The 1st i-EUS consensus on the management of pancreatic fluid collections - Part 2.

Pancreatic fluid collections (PFCs), including pancreatic pseudocysts (PPs) and walled-off pancreatic necrosis (WON), are common complications of pancreatitis and pancreatic surgery. Historically, the treatment of these conditions has relied on surgical and radiological approaches. The treatment of patients with PFCs has already focused toward an endoscopy-based approach, and with the development of dedicated lumen-apposing metal stents (LAMS), it has almost totally shifted towards interventional Endoscopic Ultrasound (EUS)-guided procedures. However, there is still limited consensus on several aspects of PFCs treatment within the multidisciplinary management. The interventional endoscopy and ultrasound (i-EUS) group is an Italian network of clinicians and scientists with special interest in biliopancreatic interventional endoscopy, especially interventional EUS. This manuscript focuses on the second part of the results of a consensus conference organized by i-EUS, with the aim of providing evidence-based guidance on several intra- and post-procedural aspects of PFCs drainage, such as clinical management and follow-up.

EUS-Guided Gallbladder Drainage Using a Lumen-Apposing Metal Stent for Acute Cholecystitis: Results of a Nationwide Study with Long-Term Follow-Up.

BACKGROUND: Although endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using lumen-apposing metal stents (LAMS) has become one of the treatments of choice for acute cholecystitis (AC) in fragile patients, scant data are available on real-life settings and long-term outcomes. METHODS: We performed a multicenter retrospective study including EUS-guided GBD using LAMS for AC in 19 Italian centers from June 2014 to July 2020. The primary outcomes were technical and clinical success, and the secondary outcomes were the rate of adverse events (AE) and long-term follow-up. RESULTS: In total, 116 patients (48.3% female) were included, with a mean age of 82.7 ± 11 years. LAMS were placed, transgastric in 44.8% of cases, transduodenal in 53.3% and transjejunal in 1.7%, in patients with altered anatomy. Technical success was achieved in 94% and clinical success in 87.1% of cases. The mean follow-up was 309 days. AEs occurred in 12/116 pts (10.3%); 8/12 were intraprocedural, while 1 was classified as early (<15 days) and 3 as delayed (>15 days). According to the ASGE lexicon, two (16.7%) were mild, three (25%) were moderate, and seven (58.3%) were severe. No fatal AEs occurred. In subgroup analysis of 40 patients with a follow-up longer than one year, no recurrence of AC was observed. CONCLUSIONS: EUS-GBD had high technical and clinical success rates, despite the non-negligible rate of AEs, thus representing an effective treatment option for fragile patients.

Direct Endoscopic Necrosectomy of a Recurrent Walled-Off Pancreatic Necrosis at High Risk for Severe Bleeding: A Hybrid Technique Using a Dedicated Device.

Direct endoscopic necrosectomy (DEN) is a challenging procedure for the debridement of walled-off pancreatic necrosis (WOPN), which may be complicated by several adverse events, primarily bleeding which may require radiological embolization or even surgery. The lack of dedicated devices for this purpose largely affects the possibility of safely performing DEN which increases the risk of complications. We present the case of a 63 years-old man who underwent an endoscopic ultrasound (EUS)-guided drainage of a WOPN, and who was readmitted one month after stent removal with clinical, endoscopic, and radiological signs of infected necrosis involving the splenic artery. A second EUS-guided drainage was performed, with clear visualization of the arterial vessel in the midst of a large amount of solid necrosis. Due to the high risk of major bleeding during DEN, a hybrid procedure in the angiographic room was performed, in order to identify and avoid, under fluoroscopic control, the splenic artery during the entire procedure guide, which was successfully performed using the EndoRotor system. We hereby review the current literature regarding DEN using the EndoRotor system. The case reported, with a literature overview, may help the management of these patients affected by benign but life-threatening conditions which involve a multidisciplinary setting.

Usefulness of Contrast-Enhanced Endoscopic Ultrasound (CH-EUS) to Guide the Treatment Choice in Superficial Rectal Lesions: A Case Series.

INTRODUCTION: Large rectal lesions can conceal submucosal invasion and cancer nodules. Despite the increasing diffusion of high-definition endoscopes and the importance of an accurate morphological evaluation, a complete assessment in this setting can be challenging. Endoscopic ultrasound (EUS) plays an established role in the locoregional staging of rectal cancer, although this technique has a tendency toward the over-estimation of the loco-regional (T) staging. However, there are still few data on contrast-enhanced endoscopic ultrasound (CH-EUS), especially if this ancillary technique may increase the accuracy for predicting invasive nodules among large rectal lesions. MATERIAL AND METHODS: Consecutive large (≥20 mm) superficial rectal lesions with high-definition endoscopy, characterized by focal areas suggestive for invasive cancer/2B type according to JNET classification, were considered for additional standardized evaluation via CH-EUS with Sonovue ©. RESULTS: From 2020 to 2023, we evaluated 12 consecutive superficial rectal lesions with sizes ranging from 20 to 180 mm. This evaluation provided additional elements to support the therapeutic decision made. Lesions were treated with surgical (3/12) or endoscopic treatment (9/12) according to their morphology and CH-EUS evaluation. CONCLUSION: Contrast-enhanced endoscopic ultrasound can provide an additional evaluation for large and difficult-to-classify rectal lesions. In our experience, CH-EUS staging corresponded to the final pathological stages in 9/12 (75%) lesions, improving the distinction between T1 and T2 lesions. Larger prospective studies and randomized trials should be conducted to support and standardize this approach.

Regret affects the choice between neoadjuvant therapy and upfront surgery for potentially resectable pancreatic cancer.

BACKGROUND: When treating potentially resectable pancreatic adenocarcinoma, therapeutic decisions are left to the sensibility of treating clinicians who, faced with a decision that post hoc can be proven wrong, may feel a sense of regret that they want to avoid. A regret-based decision model was applied to evaluate attitudes toward neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic adenocarcinoma. METHODS: Three clinical scenarios describing high-, intermediate-, and low-risk disease-specific mortality after upfront surgery were presented to 60 respondents (20 oncologists, 20 gastroenterologists, and 20 surgeons). Respondents were asked to report their regret of omission and commission regarding neoadjuvant chemotherapy on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied to analyze respondents' attitudes toward neoadjuvant therapy. RESULTS: The lowest regret of omission was elicited in the low-risk scenario, and the highest regret in the high-risk scenario (P < .001). The regret of the commission was diametrically opposite to the regret of omission (P ≤ .001). The disease-specific threshold mortality at which upfront surgery is favored over the neoadjuvant therapy progressively decreased from the low-risk to the high-risk scenarios (P ≤ .001). The nonsurgeons working in or with lower surgical volume centers (P = .010) and surgeons (P = .018) accepted higher disease-specific mortality after upfront surgery, which resulted in the lower likelihood of adopting neoadjuvant therapy. CONCLUSION: Regret drives decision making in the management of pancreatic adenocarcinoma. Being a surgeon or a specialist working in surgical centers with lower patient volumes reduces the likelihood of recommending neoadjuvant therapy.

Endoscopic Management of Postoperative Esophageal and Upper GI Defects-A Narrative Review.

Anastomotic defects are deleterious complications after either oncologic or bariatric surgery, leading to high morbidity and mortality. Besides surgical revision in early stages or instable patients, endoscopic treatment has become the mainstay. To date, many options for endoscopic treatment in this setting exist, including fully covered metal stent placement, endoscopic vacuum therapy (EVT), endoscopic internal drainage with pigtail placement (EID), leak closure with through the scope or over the scope clips, endoluminal suturing, fibrin glue sealing and a combination of all these techniques. Current evidence is mostly based on retrospective single and multicenter studies. No guidelines exist in this important field. Treatment options have to be chosen upon each case individually, taking into account clinical and anatomic criteria, such as timing, size, infectious wound complications and hemodynamic stability. Local expertise and availability of treatment devices need to be taken into account whenever choosing a treatment strategy. This review aimed to present current treatment options in terms of effectiveness, advantages and disadvantages in order to guide the clinician for his decision making. Additionally, we aimed to provide a treatment algorithm.

Dysbiosis and Gastrointestinal Surgery: Current Insights and Future Research.

Surgery of the gastrointestinal tract can result in deep changes among the gut commensals in terms of abundance, function and health consequences. Elective colorectal surgery can occur for neoplastic or inflammatory bowel disease; in these settings, microbiota imbalance is described as a preoperative condition, and it is linked to post-operative complications, as well. The study of bariatric patients led to several insights into the role of gut microbiota in obesity and after major surgical injuries. Preoperative dysbiosis and post-surgical microbiota reassessment are still poorly understood, and they could become a key part of preventing post-surgical complications. In the current review, we outline the most recent literature regarding agents and molecular pathways involved in pre- and post-operative dysbiosis in patients undergoing gastrointestinal surgery. Defining the standard method for microbiota assessment in these patients could set up the future approach and clinical practice.

A case of cystic paraduodenal pancreatitis with gastric outlet obstruction: technical pitfalls in EUS-guided gastroenteroanastomosis.

Video 1Technical pitfalls in EUS-guided gastroenteroanastomosis in an 84-year-old man with gastric outlet obstruction owing to cystic paraduodenal pancreatitis.

Determinants of outcomes of transmural EUS-guided gallbladder drainage: systematic review with proportion meta-analysis and meta-regression.

BACKGROUND AND AIMS: Transmural EUS-guided gallbladder drainage (EUS-GBD) has been increasingly used in the treatment of gallbladder diseases. Aims of the study were to provide a comprehensive meta-analysis and meta-regression of features and outcomes of this procedure. METHODS: MEDLINE, Scopus, Web of science, and Cochrane databases were searched for literature pertinent to transmural EUS-GBD up to May 2021. Random-effect meta-analysis of proportions and meta-regression of potential modifiers of outcome measures considered were applied. Outcome measures were technical success rate, overall clinical success, and procedure-related adverse events (AEs). RESULTS: Twenty-seven articles were identified including 1004 patients enrolled between February 2009 and February 2020. Acute cholecystitis was present in 98.7% of cases. Pooled technical success was 98.0% (95% CI 96.3, 99.3; heterogeneity: 23.6%), the overall clinical success was 95.4% (95% CI 92.8, 97.5; heterogeneity: 35.3%), and procedure-related AEs occurred in 14.8% (95% CI 8.8, 21.8; heterogeneity: 82.4%), being stent malfunction/dislodgement the most frequent (3.5%). Procedural-related mortality was 1‰. Meta-regression showed that center experience proxied to > 10 cases/year increased the technical success rate (odds ratio [OR]: 2.84; 95% CI 1.06, 7.59) and the overall clinical success (OR: 3.52; 95% CI 1.33, 9.33). The use of anti-migrating devices also increased the overall clinical success (OR: 2.16; 95% CI 1.07, 4.36) while reducing procedure-related AEs (OR: 0.36; 95% CI 0.14, 0.98). CONCLUSION: Physicians' experience and anti-migrating devices are the main determinants of main clinical outcomes after EUS-GBD, suggesting that treatment in expert centers would optimize results.

Biliary Diseases from the Microbiome Perspective: How Microorganisms Could Change the Approach to Benign and Malignant Diseases.

Recent evidence regarding microbiota is modifying the cornerstones on pathogenesis and the approaches to several gastrointestinal diseases, including biliary diseases. The burden of biliary diseases, indeed, is progressively increasing, considering that gallstone disease affects up to 20% of the European population. At the same time, neoplasms of the biliary system have an increasing incidence and poor prognosis. Framing the specific state of biliary eubiosis or dysbiosis is made difficult by the use of heterogeneous techniques and the sometimes unwarranted invasive sampling in healthy subjects. The influence of the microbial balance on the health status of the biliary tract could also account for some of the complications surrounding the post-liver-transplant phase. The aim of this extensive narrative review is to summarize the current evidence on this topic, to highlight gaps in the available evidence in order to guide further clinical research in these settings, and, eventually, to provide new tools to treat biliary lithiasis, biliopancreatic cancers, and even cholestatic disease.

Hybrid gastroenterostomy using a lumen-apposing metal stent: a case report focusing on misdeployment and systematic review of the current literature.

BACKGROUND: Gastric outlet obstruction can result from several benign and malignant diseases, in particular gastric, duodenal or pancreatic tumors. Surgical gastroenterostomy and enteral endoscopic stenting have represented effective therapeutic options, although recently endoscopic ultrasound-guided gastroenterostomy using lumen-apposing metal stent (LAMS) is spreading improving the outcome of this condition. However, this procedure, although mini-invasive, is burdened with not negligible complications, including misdeployment. MAIN BODY: We report the case of a 60-year-old male with gastric outlet obstruction who underwent ultrasound-guided gastroenterostomy using LAMS. The procedure was complicated by LAMS misdeployment being managed by laparoscopy-assisted placement of a second LAMS. We performed a systematic review in order to identify all reported cases of misdeployment in EUS-GE and their management. The literature shows that misdeployment occurs in up to 10% of all EUS-GE procedures with a wide spectrum of possible strategies of treatment. CONCLUSION: The here reported hybrid technique may offer an innovative strategy to manage LAMS misdeployment when this occurs. Moreover, a hybrid approach may be valuable to overcome this complication, especially in early phases of training of EUS-guided gastroenterostomy.

Role of endoscopic ultrasonography in the management of peripancreatic collections.

Pancreatic fluid collections are surrounded by a wall of granulation tissue and may contain necrotic debris. They occur following a severe acute pancreatitis and most of the cases resolve spontaneously after several weeks. However, their management may lead to a very hard-to-treat condition, requiring a multidisciplinary approach. During the last decades we assisted to a change of paradigm involving Endoscopic Ultrasonography, from a pure diagnostic technique to an interventional-therapeutic one, allowing an effective, safe and less invasive approach than other existing treatment standards, historically consisting of surgical and percutaneous drainage. Treatment of pancreatic fluid collections is indicated if they become infected or symptomatic. Over the past years, exponential developments were done in interventional endoscopic approach, making it the first line suggested modality. The use of endoscopic ultrasound allows assessment of the collection, even when it is not directly bulging on gastrointestinal wall, creation of an internal fistulous tract, checking for surrounding vessels with the use of Doppler, and deployment of a stent avoiding the discomfort of external tubes. Several types of stent have been used for endoscopic drainage: plastic double pigtail stents, fully covered self-expanding metal stents and, more recently, lumen apposing metal stents, which are considered revolutionary because of their two-side flanges and wide and short internal channel, a new design that made easier direct endoscopic necrosectomy. This review aims to go through currently available literature on the diagnostic and therapeutic role of endoscopic ultrasonography to handle pancreatic fluid collections.

Trial sequential analysis of EUS-guided gallbladder drainage versus percutaneous cholecystostomy in patients with acute cholecystitis.

BACKGROUND AND AIMS: Meta-analytic comparison of EUS-guided gallbladder drainage (EUS-GBD) versus percutaneous gallbladder drainage (PT-GBD) for acute cholecystitis (AC) brings the risk of spurious results if too few studies are included. Trial sequential analysis (TSA) can overcome this, providing information about its credibility. METHODS: Comparative studies between EUS-GBD, using lumen-apposing metal stents, and PT-GBD for AC until July 2021 were used for conventional meta-analysis and TSA, which allowed the use of monitoring boundaries and the estimation of the required information size (RIS) needed to prove credibility. RESULTS: Four studies accrued 535 patients. Technical success was in favor of PT-GBD (relative risk [RR], .967; P = .036), but TSA estimated that 1663 participants would be needed to avoid a Type I error (false positive). Clinical success was similar (RR, .965; P = .146), and TSA supported the absence of any demonstrable superiority of one therapy rather than a Type II error (false negative). EUS-GBD reduced overall adverse events (RR, .424; P < .001) and unplanned readmissions (RR, .215; P < .001), and TSA confirmed the avoidance of a Type I error, with early RIS achievement, providing necessary credibility. EUS-GBD had fewer reinterventions (RR, .244; P < .001), but a Type I error was not avoided, needing additional 97 patients to the accrued 535 to prove credibility. CONCLUSIONS: PT-GBD can provide superior technical success than EUS-GBD if a very large sample size is accrued, thus limiting the single-patient benefit. Clinical success is probably equivalent. EUS-GBD convincingly decreased overall adverse events and unplanned readmissions, whereas the need for reinterventions requires additional studies.

Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy.

Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis.

The Role of Contrast-Enhanced Harmonic Endoscopic Ultrasound in Interventional Endoscopic Ultrasound.

Over the last decades, contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) has emerged as an important diagnostic tool for the diagnosis and differentiation of several gastrointestinal diseases. The key advantage of CH-EUS is that the influx and washout of contrast in the target lesion can be observed in real time, accurately depicting microvasculature. CH-EUS is established as an evidence-based technique complementary to B-mode EUS to differentiate solid appearing structures, to characterize mass lesions, and to improve the staging of gastrointestinal and pancreatobiliary cancer. In the last few years, interest has increased in the use of CH-EUS in interventional procedures such as tissue acquisition, tumor ablation, biliary drainage, and the management of pancreatic fluid collections. The aim of this narrative review is to evaluate the available evidence and future expectations of CH-EUS in interventional EUS.

The Other Side of Malnutrition in Inflammatory Bowel Disease (IBD): Non-Alcoholic Fatty Liver Disease.

Steatohepatitis and hepatobiliary manifestations constitute some of the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD). On the other hand, non-alcoholic fatty liver disease (NAFLD) affects around 25% of the world's population and is attracting ever more attention in liver transplant programs. To outline the specific pathways linking these two conditions is a pressing task for 21st-century researchers. We are accustomed to expecting the occurrence of fatty liver disease in obese people, but current evidence suggests that there are several different pathways also occurring in underweight patients. Genetic factors, inflammatory signals and microbiota are key players that could help in understanding the entire pathogenesis of NAFLD, with the aim of defining the multiple expressions of malnutrition. In the current review, we summarize the most recent literature regarding the epidemiology, pathogenesis and future directions for the management of NAFLD in patients affected by IBD.

Dietary Habits and Gut Microbiota in Healthy Adults: Focusing on the Right Diet. A Systematic Review.

Diet is the first to affect our intestinal microbiota and therefore the state of eubiosis. Several studies are highlighting the potential benefits of taking certain nutritional supplements, but a dietary regime that can ensure the health of the intestinal microbiota, and the many pathways it governs, is not yet clearly defined. We performed a systematic review of the main studies concerning the impact of an omnivorous diet on the composition of the microbiota and the production of short-chain fatty acids (SCFAs). Some genera and phyla of interest emerged significantly and about half of the studies evaluated consider them to have an equally significant impact on the production of SCFAs, to be a source of nutrition for our colon cells, and many other processes. Although numerous randomized trials are still needed, the Mediterranean diet could play a valuable role in ensuring our health through direct interaction with our microbiota.

EUS-guided drainage using lumen apposing metal stent and percutaneous endoscopic necrosectomy as dual approach for the management of complex walled-off necrosis: a case report and a review of the literature.

BACKGROUND: Endoscopic ultrasound-guided drainage is suggested as the first approach in the management of symptomatic and complex walled-off pancreatic necrosis. Dual approach with percutaneous drainage could be the best choice when the necrosis is deep extended till the pelvic paracolic gutter; however, the available catheter could not be large enough to drain solid necrosis neither to perform necrosectomy, entailing a higher need for surgery. Therefore, percutaneous endoscopic necrosectomy through a large bore percutaneous self-expandable metal stent has been proposed. CASE PRESENTATION: In this study, we present the case of a 61-year-old man admitted to our hospital with a history of sepsis and persistent multiorgan failure secondary to walled-off pancreatic necrosis due to acute necrotizing pancreatitis. Firstly, the patient underwent transgastric endoscopic ultrasound-guided drainage using a lumen-apposing metal stent and three sessions of direct endoscopic necrosectomy. Because of recurrence of multiorgan failure and the presence of the necrosis deeper to the pelvic paracolic gutter at computed tomography scan, we decided to perform percutaneous endoscopic necrosectomy using an esophageal self-expandable metal stent. After four sessions of necrosectomy, the collection was resolved without complications. Therefore, we perform a revision of the literature, in order to provide the state-of-art on this technique. The available data are, to date, derived by case reports and case series, which showed high rates both of technical and clinical success. However, a not negligible rate of adverse events has been reported, mainly represented by fistulas and abdominal pain. CONCLUSION: Dual approach, using lumen apposing metal stent and percutaneous self-expandable metal stent, is a compelling option of treatment for patients affected by symptomatic, complex walled-off pancreatic necrosis, allowing to directly remove large amounts of necrosis avoiding surgery. Percutaneous endoscopic necrosectomy seems a promising technique that could be part of the step-up-approach, before emergency surgery. However, to date, it should be reserved in referral centers, where a multidisciplinary team is disposable.

A multicenter survey on endoscopic retrograde cholangiopancreatography during the COVID-19 pandemic in northern and central Italy.

Background and study aims COVID-19 has dramatically impacted endoscopy practice because upper endoscopy procedures can be aerosol-generating. Most elective procedures have been rescheduled. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed in emergency or urgent settings in which rescheduling is not possible. We evaluated the impact of the COVID-19 pandemic on ERCP in Italy during the SARS-CoV-2 lockdown, in areas with high incidence of COVID-19. Patients and methods We performed a retrospective survey of centers performing ERCP in high COVID-19 prevalence areas in Italy to collect information regarding clinical data from patients undergoing ERCP, staff, case-volume and organization of endoscopy units from March 8, 2020 to April 30, 2020. Results We collected data from 31 centers and 804 patients. All centers adopted a triage and/or screening protocol for SARS-CoV-2 and performed follow-up of patients 2 weeks after the procedure. ERCP case-volume was reduced by 44.1 % compared to the respective 2019 timeframe. Of the 804 patients undergoing ERCP, 22 (2.7 %) were positive for COVID-19. Adverse events occurred at a similar rate to previously published data. Of the patients, endoscopists, and nurses, 1.6 %, 11.7 %, and 4.9 %, respectively, tested positive for SARS-CoV-2 at follow up. Only 38.7 % of centers had access to a negative-pressure room for ERCP. Conclusion The case-volume reduction for ERCP during lockdown was lower than for other gastrointestinal endoscopy procedures. No definitive conclusions can be drawn about the percentage of SARS-CoV-2-positive patients and healthcare workers observed after ERCP. Appropriate triage and screening of patients and adherence to society recommendations are paramount.