Establishment of Standards for the Referral of Large Non-Pedunculated Colorectal Polyps: An International Expert Consensus Using a Modified Delphi Process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large non-pedunculated colorectal polyps are often referred to expert centres for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of our study was to establish minimum expected standards for the referral of LNPCP for potential ER. METHODS: A Delphi methodology was employed to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and three rounds of surveys were conducted to achieve consensus, with quantitative and qualitative data analysed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographics, relevant medications, lesion factors, photodocumentation and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements ranged from 7.04 to 9.29 out of 10, with high percentages of experts considering most statements as a very high priority. Subgroup analysis by continent revealed some variations in consensus rates among experts from different regions. CONCLUSION: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial).

BACKGROUND & AIMS: Several studies have compared primary endoscopic ultrasound (EUS)-guided biliary drainage to endoscopic retrograde cholangiopancreatography (ERCP) with insertion of metal stents in unresectable malignant distal biliary obstruction (MDBO) and the results were conflicting. The aim of the current study was to compare the outcomes of the procedures in a large-scale study. METHODS: This was a multicenter international randomized controlled study. Consecutive patients admitted for obstructive jaundice due to unresectable MDBO were recruited. Patients were randomly allocated to receive EUS-guided choledocho-duodenostomy (ECDS) or ERCP for drainage. The primary outcome was the 1-year stent patency rate. Other outcomes included technical success, clinical success, adverse events, time to stent dysfunction, reintervention rates, and overall survival. RESULTS: Between January 2017 and February 2021, 155 patients were recruited (ECDS 79, ERCP 76). There were no significant differences in 1-year stent patency rates (ECDS 91.1% vs ERCP 88.1%, P = .52). The ECDS group had significantly higher technical success (ECDS 96.2% vs ERCP 76.3%, P < .001), whereas clinical success was similar (ECDS 93.7% vs ERCP 90.8%, P = .559). The median (interquartile range) procedural time was significantly shorter in the ECDS group (ECDS 10 [5.75-18] vs ERCP 25 [14-40] minutes, P < .001). The rate of 30-day adverse events (P = 1) and 30-day mortality (P = .53) were similar. CONCLUSION: Both procedures could be options for primary biliary drainage in unresectable MDBO. ECDS was associated with higher technical success and shorter procedural time then ERCP. Primary ECDS may be preferred when difficult ERCPs are anticipated. This study was registered to Clinicaltrials.gov NCT03000855.

Outcomes of patients with hepaticojejunostomy anastomotic strictures undergoing endoscopic and percutaneous treatment.

Background and study aims The increase in hepaticojejunostomies has led to an increase in benign strictures of the anastomosis. Double balloon enteroscopy-assisted ERCP (DBE-ERCP) and percutaneous transhepatic biliary drainage (PTBD) are treatment options; however, there is lack of long-term outcomes, with no consensus on management. We performed a retrospective study assessing the outcomes of patients referred for endoscopic management of hepaticojejunostomy anastomotic strictures (HJAS). Patients and methods All consecutive patients at a tertiary institution underwent endoscopic intervention for suspected HJAS between 2009 and 2021 were enrolled. Results Eighty-two subjects underwent DBE-ERCP for suspected HJAS. The technical success rate was 77 % (63/82). HJAS was confirmed in 41 patients. The clinical success rate for DBE-ERCP ± PTBD was 71 % (29/41). DBE-ERCP alone achieved clinical success in 49 % of patients (20/41). PTBD was required in 49 % (20/41). Dual therapy was required in 22 % (9/41). Those with liver transplant had less technical success compared to other surgeries (72.1 % vs 82.1 % P  = 0.29), less clinical success with DBE-ERCP alone (40 % vs 62.5 % P  = 0.16) and required more PTBD (56 % vs 37.5 % P  = 0.25). All those with ischemic biliopathy (n = 9) required PTBD for clinical success, required more DBE-ERCP (4.4 vs 2.0, P = 0.004), more PTBD (4.7 vs 0.3, P  < 0.0001), longer treatment duration (181.6 vs 99.5 days P  = 0.12), and had higher rates of recurrence (55.6 % vs 30.3 % P  = 0.18) compared to those with HJAS alone. Liver transplant was the leading cause of ischemic biliopathy (89 %). The overall adverse event rate was 7 %. Conclusions DBE-ERCP is an effective diagnostic and therapeutic tool in those with altered gastrointestinal anatomy and is associated with low complication rates.

Static vs. dynamic navigation for endodontic microsurgery - A comparative review.

Digitalization of operative procedures through three-dimensional (3D) navigation is a remarkable advancement in the field of dentistry which allows both precision and accuracy while treating patients. It is an emerging technology with a wide variety of applications in dentistry. In the field of endodontics, these computer-aided 3D systems are being used for accessing and localizing canals in calcified teeth, removal of fiberglass posts, and in peri-apical surgeries etc. Preservation of important anatomical structures becomes necessary while performing root-end resection or peri-apical surgeries. However, it is clinically difficult to achieve accurate root-end resection due to the limited field of view, inconvenient perspective, and interferential bleeding among other factors. 3D guided endodontics play vital role here. 3D guided endodontics can be achieved in two ways- Static and Dynamic navigation. Due to availability of limited literature, there is a need to review new evidence comparing the effectiveness of both techniques of 3D guided endodontic navigation systems. This review paper describes the comparative evaluation of the effectiveness of static as well as dynamic navigation in the field of endodontic microsurgery.

Locoregional delivery of CAR-T cells in the clinic.

Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological malignancies. Unfortunately, this success has not been replicated in solid tumors, with only a small fraction of patients achieving complete responses. A number of obstacles to effective CAR-T cell therapy in solid tumors have been identified including tumor antigen heterogeneity, poor T cell fitness and persistence, inefficient trafficking and inability to penetrate into the tumor, immune-related adverse events due to on-target/off-tumor toxicity, and the immunosuppressive tumor microenvironment. Many preclinical studies have focused on improvements to CAR design to try to overcome some of these hurdles. However, a growing body of work has also focused on the use of local and/or regional delivery of CAR-T cells as a means to overcome poor T cell trafficking and inefficient T cell penetration into tumors. Most trials that incorporate locoregional delivery of CAR-T cells have targeted tumors of the central nervous system - repurposing an Ommaya/Rickham reservoir for repeated delivery of cells directly to the tumor cavity or ventricles. Hepatic artery infusion is another technique used for locoregional delivery to hepatic tumors. Locoregional delivery theoretically permits increased numbers of CAR-T cells within the tumor while reducing the risk of immune-related systemic toxicity. Studies to date have been almost exclusively phase I. The growing body of evidence indicates that locoregional delivery of CAR-T cells is both safe and feasible. This review focuses specifically on the use of locoregional delivery of CAR-T cells in clinical trials.

The next wave of cellular immunotherapies in pancreatic cancer.

Pancreatic cancer is an aggressive disease that is predicted to become the second leading cause of cancer-related death worldwide by 2030. The overall 5-year survival rate is around 10%. Pancreatic cancer typically presents late with locally advanced or metastatic disease, and there are limited effective treatments available. Cellular immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has had significant success in treating hematological malignancies. However, CAR T cell therapy efficacy in pancreatic cancer has been limited. This review provides an overview of current and ongoing CAR T cell clinical studies of pancreatic cancer and the major challenges and strategies to improve CAR T cell efficacy. These strategies include arming CAR T cells; developing off-the-shelf allogeneic CAR T cells; using other immune CAR cells, like natural killer cells and tumor-infiltrating lymphocytes; and combination therapy. Careful incorporation of preclinical models will enhance management of affected individuals, assisting incorporation of cellular immunotherapies. A multifaceted, personalized approach involving cellular immunotherapy treatment is required to improve pancreatic cancer outcomes.

Narrow band imaging versus white light for detecting sessile serrated lesion: A prospective randomized multicenter study.

Objectives: Colonoscopy is the gold standard diagnostic test used to detect early colorectal lesions and prevent colorectal carcinoma. Narrow band imaging (NBI) is an imaging technique that provides improved image resolution of the mucosa during endoscopy. Whether NBI improves the detection of sessile serrated lesion (SSL) is controversial-our aim was to assess this during routine colonoscopy. Methods: We conducted a multicenter, prospective, randomized, controlled trial. Patients underwent colonoscopy for screening, surveillance, or symptoms. They were randomized to either high-definition white light (HD-WL) or NBI in a 1:1 ratio. The primary outcome was SSL detection rate. Secondary outcomes were adenoma detection rate (ADR) and polyp detection rate (PDR). Results: A total of 400 patients were randomized to NBI (N = 200) or HD-WL (N = 200). The total colonoscopy time was slightly longer in the NBI group compared to HD-WL (median time 14 vs. 12 min, p = 0.033). There were no statistically significant differences in SSL detection rate (7.5% NBI vs. 8.0% HD-WL; p = 0.852), ADR (41.0% NBI vs. 37.5% HD-WL; p = 0.531), or PDR (61.0% NBI vs. 54.0% HD-WL; p = 0.157) between the two groups. No significant predictors of SSL detection were found on univariable or multivariable analysis. Increasing age and increased withdrawal time were an independent predictors of polyp detection and increasing age was also an independent predictor of adenoma detection on multivariable analysis. Conclusion: In the hands of experienced colonoscopists, NBI does not improve SSL detection compared to HD-WL. Withdrawal time and patient age remain important factors for polyp and adenoma detection.

Current endoscopic closure techniques for the management of gastrointestinal perforations.

Acute gastrointestinal perforations occur either from spontaneous or iatrogenic causes. However, particular attention should be made in acute iatrogenic perforations as timely diagnosis and endoscopic closure prevent morbidity and mortality. With the increasing use of diagnostic endoscopy and advances in therapeutic endoscopy worldwide, the endoscopist must be able to recognize and manage perforations. Depending on the size and location of the defect, a variety of endoscopic clips, stents, and suturing devices are available. This review aims to prepare and guide the endoscopist to use the right tools and techniques for optimal patient outcomes.

Exploring the Clinical Utility of Pancreatic Cancer Circulating Tumor Cells.

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type, characterized by a dismal prognosis due to late diagnosis, frequent metastases, and limited therapeutic response to standard chemotherapy. Circulating tumor cells (CTCs) are a rare subset of tumor cells found in the blood of cancer patients. CTCs has the potential utility for screening, early and definitive diagnosis, prognostic and predictive assessment, and offers the potential for personalized management. However, a gold-standard CTC detection and enrichment method remains elusive, hindering comprehensive comparisons between studies. In this review, we summarize data regarding the utility of CTCs at different stages of PDAC from early to metastatic disease and discuss the molecular profiling and culture of CTCs. The characterization of CTCs brings us closer to defining the specific CTC subpopulation responsible for metastasis with the potential to uncover new therapies and more effective management options for PDAC.

Endoscopic ultrasound-guided gallbladder and bile duct drainage with lumen apposing metal stent: A large multicenter cohort (with videos).

BACKGROUND AND AIM: Cholecystectomy and endoscopic retrograde cholangiopancreatography are the gold standard for managing acute cholecystitis and malignant biliary obstruction, respectively. Recent advances in therapeutic endoscopic ultrasound (EUS) have provided alternatives for managing patients in whom these approaches fail, namely, EUS-guided gallbladder drainage (EUS-GB) and EUS-guided bile duct drainage (EUS-BD). We aimed to assess the technical and clinical success of these techniques in the largest multicenter cohort published to date. METHODS: A retrospective, multicenter, observational study involving 17 centers across Australia and New Zealand was conducted. All patients who had EUS-GB or EUS-BD performed in a participating center using a lumen apposing metal stent between 2016 and 2020 were included. Primary outcome was technical success, defined as intra-procedural successful drainage. Secondary outcomes included clinical success and 30-day mortality. RESULTS: One hundred and fifteen patients underwent EUS-GB (n = 49) or EUS-BD (n = 66). EUS-GB was technically successful in 47 (95.9%) while EUS-BD was successful in 60 (90.9%). All failed cases were due to maldeployment of the distal flange outside of the targeted lumen. Clinical success of EUS-GB was achieved in 39 (79.6%). No patients required subsequent cholecystectomy. Clinical success of EUS-BD was achieved in 52 (78.8 %). Thirty-day mortality was 14.3% for EUS-GB and 12.1% for EUS-BD. CONCLUSIONS: EUS-guided gallbladder drainage and EUS-BD are promising alternatives for managing nonsurgical candidates with cholecystitis and malignant biliary obstruction following failed endoscopic retrograde pancreatography. Both techniques delivered high technical success with acceptable clinical success. Further research is needed to investigate the gap between technical and clinical success.

Drainage of pancreatic fluid collections using a lumen-apposing metal stent with an electrocautery-enhanced delivery system.

BACKGROUND AND AIM: Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. METHODS: A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. RESULTS: Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9 years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. CONCLUSIONS: This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

Endoscopic bariatric therapies for obesity: a review.

▪ Obesity is reaching pandemic proportions globally, with overweight or obesity affecting at least two-thirds of Australian adults. ▪ Bariatric surgery is an effective weight loss strategy but is constrained by high resource requirements and low patient acceptance. ▪ Multiple endoscopic bariatric therapies have matured, with well established and favourable safety and efficacy profiles in multiple randomised controlled trials (RCTs), and are best used within a multidisciplinary setting as an adjuvant to lifestyle intervention. ▪ Three types of intragastric balloon are currently in use in Australia offering average total weight loss ranging from 10% to 18%, with others available internationally. ▪ Endoscopic sleeve gastroplasty produces average total weight loss of 15-20% with low rates of severe complications, with RCT data anticipated in December 2021. ▪Bariatric and metabolic endoscopy is rapidly evolving, with many novel, promising therapies currently under investigation.

SAGES guidelines for the use of peroral endoscopic myotomy (POEM) for the treatment of achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is increasingly used as primary treatment for esophageal achalasia, in place of the options such as Heller myotomy (HM) and pneumatic dilatation (PD) OBJECTIVE: These evidence-based guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) intend to support clinicians, patients and others in decisions about the use of POEM for treatment of achalasia. RESULTS: The panel agreed on 4 recommendations for adults and children with achalasia. CONCLUSIONS: Strong recommendation for the use of POEM over PD was issued unless the concern of continued postoperative PPI use remains a key decision-making concern to the patient. Conditional recommendations included the option of using either POEM or HM with fundoplication to treat achalasia, and favored POEM over HM for achalasia subtype III.

Endoscopic Ultrasound-Guided Vascular Procedures: A Review.

Since the 1980s, endoscopic ultrasound has advanced from being purely diagnostic to an interventional modality. The gastrointestinal tract offers an exceptional window for assessing the vascular structures in the mediastinum and in the abdomen. This has led to a rapidly growing interest in endoscopic ultrasound-controlled vascular interventions as a minimally invasive alternative to surgical and radiological procedures.

To evaluate the minimum number of renal scans required to follow pediatric patient postpyeloplasty.

The aim of the study is to evaluate the minimum number of renal scans required to follow pediatric patients postpyeloplasty. We prospectively reviewed the renal scans of 145 children with unilateral pelvi-ureteric junction obstruction who underwent dismembered pyeloplasty. Patients were then divided into four groups based on preoperative split renal function. All patients were followed with renal scan and ultrasound for minimum of 4 years. Renal scan and ultrasound were done after stent removal at 3, 6, and 12 months and then yearly after surgery. Drainage pattern (T1/2) was seen in all groups, except in patients where there was no comment on drainage pattern. Statistical analysis was performed using the Friedman ANOVA and Wilcoxon signed-ranks test as a post hoc test with Bonferroni correction and Kruskal-Wallis test with Mann-Whitney U-test as a post hoc test with Bonferroni correction. On comparison of the pattern of drainage with time in Groups 1-4, it was found that there was no significant difference with time in Group 1. Then, further, using Wilcoxon signed-rank test as post hoc test for Friedman ANOVA, Group 2 showed statistically significant difference in drainage pattern in scans between 6 months and 1 year, Group 3 showed statistically significant difference in drainage pattern in scans between 3 months and 1 year, and Group 4 showed statistically significant difference in drainage pattern in scans done between 3 and 6 months (P < 0.05). Minimum of three renal scans were required for paediatric patients post pyeloplasty at 3 months, 6 months and 1 year in the follow up period.