Endoscopic management of gastrointestinal leaks and fistulae: Whatoption do we have?

Gastrointestinal leaks and fistulae are serious, potentially life threateningconditions that may occur with a wide variety of clinical presentations. Leaks aremostly related to post-operative anastomotic defects and are responsible for animportant share of surgical morbidity and mortality. Chronic leaks and longstanding post-operative collections may evolve in a fistula between twoepithelialized structures. Endoscopy has earned a pivotal role in the managementof gastrointestinal defects both as first line and as rescue treatment. Endotherapyis a minimally invasive, effective approach with lower morbidity and mortalitycompared to revisional surgery. Clips and luminal stents are the pioneer ofgastrointestinal (GI) defect endotherapy, whereas innovative endoscopic closuredevices and techniques, such as endoscopic internal drainage, suturing systemand vacuum therapy, has broadened the indications of endoscopy for themanagement of GI wall defect. Although several endoscopic options are currentlyused, a standardized evidence-based algorithm for management of GI defect isnot available. Successful management of gastrointestinal leaks and fistulaerequires a tailored and multidisciplinary approach based on clinical presentation,defect features (size, location and onset time), local expertise and the availabilityof devices. In this review, we analyze different endoscopic approaches, which weselected on the basis of the available literature and our own experience. Then, weevaluate the overall efficacy and procedural-specific strengths and weaknesses ofeach approach.

Non-variceal upper gastrointestinal bleeding: Rescue treatment with a modified cyanoacrylate

AIM To evaluate the safety and efficacy of a modified cyanoacrylate [N-butyl-2-cyanoacrylate associated with methacryloxysulfolane(NBCA + MS)] to treat nonvariceal upper gastrointestinal bleeding(NV-UGIB).METHODS In our retrospective study we took into account 579 out of 1177 patients receiving endoscopic treatment for NV-UGIB admitted to our institution from 2008 to 2015; the remaining 598 patients were treated with other treatments. Initial hemostasis was not achieved in 45 of 579 patients; early rebleeding occurred in 12 of 579 patients. Thirty-three patients were treated with modified cyanoacrylate: 27 patients had duodenal, gastric or anastomotic ulcers, 3 had post-mucosectomy bleeding, 2 had Dieulafoy's lesions, and 1 had duodenal diverticular bleeding.RESULTS Of the 45 patients treated endoscopically without initialhemostasis or with early rebleeding, 33(76.7%) were treated with modified cyanoacrylate glue, 16(37.2%) underwent surgery, and 3(7.0%) were treated with selective transarterial embolization. The mean age of patients treated with NBCA + MS(23 males and 10 females) was 74.5 years. Modified cyanoacrylate was used in 24 patients during the first endoscopy and in 9 patients experiencing rebleeding. Overall, hemostasis was achieved in 26 of 33 patients(78.8%): 19 out of 24(79.2%) during the first endoscopy and in 7 out of 9(77.8%) among early rebleeders. Two patients(22.2%) not responding to cyanoacrylate treatment were treated with surgery or transarterial embolization. One patient had early rebleeding after treatment with cyanoacrylate. No late rebleeding during the follow-up or complications related to the glue injection were recorded.CONCLUSION Modified cyanoacrylate solved definitively NV-UGIB after failure of conventional treatment. Some reported life-threatening adverse events with other formulations, advise to use it as last option.

Endoscopic ultrasound-guided sampling of solid pancreatic masses:the fine needle aspiration or fine needle biopsy dilemma. Is the best needle yet to come?

Fine needle aspiration (FNA) is currently the standard of care for sampling pancreatic solid masses by using endoscopic ultrasound (EUS).The accuracy of the technique is reported to be high,especially if coupled with the rapid on site evaluation (ROSE),and it has a high safety profile.However,FNA presents some limitations,such as the small amount of tissue that can be collected and the inability of obtaining a core tissue with intact histological architecture,which is relevant to perform immunohistochemical analysis,molecular profiling and,therefore,targeted therapies.Moreover,the presence of the ROSE by an expert cytopathologist is very important to maximize the diagnostic yield of FNA technique;however,it is not widely available,especially in small centers.Hence,the introduction of EUS fine needle biopsy (FNB) with a new generation of needles,which show a high safety profile too and a satisfying diagnostic accuracy even in the absence of ROSE,could be the key to overcome the limitations of FNA.However,FNB has not yet shown diagnostic superiority over FNA.Considering all the technical aspects of FNA and FNB,the different types of needle currently available,comparisons in term of diagnostic yield,and the different techniques of sampling,a tailored approach should be used in order to determine the needle that is most appropriate for the different specific scenarios.

Endoscopic ultrasound diagnostic gain over computed tomography and magnetic resonance cholang-iopancreatography in defining etiology of idiopathic acute pancreatitis

BACKGROUND About 10%-30%of acute pancreatitis remain idiopathic(IAP)even after clinical and imaging tests,including abdominal ultrasound(US),contrast-enhanced computed tomography(CECT)and magnetic resonance cholangiopancreatography(MRCP).This is a relevant issue,as up to 20%of patients with IAP have recurrent episodes and 26%of them develop chronic pancreatitis.Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques.AIM To evaluate the diagnostic gain after failure of one or more previous crosssectional exams.METHODS We retrospectively collected data about consecutive patients with AP and at least one negative test between US,CECT and MRCP,who underwent linear EUS between January 2017 and December 2020.We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these crosssectional imaging techniques for the etiologic diagnosis of AP.Types and frequency of EUS diagnosis were also analyzed,and EUS diagnosis was compared with the clinical parameters.After EUS,patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence.RESULTS We enrolled 81 patients(63%males,mean age 61±18,23%with previous cholecystectomy,17%with recurrent pancreatitis).Overall EUS diagnostic yield for AP etiological diagnosis was 79%(20%lithiasis,31%acute on chronic pancreatitis,14%pancreatic solid or cystic lesions,5%pancreas divisum,5%autoimmune pancreatitis,5%ductal abnormalities),while 21%remained idiopathic.US,CECT and MRCP,taken alone or in combination,led to AP etiological diagnosis in 16(20%)patients;among the remaining 65 patients,49(75%)obtained a diagnosis at EUS,with an overall EUS diagnostic gain of 61%.Sixty-eight patients had negative US;among them,EUS allowed etiological diagnosis in 59(87%).Sixty-three patients had a negative CECT;among them,47(74%)obtained diagnosis with EUS.Twenty-four had a negative MRCP;among them,20(83%)had EUS diagnosis.Twenty-one had negative CT+MRCP,of which 17(81%)had EUS diagnosis,with a EUS diagnostic gain of 63%.Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase(154 vs 25,P=0.010),aspartate aminotransferase(95 vs 29,P=0.018),direct bilirubin(1.2 vs 0.6,P=0.015),gammaglutamyl transpeptidase(180 vs 48,P=0.006)and alkaline phosphatase(150 vs 72,P=0.015)Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline(82%vs 21%,P<0.001).During the follow-up,AP recurred in 3 patients,one of which remained idiopathic.CONCLUSION EUS is a good test to define AP etiology.It showed a 63%diagnostic gain over CECT+MRCP.In suitable patients,EUS should always be performed in cases of IAP.Further prospective studies are needed.

Gastric per-oral endoscopic myotomy:Indications,technique,results and comparison with surgical approach

Gastroparesis is a chronic disease of the stomach that causes a delayed gastric emptying,without the presence of a stenosis.For 30 years the authors identified pylorospasm as one of the most important pathophysiological mechanisms determining gastroparesis.Studies with EndoFLIP,a device that assesses pyloric distensibility,increased the knowledge about pylorospasm.Based on this data,several pyloric-targeted therapies were developed to treat refractory gastroparesis:Surgical pyloroplasty and endoscopic approach,such as pyloric injection of botulinum and pyloric stenting.Notwithstanding,the success of most of these techniques is still not complete.In 2013,the first human gastric per-oral endoscopic myotomy(GPOEM)was performed.It was inspired by the POEM technique,with a similar dissection method,that allows pyloromyotomy.Therapeutical results of GPOEM are similar to surgical approach in term of clinical success,adverse events and post-surgical pain.In the last 8 years GPOEM has gained the attention of the scientific community,as a minimally invasive technique with high rate of clinical success,quickly prevailing as a promising therapy for gastroparesis.Not surprisingly,in referral centers,its technical success rate is 100%.One of the main goals of recent studies is to identify those patients that will respond better to the therapies targeted on pylorus and to choose the better approach for each patient.

Liver-side of inflammatory bowel diseases:Hepatobiliary and druginduced disorders

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases(IBD),both in Crohn’s disease and ulcerative colitis(UC),and therefore represent a diagnostic challenge.Immunemediated conditions include primary sclerosing cholangitis(PSC)as the main form,variant forms of PSC(namely small-duct PSC,PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis)and granulomatous hepatitis.PSC is by far the most common,presenting in up to 8%of IBD patients,more frequently in UC.Several genetic foci have been identified,but environmental factors are preponderant on disease pathogenesis.The course of the two diseases is typically independent.PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies.Risk of cholangiocarcinoma is significantly increased in PSC,as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis.No disease-modifying drugs are approved to date.Thus,PSC management is directed against symptoms and complications and includes medical therapies for pruritus,endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease.Other nonimmune-mediated hepatobiliary disorders are gallstone disease,whose incidence is higher in IBD and reported in up to one third of IBD patients,non-alcoholic fatty liver disease,pyogenic liver abscess and portal vein thrombosis.Druginduced liver injury(DILI)is an important issue in IBD,since most IBD therapies may cause liver toxicity;however,the incidence of serious adverse events is low.Thiopurines and methotrexate are the most associated with DILI,while the risk related to anti-tumor necrosis factor-αand anti-integrins is low.Data on hepatotoxicity of newer drugs approved for IBD,like anti-interleukin 12/23 and tofacitinib,are still scarce,but the evidence from other rheumatic diseases is reassuring.Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD,and adequate screening and vaccination is warranted.On the other hand,hepatitis C reactivation does not seem to be a real risk,and hepatitis C antiviral treatment does not influence IBD natural history.The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis,but it is of paramount importance to make a quick and accurate diagnosis,as it may influence the therapeutic management.

SARS-CoV-2 in inflammatory bowel disease population:Antibodies,disease and correlation with therapy

BACKGROUND Guidelines recommend to cease inflammatory bowel disease(IBD)biologic therapy during coronavirus disease 2019(COVID-19).AIM To investigate severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibody positivity in an IBD cohort,COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables.METHODS Prospective observational cohort study.IBD patients were tested for SARS-CoV-2 IgG.Data on COVID-19 disease,demographics/therapeutics and clinical features of the IBD population were collected.IgG≥7 was set for SARS-CoV-2 antibody positivity.Throat swab was performed in cases of IgG positivity.Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed.RESULTS In total,103 IBD patients were enrolled.Among them,18.4%had IgG≥7.Multivariate analysis of antibody positivity correlated only with IBD treatment.For IgG≥7,the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine,respectively,vs biologic drugs(P=0.0157 between them).COVID-19 related symptoms were reported in 63%of patients with IgG positivity.All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBDtreatment and body mass index correlated with COVID-19 disease development with symptoms.CONCLUSIONThe IBD population does not have a higher risk of severe COVID-19. The relative risk of havingSARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologictherapy and lastly mesalazine. None of the patients under biologic therapy developed severeCOVID-19.