Submucosal injection fluid and tattoo agents.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are minimally invasive endoscopic techniques, developed for the removal of benign and early malignant lesions throughout the GI tract. Submucosal injection of a marking agent can help to identify lesions during surgery. Endoscopic resection frequently involves "lifting" of the lesions by injection of a substance within the submucosal space to create a cushion for safe resection. This review summarizes the current techniques and agents available for endoscopic marking and lifting of GI tract lesions. METHODS: The MEDLINE database was searched through April 2023 for relevant articles related to the lifting and marking aspect of EMR by using key words such as "endoscopy" or "endoscopic" combined with "marking," "tattoo," and "lifting." The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. RESULTS: This technology review describes the techniques for endoscopic tattoo placement and submucosal lifting, along with currently available agents, safety, and costs. CONCLUSIONS: Endoscopists performing EMR and ESD have several choices in submucosal injection materials for lifting and marking agents for tattoos. These may be commercially prepared agents or off-the-shelf materials with or without additives to facilitate visualization. A thorough understanding of the indications, techniques, properties of various agents, costs, and adverse events is necessary in choosing the appropriate materials and technique to optimize lesion resection in EMR and ESD.

EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs).

BACKGROUND: Main-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs. METHODS: We performed a retrospective study of 369 patients who underwent resections for MD- or MT-IPMN at two tertiary centers (2000-2019). Multivariable logistic regression analyses were performed for postoperative adverse events to compare the risks between intervention (ERCP, EUS-FNA with branch duct (BD) aspirated, EUS-FNA with MD aspirated from the duct directly or cyst/mass arising from MD) versus no-intervention group. RESULTS: 33.1 % of patients had a preoperative ERCP and 69.4 % had EUS-FNA. Postoperative adverse events included: 30-day readmission (12.7 %), delayed gastric emptying (13.8 %), pancreatic fistula (10.3 %), abdominal abscess (5.7 %), cardiopulmonary adverse events (11.4 %), and mortality (1.4 %). The model was adjusted for potential confounders. There were no significant differences between the ERCP and no-ERCP groups for specific adverse events. Compared to no-EUS-FNA groups, groups of EUS-FNA with BD aspiration and EUS-FNA with MD aspiration from the main pancreatic duct directly or cyst/mass arising from MD did not show a significant increase in specific adverse events. CONCLUSIONS: Postoperative adverse events were not significantly increased among patients who had ERCP or EUS-FNA before surgical resection for MD- or MT-IPMNs. Endoscopic procedures directly sampling the MD can be safely pursued for diagnostic purposes in selected cases.

Isolation, Expansion, and Endoscopic Delivery of Autologous Enteric Neuronal Stem Cells in Swine.

The enteric nervous system (ENS) is an extensive network of neurons and glia within the wall of the gastrointestinal (GI) tract that regulates many essential GI functions. Consequently, disorders of the ENS due to developmental defects, inflammation, infection, or age-associated neurodegeneration lead to serious neurointestinal diseases. Despite the prevalence and severity of these diseases, effective treatments are lacking as they fail to directly address the underlying pathology. Neuronal stem cell therapy represents a promising approach to treating diseases of the ENS by replacing the absent or injured neurons, and an autologous source of stem cells would be optimal by obviating the need for immunosuppression. We utilized the swine model to address key questions concerning cell isolation, delivery, engraftment, and fate in a large animal relevant to human therapy. We successfully isolated neural stem cells from a segment of small intestine resected from 1-month-old swine. Enteric neuronal stem cells (ENSCs) were expanded as neurospheres that grew optimally in low-oxygen (5%) culture conditions. Enteric neuronal stem cells were labeled by lentiviral green fluorescent protein (GFP) transduction, then transplanted into the same swine from which they had been harvested. Endoscopic ultrasound was then utilized to deliver the ENSCs (10,000-30,000 neurospheres per animal) into the rectal wall. At 10 and 28 days following injection, autologously derived ENSCs were found to have engrafted within rectal wall, with neuroglial differentiation and no evidence of ectopic spreading. These findings strongly support the feasibility of autologous cell isolation and delivery using a clinically useful and minimally invasive technique, bringing us closer to first-in-human ENSC therapy for neurointestinal diseases.

A Multi-Institutional Safety and Feasibility Study Exploring the Use of Hydrogel to Create Spatial Separation between the Pancreas and Duodenum in Patients with Pancreatic Cancer.

PURPOSE: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum. METHODS AND MATERIALS: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT. RESULTS: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove was pathologically confirmed with no evidence of damage to the duodenum. CONCLUSIONS: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit to translate into clinically improved tumor control.

Utilizing mollusk soft tissue and shells as biomarkers for monitoring heavy metal pollution in mangrove forests.

The primary objective of the study was to examine the distribution of various elements, namely Cadmium (Cd), Copper (Cu), Iron (Fe), Nickel (Ni), and Lead (Pb), in the soft tissues, shells, and associated surface sediments of Cerithidea obtusa (C. obtusa) mangrove snails collected from Sungai Besar Sepang. To conduct the analysis, the preferred and most convenient methods employed were Instrumental Neutron Activation Analysis (INAA) and Atomic absorption spectrometry (AAS). The results showed that the mean concentration of elements in the sediments and soft tissues followed the order Fe > Cu > Ni > Pb > Cd, while for the shell of C. obtusa, it was Fe > Ni > Cu > Pb > Cd.•Iron (Fe) showed the highest concentration among all elements monitored in sediments, soft tissues, and shells of C. obtusa.•The PF results indicated higher incorporation of Pb and Ni into shells.•BSAF results showed that C. obtusa shells accumulated more Cu and Cd from sediments, making them effective biomonitors.

"Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections".

OBJECTIVE: The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. SUMMARY BACKGROUND DATA: Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. METHODS: Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. RESULTS: A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. CONCLUSIONS: Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

Concordance of EUS and MRI/MRCP findings among high-risk individuals undergoing pancreatic cancer screening.

BACKGROUND/OBJECTIVES: Surveillance with endoscopic ultrasonography (EUS) and MRI/magnetic retrograde cholangiopancreatography (MRCP) is recommended for individuals at high risk for pancreatic cancer. We sought to characterize the findings of these surveillance exams and define the level of concordance between these two modalities. METHODS: 173 asymptomatic high-risk individuals (HRIs) meeting criteria for pancreatic cancer surveillance underwent EUS, MRI/MRCP, or both between 2008 and 2021. Clinical records were reviewed in all cases. RESULTS: HRIs underwent an average of 3.6 ± 3.2 surveillance exams over a period of 3.3 ± 3.5 years. Abnormalities including intraductal papillary mucinous neoplasms (IPMNs), solid lesions, and parenchymal irregularities were identified in 50.9% (n = 88). Four of these abnormalities (2.3%) had worrisome features, defined by cyst size, thickened/enhancing cyst walls, rapid growth rate, or change in main pancreatic duct diameter. All four worrisome lesions were seen on both MRI/MRCP and EUS. No pancreatic cancers were detected. Baseline EUS and MRI/MRCP exams were compared in 106 patients for concordance, and most (n = 66, 62.3%) were concordant. High levels of concordance were specifically observed for a dilated main pancreatic duct (p < 0.01) and cystic lesions >5 mm (p = 0.01). Among discordant cases, most (30/40; 75%) involved abnormal tissue heterogeneity seen primarily on EUS. None of these discordant lesions ultimately developed worrisome features. CONCLUSIONS: Worrisome pancreatic lesions were uncommon in our high-risk pancreatic cancer population and were detected by both EUS and MRI/MRCP. There was mild discordance with respect to less worrisome findings, but these discrepancies were not associated with any adverse clinical outcomes.

Treatment and Prevention of Intraabdominal Bleeding in Necrotizing Pancreatitis Patients Treated With a Step-Up Approach.

OBJECTIVES: A minimally invasive step-up (MIS) approach for management of necrotizing pancreatitis (NP) has been associated with reduced morbidity and mortality compared with open surgical techniques. We sought to evaluate bleeding complications in NP patients treated with a MIS approach and to describe the management and outcomes of these events. METHODS: An observational, cohort study was performed using a prospectively maintained NP database at a tertiary referral center from 2013 to 2019. RESULTS: Of 119 NP patients, 13% suffering bleeding events, and 18% underwent an intervention. There was a 6-fold higher mortality rate in patients with bleeding events (n = 3; 18.8%) compared with those without (n = 3; 2.9%) ( P = 0.031). The most common intervention for hemorrhage control was endovascular coil embolization (75%), which was successful 88% of the time. Seven patients underwent prophylactic vascular intervention, which was 100% successful in preventing bleeding events from the embolized vessel. CONCLUSIONS: Bleeding events in NP patients treated with a MIS approach are associated with a 6-fold increase in mortality. Endovascular intervention is an effective strategy for the management of bleeding events. Prophylactic embolization may be an effective technique for reducing bleeding complications.

Devices for esophageal function testing.

BACKGROUND AND AIMS: Esophageal function testing is an integral component of the evaluation of refractory GERD and esophageal motility disorders. This review summarizes the current technologies available for esophageal function testing, including the functional luminal imaging probe (FLIP), high-resolution esophageal manometry (HRM), and multichannel intraluminal impedance (MII) and pH monitoring. METHODS: We performed a MEDLINE, PubMed, and MAUDE database literature search to identify pertinent clinical studies through March 2021 using the following key words: esophageal manometry, HRM, esophageal impedance, FLIP, MII, and esophageal pH testing. Technical data were gathered from traditional and web-based publications, proprietary publications, and informal communications with pertinent vendors. The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. RESULTS: FLIP is a high-resolution impedance planimetry system used for pressure and dimension measurement in the esophagus, pylorus, and anal sphincter. FLIP provides complementary information to HRM for esophageal motility disorders, especially achalasia. The Chicago classification, based on HRM data, is a widely adopted algorithmic scheme used to diagnose esophageal motility disorders. MII detects intraluminal bolus movement and, combined with pH measurement or manometry, provides information on acid and non-acid gastroesophageal reflux and bolus transit in patients with refractory GERD and for preoperative evaluation for anti-reflux procedures. CONCLUSIONS: Esophageal function testing techniques (FLIP, HRM, and MII-pH) have diagnostic and prognostic value in the evaluation of esophageal motility disorders and refractory GERD. Newer technologies and classification systems have enabled an increased understanding of these diseases.

Next-generation sequencing in the evaluation of biliary strictures in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC. METHODS: This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA. RESULTS: NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples. CONCLUSIONS: Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.

Outcomes of EUS-guided transluminal gallbladder drainage in patients without cholecystitis.

BACKGROUND AND OBJECTIVES: Cholecystectomy is the gold standard for most gallbladder-related disease. However, many patients with gallbladder disease are poor surgical candidates. Current nonsurgical gallbladder drainage (GBD) methods include percutaneous cholecystostomy and endoscopic ultrasound-guided transluminal GBD (EUS-GBD). Outcomes for EUS-GBD for the treatment of noncholecystitis (NC) gallbladder disease have not been defined. MATERIALS AND METHODS: Cases were identified using procedural data from a quaternary academic hospital for endoscopic procedures from 2015 to 2020. Patients who underwent EUS-GBD for acute cholecystitis, biliary colic, gallstone pancreatitis, and secondary prevention of gallstone disease were included. RESULTS: Fifty-five cases of EUS-GBD were identified over the 5-year study period. Forty-one cases were performed for acute cholecystitis, and 15 were performed for other NC indications. Indications for NC drainage included primary treatment of symptomatic biliary colic and secondary prevention of gallstone pancreatitis and choledocholithiasis. There was no statistically significant difference in complications, mortality, or reintervention requirements. There was a 13.3% rate of immediate complications in the NC group, which were all medically managed. CONCLUSIONS: EUS-GBD appears to be a safe and effective way to manage gallstone disease in nonsurgical candidates with NC gallbladder-related disease. Overall complications and readmissions were infrequent. Complication rates were similar to those published in patients who underwent EUS-GBD for acute cholecystitis.

Endoscopic therapies for gallbladder drainage.

BACKGROUND AND AIMS: Endoscopic management of acute cholecystitis has expanded in patients who are considered nonoperative candidates. Traditionally managed with percutaneous cholecystostomy (PC), improvement in techniques and devices has led to increased use of endoscopic methods for gallbladder drainage. This document reviews technical aspects of endoscopic transpapillary gallbladder drainage (ET-GBD) and EUS-guided GBD (EUS-GBD) as well as their respective technical/clinical success and adverse event rates. Available comparative data are also reviewed among nonsurgical gallbladder drainage techniques (PC, ET-GBD, and EUS-GBD). METHODS: The MEDLINE database was searched through March 2021 for relevant articles by using keywords including "acute cholecystitis," "interventional EUS," "percutaneous cholecystostomy," "transpapillary gallbladder drainage," "EUS-guided gallbladder drainage," "lumen-apposing metal stent," "gallbladder stenting," and "endoscopic gallbladder drainage." The manuscript was drafted by 2 authors and reviewed by members of the American Society for Gastrointestinal Endoscopy Technology Committee and subsequently by the American Society for Gastrointestinal Endoscopy Governing Board. RESULTS: Multiple studies have demonstrated acceptable outcomes comparing PC and both endoscopic gallbladder drainage techniques, ET-GBD and EUS-GBD. Published data suggest that endoscopic gallbladder drainage techniques may be associated with lower rates of adverse events and improved quality of life. However, there are important clinical considerations for choosing among these treatment options, requiring a multidisciplinary and collaborative approach to therapeutic decision-making in these patients. CONCLUSIONS: The implementation of EUS-GBD and ET-GBD in high-risk surgical patients with acute cholecystitis may result in favorable outcomes when compared with PC. Further improvements in techniques and training should lead to more widespread acceptance and dissemination of these treatment options.

Endoscopic polypectomy devices.

Video 1Use of submucosal injection prior to en-bloc endoscopic mucosal resection.Video 2Use of a detachable loop ligating device prior to hot snare resection of a pedunculated polyp.