Malignant gastric outlet obstruction:Which is the best therapeutic option?

Malignant gastric outlet obstruction(MGOO)is a clinical condition characterized by the mechanical obstruction of the pylorus or the duodenum due to tumor compression/infiltration,with consequent reduction or impossibility of an adequate oral intake.MGOO is mainly secondary to advanced pancreatic or gastric cancers,and significantly impacts on patients’survival and quality of life.Patients suffering from this condition often present with intractable vomiting and severe malnutrition,which further compromise therapeutic chances.Currently,palliative strategies are based primarily on surgical gastrojejunostomy and endoscopic enteral stenting with self-expanding metal stents.Several studies have shown that surgical approach has the advantage of a more durable relief of symptoms and the need of fewer re-interventions,at the cost of higher procedure-related risks and longer hospital stay.On the other hand,enteral stenting provides rapid clinical improvement,but have the limit of higher stent dysfunction rate due to tumor ingrowth and a subsequent need of frequent reinterventions.Recently,a third way has come from interventional endoscopic ultrasound,through the development of endoscopic ultrasound-guided gastroenterostomy technique with lumen-apposing metal stent.This new technique may ideally encompass the minimal invasiveness of an endoscopic procedure and the long-lasting effect of the surgical gastrojejunostomy,and brought encouraging results so far,even if prospective comparative trial are still lacking.In this Review,we described technical aspects and clinical outcomes of the above-cited therapeutic approaches,and discussed the open questions about the current management of MGOO.

Treatment of peri-anal fistula in Crohn's disease

Anal fistulas are a common manifestation of Crohn's disease(CD). The first manifestation of the disease is often in the peri-anal region, which can occur years before a diagnosis, particularly in CD affecting the colon and rectum. The treatment of peri-anal fistulas is difficult and always multidisciplinary. The European guidelines recommend combined surgical and medical treatment with biologic drugs to achieve best results. Several different surgical techniques are currently em-ployed. However, at the moment, none of these tech-niques appear superior to the others in terms of healing rate. Surgery is always indicated to treat symptomatic, simple, low intersphincteric fistulas refractory to medi-cal therapy and those causing disabling symptoms. Ut-most attention should be paid to correcting the balance between eradication of the fistula and the preservationof fecal continence.

Lumen-apposing metal stents for malignant biliary obstruction: Is this the ultimate horizon of our experience?

In the last years, endoscopic ultrasonography (EUS) has evolved from a purely diagnostic technique to a more and more complex interventional procedure, with the possibility to perform several type of therapeutic interventions. Among these, EUS-guided biliary drainage (BD) is gaining popularity as a therapeutic approach after failed endoscopic retrograde cholangiopancreatography in distal malignant biliary obstruction (MBO), due to the avoidance of external drainage, a lower rate of adverse events and re-interventions, and lower costs compared to percutaneous trans-hepatic BD. Initially, devices created for luminal procedures (e.g., luminal biliary stents) have been adapted to the new trans-luminal EUSguided interventions, with predictable shortcomings in technical success, outcome and adverse events. More recently, new metal stents specifically designed for transluminal drainage, namely lumen-apposing metal stents (LAMS), have been made available for EUS-guided procedures. An electrocautery enhanced delivery system (EC-LAMS), which allows direct access of the delivery system to the target lumen, has subsequently simplified the classic multi-step procedure of EUS-guided drainages. EUS-BD using LAMS and ECLAMS has been demonstrated effective and safe, and currently seems one of the most performing techniques for EUS-BD. In this Review, we summarize the evolution of the EUS-BD in distal MBO, focusing on the novelty of LAMS and analyzing the unresolved questions about the possible role of EUS as the first therapeutic option to achieve BD in this setting of patients.

Impairment of ghrelin synthesis in Helicobacter pyloricolonized stomach:New clues for the pathogenesis of H.pylori-related gastric inflammation

Ghrelin,the ligand of growth hormone secretagogue receptor 1a,takes part in several functions of the digestive system,including regulation of appetite,energy homeostasis,gastric acid secretion and motility.Ghrelin has also immunoregulatory properties and is supposed to inhibit some inflammatory pathways that can mediate gastric damage.Interestingly,ghrelin synthesis is reduced in the gastric mucosa of patients with Helicobacter pylori(H.pylori)infection,a worldwide condition inducing a T helper(Th)1/Th17 cell responsedriven gastritis,which may evolve towards gastric atrophy and cancer.In this article,we review the available data on the expression of ghrelin in H.pylori infection and discuss how the defective ghrelin synthesis may contribute to sustain the ongoing inflammatory response in this disease.

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM:To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori(H.pylori) eradication.METHODS:A total of 142(99 women,43 men; mean 53.0 ± 12.7 years) non-responders to more than two H.pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole,20 mg b.i.d.,levofloxacin,500 mg b.i.d.,and doxycycline,100 mg b.i.d.,randomly associated with(n = 71) or without(n = 71) Lactobacillus casei DG.H.pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy.Compliance and tolerability of regimens were also assessed.RESULTS:H.pylori eradication was achieved in < 50% of patients [per prototol(PP) = 49%; intention to treat(ITT) = 46%].Eradication rate was higher in patients administered probiotics than in those without(PP = 55% vs 43%; ITT = 54% vs 40%).Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%.Therapy was well tolerated,and side effects were generally mild,with only one patient experiencing severe effects.CONCLUSION:Third-line levofloxacin-doxycycline triple therapy had a low H.pylori eradication efficacy,though the success and tolerability of this treatment may be enhanced with probiotics.

Familial colorectal cancer screening: When and what to do?

Colorectal cancer(CRC) is the third leading cause of death worldwide and represents a clinical challenge.Family members of patients affected by CRC have an increased risk of CRC development.In these individuals,screening is strongly recommended and should be started earlier than in the population with average risk,in order to detect neoplastic precursors,such as adenoma,advanced adenoma,and nonpolypoid adenomatous lesions of the colon.Fecal occult blood test(FOBT) is a non invasive,widespread screening method that can reduce CRC-related mortality.Sigmoidoscopy,alone or in addition to FOBT,represents another screening strategy that reduces CRC mortality.Colonoscopy is the best choice for screening highrisk populations,as it allows simultaneous detection and removal of preneoplastic lesions.The choice of test depends on local health policy and varies among countries.

Tips and tricks for the diagnosis and management of biliary stenosis-state of the art review

Biliary stenosis may represent a diagnostic and therapeutic challenge resulting in a delay in diagnosis and initiation of therapy due to the frequent difficulty in distinguishing a benign from a malignant stricture.In such cases,the diagnostic flowchart includes the sequential execution of imaging techniques,such as magnetic resonance,magnetic resonance cholangiopancreatography,and endoscopic ultrasound,while endoscopic retrograde cholangiopancreatography is performed to collect tissue for histopathological/cytological diagnosis or to treat the stenosis by insertion of stent.The execution of percutaneous transhepatic drainage with subsequent biopsy has been shown to increase the possibility of tissue diagnosis after failure of the above techniques.Although the diagnostic yield of histopathology and imaging has increased with improvements in endoscopic ultrasound and peroral cholangioscopy,differential diagnosis between malignant and benign stenosis may not be easy in some patients,and strictures are classified as indeterminate.In these cases,a multidisciplinary workup including biochemical marker assays and advanced technologies available may speed up a diagnosis of malignancy or avoid unnecessary surgery in the event of a benign stricture.Here,we review recent advancements in the diagnosis and management of biliary strictures and describe tips and tricks to increase diagnostic yields in clinical routine.