Deep learning and automatic differentiation of pancreatic lesions in endoscopic ultrasound - a transatlantic study.

Endoscopic ultrasound (EUS) allows characterization and biopsy of pancreatic lesions. Pancreatic cystic neoplasms (PCN) include in mucinous (M-PCN) and non-mucinous lesions (NM-PCN). Pancreatic ductal adenocarcinoma (P-DAC) is the commonest pancreatic solid lesion (PSL), followed by pancreatic neuroendocrine tumor (P-NET). While EUS is preferred for pancreatic lesion evaluation, its diagnostic accuracy is suboptimal. This multicentric study aims to develop a convolutional neural network (CNN) for detecting and distinguishing PCN (namely M-PCN and NM-PCN) and PSL (particularly P-DAC and P-NET). A CNN was developed with 378 EUS exams from 4 international reference centers (Centro Hospitalar Universitário São João, Hospital Universitario Puerta de Hierro Majadahonda, New York University Hospitals, Hospital das Clínicas FMUSP). 126.000 images were obtained - 19.528 M-PCN, 8.175 NM-PCN, 64.286 P-DAC, 29.153 P-NET and 4.858 normal pancreas images. A trinary CNN differentiated normal pancreas tissue from M-PCN and NM-PCN. A binary CNN distinguished P-DAC from P-NET. The total dataset was divided in a training and testing dataset (used for model's evaluation) in a 90/10% ratio. The model was evaluated through its sensitivity, specificity, positive and negative predictive values and accuracy. The CNN had 99.1% accuracy for identifying normal pancreatic tissue, 99.0% and 99.8% for M-PCN and NM-PCN, respectively. P-DAC and P-NET were distinguished with 94.0% accuracy. Our group developed the first worldwide CNN capable of detecting and differentiating the commonest PCN and PSL in EUS images, using exams from 4 centers in two continents, minimizing the impact of the demographic bias. Larger multicentric studies are needed for technology implementation.

Enhanced Complement Expression in the Tumor Microenvironment Following Neoadjuvant Therapy: Implications for Immunomodulation and Survival in Pancreatic Ductal Adenocarcinoma.

Background: Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC) treatment. However, its specific effects on carcinoma cells and the tumor microenvironment (TME) are not fully understood. This study aims to investigate how NAT differentially impacts PDAC's carcinoma cells and TME. Methods: Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME between 23 NAT-treated and 13 NAT-naïve PDAC patients, correlating with their clinicopathologic features. Analysis of an online single-nucleus RNA sequencing (snRNA-seq) dataset was performed for validation of the specific cell types responsible for NAT-induced gene expression alterations. Results: NAT not only induces apoptosis and inhibits proliferation in carcinoma cells but also significantly remodels the TME. Notably, NAT induces a coordinated upregulation of multiple key complement genes (C3, C1S, C1R, C4B and C7) in the TME, making the complement pathway one of the most significantly affected pathways by NAT. Patients with higher TME complement expression following NAT exhibit improved overall survival. These patients also exhibit increased immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4+ T cells, monocytes, and mast cells; and reduced immune exhaustion gene expression. snRNA-seq analysis demonstrates C3 complement was specifically upregulated in CAFs but not in other stroma cell types. Conclusions: NAT can enhance complement production and signaling within the TME, which is associated with reduced immunosuppression in PDAC. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response and resistance, and guiding therapeutic strategies in NAT-treated PDAC patients.

Management of severe acute pancreatitis in 2019.

Pancreatic fluid collections (PFCs) are frequent complications in severe acute pancreatitis that are the result of damage to the pancreas to include but not limited to trauma, surgery, autoimmune diseases, alcohol abuse, infections, medications, gallstones, metabolic disorders, and premalignant or malignant conditions. The majority of these collections resolve spontaneously; however, if the collection is infected or causes symptoms to include abdominal pain, nausea, vomiting, diarrhea, fevers, and tachycardia, drainage is indicated. Drainage of PFCs can be accomplished surgically, percutaneously, or endoscopically and should be approached in a multidisciplinary fashion for best overall patient care and outcomes. Before the introduction of endoscopic procedures, surgical and percutaneous drainage was the preferred modality. Today a minimally-invasive "step-up" approach is generally accepted depending upon the specific characteristics of the PFC and clinical presentation. Endoscopic ultrasound-guided PFC drainage is favored due to high success rates, shorter hospital stays, and lower cost. Direct debridement of walled-off pancreatitis can now be performed endoscopically with higher success rates with larger caliber fully covered metal stents. At large, the field of endoscopic techniques has evolved, and more specifically, the management of PFCs continues to evolve with increasing experience and with the advent of new stents and accessories, leading to increased efficacy with less adverse events.

Digital single-operator cholangioscopy interobserver study using a new classification: the Mendoza Classification (with video).

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (DSOC) allows direct visualization of the biliary tree for evaluation of biliary strictures. Our objective was to assess the interobserver agreement (IOA) of DSOC interpretation for indeterminate biliary strictures using newly refined criteria. METHODS: Fourteen endoscopists were asked to review an atlas of reference clips and images of 5 criteria derived from expert consensus. They then proceeded to score 50 deidentified DSOC video clips based on the visualization of tortuous and dilated vessels, irregular nodulations, raised intraductal lesions, irregular surface with or without ulcerations, and friability. The endoscopists then diagnosed the clips as neoplastic or non-neoplastic. Intraclass correlation (ICC) analysis was done to evaluate inter-rater agreement for both criteria sets and final diagnosis. RESULTS: Clips of 41 malignant lesions and 9 benign lesions were scored. Three of 5 revised criteria had almost perfect agreement. ICC was almost perfect for presence of tortuous and dilated vessels (.86), raised intraductal lesions (.90), and presence of friability (.83); substantial agreement for presence of irregular nodulations (.71); and moderate agreement for presence of irregular surface with or without ulcerations (.44). The diagnostic ICC was almost perfect for neoplastic (.90) and non-neoplastic (.90) diagnoses. The overall diagnostic accuracy using the revised criteria was 77%, ranging from 64% to 88%. CONCLUSIONS: The IOA and accuracy rate of DSOC using the new Mendoza criteria shows a significant increase of 16% and 20% compared with previous criteria. The reference atlas helps with formal training and may improve diagnostic accuracy. (Clinical trial registration number: NCT02166099.).

EUS guided gallbladder drainage.

Cholecystectomy is the gold standard treatment for acute cholecystitis, but it may not be appropriate for patients with significant comorbidities. Percutaneous gallbladder drainage (PT-GBD) and endoscopic transpapillary gallbladder drainage (ET-GBD) are alternatives with good technical and clinical success rates, but are limited by technical challenges and the need for definitive therapy. EUS-guided gallbladder drainage (EUS-GBD) is quickly becoming the preferred modality of treatment at expert centers in this cohort of patients due to increased efficacy and minimal adverse events. Technicalities of the procedure, including selection of access site, should be informed by the ultimate needs and anatomy of each patient. With the evolution of new stents and accessories, including a cautery-enhanced lumen apposing metal stent deployment system, success rates and adverse events are favorable. A review of published case series demonstrates an overall clinical success rate of approximately 97% for EUS-GBD. The most common complication is pneumoperitoneum, so the evolution of self-expanding LAMS is promising. EUS-GBD has been successfully described in cases where definitive therapy or a bridge to cholecystectomy is needed. As the procedure's applications continue to evolve, there should be greater discussion about specific details including access site and stent selection.

Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. METHODS: We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. RESULTS: Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

Fully-covered metal stents with endoscopic suturing vs. partially-covered metal stents for benign upper gastrointestinal diseases: a comparative study.

BACKGROUND AND STUDY AIMS: Self-expandable metallic stents (SEMS) have been increasingly used in benign conditions (e. g. strictures, fistulas, leaks, and perforations). Fully covered SEMS (FSEMS) were introduced to avoid undesirable consequences of partially covered SEMS (PSEMS), but come with higher risk of stent migration. Endoscopic suturing (ES) for stent fixation has been shown to reduce migration of FSEMS. Our aim was to compare the outcomes of FSEMS with ES (FS/ES) versus PSEMS in patients with benign upper gastrointestinal conditions. PATIENTS AND METHODS: We retrospectively identified all patients who underwent stent placement for benign gastrointestinal conditions at seven US tertiary-care centers. Patients were divided into two groups: FSEMS with ES (FS/ES group) and PSEMS (PSEMS group). Clinical outcomes between the two groups were compared. RESULTS: A total of 74 (FS/ES 46, PSEMS 28) patients were included. On multivariable analysis, there was no significant difference in rate of stent migration between FS/ES (43 %) and PSEMS (15 %) (adjusted odds ratio 0.56; 95 % CI 0.15 - 2.00). Clinical success was similar [68 % vs. 64 %; P  = 0.81]. Rate of adverse events (AEs) was higher in PSEMS group [13 (46 %) vs. 10 (21 %); P  = 0.03). Difficult stent removal was higher in the PSEMS group (n = 5;17 %) vs. 0 % in the FS/ES group; P  = 0.005. CONCLUSIONS: The proportion of stent migration of FS/ES and PSEMS are similar. Rates of other stent-related AEs were higher in the PSEMS group. PSEMS was associated with tissue ingrowth or overgrowth leading to difficult stent removal, and secondary stricture formation. Thus, FSEMS with ES for stent fixation may be the preferred modality over PSEMS for the treatment of benign upper gastrointestinal conditions.

Endoscopic suturing for the prevention of stent migration in benign upper gastrointestinal conditions: a comparative multicenter study.

BACKGROUND AND STUDY AIMS: Fully covered self-expandable metal stents (FCSEMSs) have increasingly been used in benign upper gastrointestinal (UGI) conditions; however, stent migration remains a major limitation. Endoscopic suture fixation (ESF) may prevent stent migration. The aims of this study were to compare the frequency of stent migration in patients who received endoscopic suturing for stent fixation (ESF group) compared with those who did not (NSF group) and to assess the impact of ESF on clinical outcome. PATIENTS AND METHODS: This was a retrospective study of patients who underwent FCSEMS placement for benign UGI diseases. Patients were divided into either the NSF or ESF group. Outcome variables, including stent migration, clinical success (resolution of underlying pathology), and adverse events, were compared. RESULTS: A total of 125 patients (44 in ESF group, 81 in NSF group; 56 benign strictures, 69 leaks/fistulas/perforations) underwent 224 stenting procedures. Stent migration was significantly more common in the NSF group (33 % vs. 16 %; P = 0.03). Time to stent migration was longer in the ESF group (P = 0.02). ESF appeared to protect against stent migration in patients with a history of stent migration (adjusted odds ratio [OR] 0.09; P = 0.002). ESF was also significantly associated with a higher rate of clinical success (60 % vs. 38 %; P = 0.03). Rates of adverse events were similar between the two groups. CONCLUSIONS: Endoscopic suturing for stent fixation is safe and associated with a decreased migration rate, particularly in patients with a prior history of stent migration. It may also improve clinical response, likely because of the reduction in stent migration.

A Large Multicenter Experience With Endoscopic Suturing for Management of Gastrointestinal Defects and Stent Anchorage in 122 Patients: A Retrospective Review.

GOALS: To describe a multicenter experience using an endoscopic suturing device for management of gastrointestinal (GI) defects and stent anchorage. BACKGROUND: Endoscopic closure of GI defects including perforations, fistulas, and anastomotic leaks as well as stent anchorage has improved with technological advances. An endoscopic suturing device (OverStitch; Apollo Endosurgery Inc.) has been used. STUDY: Retrospective study of consecutive patients who underwent endoscopic suturing for management of GI defects and/or stent anchorage were enrolled between March 2012 and January 2014 at multiple academic medical centers. Data regarding demographic information and outcomes including long-term success were collected. RESULTS: One hundred and twenty-two patients (mean age, 52.6 y; 64.2% females) underwent endoscopic suturing at 8 centers for stent anchorage (n=47; 38.5%), fistulas (n=40; 32.7%), leaks (n=15; 12.3%), and perforations (n=20; 16.4%). A total of 44.2% underwent prior therapy and 97.5% achieved technical success. Immediate clinical success was achieved in 79.5%. Long-term clinical success was noted in 78.8% with mean follow-up of 68 days. Clinical success was 91.4% in stent anchorage, 93% in perforations, 80% in fistulas, but only 27% in anastomotic leak closure. CONCLUSIONS: Endoscopic suturing for management of GI defects and stent anchoring is safe and efficacious. Stent migration after stent anchoring was reduced compared with published data. Long-term success without further intervention was achieved in the majority of patients. The role of endoscopic suturing for repair of anastomotic leaks remains unclear given limited success in this retrospective study.