesion detection: Italian AIGO-SIED-SIGE joint position statement.

Esophagogastroduodenoscopy (EGD) plays a crucial role in the management of gastroduodenal diseases by allowing a direct and accurate evaluation of the mucosa and the execution of several operative maneuvers. Despite a constant development of new imaging tools and operative devices, the widespread use of EGD has not resulted in a significant reduction of mortality for patients affected by esophageal/gastric cancer during the last three decades in Western countries. Evidence indicates that this disheartening scenario derives from a high variability of execution of EGD which determines its quality and diagnostic yield, delaying the diagnosis of neoplastic diseases. Based on this evidence, in recent years many scientific societies have produced different position papers aimed at defining quality performance measures in EGD. Thus, the Italian Association of Gastroenterologists and Endoscopists, the Italian Society of Digestive Endoscopy and the Italian Society of Gastroenterology have produced this joint document based on the review of ASGE, ACG, BSG, ESGE and Asian Consensus EGD position papers with the aim of indicating the quality standards of EGD (pre-, intra- and post-procedure) focused on lesion detection to be adopted in the Italian context.

Rescue Therapies for H. pylori Infection in Italy.

Background/Aims: Curing Helicobacter pylori infection remains challenging for clinicians, as no proposed first-line therapy achieves bacterial eradication in all treated patients so that several patients need two or more consecutive treatments. Bacterial culture with antibiotics susceptibility testing is largely unachievable in Italy, and empiric second-line and rescue therapies are generally used. This study aimed to identify what eradication regimens perform better in Italy, following first-line therapy failure. Methods: We performed a literature search on PubMed for studies on standard therapy regimens used as second-line or rescue treatments performed in adult patients. Studies including modified drug combinations were not considered. Both intention-to-treat and per- protocol analyses were computed for each therapy subgroup. Results: Data from 35 studies with a total of 4830 patients were eventually considered. As a second-line therapy, Pylera® (90.6%) and a sequential regimen (89.8%) achieved eradication rates significantly higher than other therapies. For third-line therapy, a levofloxacin-based regimen and Pylera® achieved comparable eradication rates (88.2% vs. 84.7%; p = 0.2). Among therapies used as fourth (or more) attempts, Pylera® and a rifabutin-based therapy achieved 77.4% and 66.4% cure rates, respectively (p = 0.013). A therapy sequence based on the type of first-line therapy used was proposed. Conclusions: Data obtained through our review indicate that standard therapies for H. pylori eradication can be used when following an appropriate sequence, allowing clinicians to improve the cure rate without resorting to bacterial culture.

Helicobacter pylori eradication following first-line treatment failure in Europe: What, how and when chose among different standard regimens? A systematic review.

Cure rate following standard first-line regimens for Helicobacter pylori eradication is decreasing so several patients require two or more treatments. Antibiotic susceptibility-based therapy, advised in current guidelines, is largely impracticable in clinical practice. Some 'standard' regimens (triple therapies based on either levofloxacin or rifabutin, bismuth-based quadruple therapies, sequential, concomitant and hybrid therapies) were empirically used as rescue therapies. We performed a systematic review on recent studies carried out in European countries dealing with these regimens. A total of 24 studies, with 3804 patients, were identified. As second-line therapy, Pylera (89.2%) and sequential therapy (92.5%) achieved significantly higher cure rates as compared to all the other regimens. As third-line therapy, levofloxacin-based therapy (84.1%) and Pylera (83.6%) achieved similarly high cure rates, whereas standard, bismuth-based quadruple therapy (64.1%) achieved the lowest. As a rescue therapy, the success rate was close to 75% following all therapies used, with data on rifabutin-based regimen consolidated in the larger sample size. Overall, levofloxacin-amoxicillin triple therapy achieved higher eradication rates when the 14- rather than 10-day regimen was used (87.1 vs. 72.2%; P = 0.003). Among bismuth-based therapies, Pylera achieved a significantly higher eradication rate than standard quadruple therapy (88 vs. 67%; P < 0.0001). These data suggest that a wise 'therapeutic package' following first-line therapy could be Pylera, levofloxacin- and rifabutin-based therapy, as long as Pylera therapy was not used as a first-line regimen and levofloxacin-based regimen was administered for 14 days.

Endoscopic submucosal dissection of gastric neoplastic lesions in Western countries: systematic review and meta-analysis.

Endoscopic submucosal dissection (ESD) for gastric neoplastic lesions removal is largely performed in Asian countries. Unfortunately, ESD diffusion, particularly for gastric lesion removal, is still limited in Western countries. We performed a systematic review of available data coming from Western centers. The en bloc and the R0 resection rates for all neoplastic lesions, including early gastric cancer (EGC) and dysplasia, were calculated, as well as the curative rate for EGC. Complications and the 1-month mortality rates were computed. A total of 22 studies from Europe (N = 15), Latina America (N = 6), and Canada (N = 1) were retrieved, with 1152 patients and 1210 lesions. The en bloc resection was successful in 96% [95% confidence interval (CI) 93-98] with a significant heterogeneity (I2 = 63.5%; P < 0.0001). The R0 was achieved in 84% (95% CI 79-89; I2 = 79.9%; P < 0.001). The resection rate was curative in 72% out of 340 patients with EGC (95% CI 65-79, I2 = 8%; P = 0.36). Overall, complications occurred in 9.5% of patients, including bleeding (5.8%), perforation (3.4%), and stenosis (0.35%). A total of three (0.26%) patients deceased within 1 month, but none was directly related to the procedure. Lesion recurrence was observed in 38 (3.5%; 95% CI 2.3-4.4) cases, including 21 EGC and 17 dysplasia. In Western countries, the en bloc and the R0 resections were successful in the large majority of cases, whilst the resection was curative in 72% of patients with EGC. The complications rate was acceptably low.

Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO).

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND & AIMS: Different remission rates of gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma have been reported after Helicobacter pylori eradication. We assessed the long-term remission and relapse rates of early stage MALT lymphoma in patients treated only by H pylori eradication and identified factors that might predict outcome. METHODS: This systematic review analyzed data from 32 studies, including 1408 patients. RESULTS: The MALT lymphoma remission rate was 77.5% (95% confidence interval, 75.3-79.7), and was significantly higher in patients with stage I than stage II(1) lymphoma (78.4% vs 55.6%; P = .0003) and in Asian than in Western groups (84.1% vs 73.8%; P = .0001). Neoplasia confined to the submucosa regressed more frequently than that with deeper invasion (82.2% vs 54.5%; P = .0001); patients with lymphoma localized to the distal stomach experienced regression more frequently than those with lymphoma of the proximal stomach (91.8% vs 75.7%; P = .0037). The remission rate was higher among patients without the API2-MALT1 translocation than in those with this translocation (78% vs 22.2%; P = .0001). In an analysis of data from 994 patients, 7.2% experienced lymphoma relapse during 3253 patient-years of follow-up evaluation, with a yearly recurrence rate of 2.2%. Infection and lymphoma were cured by additional eradication therapy in all patients with H pylori recurrence (16.7%). Five (0.05%) of the patients initially cured of lymphoma developed high-grade lymphoma within 6 to 25 months of therapy. CONCLUSIONS: H pylori eradication is effective in treating approximately 75% of patients with early stage gastric lymphoma. Long-term follow-up evaluation of these patients is needed to detect early lymphoma relapse or progression.

Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits.

INTRODUCTION: Primary clarithromycin resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. However, the clinical consequence of either phenotypic or genotypic resistance still remains unclear. This study aimed to evaluate: (i) the concordance between phenotypic (culture) and genotypic (real-time PCR) tests in assessing primary clarithromycin resistance; and (ii) the role of both in therapeutic outcome. METHODS: A post hoc subgroup study was selected from a double-blind, placebo-controlled trial, enrolling 146 patients with dyspepsia or peptic ulcers never previously treated. Real-time PCR and Etest on bacterial culture for assessing clarithromycin resistance were performed. [(13)C]urea breath test (UBT), histology and rapid urease tests at entry and UBT after 4-8 weeks were used to assess infection and eradication. All patients received a 10 day therapy. RESULTS: Prevalence of clarithromycin phenotypic resistance was significantly lower as compared with genotypic resistance (18.4% versus 37.6%, P < 0.001). A concordance between the two methods was present in 71.2% of cases. A significant difference in the eradication rate was seen between clarithromycin-susceptible and -resistant strains, when assessed with either Etest (92.4% versus 55.5%, P < 0.001) or a PCR-based method (94.5% versus 70.9%; P < 0.001). Of note, the eradication rate showed the lowest value (30.7%) when phenotypic bacterial resistance was genetically linked to the A2143G point mutation. CONCLUSIONS: This study showed that: (i) there is a relevant discordance between the two methods; and (ii) phenotypic clarithromycin resistance markedly reduces H. pylori eradication when it is linked to a specific point mutation.

Cost-effectiveness of endoscopic surveillance for gastric intestinal metaplasia.

BACKGROUND: Patients with intestinal metaplasia (IM) are at increased risk for gastric cancer. Endoscopic surveillance has been shown to anticipate cancer diagnosis in an earlier stage. Cost-effectiveness of endoscopic surveillance in IM patients is unknown. To assess the efficacy and cost-effectiveness of an yearly endoscopic surveillance in patients with IM. METHODS: A decision analysis model was constructed in order to compare a strategy of performing an EGD every year for a 10-year period (surveillance strategy) following a new diagnosis of IM to a policy of nonsurveillance in a simulated cohort of 10,000 American patients. A 1.8% 10-year cumulative incidence of gastric cancer in IM patients was estimated from the literature. Endoscopic surveillance was simulated to downstage the detected cancers by 58-84%. Costs of EGD and cancer care were estimated from Medicare reimbursement data. The main outcome measurement was the incremental cost-effectiveness ratio. RESULTS: The number of EGDs required to detect one cancer and to prevent one gastric cancer-related death in the surveillance arm were 556 and 3738, respectively. The incremental cost-effectiveness ratio of endoscopic surveillance as compared to a nonsurveillance policy was $72,519 per life-year gained (5-95% percentiles Monte Carlo analysis: $54,843-$98,853). At sensitivity analysis, cancer incidence and the rate of downstaging were the most important variables. CONCLUSIONS: According to our simulation, the relatively high risk of cancer in patients with IM and the substantial efficacy of endoscopic surveillance in reducing cancer-related mortality would support the cost-effectiveness of an endoscopic surveillance program in patients with IM. Further research is needed before implementing it in the clinical practice.