Endoscopic ultrasonography-guided biliary drainage for malignant jaundice by using electrocautery-enhanced lumen-apposing metal stents (Hot-SPAXUS stent).

Background: Biliary drainage with endoscopic retrograde cholangiopancreatography (ERCP) for tumoral jaundice fails in a certain percentage of patients. In these patients, endoscopic ultrasonography-guided lumen-apposing metal stents (LAMS) with electrocautery-enhanced (ECE) technology allows a single-step, radiation-free palliative treatment. Methods: We reviewed the data of patients who underwent choledochoduodenostomy with placement of ECE-LAMS (Hot-SPAXUS stent) after ERCP failure in a single tertiary center. Technical and clinical success rates were calculated and adverse events recorded. Results: Data of 15 patients (8 male, median age 72 years) were collected. The procedure was technically successful in all patients, whilst clinical success was achieved in 14 (93.3%) patients. One (6.7%) patient presented delayed bleeding treated endoscopically. At follow up, stent occlusion with recurrence of jaundice occurred in 2 (13.3%) patients, due to food impaction (n=1), or neoplastic ingrowth (n=1). Conclusion: Our results suggest that the Hot-SPAXUS procedure is effective and safe for palliative treatment in patients with distal biliary malignant obstruction after failure of ERCP.

Helicobacter pylori culture: from bench to bedside.

Helicobacter pylori (H. pylori) infection is a widespread infection that causes various gastroduodenal diseases and some extraintestinal disorders. Curing this infection remains challenging for clinicians, mainly because of bacterial resistance towards the few available antibiotics. Therefore, as for other infectious diseases, therapeutic approaches should be opportunely designed using the principles of antimicrobial stewardship. Theoretically, only susceptibility-based antimicrobial therapy should be considered as appropriate for treating this infection. Unfortunately, H. pylori owns some particular characteristics that make the infection slightly peculiar. More specifically, it is "fastidious" about growing in culture, and its isolation is not easily achieved, even in dedicated laboratories that, to make matters worse, are only scantily spread among countries. We examined the pros and cons of bacterial culture for antibiotic susceptibility testing before different therapy lines, and its applicability in the real clinical life.

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review.

Background: Primary antibiotic resistance in Helicobacter pylori (H. pylori) strains is increasing worldwide, affecting therapy success. The use of therapies tailored on susceptibility pre-testing at culture has been proposed, but data are still conflicting. Method: We performed a systematic review to evaluate the role of a culture-based therapeutic approach for H. pylori treatment, taking into account the sensitivity of culture and the success rates achieved with tailored therapies in different therapeutic steps. Results: We analyzed data from 51 studies. Overall, H. pylori strains were isolated in 80.7% of 7889 patients, the success rates being 78.1%, 77.5%, 86.3% and 86.6%, before first-, second-, third-line or more therapies, respectively. In comparative studies, the infection was cured in 89.9% of 2052 patients treated with tailored therapies, and in 77.6% of 2516 patients receiving empiric therapy (P<0.001). However, in the subanalysis, the tailored approach achieved optimal eradication rates (>90%) only when it was applied before first- and second-line therapies, but not before third-line or more attempts (<80%). Moreover, no significant difference emerged between the 2 approaches when data from only the most recent (last 5 years) studies were considered, as well as in those performed in Western populations. Conclusions: The attempt to achieve antibiotic susceptibility testing before treatment failed in 20% of infected patients managed in dedicated laboratories. Culture-tailored therapies administered after 2 or more therapies achieved suboptimal eradication rates. The role of bacterial culture in patients whose therapeutic management failed to eradicate H. pylori probably needs to be corroborated by further data.

Preliminary considerations regarding the risk of COVID-19 and disease severity in chronic gastrointestinal conditions.

The novel RNA betacoronavirus SARS-CoV-2 is driving great efforts in clinical and basic research and several studies of the epidemiology, risk factors, clinical and virological features of this infection are already available. However COVID-19 is a totally new pathological entity, and many gray areas regarding associated diseases still need to be elucidated, especially in the group of patients who suffer from preexistent gastrointestinal disease. The aim of this review is to summarize the published data on the correlation between chronic gastrointestinal disorders and COVID-19.

Paradigm shift: the Copernican revolution in diverticular disease.

Diverticular disease (DD) is an umbrella definition that includes different clinical conditions ranging from diverticulosis to severe and potentially life-threatening complications. In the last decade, new concepts regarding pathogenetic alterations have been developed, while the diagnostic, clinical and therapeutic approaches to the management of DD patients have changed. The protective role of dietary factors (i.e., fiber) has been questioned, whilst some drugs widely used in clinical practice have been found to have a deleterious effect. The use of antibiotics in all patients with acute uncomplicated diverticulitis was reconsidered, as well as the need for a surgical approach in these patients. Conflicting recommendations in different guidelines were proposed for the treatment of symptomatic uncomplicated DD. An endoscopic classification of DD was introduced, and a "curative" endoscopic approach has been pioneered. Based on these observations, which together amount to a kind of "Copernican revolution" in the management of DD patients, we performed a comprehensive and critical reappraisal of the proposed modifications, aiming to discriminate between certainties and doubts on this issue.

A very unusual cause of dysphagia: mantle cell lymphoma.

Dysphagia is an alarm symptom requiring a prompt investigation. Different benign and malignant diseases may present such a symptom. We describe a case of a 79-year-old patient who complained of fluctuating dysphagia episodes following solid food ingestion in the previous 5 months with mild weight loss. No other gastrointestinal symptoms were present. The patient was referred by the General Practitioner for a videofluoroscopic swallow examination which revealed nodularity of mucosa surface in the oropharynx, esophagus, fundus, and gastric body. Upper endoscopy confirmed the feature, also showing a normal mucosa of the antrum and duodenum. The histological examination revealed a mantle cell lymphoma (MCL). A stage III, MCL involving the esophagus and proximal stomach was eventually diagnosed. Esophageal MCL localization is extremely rare, and this is the first report showing a clinical onset with dysphagia.

High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study.

BACKGROUND: The prevalence of resistance to clarithromycin and metronidazole has considerably increased, with a corresponding decrease in the eradication rate for Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is extremely low, and esomeprazole was found to exert a noteworthy antimicrobial activity in vitro against H. pylori. A dual therapy with high-dose of esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first-line treatment for H. pylori eradication. We aimed to assess the efficacy of a first-line 10-day, high-dose dual therapy consisting of amoxicillin and esomeprazole to eradicate H. pylori infection. METHODS: Consecutive naïve H. pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals due to dyspeptic symptoms and found to be infected at routine histological assessment, were invited to participate. Patients enrolled received a 10-day, high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g t.i.d.). At least 4 weeks after the end of the treatment a (13)C-urea breath test was performed to evaluate the eradication. RESULTS: A total of 56 patients agreed to participate in the study and were all followed-up. The overall eradication was 87.5% (95% CI=78.8•96.2), without a statistically significant difference among centres. Overall, 5 (8.9%; 1.5•16.4%) patients complained of side-effects. CONCLUSIONS: The 10-day, high-dose dual therapy with esomeprazole and amoxicillin might be an effective and safe first-line regimen. The efficacy of a longer 14-day regimen should be tested.

First- and second-line Helicobacter pylori eradication with modified sequential therapy and modified levofloxacin-amoxicillin-based triple therapy.

BACKGROUND: Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although highly effective, the standard sequential therapy fails in a certain number of patients. Moreover, the cure rate following a levofloxacin-amoxicillin second-line triple therapy seems to be decreasing. We tested the efficacy of modified 10-day sequential therapy, and an intensified levofloxacin-amoxicillin regimen as first- and second-line therapy respectively. METHODS: In this prospective, open label, multicenter, pilot study H. pylori-infected patients received a first-line modified 10-day sequential therapy regimen including rabeprazole 20 mg, and amoxicillin 1 g for the first 3 days, followed by rabeprazole 20 mg, clarithromycin 250 mg, and metronidazole 250 mg, for the remaining 7 days, all drugs given thrice daily. An 8-day therapy regimen with rabeprazole 20 mg, levofloxacin 250 mg, and amoxicillin 1 g, all thrice daily, was administered a second-line therapy. RESULTS: A total of 99 and 15 patients were enrolled for first- and second-line therapy. The eradication rates were 85.9% (95% CI 80-93) and 93.4% (95% CI 88-98) according to ITT and PP analyses following modified sequential therapy, and 60% (95% CI 35-86) and 64.3% (95% CI 39-89) following the intensified second-line therapy. CONCLUSION: A modified sequential 3- plus 7-day regimen with thrice daily drug administration failed to achieve very high eradication rate at ITT analysis. The intensified second-line regimen achieved disappointingly low eradication rate. Novel levofloxacin-free second-line therapies are urged in Italy.

Is concomitant quadruple therapy for Helicobacter pylori eradication really needed for Japanese patients?

The study found that the 7 d of concomitant therapy (lansoprazole, amoxicillin, clarithromycin and metronidazole) achieved significantly higher eradication rates compared to 7 d of triple therapy (lansoprazole, amoxicillin, clarithromycin), the intention to treat (ITT) cure rates being 94.9% and 68.3%, respectively. According to our opinion, this study is clinically relevant for Japanese physicians for at least 2 reasons: (1) the standard triple therapy (clarithromycin plus amoxicillin) achieved disappointing cure rates in Japan - in agreement with what was observed in several countries; and (2) the concomitant quadruple therapy is an effective therapeutic alternative.

Mechanisms of Helicobacter pylori antibiotic resistance: An updated appraisal.

Helicobacter pylori (H. pylori) antibiotic resistance is the main factor affecting the efficacy of the current eradicating therapies. The aim of this editorial is to report on the recent information about the mechanisms accounting for the resistance to the different antibiotics currently utilized in H. pylori eradicating treatments. Different mechanisms of resistance to clarithromycin, metronidazole, quinolones, amoxicillin and tetracycline are accurately detailed (point mutations, redox intracellular potential, pump efflux systems, membrane permeability) on the basis of the most recent data available from the literature. The next hope for the future is that by improving the knowledge of resistance mechanisms, the elaboration of rational and efficacious associations for the treatment of the infection will be possible. Another auspicious progress might be the possibility of a cheap, feasible and reliable laboratory test to predict the outcome of a therapeutic scheme.

From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways.

Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase re-expression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are non-specific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.