Endohepatology: The endoscopic armamentarium in the hand of the hepatologist.

ABSTRACT: Recent advances in the field of hepatology include new and effective treatments for viral hepatitis. Further effort is now being directed to other disease entities, such as non-alcoholic fatty liver disease, with an increased need for assessment of liver function and histology. In fact, with the evolving nomenclature of fat-associated liver disease and the emergence of the term "metabolic-associated fatty liver disease" (MAFLD), new diagnostic challenges have emerged as patients with histologic absence of steatosis can still be classified under the umbrella of MAFLD. Currently, there is a growing number of endoscopic procedures that are pertinent to patients with liver disease. Indeed, interventional radiologists mostly perform interventional procedures such as percutaneous and intravascular procedures, whereas endoscopists focus on screening for and treatment of esophageal and gastric varices. EUS has proven to be of value in many areas within the realm of hepatology, including liver biopsy, assessment of liver fibrosis, measurement of portal pressure, managing variceal bleeding, and EUS-guided paracentesis. In this review article, we will address the endoscopic applications that are used to manage patients with chronic liver disease.

Protocol for a randomized controlled trial of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN) with vs without bupivacaine.

BACKGROUND: Pancreatic cancer is a devastating disease with less than 5% 5-year survival. Inoperable patients often present with pain. Randomized controlled trial have shown that endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) improves pain control. It is usually performed by injecting bupivacaine followed by absolute alcohol around the celiac axis. STUDY DESIGN: Single center, randomized, double blind controlled trial of EUS-CPN with and without bupivacaine in patients with inoperable malignancy (pancreatic or other) involving the celiac plexus. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on ClinicalTrials.gov (NCT04951804). DISCUSSION: We hypothesize that bupivacaine is superfluous and may actually reduce pain control by diluting the neurolytic effect of alcohol. Bupivacaine is also potentially dangerous in that it may produce serious adverse events such as arrythmias and cardiac arrest if inadvertently injected intravascularly. CONCLUSION: This randomized trial is designed to assess whether bupivacaine is of any value during EUS-CPN.

Endoscopic Ultrasound Guided Fine Needle Aspiration versus Endoscopic Ultrasound Guided Fine Needle Biopsy for Pancreatic Cancer Diagnosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: One of the most effective diagnostic tools for pancreatic cancer is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or biopsy (EUS-FNB). Several randomized clinical trials have compared different EUS tissue sampling needles for the diagnosis of pancreatic cancer. OBJECTIVE: To compare the diagnostic accuracy of EUS-guided FNA as EUS-FNB needles for the diagnosis of pancreatic cancer using a systematic review and meta-analysis. METHOD: A literature review with a meta-analysis was performed according to the PRISMA guide. The databases of PubMed, Cochrane and Google Scholar were used, including studies published between 2011-2021 comparing the diagnostic yield (diagnostic accuracy or probability of positivity, sensitivity, specificity, predictive value) of EUS-FNA and EUS-FNB for the diagnosis of pancreatic cancer. The primary outcome was diagnostic accuracy. Random effect models allowed estimation of the pooled odds ratio with a confidence interval (CI) of 95%. RESULTS: Nine randomized control trials were selected out of 5802 articles identified. Among these, five studies found no statistically significant difference between the EUS-FNA and EUS-FNB, whereas the other four did. The meta-analysis found EUS-FNB accuracy superior to EUS-FNA for the diagnosis of pancreatic cancer with a pooled odds ratio of 1.87 (IC 95%: 1.33-2.63). CONCLUSION: As compared to EUS-FNA, EUS-FNB seems to improve diagnostic accuracy when applied to suspicious pancreatic lesions.

EUS-guided celiac plexus neurolysis for pancreas cancer - Finally established or still under review?

Patients with pancreas cancer must deal frequently with intractable and refractory pain. Endoscopic ultrasound guided-celiac plexus neurolysis (EUS-CPN) has been the most studied and used therapeutic technique aimed to destroy the pain fibres that allow the pancreas to communicate with the central nervous system. A neurolytic agent, most commonly ethanol, is optimally spread around the celiac axis in order to reduce pain and mitigate narcotic requirements. This can be performed early to prevent the spiral of pain and medication use, or more historically as salvage therapy. Different techniques to best administer the ethanol for effective EUS-CPN are still being debated. New EUS-guided injection techniques with radiofrequency, radioactive, and/or chemotherapeutic agents need more study.

Controversies in EUS: Do we need miniprobes?

This is the fifth in a series of papers entitled "Controversies in EUS." In the current paper, we deal with high-resolution catheter probes, otherwise known as EUS miniprobes (EUS-MPs). The application of miniprobes for early carcinomas in the entire intestinal tract, for subepithelial lesions, and for findings in the bile duct and pancreatic duct as well as endobronchial use is critically discussed. Submucous lesions, especially in the colon, but also early carcinomas in special cases are considered the most important indications. The argument is illustrated by numerous examples.

A randomized noninferiority trial comparing the diagnostic yield of the 25G ProCore needle to the standard 25G needle in suspicious pancreatic lesions.

BACKGROUND AND OBJECTIVES: The aim of the study was to perform the first randomized trial comparing the diagnostic yield, bloodiness, and cellularity of the 25G standard needle (25S) and the 25G ProCore™ needle (25P). MATERIALS AND METHODS: All patients referred to the tertiary care referral center for EUS guided fine-needle aspiration (EUS-FNA) of suspicious solid pancreatic lesions were eligible. EUS-FNA was performed in each lesion with both 25S and 25P needles (the choice of the first needle was randomized), using a multipass sampling pattern, without stylet or suction. Rapid on-site evaluation was used when possible. Pap-stained slides were read by a single experienced cytopathologist, blinded to the needle type. RESULTS: One hundred and forty-three patients were recruited. Samples were positive for cancer in 122/143 (85.3%) with the 25S needle versus 126/143 (88.1%) with the 25P needle, negative in 17/143 (11.9%) with the 25S needle versus 13/143 (9.1%) with the 25P needle, and suspicious in 4/143 (2.8%) with each needle. There was no difference in any outcome based on the type of the first needle. No carryover effect was detected (P = 0.214; NS). Cumulative logistic regression analyses showed no associations between the type of needle and diagnostic yield for cancer, cellularity, or bloodiness. The difference in the yield for cancer was 2.9% (-4.2; 10.1%); with the confidence interval upper within the predetermined noninferiority margin of 15%. CONCLUSION: The 25S needle is noninferior to the 25P needle for diagnosing cancer in suspicious pancreatic lesions.

An international, multi-institution survey on performing EUS-FNA and fine needle biopsy.

BACKGROUND AND OBJECTIVES: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and fine needle biopsy (FNB) are effective techniques that are widely used for tissue acquisition. However, it remains unclear how to obtain high-quality specimens. Therefore, we conducted a survey of EUS-FNA and FNB techniques to determine practice patterns worldwide and to develop strong recommendations based on the experience of experts in the field. METHODS: This was a worldwide multi-institutional survey among members of the International Society of EUS Task Force (ISEUS-TF). The survey was administered by E-mail through the SurveyMonkey website. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Another questionnaire about the level of recommendation was designed to assess the respondents' answers. RESULTS: ISEUS-TF members developed a questionnaire containing 17 questions that was sent to 53 experts. Thirty-five experts completed the survey within the specified period. Among them, 40% and 54.3% performed 50-200 and more than 200 EUS sampling procedures annually, respectively. Some practice patterns regarding FNA/FNB were recommended. CONCLUSION: This is the first worldwide survey of EUS-FNA and FNB practice patterns. The results showed wide variations in practice patterns. Randomized studies are urgently needed to establish the best approach for optimizing the FNA/FNB procedures.

How to perform EUS-guided tattooing?

Recently, we introduced a series of papers describing on how to perform certain techniques and controversies in EUS. In the first paper, "What should be known before performing EUS examinations, Part I," the authors discussed clinical information and whether other imaging modalities should be needed before embarking in EUS examination. In Part II, some technical controversies on how EUS is performed are discussed from different points of view by providing the relevant available evidence. Herewith, we describe on how to perform EUS-guided fine needle tattooing (FNT) in daily practice. The aim of this paper is to discuss pros and cons for several issues including historical remarks, injecting material, technical approach, and how to perform EUS-FNT including argues in favor and against.

A proposal for the ideal algorithm for the diagnosis, staging, and treatment of pancreas masses suspicious for pancreatic adenocarcinoma: Results of a working group of the Canadian Society for Endoscopic Ultrasound.

Numerous clinical pathways exist for patients presenting with a suspicious pancreatic mass. These range from direct surgical intervention following staging, with preoperative cross-sectional imaging, EUS with or without fine-needle aspiration or fine-needle core biopsy; neoadjuvant chemotherapy and/or radiation therapy; or palliation. Although international guidelines exist for pancreas cancer management, the ideal workup and treatment for a suspicious pancreas mass is unclear. During its annual meeting in September 2017 (The Forum for Canadian Endoscopic Ultrasonography), the Canadian Society of Endoscopic Ultrasound organized a working group of experienced endosonographers and hepatobiliary surgeons from across Canada to achieve this goal.

A multi-institution consensus on how to perform EUS-guided biliary drainage for malignant biliary obstruction.

BACKGROUND AND OBJECTIVES: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed. METHODS: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD. RESULTS: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the first choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended. CONCLUSION: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition.

Endoscopic Ultrasound-Guided Management of Pain in Chronic Pancreatitis and Pancreatic Cancer: an Update.

OPINION STATEMENT: PURPOSE OF REVIEW: Unrelenting pain from chronic pancreatitis (CP) and pancreatic cancer (PC) remain clinical challenges for the physician and a significant cause of decreased quality of life for the patient. Endoscopic ultrasound (EUS)-guided therapy for each condition is distinct and builds on the endosonographer's straightforward access to the celiac axis. RECENT FINDINGS: Over the past 20 years, generally small studies of modest methodology have surfaced for both EUS-guided celiac plexus block (CPB) and celiac plexus neurolysis (CPN). Our review aims to synthesize, analyze, and update the latest literature on the technique, efficacy, and safety of these procedures. EUS-CPB's role in treating CP pain is likely still relevant for a subset of patients and studies have shown efficacy and safety. However, a dramatic drop in research publications on the topic will make optimizing its role (including technique, injectate, and patient selection) increasingly difficult. However, EUS-CPN for PC pain is actively being refined with new information, data, and even guidelines. New EUS-guided strategies to treat PC pain besides conventional neurolysis are also likely to evolve in coming years.

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis.

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one. CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

Onsite evaluation of endoscopic ultrasound fine needle aspiration: the endosonographer, the cytotechnologist and the cytopathologist.

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has become an essential tool in the management of multiple diseases. Its accuracy is related to different aspects of the technique, one of the most important being the experience and interaction of the endosonographer and pathologist. Certain studies over the past years have highlighted the importance of having rapid on-site evaluation (ROSE) of samples obtained at the time of EUS-FNA. We have reviewed the role of ROSE, performed by the same endosonographer, a cytotechnologist and an expert cytopathologist. The available data suggest that ROSE (either by the endosonographer, the cytotechnologist, or the cytopathologist) improves sample adequacy and diagnostic yield, with the best option to have ROSE performed by an expert cytopathologist. However, if non-ROSE accuracy is already very high, any improvement is harder to achieve.

Endoscopic ultrasound-guided FNA of pelvic lesions: A large single-center experience.

BACKGROUND: Pelvic endoscopic ultrasound-guided fine-needle aspiration (PEUS-FNA) of rectal or perirectal lesions is safe, minimally invasive, and well tolerated. It provides valuable information, which can greatly influence patient management. Herein, the authors present what to their knowledge is the largest series to date of PEUS-FNA. METHODS: PEUS-FNA specimens were retrieved from the archives of the study institution from January 2001 to March 2015. Only patients with solid pelvic lesions were examined. The cytopathology findings, immunohistochemistry, corresponding histology, and clinical data were collected. For analysis of accuracy, atypical or suspicious results were classified as "negative." The sensitivity and specificity of PEUS-FNA were calculated in a subset of patients with available surgical pathology. RESULTS: A total of 127 cases meeting the current study criteria were obtained from patients who underwent PEUS-FNA at the study institution between January 2001 and March 2015. The mean age of the patients was 60 years, and 53% were female. Pelvic lesions were comprised of 72% masses and 28% lymph nodes, with a mean mass diameter of 27.38 mm (range, 5-100 mm). PEUS-FNA was positive for malignancy in 45% of cases, atypical/suspicious in 4.7% of cases, and negative for malignancy in 50.3% of cases. Surgical pathology was available for 44 patients. PEUS-FNA demonstrated 89.3% sensitivity, 100% specificity, a diagnostic accuracy of 93.2%, a positive predictive value of 100%, and a negative predictive value of 84.2%. No complications were noted. CONCLUSIONS: PEUS-FNA is safe and effective for the investigation of pelvic lesions. Cancer Cytopathol 2016;124:836-41. © 2016 American Cancer Society.

Randomized controlled trial comparing stylet-free endoscopic ultrasound-guided fine-needle aspiration with 22-G and 25-G needles.

BACKGROUND AND AIM: Previous studies comparing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) results with different gauge needles have all been carried out with the stylet in place and show no clear advantage to the larger 22-G needle. Similar data for stylet-free EUS-FNA (SF-EUS-FNA) are unavailable. The aim of the present study was to determine whether diagnostic yield and specimen adequacy is superior with the 22-G needle as compared to the 25-G needle. METHODS: All patients ≥ 18 years referred for solid-lesion EUS-FNA were eligible. Patients with suspected diagnosis of lymphoma, gastrointestinal stromal tumor, sarcoidosis, significant coagulopathy (international normalized ratio > 1.5 or platelets < 50000/mm(3)), use of clopidogrel within 7 days of EUS, and pregnancy were excluded. The two needles were compared regarding diagnostic yield, sample adequacy, bloodiness, ease of puncture, visibility, number of passes, failures, and complications. RESULTS: One hundred and twenty consecutive patients were included and 126 lesions were sampled. Sensitivity, specificity, positive predictive value and negative predictive value for the 22-G SF-EUS-FNA were 83%, 100%, 100% and 56%, respectively, and for the 25-G SF-EUS-FNA were 88.8%, 100%, 100% and 76.5%, respectively (P=NS). There were no significant differences between the 22-G and the 25-G FNA needles in sample adequacy, bloodiness, ease of puncture, FNA failure, visibility, number of passes and complications; and no significant differences between either needle were found in relation to lesion site. CONCLUSION: For SF-EUS-FNA, the larger 22-G needle offers no advantage over the smaller 25-G needle.

Celiac plexus neurolysis in the management of unresectable pancreatic cancer: when and how?

Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20% resectability at diagnosis, and overall 5-year survival of 5%. Pain is common in pancreatic cancer patients with 70%-80% suffering substantial pain. Celiac plexus neurolysis (CPN) is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption. CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia. This review sets out to explore the current status of CPN in non-resectable pancreatic cancer. We will examine: (1) the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN; (2) specific technique modifications including bilateral (vs central) injections and celiac ganglia neurolysis; and (3) the issue of CPN timing, early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.