Recent advances in endoscopic management of gastric neoplasms.

The development and clinical application of new diagnostic endoscopic technologies such as endoscopic ultrasonography with biopsy, magnification endoscopy, and narrow-band imaging, more recently supplemented by artificial intelligence, have enabled wider recognition and detection of various gastric neoplasms including early gastric cancer (EGC) and subepithelial tumors, such as gastrointestinal stromal tumors and neuroendocrine tumors. Over the last decade, the evolution of novel advanced therapeutic endoscopic techniques, such as endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection, along with the advent of a broad array of endoscopic accessories, has provided a promising and yet less invasive strategy for treating gastric neoplasms with the advantage of a reduced need for gastric surgery. Thus, the management algorithms of various gastric tumors in a defined subset of the patient population at low risk of lymph node metastasis and amenable to endoscopic resection, may require revision considering upcoming data given the high success rate of en bloc resection by experienced endoscopists. Moreover, endoscopic surveillance protocols for precancerous gastric lesions will continue to be refined by systematic reviews and meta-analyses of further research. However, the lack of familiarity with subtle endoscopic changes associated with EGC, as well as longer procedural time, evolving resection techniques and tools, a steep learning curve of such high-risk procedures, and lack of coding are issues that do not appeal to many gastroenterologists in the field. This review summarizes recent advances in the endoscopic management of gastric neoplasms, with special emphasis on diagnostic and therapeutic methods and their future prospects.

Pancreatic Cancer Screening for At-Risk Individuals (Pancreas Scan Study): Yield, Harms, and Outcomes From a Prospective Multicenter Study.

INTRODUCTION: Guidelines endorse pancreatic cancer screening in genetically susceptible individuals. We conducted a prospective, multicenter study to determine yield, harms, and outcomes of pancreatic cancer screening. METHODS: All high-risk individuals undergoing pancreatic cancer screening at 5 centers from 2020 to 2022 were prospectively enrolled. Pancreas findings were designated as low-risk (fatty or chronic pancreatitis-like changes), intermediate-risk (neuroendocrine tumor [NET] <2 cm or branch-duct intraductal papillary mucinous neoplasm [IPMN]), or high-risk lesions (high-grade pancreatic intraepithelial neoplasia/dysplasia, main-duct IPMN, NET >2 cm, or pancreatic cancer). Harms from screening included adverse events during screening or undergoing low-yield pancreatic surgery. Annual screening was performed using endoscopic ultrasound and or magnetic resonance cholangiopancreatography. Annual screening for new-onset diabetes using fasting blood sugar was also performed ( ClinicalTrials.gov : NCT05006131). RESULTS: During the study period, 252 patients underwent pancreatic cancer screening. Mean age was 59.9 years, 69% were female, and 79.4% were White. Common indications were BRCA 1/2 (36.9%), familial pancreatic cancer syndrome kindred (31.7%), ataxia telangiectasia mutated (3.5%), Lynch syndrome (6.7%), Peutz-Jeghers (4.3%), and familial atypical multiple mole melanoma (3.5%). Low-risk lesions were noted in 23.4% and intermediate-risk lesions in 31.7%, almost all of which were branch-duct IPMN without worrisome features. High-risk lesions were noted in 2 patients (0.8%), who were diagnosed with pancreas cancer at stages T2N1M0 and T2N1M1. Prediabetes was noted in 18.2% and new-onset diabetes in 1.7%. Abnormal fasting blood sugar was not associated with pancreatic lesions. There were no adverse events from screening tests, and no patient underwent low-yield pancreatic surgery. DISCUSSION: Pancreatic cancer screening detected high-risk lesions with lower frequency than previously reported. No harms from screening were noted.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Early prediction of post-ERCP pancreatitis by post-procedure amylase and lipase levels: A systematic review and meta-analysis.

Background and study aims Post-ERCP pancreatitis (PEP) is the most common complication attributed to the procedure, its incidence being approximately 9.7 %. Numerous studies have evaluated the predictive efficacy of post-procedure serum amylase and lipase levels but with varied procedure-to-test time intervals and cut-off values. The aim of this meta-analysis was to present pooled data from available studies to compare the predictive accuracies of serum amylase and lipase for PEP. Patients and methods A total of 18 studies were identified after a comprehensive search of various databases until June 2021 that reported the use of pancreatic enzymes for PEP. Results The sample size consisted of 11,790 ERCPs, of which PEP occurred in 764 (6.48 %). Subgroups for serum lipase and amylase were created based on the cut-off used for diagnosing PEP, and meta-analysis was done for each subgroup. Results showed that serum lipase more than three to four times the upper limit of normal (ULN) performed within 2 to 4 hours of ERCP had the highest pooled sensitivity (92 %) for PEP. Amylase level more than five to six times the ULN was the most specific serum marker with a pooled specificity of 93 %. Conclusions Our analysis indicates that a lipase level less than three times the ULN within 2 to 4 hours of ERCP can be used as a good predictor to rule out PEP when used as an adjunct to patient clinical presentation. Multicenter randomized controlled trials using lipase and amylase are warranted to further evaluate their PEP predictive accuracy, especially in high-risk patients.

Comparison Between Intravenous and Intramuscular Octreotide in the Management of Heyde's Syndrome.

Heyde's syndrome is defined as a triad of aortic stenosis, anemia due to angiodysplasia-related bleeding, and von Willebrand syndrome type 2A. It is a rare disease and a diagnostic challenge. Treatment modalities include symptomatic management, blood transfusions, aortic valve replacement, and medications such as octreotide. Here, we report the case of a patient who was resistant to symptomatic management, aortic valve replacement, as well as intravenous octreotide.

A Case of Duodenal "Spot" Diagnosis.

Pseudomelanosis duodeni is a rare finding usually described as a black/brown speckled or tattooed appearance of the intestinal mucosa. Although an incidental finding, it has been associated with different medications and chronic medical conditions such as diabetes mellitus and chronic renal failure. We describe an elderly male who presented with epigastric pain and melena. Endoscopy showed pseudomelanosis duodeni related to intravenous (IV) iron transfusion. To our knowledge, this is the first report of pseudomelanosis duodeni related to IV iron use. In spite of its benign nature, the diagnosis of pseudomelanosis duodeni is essential to rule out other serious medical conditions that mimic its physical findings.

Gastrointestinal endoscope contamination rates - elevators are not only to blame: a systematic review and meta-analysis.

Background and study aims Duodenoscopes that are contaminated due to inadequate reprocessing are well-documented. However, studies have demonstrated poor reprocessing of other kinds of endoscopes as well, including echoendoscopes, gastroscopes, and colonoscopes. We estimated the contamination rate beyond the elevator of gastrointestinal endoscopes based on available data. Methods We searched PubMed and Embase from January 1, 2010 to October 10, 2020, for studies investigating contamination rates of reprocessed gastrointestinal endoscopes. A random-effects model was used to calculate the contamination rate of patient-ready gastrointestinal endoscopes. Subgroup analyses were conducted to investigate differences among endoscope types, countries, and colony-forming unit (CFU) thresholds. Results Twenty studies fulfilled the inclusion criteria, including 1,059 positive cultures from 7,903 samples. The total contamination rate was 19.98 % ±â€Š0.024 (95 % confidence interval [Cl]: 15.29 %-24.68 %; I 2  = 98.6 %). The contamination rates of colonoscope and gastroscope channels were 31.95 % ±â€Š0.084 and 28.22 % ±â€Š0.076, respectively. Duodenoscope channels showed a contamination rate of 14.41 % ±â€Š0.029. The contamination rates among studies conducted in North America and Europe were 6.01 % ±â€Š0.011 and 18.16% ±â€Š0.053 %, respectively. The contamination rate among studies using a CFU threshold > 20 showed contamination of 30.36 % ±â€Š0.094, whereas studies using a CFU threshold < 20 showed a contamination rate of 11 % ±â€Š0.026. Conclusions On average, 19.98 % of reprocessed gastrointestinal endoscopes may be contaminated when used in patients and varies between different geographies. These findings highlight that the elevator mechanism is not the only obstacle when reprocessing reusable endoscopes; therefore, guidelines should recommend more surveillance of the endoscope channels as well.

Application of artificial intelligence in diagnosis of pancreatic malignancies by endoscopic ultrasound: a systemic review.

Background: Pancreatic cancer (PC) is a highly fatal malignancy with a global overall 5-year survival of under 10%. Screening of PC is not recommended outside of clinical trials. Endoscopic ultrasonography (EUS) is a very sensitive test to identify PC but lacks specificity and is operator-dependent, especially in the presence of chronic pancreatitis (CP). Artificial Intelligence (AI) is a growing field with a wide range of applications to augment the currently available modalities. This study was undertaken to study the effectiveness of AI with EUS in the diagnosis of PC. Methods: Studies from MEDLINE and EMBASE databases reporting the AI performance applied to EUS imaging for recognizing PC. Data were analyzed using descriptive statistics. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of the included studies. Results: A total of 11 articles reported the role of EUS in the diagnosis of PC. The overall accuracy, sensitivity, and specificity of AI in recognizing PC were 80-97.5%, 83-100%, and 50-99%, respectively, with corresponding positive predictive value (PPV) and negative predictive value (NPV) of 75-99% and 57-100%, respectively. Types of AI studied were artificial neural networks (ANNs), convolutional neural networks (CNN), and support vector machine (SVM). Seven studies using other than basic ANN reported a sensitivity and specificity of 88-96% and 83-94% to differentiate PC from CP. Two studies using SVM reported a 94-96% sensitivity, 93%-99% specificity, and 94-98% accuracy to diagnose PC from CP. The reported sensitivity and specificity of detection of malignant from benign Intraductal Papillary Mucinous Neoplasms (IPMNs) was 96% and 92%, respectively. Conclusion: AI reported a high sensitivity with high specificity and accuracy to diagnose PC, differentiate PC from CP, and differentiate benign from malignant IPMN when used with EUS.

The h-ANN Model: Comprehensive Colonoscopy Concept Compilation Using Combined Contextual Embeddings.

Colonoscopy is a screening and diagnostic procedure for detection of colorectal carcinomas with specific quality metrics that monitor and improve adenoma detection rates. These quality metrics are stored in disparate documents i.e., colonoscopy, pathology, and radiology reports. The lack of integrated standardized documentation is impeding colorectal cancer research. Clinical concept extraction using Natural Language Processing (NLP) and Machine Learning (ML) techniques is an alternative to manual data abstraction. Contextual word embedding models such as BERT (Bidirectional Encoder Representations from Transformers) and FLAIR have enhanced performance of NLP tasks. Combining multiple clinically-trained embeddings can improve word representations and boost the performance of the clinical NLP systems. The objective of this study is to extract comprehensive clinical concepts from the consolidated colonoscopy documents using concatenated clinical embeddings. We built high-quality annotated corpora for three report types. BERT and FLAIR embeddings were trained on unlabeled colonoscopy related documents. We built a hybrid Artificial Neural Network (h-ANN) to concatenate and fine-tune BERT and FLAIR embeddings. To extract concepts of interest from three report types, 3 models were initialized from the h-ANN and fine-tuned using the annotated corpora. The models achieved best F1-scores of 91.76%, 92.25%, and 88.55% for colonoscopy, pathology, and radiology reports respectively.

TAX-Corpus: Taxonomy based Annotations for Colonoscopy Evaluation.

Colonoscopy plays a critical role in screening of colorectal carcinomas (CC). Unfortunately, the data related to this procedure are stored in disparate documents, colonoscopy, pathology, and radiology reports respectively. The lack of integrated standardized documentation is impeding accurate reporting of quality metrics and clinical and translational research. Natural language processing (NLP) has been used as an alternative to manual data abstraction. Performance of Machine Learning (ML) based NLP solutions is heavily dependent on the accuracy of annotated corpora. Availability of large volume annotated corpora is limited due to data privacy laws and the cost and effort required. In addition, the manual annotation process is error-prone, making the lack of quality annotated corpora the largest bottleneck in deploying ML solutions. The objective of this study is to identify clinical entities critical to colonoscopy quality, and build a high-quality annotated corpus using domain specific taxonomies following standardized annotation guidelines. The annotated corpus can be used to train ML models for a variety of downstream tasks.

Sarcopenia in hepatocellular carcinoma: Current knowledge and future directions.

Liver cancer is the second most occurring cancer worldwide and is one of the leading causes of cancer-related deaths. Hepatocellular carcinoma (HCC) is the most common (80%-90%) type among malignant liver cancers. Sarcopenia occurs very early in HCC and can predict and provide an opportunity to improve muscle health before engaging in the treatment options such as loco-regional, systemic, and transplant management. Multiple prognostic stating systems have been developed in HCC, such as Barcelona Clinic Liver Cancer, Child-Pugh score and Albumin-Bilirubin grade. However, the evaluation of patients' performance status is a major limitation of these scoring systems. In this review, we aim to summarize the current knowledge and recent advances about the role of sarcopenia in cirrhosis in general, while focusing specifically on HCC. Additionally, the role of sarcopenia in predicting clinical outcomes and prognostication in HCC patients undergoing loco-regional therapies, liver resection, liver transplantation and systematic therapy has been discussed. A literature review was performed using databases PubMed/MEDLINE, EMBASE, Cochrane, Web of Science, and CINAHL on April 1, 2021, to identify published reports on sarcopenia in HCC. Sarcopenia can independently predict HCC-related mortality especially in patients undergoing treatments such as loco-regional, surgical liver transplantation and systemic therapies. Basic research is focused on evaluating a balance of anabolic and catabolic pathways responsible for muscle health. Early clinical studies have shown promising results in methods to improve sarcopenia in HCC which can potentially increase prognosis in these patients. As sarcopenia occurs very early in HCC, it can predict and provide an opportunity to improve muscle health before engaging in the treatment options such as loco-regional, systemic, and transplant management. Further, sarcopenia measurement can obviate the confounding caused by the abdominal ascites in these patients. The use of sarcopenia can add to the existing scoring systems to better prognosticate the HCC.

Comparison of Biliary Drainage Techniques for Malignant Biliary Obstruction: A Systematic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage, and endoscopic ultrasound (EUS)-guided biliary drainage are all established techniques for drainage of malignant biliary obstruction. This network meta-analysis (NMA) was aimed at comparing all 3 modalities to each other. MATERIALS AND METHODS: Multiple databases were searched from inception to October 2019 to identify relevant studies. All the patients were eligible to receive any one of the 3 interventions. Data extraction and risk of bias assessment was performed using standardized tools. Outcomes of interest were technical success, clinical success, adverse events, and reintervention. Direct meta-analyses were performed using the random-effects model. NMA was conducted using a multivariate, consistency model with random-effects meta-regression. The GRADE approach was followed to rate the certainty of evidence. RESULTS: The final analysis included 17 studies with 1566 patients. Direct meta-analysis suggested that EUS-guided biliary drainage had a lower reintervention rate than ERCP. NMA did not show statistically significant differences to favor any one intervention with certainty across all the outcomes. The overall certainty of evidence was found to be low to very low for all the outcomes. CONCLUSIONS: The available evidence did not favor any intervention for drainage of malignant biliary obstruction across all the outcomes assessed. ERCP with or without EUS should be considered first to allow simultaneous tissue acquisition and biliary drainage.

Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience.

BACKGROUND: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. METHODS: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. RESULTS: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). CONCLUSIONS: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.

Safety and efficacy of a novel resection system for direct endoscopic necrosectomy of walled-off pancreas necrosis: a prospective, international, multicenter trial.

BACKGROUND AND AIMS: Direct endoscopic necrosectomy (DEN) of walled-off pancreatic necrosis (WOPN) lacks dedicated instruments and requires repetitive and cumbersome procedures. This study evaluated the safety and efficacy of a new powered endoscopic debridement (PED) system designed to simultaneously resect and remove solid debris within WOPN. METHODS: This was a single-arm, prospective, multicenter, international device trial conducted from November 2018 to August 2019 at 10 sites. Patients with WOPN ≥6 cm and ≤22 cm and with >30% solid debris were enrolled. The primary endpoint was safety through 21 days after the last DEN procedure. Efficacy outcomes included clearance of necrosis, procedural time, adequacy of debridement, number of procedures until resolution, hospital stay duration, and quality of life. RESULTS: Thirty patients (mean age, 55 years; 60% men) underwent DEN with no device-related adverse events. Of 30 patients, 15 (50%) achieved complete debridement in 1 session and 20 (67%) achieved complete debridement within 2 or fewer sessions. A median of 1.5 interventions (range, 1-7) were required. Median hospital stay was 10 days (interquartile range, 22). There was an overall reduction of 91% in percent necrosis within WOPN from baseline to follow-up and 85% in collection volume. Baseline WOPN volume was positively correlated with the total number of interventions (ρ = .363, P = .049). CONCLUSIONS: The new PED system seems to be a safe and effective treatment tool for WOPN, resulting in fewer interventions and lower hospital duration when compared with published data on using conventional instruments. Randomized controlled trials comparing the PED system with conventional DEN are needed. (Clinical trial registration number: NCT03694210.).

Big Brother Is Watching: Artificial Intelligence in Endoscopy - Hype or Reality?

Artificial intelligence (AI) has become a part of many image-based specialties, such as radiology and pathology, as well as medical specialties in which "oscopy" is the key to current practice. In gastroenterology, for example, AI is being explored as an aid to endoscopists to visually distinguish precancerous lesions in upper and lower endoscopy. Although there have been a variety of approaches to the employment of AI for this purpose, deep-learning algorithms, which combine the extraction and classification of image features using deep neural networks,1 have the capability of self-learning.

Endoscopic ultrasound-guided vascular interventions: Current insights and emerging techniques.

Endoscopic ultrasound (EUS) is one of the significant breakthroughs in the field of advanced endoscopy. In the last two decades, EUS has evolved from a diagnostic tool to a real-time therapeutic modality. The luminal gastrointestinal (GI) tract provides a unique opportunity to access multiple vascular structures, especially in the mediastinum and abdomen, thus permitting a variety of EUS-guided vascular interventions. The addition of the doppler and contrast-enhanced capability to EUS has further helped provide real-time visualization of blood flow in vessels through the GI tract. EUS-guided vascular interventions rely on standard endoscopic accessories and interventional tools such as fine-needle aspiration needles and fine-needle biopsy. EUS allows the visualization of various structures in real-time by differentiating tissue densities and vascularity, thus, avoiding radiation exposure. EUS-guided techniques also allow real-time microscopic examination after target biopsy. Furthermore, many necessary interventions can be done during the same procedure after diagnosis. This article provides an overview of EUS-guided vascular interventions such as variceal, non-variceal bleeding interventions, EUSguided portal vein (PV) access with the formation of an intrahepatic portosystemic shunt, and techniques related to diagnosis of GI malignancies. Furthermore, we discuss current insights and future outlook of therapeutic modalities like PV embolization, PV sampling, angiography, drug administration, and portal pressure measurement.