Bowel function and inflammation: Is motility the other side of the coin?

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel.On the flip side,functions also arise from its role as an interface with the environment.Indeed,the gut houses microorganisms,collectively known as the gut microbiota,which interact with the host,and is the site of complex immune activities.Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut,especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems.This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

Kyoto classification of gastritis,virtual chromoendoscopy and artificial intelligence:Where are we going?What do we need?

Chronic gastritis(CG)is a widespread and frequent disease,mainly caused by Helicobacter pylori infection,which is associated with an increased risk of gastric cancer.Virtual chromoendoscopy improves the endoscopic diagnostic efficacy,which is essential to establish the most appropriate therapy and to enable cancer prevention.Artificial intelligence provides algorithms for the diagnosis of gastritis and,in particular,early gastric cancer,but it is not yet used in practice.Thus,technological innovation,through image resolution and processing,optimizes the diagnosis and management of CG and gastric cancer.The endoscopic Kyoto classification of gastritis improves the diagnosis and management of this disease,but through the analysis of the most recent literature,new algorithms can be proposed.

Artificial intelligence in detection of small bowel lesions and their bleeding risk:A new step forward

The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

The role of computed tomography for the prediction of esophageal variceal bleeding:Current status and future perspectives

Esophageal variceal bleeding(EVB)is one of the most common and severe complications related to portal hypertension(PH).Despite marked advances in its management during the last three decades,EVB is still associated with significant morbidity and mortality.The risk of first EVB is related to the severity of both PH and liver disease,and to the size and endoscopic appearance of esophageal varices.Indeed,hepatic venous pressure gradient(HVPG)and esophagogastroduodenoscopy(EGD)are currently recognized as the“gold standard”and the diagnostic reference standard for the prediction of EVB,respectively.However,HVPG is an invasive,expensive,and technically complex procedure,not widely available in clinical practice,whereas EGD is mainly limited by its invasive nature.In this scenario,computed tomography(CT)has been recently proposed as a promising modality for the non-invasive prediction of EVB.Although CT is only a diagnostic modality,thus being not capable of supplanting EGD or HVPG in providing therapeutic and physiological data,it could potentially assist liver disease scores,HVPG,and EGD in a more effective prediction of EVB.However,to date,evidence concerning the role of CT in this setting is still lacking.Our review aimed to summarize and discuss the current evidence concerning the role of CT in predicting the risk of EVB.

Lumen-apposing-metal stent misdeployment in endoscopic ultrasound-guided drainages:A systematic review focusing on issues and rescue management

BACKGROUND The introduction of lumen-apposing metal stents(LAMS)for endoscopic ultrasound(EUS)-guided drainages has marked a turning point in the field of interventional ultrasound and it is gathering worldwide diffusion in different clinical settings.Nevertheless,the procedure may conceal unexpected pitfalls.LAMS misdeployment is the most frequent cause of technical failure and it can be considered a procedure-related adverse event when it hampers the conclusion of the planned procedure or results in significant clinical consequences.Stent misdeployment can be managed successfully by endoscopic rescue maneuvers to allow the completion of the procedure.To date,no standardized indication is available to guide an appropriate rescue strategy depending on the type of procedure or of misdeployment.AIM To evaluate the incidence of LAMS misdeployment during EUS-guided choledochoduodenostomy(EUS-CDS),gallbladder drainage(EUS-GBD)and pancreatic fluid collections drainage(EUS-PFC)and to describe the endoscopic rescue strategies adopted under the circumstance.METHODS We conducted a systematic review of the literature on PubMed by searching for studies published up to October 2022.The search was carried out using the exploded medical subject heading terms“lumen apposing metal stent”,“LAMS”,“endoscopic ultrasound”and“choledochoduodenostomy”or“gallbladder”or“pancreatic fluid collections”.We included in the review on-label EUS-guided procedures namely EUS-CDS,EUS-GBD and EUS-PFC.Only those publications reporting EUS-guided LAMS positioning were considered.The studies reporting a technical success rate of 100%and other procedure-related adverse events were considered to calculate the overall rate of LAMS misdeployment,while studies not reporting the causes of technical failure were excluded.Case reports were considered only for the extraction of data regarding the issues of misdeployment and rescue techniques.The following data were collected from each study:Author,year of publication,study design,study population,clinical indication,technical success,reported number of misdeployment,stent type and size,flange misdeployed and type of rescue strategy.RESULTS The overall technical success rate of EUS-CDS,EUS-GBD and EUS-PFC was 93.7%,96.1%,and 98.1%respectively.Significant rates of LAMS misdeployment have been reported for EUS-CDS,EUS-GBD and EUS-PFC drainage,respectively 5.8%,3.4%,and 2.0%.Endoscopic rescue treatment was feasible in 86.8%,80%,and 96.8%of cases.Non endoscopic rescue strategies were required only in 10.3%,16%and 3.2%for EUS-CDS,EUS-GBD,and EUS-PFC.The endoscopic rescue techniques described were over-the-wire deployment of a new stent through the created fistula tract in 44.1%,8%and 64.5%and stent-in-stent in 23.5%,60%,and 12.9%,respectively for EUSCDS,EUS-GBD,and EUS-PFC.Further therapeutic option were endoscopic rendezvous in 11.8%of EUS-CDS and repeated procedure of EUS-guided drainage in 16.1%of EUS-PFC.CONCLUSION LAMS misdeployment is a relatively common adverse event in EUS-guided drainages.There is no consensus on the best rescue approach in these cases and the choice is often made by the endoscopist relying upon the clinical scenario,anatomical characteristics,and local expertise.In this review,we investigated the misdeployment of LAMS for each of the on-label indications focusing on the rescue therapies used,with the aim of providing useful data for endoscopists and to improve patient outcomes.

MUTYH-associated polyposis: Is it time to change upper gastrointestinal surveillance? A single-center case series and a literature overview

BACKGROUND The presence of Spigelman stage(SS)IV duodenal polyposis is considered the most significant risk factor for duodenal cancer in patients with MUTYH-associated polyposis(MAP).However,advanced SS disease is rarely reported in MAP patients,and no clear recommendations on small bowel(SB)surveillance have been proposed in this patient setting.AIM To research more because that case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced benign SS disease and often involve the distal portion of the duodenum.METHODS We describe a series of MAP patients followed up at the Regina Elena National Cancer Institute of Rome(Italy).A literature overview on previously reported SB cancers in MAP is also provided.RESULTS We identified two(6%)SB adenocarcinomas with no previous history of duodenal polyposis.Our observations,supported by literature evidence,suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer may need to be adjusted to take this into account rather than focusing solely on the presence or absence of SS IV disease.Core Tip:Case reports of duodenal cancers in MUTYH-associated polyposis suggest that they may develop in the absence of advanced Spigelman stage(SS)benign disease and often involve the distal portion of the duodenum.In our case series,we identified two(6%)small-bowel adenocarcinomas with no previous history of duodenal polyposis.Our observations,supported by literature evidence,suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer should be adjusted to take into consideration the presence of SS IV disease,rather than focusing only on this feature.suggestive of invasive adenocarcinoma.

Endoscopic resection of non-ampullary duodenal adenomas: Is cold snaring the promised land?

Due to the high risk of morbidity and mortality associated with surgical resection in this tract,endoscopic resection(ER)has taken the place of surgical resection as the first line treatment for non-ampullary duodenal adenomas.However,due to the anatomical characteristics of this area,which enhance the risk of post-ER problems,ER in the duodenum is particularly difficult.Due to a lack of data,no ER technique for superficial non-ampullary duodenal epithelial tumours(SNADETs)has yet been backed by strong,high-quality evidence;yet,traditional hot snare-based techniques are still regarded as the standard treatment.Despite having a favourable efficiency profile,adverse events during duodenal hot snare polypectomy(HSP)and hot endoscopic mucosal resection,such as delayed bleeding and perforation,have been reported to be frequent.These events are primarily caused by electrocautery-induced damage.Thus,ER techniques with a better safety profile are needed to overcome these shortcomings.Cold snare polypectomy,which has already been shown as a safer,equally effective pro-cedure compared to HSP for treatment of small colorectal polyps,is being increasingly evaluated as a potential therapeutic option for non-ampullary duodenal adenomas.The aim of this review is to report and discuss the early outcomes of the first experiences with cold snaring for SNADETs.

Use of endoscopic ultrasound-guided gallbladder drainage as a rescue approach in cases of unsuccessful biliary drainage

This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.

Device-assisted enteroscopy: Are we ready to dismiss the spiral?

Motorized spiral enteroscopy(MSE)is the latest advance in device-assisted enteroscopy.Adverse events related to MSE were discussed in a recent large systematic review and meta-analysis and were directly compared with those of balloon enteroscopy in a case-matched study and a randomized controlled trial.Following the real-life application of MSE,an unexpected safety issue emerged regarding esophageal injury and the technique has been withdrawn from the global market,despite encouraging results in terms of diagnostic and therapeutic yield.We conducted an Italian multicenter real-life prospective study,which was prematurely terminated after the withdrawal of MSE from the market.The primary goals were the evaluation of MSE performance(both diagnostic and therapeutic)and its safety in routine endoscopic practice,particularly in the early phase of introduction in the endoscopic unit.A subanalysis,which involved patients who underwent MSE after unsuccessful balloon enteroscopy,demonstrated,for the first time,the promising performance of MSE as a rescue procedure.Given its remarkable performance in clinical practice and its potential role as a backup technique following a previously failed enteroscopy,it may be more appropriate to refine and enhance MSE in the future rather than completely abandoning it.

Gastric low-grade mucosal-associated lymphoid tissue-lymphoma: Helicobacter pylori and beyond

The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.

Follow-up of intestinal metaplasia in the stomach: When, how and why

Gastric cancer remains the second most frequent cause of cancer-related mortality in the world. Screening programs in some Asian countries are impractical in the majority of other countries worldwide. Therefore, follow-up of precancerous lesions is advisable for secondary gastric cancer prevention. Intestinal metaplasia (IM) is recognized as a precancerous lesion for gastric cancer, increasing the risk by 6-fold. IM is highly prevalent in the general population, being detected in nearly 1 of every 4 patients undergoing upper endoscopy. The IM prevalence rate is significantly higher in patients with Helicobacter pylori (H. pylori) infection, in first-degree relatives of gastric cancer patients, in smokers and it increases with patient age. IM is the "breaking point" in the gastric carcinogenesis cascade and does not appear to regress following H. pylori eradication, although the cure of infection may slow its progression. Gastric cancer risk is higher in patients with incomplete-type IM, in those with both antral and gastric body involvement, and the risk significantly increases with IM extension over 20% of the gastric mucosa. Scheduled endoscopic control could be cost-effective in IM patients, depending on the yearly incidence of gastric cancer in IM patients, the stage of gastric cancer at diagnosis discovered at surveillance, and the cost of endoscopy. As a pragmatic behavior, yearly endoscopic control would appear justified in all IM patients with at least one of these conditions: (1) IM extension > 20%; (2) the presence of incomplete type IM; (3) first-degree relative of gastric cancer patients; and (4) smokers. In the remaining IM patients, a less intensive (2-3 years) could be proposed.

Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives

Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.

Implications of small-bowel transit time in the detection rate of capsule endoscopy: A multivariable multicenter study of patients with obscure gastrointestinal bleeding

AIM To define the role of small-bowel transit time in the detection rate of significant small-bowel lesions.METHODS Small-bowel capsule endoscopy records, prospectively collected from 30 participating centers in the Lombardy Registry from October 2011 to December 2013, were included in the study if the clinical indication was obscure gastrointestinal bleeding and the capsule reached the cecum. Based on capsule findings, we created two groups: P2(significant findings) and P0-1(normal/negligible findings). Groups were compared for age, gender, small-bowel transit time, type of instrument, modality of capsule performance(outpatients vs inpatients), bowel cleanliness, and center volume.RESULTS We retrieved and scrutinized 1,433 out of 2,295 capsule endoscopy records(62.4%) fulfilling the inclusion criteria. Patients were 67 ± 15 years old, and 815(57%) were males. In comparison with patients in the P0-1 group, those in the P2 group(n = 776, 54%) were older(P < 0.0001), had a longer small-bowel transit time(P = 0.0015), and were more frequently examined in low-volume centers(P < 0.001). Age and smallbowel transit time were correlated(P < 0.001), with age as the sole independent predictor on multivariable analysis. Findings of the P2 group were artero-venous malformations(54.5%), inflammatory(23.6%) and protruding(10.4%) lesions, and luminal blood(11.5%).CONCLUSION In this selected, prospectively collected cohort of small-bowel capsule endoscopy performed for obscure gastrointestinal bleeding, a longer small-bowel transit time was associated with a higher detection rate of significant lesions, along with age and a low center volume, with age serving as an independent predictor.

Negative capsule endoscopy in patients with obscure gastrointestinal bleeding reliable: Recurrence of bleeding on long-term follow-up

AIM: To assess the rate of recurrent bleeding of the small bowel in patients with obscure bleeding already undergone capsule endoscopy (CE) with negative results. METHODS: We reviewed the medical records related to 696 consecutive CE performed from December 2002 to January 2011, focusing our attention on patients with recurrence of obscure bleeding and negative CE. Evaluating the patient follow-up, we analyzed the recurrence rate of obscure bleeding in patient with a negative CE. Actuarial rates of rebleeding during follow-up were calculated, and factors associated with rebleeding were assessed through an univariate and multivariate analysis. A P value of less than 0.05 was regarded as statistically significant. The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of negative CE were calculated. RESULTS: Two hundred and seven out of 696 (29.7%) CE studies resulted negative in patient with obscure/overt gastrointestinal bleeding. Overall, 489 CE (70.2%) were positive studies. The median follow-up was 24 mo (range 12-36 mo). During follow-up, recurrence of obscure bleeding was observed only in 34 out of 207 negative CE patients (16.4%); 26 out of 34 with obscure overt bleeding and 8 out of 34 with obscure occult bleeding. The younger age (< 65 years) and the onset of bleeding such as melena are independent risk factors of rebleeding after a negative CE (OR = 2.6703, 95%CI: 1.1651-6.1202, P = 0.0203; OR 4.7718, 95%CI: 1.9739-11.5350, P = 0.0005). The rebleeding rate (CE+ vs CE-) was 16.4% vs 45.1% (χ 2 test, P = 0.00001). The sensitivity, specificity, and PPV and NPV were 93.8%, 100%, 100%, 80.1%, respectively. CONCLUSION: Patients with obscure gastrointestinal bleeding and negative CE had a significantly lower rebleeding rate, and further invasive investigations can be deferred.

Outcome of stenting in biliary and pancreatic benign and malignant diseases:A comprehensive review

Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks,pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review,relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases.

Furazolidone therapy for Helicobacter pylori:Is it effective and safe?

Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori(H pylori) infection should be remarked,especially regarding its potential oncologic risk.The inclusion of furazolidone in a treatment regimen for H pylori infection is,at least,controversial,and it does not appear to be safe.

Helicobacter pylori and functional dyspepsia: An unsolved issue?

Patients with Helicobacter pylori(H. pylori) infection may complain of dyspeptic symptoms without presence of macroscopic lesions on gastroduodenal mucosa. Such a condition is usually recognized as functional dyspepsia, and different pathogenetic mechanisms are involved. The role of H. pylori in these patients is controversial. Several trials assessed the potential role of H. pylori eradication in improving dyspeptic symptoms, and data of some meta-analyses demonstrated that cure of infection is associated with a small(10%), but significant therapeutic gain as compared to placebo. The reason for which dyspeptic symptoms regress in some patients following bacterial eradication, but persist in others remains unclear. Regrettably, trials included in the meta-analyses are somewhat different for study design, definition of symptoms, assessment of symptoms changes, and some may be flawed by potential pitfalls. Consequently, the information could be not consistent. We critically reviewed the main available trials, attempting to address future research in this

Helicobacter pylori eradication and reflux disease onset:Did gastric acid get "crazy"?

Gastroesophageal reflux disease (GORD) is highly prevalent in the general population.In the last decade,a potential relationship between Helicobacter pylori (H.pylori) eradication and GORD onset has been claimed.The main putative mechanism is the gastric acid hypersecretion that develops after bacterial cure in those patients with corpus-predominant gastritis.We performed a critical reappraisal of the intricate pathogenesis and clinical data available in this field.Oesophagitis onset after H.pylori eradication in duodenal ulcer patients has been ascribed to a gastric acid hypersecretion,which could develop following body gastritis healing.However,the absence of an acid hypersecretive status in these patients is documented by both pathophysiology and clinical studies.Indeed,duodenal ulcer recurrence is virtually abolished followingH.pylori eradication.In addition,intra-oesophageal pH recording studies failed to demonstrated increased acid reflux following bacterial eradication.Moreover,oesophageal manometric studies suggest that H.pylori eradication would reduce-rather than favor-acid reflux into the oesophagus.Finally,data of clinical studies would suggest that H.pylori eradication is not significantly associated with eitherreflux symptoms or erosive oesophagitis onset,some data suggesting also an advantage in curing the infection when oesophagitis is already present.Therefore,the legend of "crazy acid" remains-as all the others a fascinating,but imaginary tale.

Bio-feedback treatment of fecal incontinence: Where are we, and where are we going?

Fecal incontinence is a disabling disease, often observed in young subjects, that may have devastating psycho-social consequences. In the last years, numerous evidences have been reported on the efficacy of bio-feedback techniques for the treatment of this disorder. Overall, the literature data claim a success rate in more than 70% of cases in the short term. However, recent controlled trials have not confirmed this optimistic view, thus emphasizing the role of standard care. Nonetheless, many authors believe that this should be the first therapeutic approach for fecal incontinence due to the efficacy, lack of side-effects,and scarce invasiveness. Well-designed randomized,controlled trial are eagerly awaited to solve this therapeutic dilemma.