The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review.

Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.

EUS-directed transenteric ERCP with giant intrahepatic stone lithotripsy after a LAMS-in-LAMS rescue in response to a misdeployment.

Video 1LAMS-in-LAMS rescue of a misdeployment during EUS-directed transenteric ERCP. LAMS, Lumen-apposing metal stent.

Same-session endoscopic diagnosis and symptom palliation in pancreato-biliary malignancies: Clinical impact of rapid on-site evaluation (ROSE).

Background and study aims Besides increasing adequacy, rapid on-site evaluation (ROSE) during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) may impact choices and timing of subsequent therapeutic procedures, yet has been unexplored. Patients and methods This was a retrospective evaluation of a prospectively maintained database of a tertiary, academic centre with availability of ROSE and hybrid EUS-ERCP suites. All consecutive patients referred for pathological confirmation of suspected malignancy and jaundice or gastric outlet obstruction (GOO) between Jan-2020 and Sep-2022 were included. Results Of 541 patients with underlying malignancy, 323 (59.7%) required same-session pathological diagnosis (male: 54.8%; age 70 [interquartile range 63-78]; pancreatic cancer: 76.8%, biliary tract adenocarcinoma 16.1%). ROSE adequacy was 96.6%, higher for EUS versus ERCP. Among 302 patients with jaundice, ERCP-guided stenting was successful in 83.1%, but final drainage was completed in 97.4% thanks to 43 EUS-guided biliary drainage procedures. Twenty-one patients with GOO were treated with 15 EUS-gastroenterostomies and six duodenal stents. All 58 therapeutic EUS procedures occurred after adequate ROSE. With ERCP-guided placement of stents, the use of plastic stents was significantly higher among patients with inadequate ROSE (10/11; 90.9%) versus adequate sampling (14/240; 5.8%) P <0.0001; OR 161; 95%CI 19-1352). Median hospital stay for diagnosis and palliation was 3 days (range, 2-7) and median time to chemotherapy was 33 days (range, 24-47). Conclusions Nearly two-thirds of oncological candidates for endoscopic palliation require contemporary pathological diagnosis. ROSE adequacy allows, since the index procedure, state-of-the-art therapeutics standardly restricted to pathologically confirmed malignancies (e.g. uncovered SEMS or therapeutic EUS), potentially reducing hospitalization and time to oncological treatments.

Two clues make a proof: EUS-directed transgastric ERCP in twice-surgically altered anatomy-Roux-en-Y gastric bypass conversion of a sleeve gastrectomy.

Video 1EUS-directed transgastric ERCP in twice-surgically-altered anatomy: Roux-en-Y gastric bypass conversion of a sleeve gastrectomy.

Managing dysfunctions and reinterventions in endoscopic ultrasound-guided choledochoduodenostomy with lumen apposing metal stents: Illustrated technical review (with videos).

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with lumen apposing metal stent is emerging both as a rescue strategy and a primary treatment for distal malignant biliary obstruction. The large-scale diffusion of the procedure and improved overall survival of patients with pancreatobiliary neoplasms is resulting in a growing population of long-term EUS-CDS lumen apposing metal stent carriers. Recent studies have reported a need for reintervention during follow-up as high as 55%, and the Leuven-Amsterdam-Milan Study Group classification has been developed, identifying five mechanisms of stent dysfunction and 11 possible rescue strategies aimed at restoring biliary drainage. This illustrated technical review aims to further dissect the recent classification through a comprehensive analysis of nine illustrative cases, offering insights into the pathophysiology underlying dysfunction and clinical reasoning behind rescue interventions, as well as technical considerations and practical tips and tricks. By exploring mechanisms of dysfunction, this review also assists clinicians in selecting the ideal candidates for EUS-CDS while identifying patients deemed high risk for dysfunction or clinical failure.

Fully covered versus partially covered self-expandable metal stents for palliation of distal malignant biliary obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Self-expandable metal stents (SEMSs) are standardly used for distal malignant biliary obstruction (dMBO). Although data suggest that covered versus uncovered SEMSs increase the time to recurrent biliary obstruction (TRBO), no data are available for fully covered (FC) versus partially covered (PC) designs. METHODS: PubMed, Scopus, and Cochrane databases were screened up to January 2023 for studies concerning dMBO treated by an FC- or PC-SEMS and describing adverse events (AEs), recurrences, or TRBO for specific design subpopulations. Pooled proportions or means were calculated using a random-effects model. Several subanalyses were preplanned, including a subanalysis restricted to prospective studies and unresectable diseases. Heterogeneity and publication bias were explored. Standardized differences (d-values) were calculated between groups. RESULTS: From 1290 records, 62 studies (3327 using FC-SEMSs and 2322 using PC-SEMSs) were included. FC- versus PC-SEMSs showed negligible differences in the rate of total AEs (12% vs 9.9%) and all specific AEs, including cholecystitis (2.5% vs 2.6%). In a subanalysis restricted to prospective studies and unresectable diseases, the rate of RBO was comparable between FC-SEMSs (27.3% [95% confidence interval {CI}, 23.7-31.2], I2 = 35.34%) and PC-SEMSs (25.3% [95% CI, 20.2-30.7], I2 = 85.09%), despite small differences (d-values between .186 and .216) in the rate of ingrowth (.5% vs 2.9%) favoring FC-SEMSs and migration (9.8% vs 4.3%) favoring PC-SEMSs. TRBO was shorter for FC-SEMSs (238 days [95% CI, 191-286], I2 = 63.1%) versus PC-SEMSs (369 days [95% CI, 290-449], I2 = 71.9%; d-value = .116). CONCLUSIONS: Despite considerable heterogeneity and small standardized differences, PC-SEMSs consistently exhibited longer TRBO than FC-SEMSs across analyses, without any other differences in AE rates, potentially proposing PC-SEMSs as the standard comparator and TRBO as the primary outcome for future randomized studies on dMBO. (Clinical trial registration number: CRD42023393965.).

Managing complications of chronic pancreatitis: a guide for the gastroenterologist.

INTRODUCTION: Chronic pancreatitis is a heterogeneous and complex syndrome that, in most cases, causes pain as a cardinal symptom and affects both the morphology and function of the pancreas, leading to several serious complications. AREAS COVERED: The present review, based on a non-systematic PubMed search updated to June 2023, aims to present the current available evidence on the role of gastroenterologists in the diagnosis and treatment of both local and systemic complications by either endoscopic or medical treatments. EXPERT OPINION: At diagnosis and during chronic pancreatitis follow-up, particular care is needed to consider not only the clinically manifest signs and symptoms of the disease, such as pain, jaundice, gastrointestinal obstruction, and pseudocysts, which require multidisciplinary discussion to establish the best treatment option (endoscopic or surgical), but also less evident systemic complications. Pancreatic exocrine and endocrine insufficiency, together with chronic inflammation, addiction, and dysbiosis, contribute to malnutrition, sarcopenia, and osteopathy. These complications, in turn, increase the risk of infection, thromboembolic events, and death. Patients with chronic pancreatitis also have an increased risk of psychiatric disorders and pancreatic cancer onset. Overall, patients with chronic pancreatitis should receive a holistic evaluation, considering all these aspects, possibly through multidisciplinary care in dedicated expert centers.

A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma.

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10-9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10-6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data.

EUS-guided gastroenterostomy for management of malignant gastric outlet obstruction: a prospective cohort study with matched comparison with enteral stenting.

BACKGROUND AND AIMS: Retrospective studies on malignant gastric outlet obstruction (mGOO) highlighted several advantages of EUS-guided gastroenterostomy (EUS-GE) over enteral stenting (ES). However, no prospective evidence is available. The aim of this study was to report on clinical outcomes of EUS-GE in a prospective cohort study, with a subgroup comparison versus ES. METHODS: All consecutive patients endoscopically treated for mGOO between December 2020 and December 2022 in a tertiary, academic center were enrolled in a prospective registry (Prospective Registry of Therapeutic Endoscopic Ultrasound [PROTECT]; NCT04813055) and followed up every 30 days to register efficacy/safety outcomes. EUS-GE and ES cohorts were matched according to baseline frailty and oncologic disease. RESULTS: A total of 104 patients were treated for mGOO during the study; 70 (58.6% male subjects; median age, 64 [interquartile range, 58-73] years; 75.7% pancreatic cancer, 60.0% metastatic cancer) underwent EUS-GE via the wireless simplified technique. Technical success was 97.1% and clinical success was 97.1% after a median of 1.5 (interquartile range, 1-2) days. Adverse events occurred in 9 (12.9%) patients. After a median follow-up of 105 (49-187) days, symptom recurrence was 7.6%. In the matched comparison versus ES (28 patients per arm), EUS-GE-treated patients experienced higher and faster clinical success (100% vs 75.0%, P = .006), reduced recurrences (3.7% vs 33.3%, P = .02), and a trend toward shorter time to chemotherapy. CONCLUSIONS: In this first, prospective, single-center comparison, EUS-GE showed excellent efficacy in treating mGOO, with an acceptable safety profile and long-term patency, and several clinically significant advantages over ES. While awaiting randomized trials, these results might endorse EUS-GE as first-line strategy for mGOO, where adequate expertise is available.

Same-session double EUS-guided bypass versus surgical gastroenterostomy and hepaticojejunostomy: an international multicenter comparison.

BACKGROUND AND AIMS: Gastric outlet and biliary obstruction are common manifestations of GI malignancies and some benign diseases for which standard treatment would be surgical gastroenterostomy and hepaticojejunostomy (ie, "double bypass"). Therapeutic EUS has allowed for the creation of an EUS-guided double bypass. However, same-session double EUS-guided bypass has only been described in small proof-of-concept series and lacks a comparison with surgical double bypass. METHODS: A retrospective multicenter analysis was performed of all consecutive same-session double EUS-guided bypass procedures performed in 5 academic centers. Surgical comparators were extracted from these centers' databases from the same time interval. Efficacy, safety, hospital stay, nutrition and chemotherapy resumption, long-term patency, and survival were compared. RESULTS: Of 154 identified patients, 53 (34.4%) received treatment with EUS and 101 (65.6%) with surgery. At baseline, patients undergoing EUS exhibited higher American Society of Anesthesiologists scores and a higher median Charlson Comorbidity Index (9.0 [interquartile range {IQR}, 7.0-10.0] vs 7.0 [IQR, 5.0-9.0], P < .001). Technical success (96.2% vs 100%, P = .117) and clinical success rates (90.6% vs 82.2%, P = .234) were similar when comparing EUS and surgery. Overall (11.3% vs 34.7%, P = .002) and severe adverse events (3.8% vs 19.8%, P = .007) occurred more frequently in the surgical group. In the EUS group, median time to oral intake (0 days [IQR, 0-1] vs 6 days [IQR, 3-7], P < .001) and hospital stay (4.0 days [IQR, 3-9] vs 13 days [IQR, 9-22], P < .001) were significantly shorter. CONCLUSIONS: Despite being used in a patient population with more comorbidities, same-session double EUS-guided bypass achieved similar technical and clinical success and was associated with fewer overall and severe adverse events when compared with surgical gastroenterostomy and hepaticojejunostomy.

Combined endoscopic mAnagement of BiliaRy and gastrIc OutLET obstruction (CABRIOLET Study): A multicenter retrospective analysis.

Objectives: Combined biliary obstruction and gastric outlet obstruction (GOO) represent a challenging clinical scenario despite developments in therapeutic endoscopic ultrasonography (EUS) as GOO might impair EUS-guided biliary drainage. Little is known about the effectiveness of different therapeutic combinations used to treat double obstruction, especially regarding stent patency. Methods: All consecutive patients with double obstruction treated between 2016 and 2021 in three tertiary academic centres were eligible for inclusion. Five combinations involving enteral stenting (ES), EUS-guided gastroenterostomy (EUS-GE), hepaticogastrostomy (EUS-HGS), choledochoduodenostomy (EUS-CDS), and transpapillary biliary stenting (TPS) were evaluated for dysfunction during follow-up, either as proportions or dysfunction-free survival (DFS) using Kaplan-Meier estimates. Results: Ninety-three patients were included (male 46%; age 67 [interquartile range 60-76] years; pancreatic cancer 73%, metastatic 57%), resulting in 103 procedure combinations. Different combinations showed significantly different overall dysfunction rates (p = 0.009), ranging from the null rate of EUS-GE+HG to the 18% rate of EUS-GE+TPS, 31% of EUS-GE+EUS-CD, 53% of ES+TPS and 83% of ES+EUS-CDS. Sub-analyses restricted to biliary dysfunction confirmed these trends. A multivariate Cox proportional-hazards regression of DFS, a stenosis distal to the papilla (HR 3.2 [1.5-6.9]) and ES+EUS-CDS (HR 5.6 [2-15.7]) independently predicted dysfunction. Conclusions: Despite a lack of statistical power per combination, this study introduces new associations beyond the increased risk of GOO recurrence with ES versus EUS-GE. EUS-CDS showed reduced effectiveness and frequent dysfunction in the context of GOO, especially when combined with ES. EUS-GE+HGS or EUS-GE+TPS in this setting might result in superior patency. These results suggest that a prospective evaluation of the optimal endoscopic approach to malignant double obstruction is needed.

Classification, risk factors, and management of lumen apposing metal stent dysfunction during follow-up of endoscopic ultrasound-guided choledochoduodenostomy: Multicenter evaluation from the Leuven-Amsterdam-Milan Study Group.

OBJECTIVES: Long-term outcomes of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) performed with lumen apposing metal stents (LAMS) have been poorly evaluated in small or retrospective series, leading to an underestimation of LAMS dysfunction. METHODS: All consecutive EUS-CDS performed in three academic referral centers were included in prospectively maintained databases. Technical/clinical success, adverse events (AEs), and dysfunction during follow-up were retrospectively analyzed. Kaplan-Meier analysis was used to estimate dysfunction-free survival (DFS), with Cox proportional hazard regression to evaluate independent predictors of dysfunction. RESULTS: Ninety-three patients were included (male 56%; mean age, 70 years [95% confidence interval (CI) 68-72]; pancreatic cancer 81%, metastatic disease 47%). In 67% of procedures, 6 mm LAMS were used. Technical and clinical success were achieved in 97.8% and 93.4% of patients, respectively, with AEs occurring in 9.7% (78% mild/moderate). Dysfunction occurred in 31.8% of patients after a mean of 166 days (95% CI 91-241), with an estimated 6 month and 12 month DFS of 75% and 52%, respectively; mean DFS of 394 (95% CI 307-482) days. Almost all dysfunctions (96%) were successfully managed by endoscopic reintervention. Duodenal invasion (hazard ratio 2.7 [95% CI 1.1-6.8]) was the only independent predictor of dysfunction. CONCLUSIONS: Endoscopic ultrasound-guided choledochoduodenostomy shows excellent initial efficacy and safety, although stent dysfunctions occurs frequently during long-term follow-up. Almost all stent dysfunctions can be managed successfully by endoscopic reinterventions. We propose a comprehensive classification of the different types of dysfunction that may be encountered and rescue procedures that may be employed under these circumstances. Duodenal invasion seems to increase the risk of developing EUS-CDS dysfunction, potentially representing a relative contraindication for this technique.

Endoscopic ultrasound guided biliary interventions.

Endoscopic Retrograde Cholangiopancreatography (ERCP), even in expert hands, may fail in 5-10% of cases, especially in cases of papillary infiltration, malignant gastric outlet obstruction, or surgically altered anatomy. Percutaneous transhepatic biliary drainage (PTBD) has represented the traditional rescue therapy, despite associated with high rate of adverse events, need for re-interventions and an inferior quality of life. The evolution of Endoscopic Ultrasound (EUS) from a diagnostic to a therapeutic tool offers an effective and safe alternative for internal biliary drainage (BD) into the stomach or the duodenum. EUS-BD is reported to have similar or even improved efficacy and increased safety when compared to PTBD and can be performed in the same session of a failed ERCP. This review summarizes technical aspects of intra-hepatic and extra-hepatic EUS-BD (including hepatico-gastrostomy, choledocho-duodenostomy and rendezvous) together with current evidence and future perspectives that steadily cements EUS-BD's place in multidisciplinary management of bilio-pancreatic diseases.

Radiation exposure during modern therapeutic endoscopic ultrasound procedures and standard alternatives.

Background and study aims Therapeutic EUS (t-EUS) is increasingly being adopted in clinical practice in tertiary referral centers; however, little is known about radiation exposure (RE) metrics and diagnostic reference limits for it. Methods Kerma-area product (KAP [Gy·cm 2 ]), Air Kerma and fluoroscopy time were retrospectively evaluated for all consecutive t-EUS procedures performed in San Raffaele Institute between 2019 and 2021. For EUS-guided choledochoduodenostomies (EUS-CDS) and gastroenterostomies (EUS-GE), an equal number of endoscopic retrograde cholangiopancreatographies (ERCPs) plus metal stenting and duodenal stents were included respectively for comparison. Results Data from 141 t-EUS procedures were retrieved (49 % pancreatic cancer, 38 % peripancreatic fluid collections). EUS-CDS (N = 44) were mainly performed fluoroless, while ERCPs required a significantly higher RE (KAP = 25 [17-55], P < 0.0001). Fluid collection drainage (EUS-FCD) with lumen apposing metal stents (LAMS, N = 26) were performed fluoroless, while EUS-FCD with double-pigtail plastic stents (DPPS, N = 28) required higher RE (KAP = 23 [13-45]). EUS-guided gallbladder drainage (EUS-GBD, N = 6) required scarce RE (KAP = 9 [3-21]) for coaxial DPPS placement. EUS-GE (N = 27) required higher RE than duodenal stenting (KAP = 44 [28-88] versus 29 [19-46], P = 0.03). EUS-guided hepaticogastrostomies (EUS-HGS, N = 10) had the highest RE among t-EUS procedures (KAP = 81 [49-123]). Procedure complexity or intervening complications were evaluated and resulted in higher RE within each procedure. Conclusions t-EUS procedures have different RE ( P  < 0.000001). EUS-CDS, EUS-GBD, and EUS-FCD with LAMS can be performed with no-to-mild radioscopy, unlike standard alternatives. However, radioscopy remains essential in case of technical difficulties or complications. EUS-GE and EUS-HGS involve a high RE. Endoscopists involved in t-EUS might experience RE higher than category standards, which indicates a need for increased awareness and personalized preventive measures.

Endoscopic ultrasound-guided biliary drainage and gastrointestinal anastomoses: the journey from promising innovations to standard of care.

Biliary obstruction (BO) and gastric outlet obstruction (GOO) are frequent complications of pancreatobiliary and gastroduodenal neoplasia, which can severely impact oncological outcomes, patient survival and quality of life. Although endoscopic retrograde cholangiopancreatography (ERCP) remains the gold standard for biliary drainage, this may fail or be unfeasible because of duodenal/papillary infiltration or surgically-altered anatomy. Percutaneous transhepatic biliary drainage (PTBD) has been the standard rescue therapy in this setting, but is burdened by high morbidity and reduced quality of life. As for GOO, surgical gastroenterostomy and enteral stenting are limited by invasiveness and suboptimal long-term outcomes, respectively. Endoscopic ultrasound (EUS) has evolved from a diagnostic to a therapeutic modality, providing a safe and effective alternative for draining the pancreatobiliary tract into the stomach or duodenum. EUS-guided biliary drainage (EUS-BD) has already demonstrated similar efficacy, greater safety and fewer reinterventions compared to PTBD, and can be performed in the same session after ERCP failure. Further development of lumen apposing metal stents has paved the way towards the creation of EUS-guided anastomoses. EUS-guided gastroenterostomy (EUS-GE) is nowadays increasingly used to treat GOO, combining the minimal invasiveness of endoscopy with surgical-range efficacy. This review summarizes the technical details, current evidence and society recommendations contributing to EUS-BD and EUS-GE gaining ground in everyday practice or tertiary referral centers and becoming crucial in improving the multidisciplinary management of cancer-related symptoms.

Risk factors for the occurrence of ampullary tumors: A case-control study.

BACKGROUND: The incidence of ampullary tumors is increasing but data on association with an increased exposure to certain risk factors are scanty. OBJECTIVE: To investigate risk and protective factors associated with the occurrence of ampullary tumors and whether these factors differ between ampullary tumors of the intestinal and pancreatobiliary subtypes or between adenomas and carcinomas. METHODS: The association between a large set of exposome features and ampullary tumors occurrence was investigated in a bi-centric case-control study after ethic committee approval and power calculation. RESULTS: In 223 histologically confirmed patients and 446 controls, previous cholecystectomy (odd ratio [OR] = 2.07; 95% confidence interval [CI] = 1.34-3.20) and proton pump inhibitors use (OR = 1.66; 95% CI = 1.16-2.37) were associated with increased risk of ampullary tumors, aspirin use (OR = 0.57; 95% CI = 0.36-0.90) and light alcohol intake (OR = 0.54; 95% CI = 0.38-0.76) with reduced risk. A previous cholecystectomy was also associated with tumors of intestinal subtype and with both adenomas and carcinomas, and proton pump inhibitors use with adenomas only. Smoking, body mass index, family history of cancers, previous ulcer, diabetes and use of statins, insulin and metformin were not significant factors. CONCLUSION: This is the first case-control study specifically highlighting factors associated with the occurrence of ampullary tumors. We report factors that are novel and plausible, in keeping with mechanisms described for other gastrointestinal tumors and with potential clinical relevance.

Feasibility of therapeutic endoscopic ultrasound in the bridge-to-surgery scenario: The example of pancreatic adenocarcinoma.

Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma, as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments. Jaundice, gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity, resulting in potentially deleterious chemotherapy discontinuation, whose resumption relies on effective, prompt and long-lasting management of these complications. Although therapeutic endoscopic ultrasound (t-EUS) can potentially offer some advantages over comparators, its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery. This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy, gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario. Proof-of-concept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery. Moreover, the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation, potentially resulting in higher subsequent resectability. Available evidence is discussed in this short paper, together with technical notes that might be useful for endoscopists and surgeons operating in this scenario. No published evidence supports restricting t-EUS in potential surgical candidates, especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy. Bridge-to-surgery t-EUS deserves further prospective evaluation.

EUS-guided gallbladder drainage and subsequent peroral endoscopic cholecystolithotomy: A tool to reduce chemotherapy discontinuation in neoplastic patients?

Background and Aims: EUS-guided gallbladder drainage (EUS-GBD) is emerging as a valuable treatment for acute cholecystitis (AC) in patients unfit for surgery. When lumen-apposing metal stents are used, large-caliber access to the gallbladder allows for subsequent direct peroral endoscopic cholecystoscopy (POEC) and eventual cholecystolithotomy (CL), offering a potentially "curative" solution for frailer patients. The aim of this series was to evaluate the outcome of these procedures in oncologic patients experiencing AC, with a specific focus on chemotherapy continuity. Methods: A prospective registry of all consecutive therapeutic EUS procedures performed in the San Raffaele Institute between December 2020 and April 2021 was searched for EUS-GBD + POEC-CL performed in chemotherapy candidates. Clinical and technical variables were prospectively registered, as were days of chemotherapy delay and postprocedural outcomes. Results: Three consecutive patients with a diagnosis of a malignancy (2 pancreatic cancers and 1 severe myeloproliferative disease with skeletal lesions) experienced AC and were primarily treated by EUS-GBD. After 4 weeks, they were systematically scheduled for POEC-CL and lumen-apposing metal stent exchange for a double-pigtail plastic stent. All procedures and revisions were successful, with rapid clinical improvement. All gallbladders were cleared of food debris and stones between 3 and 15 mm using grasping forceps, polypectomy snares, Dormia baskets, and mechanical lithotripsy. One mild adverse event without any clinical consequence was registered during POEC-CL. Revisions did not interfere with the chemotherapy schedule. Technical variables (eg, gastric vs duodenal drainage or need for coaxial double-pigtail plastic stent) are discussed. Conclusions: EUS-GBD and subsequent POEC-CL allows a highly effective and minimally invasive solution for AC. These initial experiences promote further evaluation of this approach for all those individuals in whom surgical interventions are undesirable, such as oncologic patients whose prognosis depends on chemotherapy continuity, although further prospective confirmation in this setting should be pursued.

Endoscopic ultrasound-guided gastroenterostomy versus duodenal stenting for malignant gastric outlet obstruction: an international, multicenter, propensity score-matched comparison.

BACKGROUND: Endoscopic duodenal stenting is the current standard treatment for malignant gastric outlet obstruction (GOO) in patients with limited life expectancy. However, duodenal stenting is prone to stent dysfunction. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a novel technique with potentially superior stent patency. We compared clinical success, safety, and stent dysfunction of EUS-GE and duodenal stenting in patients with malignant GOO using propensity score matching. METHODS: This international, multicenter, retrospective study analyzed consecutive patients undergoing EUS-GE or duodenal stenting for GOO between 2015 and 2021 in three European centers. Primary outcomes were clinical success (GOO scoring system [GOOSS] ≥ 2) and stent dysfunction (GOOSS ≤ 1 after initial clinical success). A propensity score matching (1:1) analysis was performed using age, sex, underlying disease, disease stage, ascites, and peritoneal carcinomatosis as variables. RESULTS: 214 patients underwent EUS-GE (n = 107) or duodenal stenting (n = 107). After propensity score matching, 176 patients were matched and compared. Technical success rates for EUS-GE and duodenal stenting were 94 % (95 %CI 89 %-99 %) vs. 98 % (95 %CI 95 %-100 %), respectively (P = 0.44). Clinical success rates were 91 % (95 %CI 85 %-97 %) vs. 75 % (95 %CI 66 %-84 %; P = 0.008). Stent dysfunction occurred in 1 % (95 %CI 0-4 %) vs. 26 % (95 %CI 15 %-37 %) of patients (P < 0.001). Adverse event rate was 10 % (95 %CI 4 %-17 %) vs. 21 % (95 %CI 12 %-29 %; P = 0.09). CONCLUSION: EUS-GE had higher clinical success and lower stent dysfunction, with similar safety, compared with duodenal stenting, suggesting that EUS-GE may be preferred over duodenal stenting in patients with malignant GOO.