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Competing Interests: Disclosure The author disclosed no financial relationships.

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary The diagnostic accuracy of differentiating benign from malignant pancreatic cystic lesions is suboptimal, dependent on imaging in combination with cyst fluid markers and cytologic analysis, and more recently molecular markers. All modalities are often considered in combination to make the best assessment. In this case, a patient underwent EUS-FNA of a 2-cm pancreatic cyst because of the alarm feature of a mural nodule. Fluid analysis markers suggested the lesion to be benign, with high glucose and amylase levels and a low carcinoembryonic antigen. However, cytologic analysis revealed the presence of tumor cells from the mural nodule sampling consistent with neuroendocrine tumor. This case nicely illustrates the necessity of using multiple modalities for the diagnosis of pancreatic cysts, inasmuch as fluid analysis alone is not adequate for accurate diagnosis. Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Background and Aims: EUS-guided ethanol ablation is a recently introduced treatment approach for pancreatic cystic lesions (PCLs), including branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). However, the utility of this procedure is limited because of its relatively low efficacy in treating PCLs., Methods: We retrospectively reviewed patients with PCLs, including those with enlarging suspected BD-IPMNs or those with PCLs measuring >3 cm, who were suboptimal candidates for surgery and had been managed using EUS-guided rapid ethanol lavage (EUS-REL; immediate ethanol lavage performed 4 times, 2015-2022) or surveillance only (SO; 2007- 2022). Propensity score matching (PSM) was performed to minimize bias. The primary outcome was the cumulative incidence rate of BD-IPMN progression. Secondary outcomes were the efficacy and safety of EUS-REL, surgical resection rate (SR), overall survival (OS), and disease-specific survival (DSS) in both groups., Results: Overall, 169 and 610 patients were included in the EUS-REL and SO groups, respectively. PSM created 159 matched pairs. The radiologic complete resolution rate after EUS-REL was 74%. Procedure-related pancreatitis in the EUS-REL group was 13.0% (n = 22; 19 mild and 3 moderate grade); no severe adverse events were reported. The 10-year cumulative incidence rate of BD-IPMN progression was significantly lower in the EUS-REL group than in the SO group (1.6% vs 21.2%; hazard ratio, 12.35; P = .003). EUS-REL showed a lower tendency of SR compared with that associated with SO. The rates of 10-year OS and 10-year DSS were comparable in both groups., Conclusions: EUS-REL was associated with a significantly lower 10-year cumulative incidence rate of BD-IPMN progression and a lower tendency of SR, whereas its 10-year OS and DSS rates were similar to those of SO for PCLs. EUS-REL may be a viable alternative to SO for managing patients with enlarging suspected BD-IPMNs or those with PCLs >3 cm who are suboptimal candidates for surgery., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Pancreatic cystic neoplasms (PCNs) represent a difficult preoperative diagnosis despite improvements in imaging. In this study, we compared preoperative and final pathologic diagnosis in a large cohort of resected PCNs, evaluating diagnostic accuracy with a specific focus on the value of EUS., Methods: A retrospective analysis of patients undergoing resection between 2009 and 2019 for presumed PCNs was performed. Preoperative workup was reviewed by analyzing the role of imaging and EUS. Patients with a benign histology who did not show absolute indication were categorized as "delayable surgery.", Results: Of 585 patients who were retrospectively analyzed, in 108 (18.5%) final histology did not confirm preoperative diagnosis. EUS was associated with a lower rate of incorrect diagnosis (16%; P = .03), but the risk of overtreatment was similar regardless of instrumental diagnostic path (33/131 vs 68/328, P = .298). Dilatation of the main pancreatic duct and cytologic sampling were the only variables independently associated with a correct diagnosis (P < .001 and P = .041, respectively). Based on clinical presentation and final histology, pancreatic resection could have been spared or delayed in 101 of 459 patients (22%), and this was influenced by age (odds ratio [OR], .97; P = .002), cyst larger than 30 mm (OR, 1.89; P = .005), and type of operation (OR, 3.46 [P < .001] and 3.18 [P = .023] for distal pancreatectomies and other resections, respectively)., Conclusions: The overall risk of unnecessary immediate surgery for PCNs is about 22% in a high-volume referral center. EUS with cytologic sampling is a useful procedure in the diagnostic management of PCNs, improving their diagnostic accuracy., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Pancreatic cysts are common and often incidentally detected on abdominal imaging. Their prevalence in asymptomatic individuals depends on the screening modality used. The incidence of these lesions increases with age and may be detected in nearly half of elderly patients undergoing high-resolution magnetic resonance imaging. Some, but not all, pancreas cysts have malignant potential. The overall risk is small but induces significant anxiety for the patient. When determining management options, it is important to consider the patient's age, medical comorbidities, and surgical risks as well as the wishes of the patient. Current strategies include imaging surveillance or surgical resection. Before embarking on cyst surveillance, a clinician must factor in patients' risk of developing malignancy, their life expectancy, medical comorbidities, and if they are a surgical candidate. Surgery poses significant adverse events and mortality, whereas radiographic surveillance imposes healthcare costs and psychological distress to patients with the looming possibility of malignancy. The development and use of endoscopic ultrasound cyst ablation is a minimally invasive alternative in treating pancreatic cystic lesions. This review focuses on the modalities of ethanol ablation, paclitaxel ablation, and radiofrequency ablation of pancreatic cystic lesions., (Copyright © 2020. Published by Elsevier Inc.)

Background and Aims: Currently, 3 guidelines are available for the management of pancreatic cysts. These guidelines vary in their indication for resection of high-risk cysts. We retrospectively compared the final pathologic outcome of surgically removed pancreatic cysts with the indications for resection according to 3 different guidelines., Methods: Patients who underwent pancreatic resection were extracted from our prospective pancreatic cyst database (2006-present). The final histopathologic diagnosis was compared with the initial indication for surgery stated by the guidelines of the International Association of Pancreatology (IAP), European Study Group on Cystic tumors of the Pancreas and American Gastroenterological Association (AGA). We considered surgery in retrospect justified for malignancy, high-grade dysplasia, solid pseudopapillary neoplasms, neuroendocrine tumors or symptom improvement. Furthermore, we evaluated the patients with suspected intraductal papillary mucinous neoplasm (IPMN) separately., Results: Overall, 115 patients underwent pancreatic resection. The preoperative diagnosis was correct in 83 of 115 patients (72%) and differentiation between benign and premalignant in 99 of 115 patients (86%). In retrospect, surgery was justified according to the aforementioned criteria in 52 of 115 patients (45%). For patients with suspected IPMN (n = 75) resection was justified in 36 of 67 (54%), 36 of 68 (53%), and 32 of 54 (59%) of patients who would have had surgery based on the IAP, European, or AGA guidelines, respectively. The AGA guideline would have avoided resection in 21 of 75 (28%) patients, versus 8 of 75 (11%) and 7 of 75 (9%) when the IAP or European guideline would have been applied strictly. Nevertheless, 4 of 33 patients (12%) with high-grade dysplasia or malignancy would have been missed with the AGA guidelines, compared with none with the IAP or European guidelines., Conclusion: Although fewer patients undergo unnecessary surgery based on the AGA guidelines, the risk of missing malignancy or high-grade dysplasia with this guideline seems considerably high., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The role of pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts remains unclear., Objective: Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cysts., Design: Prospective, multicenter study., Patients: Patients with pancreatic cysts presenting for EUS evaluation., Intervention: EUS-guided pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA) level determination, and a detailed DNA analysis; incorporating DNA quantification, k-ras mutation and multiple allelic loss analysis, mutational amplitude, and sequence determination., Main Outcome Measurements: Cyst fluid analysis compared with surgical pathologic or malignant cytologic examination., Results: The study cohort consisted of 113 patients with 40 malignant, 48 premalignant, and 25 benign cysts. Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver-operator characteristic curve analysis indicated optimal cutoff points for allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and CEA (AUC 0.74; optimal value >148 ng/mL). Components of DNA analysis detecting malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA amount (optical density ratio >10, AUC 0.79). The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy. All malignant cysts with negative cytologic evaluation (10/40) could be diagnosed as malignant by using DNA analysis., Limitations: Limited follow-up, selection bias., Conclusions: Elevated amounts of pancreatic cyst fluid DNA, high-amplitude mutations, and specific mutation acquisition sequences are indicators of malignancy. The presence of a k-ras mutation is also indicative of a mucinous cyst. DNA analysis should be considered when cyst cytologic examination is negative for malignancy.

Background: Endoscopic therapy of walled-off pancreatic necrosis (WOPN) via direct intracavitary debridement is described., Objective: To compare direct endoscopic necrosectomy with conventional transmural endoscopic drainage for the treatment of WOPN., Design: Retrospective, comparative study., Setting: Academic tertiary-care center., Patients: Patients referred to Mayo Clinic, Rochester, Minnesota, since April 1998 for endoscopic drainage of WOPN., Interventions: Each patient underwent standard endoscopic drainage that consisted of transmural cavity puncture, dilation of the fistula tract, and placement of a large-bore stent(s). Patients were classified into the direct endoscopic necrosectomy group if, during any of their procedures, adjunctive direct endoscopic necrosectomy was performed; all others were in the standard drainage group., Main Outcome Measurements: Success was defined as resolution of the necrotic cavity without the need for operative or percutaneous intervention., Results: Forty-five patients were identified who met study criteria: 25 underwent direct endoscopic necrosectomy, and 20 underwent standard endoscopic drainage. There were no differences in baseline patient or cavity characteristics. Successful resolution was accomplished in 88% who underwent direct endoscopic necrosectomy versus 45% who received standard drainage (P < .01), without a change in the total number of procedures. The maximum size of tract dilation was larger in the direct endoscopic necrosectomy group (17 mm vs 14 mm, P < .02). Complications were limited to mild periprocedural bleeding with equivalent rates between groups., Limitations: Retrospective, referral bias, single center., Conclusions: Direct endoscopic necrosectomy achieves higher rates of resolution, without a concomitant change in the number of endoscopic procedures, complication rate, or time to resolution compared with standard endoscopic drainage for WOPN. The need for fewer postprocedural inpatient hospital days and a decrease in the rate of cavity recurrence are also likely benefits of this technique.

Background: Lymphoepithelial cysts (LEC) of the pancreas are rare benign lesions that can be misdiagnosed as pancreatic masses or cystic neoplasms. With widespread use of abdominal cross-sectional imaging, more pancreatic lesions are being discovered, with EUS being used to further evaluate the abnormality., Objective: Our purpose was to describe EUS and cyst aspirate features of LEC of the pancreas., Design: Case series., Setting: Single tertiary referral center., Patients: Nine patients with lymphoepithelial cysts who underwent EUS-FNA., Results: Five male and 4 female patients were identified (mean age 51 years). All lesions were discovered by CT and described as "peripancreatic" in 67% of cases (6/9). EUS examination described a solid-appearing hypoechoic and heterogeneous mass with subtle postacoustic enhancement in 5 of 9 cases. Four lesions were described as purely cystic: 2 were septated, 1 was unilocular, and 1 had internal papillary fronds. Mean cyst size was 5.2 cm (range 1.7-12 cm). Cyst aspirates revealed a thick milky, creamy, or frothy aspirate in 56% of cases (5/9). Cyst cytologic examination revealed squamous material (nucleated/anucleated cells or keratin debris) in all cases. Lymphocytes were seen in 56% of aspirates (5/9). Carcinoembryonic antigen (CEA) levels were obtained in 5 cases (median 6.5 ng/mL [range 2.9-493.4 ng/mL]). Six patients have avoided surgery on the basis of EUS-FNA cytologic results confirming the diagnosis of LEC. Three patients underwent surgical resection: 2 for symptomatic lesions and 1 for concern for a mucinous cystic neoplasm given an elevated aspirate CEA level. Surgical pathologic examination confirmed LEC in each., Limitations: Retrospective single-center study., Conclusions: LEC should be considered whenever a large, well-defined solid or cystic peripheral pancreatic lesion is found. A thick milky, creamy, or frothy aspirate is common. The presence of squamous material and lymphocytes on cytologic examination is diagnostic of LEC. Aspirate CEA level may be elevated and should be considered in conjunction with cytologic results to avoid misdiagnosis as a mucinous cystic neoplasm. Asymptomatic LEC should be managed conservatively.

Background: Complications from EUS-guided FNA of cystic lesions of the pancreas are infrequent. Although several studies have evaluated infectious complications of EUS-guided FNA in this setting, the frequency and the clinical significance of intracystic hemorrhage have not been determined. This study assessed the frequency of acute intracystic hemorrhage during EUS-guided FNA of pancreatic cystic lesions. The characteristic EUS appearance is described., Methods: EUS-guided FNA of pancreatic cyst lesions was performed in 50 patients (July 2000 to June 2003). Patients were followed prospectively for the development of complications., Observations: Acute intracystic hemorrhage occurred during EUS-guided FNA at the site of aspiration in 3 patients (6%: 95% confidence interval [1.3%, 16.6%]). Endosonographically, the bleeding manifested as a small hyperechoic area at the puncture site that progressed gradually over a few minutes to involve the majority of the cyst cavity. EUS-guided FNA was terminated when bleeding was observed. One patient was asymptomatic, but two patients experienced abdominal pain transiently. All patients were treated with a short course of orally administered antibiotics and were observed as outpatients. Clinical history and laboratory parameters did not predict which patients were at risk for intracystic hemorrhage., Conclusions: Acute intracystic hemorrhage is a rare complication of EUS-guided FNA; it has a characteristic EUS appearance. Recognition of this event is important, because it permits termination of the procedure and thereby minimizes the potential for more serious bleeding.

Background: Much attention has been focused on the competence to perform endoscopic procedures. The aim of this study was to determine the impact of procedure experience on patient outcomes after endoscopic pancreatic fluid collection drainage., Methods: Outcomes for consecutive patients with symptoms from pancreatic fluid collections who were referred for endoscopic transmural and/or transpapillary drainage were analyzed retrospectively. Collections were classified as acute pseudocyst, chronic pseudocyst, and pancreatic necrosis. To assess the impact of endoscopist experience, outcomes for patients who underwent the first 20 procedures were compared with those for patients who had subsequent procedures., Results: In total, 175 patients underwent pancreatic fluid collection drainage; 40 (23%) acute pseudocyst, 78 (44%) chronic pseudocyst, and 57 (33%) pancreatic necrosis. Procedure complication rates, collection recurrence rates, and patient outcomes after acute pseudocyst drainage were independent of endoscopist experience. There was a dramatic improvement in chronic pseudocyst resolution rates after the first 20 procedures versus subsequent procedures (45% vs. 93%; p = 0.0002) and a reduction in days to resolution (50 days, initial 20 procedures vs. 33.5 days, subsequent procedures; p = 0.05). In patients with pancreatic necrosis, there was a decrease in median hospital stay with greater experience (23 days to 15 days; p = 0.04)., Conclusions: Resolution of chronic pseudocyst after endoscopic drainage improves markedly with increasing endoscopist experience. Future prospective studies assessing skill acquisition are required to define the minimum number of collection drainage procedures at which competence can be achieved.

Background: A prerequisite for endoscopic drainage of pancreatic fluid collections without EUS is the presence of a visible bulge in the GI wall. Our experience with endoscopic cystostomy of nonbulging pancreatic fluid collections is described., Methods: Thirty-three patients underwent 34 endoscopic attempts at transmural drainage of nonbulging pancreatic fluid collections over a 2-year period. The etiology of the nonbulging pancreatic fluid collections was chronic pancreatitis in 26 cases and acute pancreatitis in 7. Indications for drainage included one or more of the following: abdominal pain, infection, biliary obstruction, and external fistula. The diameter of the collections ranged from 20 to 160 mm (median 52 mm)., Results: Thirty-two of 34 drainage attempts were successful (94%). Eighteen cystostomies were performed under fluoroscopy alone and 14 by EUS together with fluoroscopy. Procedure-related complications occurred with 3 of 34 attempts (8%). Surgery was not required for treatment of the complications and there were no deaths from the procedure. Follow-up was available for 31 patients (median 21 months, range 9 to 40 months). One nonbulging pancreatic fluid collections recurred 7 months after drainage., Conclusions: Endoscopic cystenterostomy of nonbulging pancreatic collections is feasible, and the results of the procedure are similar to those of cystenterostomy for bulging collections.

Background: EUS can provide detailed imaging of pancreatic malignancies and direct fine needle aspiration (FNA) of pancreatic masses. The ability of EUS to detect and stage malignancy in cystic and intraductal lesions has not been investigated. Our aim was to determine the sensitivity and specificity of EUS imaging and FNA in detecting and staging of malignancy in solid, cystic, and intraductal lesions of the pancreas., Methods: The records of 96 patients (46 solid, 26 cystic, 24 intraductal lesions) who underwent EUS followed by surgical exploration over a 3-year period were reviewed. The accuracy of EUS for detecting and staging malignancy was calculated based on the results of surgery and histology., Results: EUS-guided FNA provided evidence of malignancy in solid, cystic, and ductal lesions with sensitivities of 59.5%, 50%, and 60%, respectively. The accuracy of staging by EUS was significantly less for intraductal lesions (47%), compared with cystic (100%) and solid lesions (85%) (p < 0. 05)., Conclusions: EUS can be used to detect malignancy in cystic and intraductal tumors of the pancreas.